Patent Document

This application is a continuation of application Ser. No. 08/021,608, filed Feb. 22, 1993 now U.S. Pat. No. 5,580,760. 
    
    
     FILED OF THE INVENTION 
     The present invention relates to a novel human cDNA and the encoded protein which interacts with a cis-element activator, known as the FUSE binding protein. A novel DNA-binding regulator of c-myc expression (&#34;DROME&#34;) was purified, and then proteolytically and chemically degraded to peptides. These peptides were separated by HPLC and the sequences of multiple peptides were determined. Using the information from the peptide sequence, specific oligonucleotide primers were synthesized and then used as primers for the polymerase chain reaction employing human cDNA as a template. The resulting products were cloned and sequenced, and shown to encode additional peptides of the DROME protein. These DNA segments were then employed as probes to screen multiple phage libraries in order to reconstruct a full length reading frame from several overlapping clones. This information allows the expression of a full length protein. As used herein, the terms DROME and FUSE binding protein (&#34;FBP&#34;) are synonymous. 
     BACKGROUND OF THE INVENTION 
     The c-myc proto-oncogene plays a central role in normal cell proliferation and programmed cell death (Y. Shi, J. Glynn, L. Guilbert, T. Cotter, R. Bissonnette, and D. Green, &#34;Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas,&#34; Science, 257:212-214 (1992)) and its deregulation contributes to the formation of a variety of tumors. (J. M. Bishop, Annu. Rev. Biochem. 52,301-354 (1983); M. D. Cole, &#34;The myc oncogene: its role in transformation and differentiation.&#34; Annu. Rev. Genet. 20, 361-384 (1986); S. Cory, Adv. Cancer Res. 47, 189-234 (1986)). 
     Down regulation of the c-myc proto-oncogene occurs in the human promonomyelocytic leukemia cell line HL60 and human monoblastic line, U937, upon induction of differentiation. (C. Dony, M. Kessel, and P. Gruss, Nature. 317, 636-639 (1985); L. E. Grosso, and H. C. Pitot, Cancer Res. 45, 847-850 (1985); T. Watanabe, E. Sariban, T. Mitchell, and D. Kufe, Biochem. Biophys. Res. Commun. 126, 999-1005 (1985); D. L. Bentley, and M. Groudine, Nature, 321, 702-706 (1986); D. Eick and G. W. Bornkamm, Nucleic Acids Res. 14, 8331-8346 (1986); T. Endo, and B. Nadal-Ginard, Mol. Cell. Biol. 6, 1412-1421 (1986)). This suppression of c-myc expression occurs by two mechanisms; within three hours there is a block to elongation which can be reversed by removal of the differentiation agent. Subsequently, transcriptional initiation ceases, coinciding with irreversible commitment to the differentiation pathway. (U. Siebenlist, P. Bressler, and K. Kelly, Mol. Cel. Biol. 8, 867-874 (1988)). 
     A Far Upstream Element (&#34;FUSE&#34;) which is required for maximal transcription of c-myc, binds a factor (DROME or FUSE binding protein (&#34;FBP&#34;)) which is present in extracts of undifferentiated cells, but disappears upon differentiation. (M. I. Avigan, B. Strober, and D. Levens, &#34;A Far Upstream Element Stimulates c-myc Expression In Undifferentiated Leukemia Cells.&#34; J. Biol. Chem. 265, 18538-18545 (1990)). The disappearance of this binding activity occurs 24 hours after addition of the differentiation agent coinciding with the loss of initiation of c-myc transcription. The FUSE site differs from other described positive regulatory elements for myc in a number of ways. Despite its placement a long distance from the transcription start site (-1500 bp relative to the myc P1 promoter), the FUSE element will not act as a traditional enhancer; multiple copies inserted upstream of a heterologous promoter do not stimulate transcription in transection experiments. However, when the FUSE site is present with additional c-myc regulatory sequences, specific stimulation of the c-myc promoter is observed, indicating that FUSE works in concert with other myc elements. These features suggest that the factor binding to this site may act to stimulate transcription by an unusual mechanism. 
     SUMMARY OF THE INVENTION 
     The nucleotide sequence for a novel DNA-binding regulator of c-myc expression is provided, together with the amino acid sequence for the encoded protein. The protein interacts with an activator cis-element approximately 1500 basepairs 5&#39; of the human c-myc gene promoter P1. The cDNA and variations thereof have the nucleotide sequences of SEQ ID NO:1, SEQ ID NO:5, SEQ ID NO:7 and SEQ ID NO:9, and the proteins have the amino acid sequences of SEQ ID NO:2, SEQ ID NO:6, SEQ ID NO:8 and SEQ ID NO:10. 
     With the given sequence for the cDNA and protein of the present invention, one may now study genetic abnormalities of c-myc expression, in addition to numerous other uses of the gene and encoded protein. 
     The gene encoding the DROME or FUSE binding protein is useful in the diagnosis of disease states. Specific nucleic acid probes derived from knowledge of the DROME sequence and genetic map for PCR or hybridization are useful to analyze mutations, translocations and other genetic derangements that are associated with abnormalities of DROME or c-myc expression. Because DROME is highly activated during T-cell stimulation, these probes are useful to analyze immune system abnormalities. The DROME probes are also useful to analyze a variety of physiologic and pathologic conditions. 
     Knowledge of the cDNA and genomic structures of DROME allows the construction of vectors which express DROME or which express anti-sense DROME sequence. Oligonucleotide and expression vector anti-sense approaches to block DROME expression are useful to modulate DROME expression in vivo, which results in therapeutic modification of the levels of expression of genes regulated by DROME. Such strategies are of therapeutic value to certain pathologic conditions or can be used to provide prophylactic or beneficial changes in DROME expression in pre-pathologic conditions. If genetic disorders can be ascribed to abnormalities of the DROME protein or its expression, then gene therapy for such disorders will be heavily dependent on the information and materials derived from the characterization of the DROME gene and its cDNA. 
     Expression of the DROME protein itself in prokaryotic and eukaryotic expression vectors is useful in several regards. The DROME protein or fragments thereof are useful as an immunogen to generate polyclonal and monoclonal antibodies which can then be used to detect and quantitate the DROME protein. The DROME protein itself is useful as a probe to identify and quantify proteins which interact with or modify DROME; similarly, if the DROME protein is immobilized as a ligand for larger scale operations, the DROME interacting or modifying molecules can be purified. All of these proteins can be employed singly or in combination together with existing technologies as assay kits to detect, quantitate and analyze DROME protein. 
     Structural analysis of the DROME protein has defined a new DNA binding motif composed of a unique repeating element followed by an amphipathic helix. Knowledge of these structural elements together with knowledge of the complete cDNA sequence permits the identification, cloning and characterization of the genes for related proteins and DROME homologs using hybridization based or PCR based methods. 
     Because proteins which share structural motifs often share biochemical properties as well as functional and physiological roles, it is expected that DROME homologs and other proteins with the newly defined DNA binding motif are also important regulators of cell growth and other cellular processes. The same approaches used to modify DROME expression by sense and anti-sense vectors and anti-sense oligonucleotides is applied to DROME homologs and proteins sharing the DROME DNA binding motif in order to alter cell growth and cellular properties. These proteins or fragments thereof, which are either DROME homologs or recognizable as DNA binding proteins because they possess the DNA binding motif described herein, are useful for the generation of antibodies and diagnostic kits to relate these molecules to cancer, genetic and other human maladies. These proteins, antibodies and kits are useful in the diagnosis, treatment and study of human diseases. 
     Similarly, altered forms of the protein, either due to post-translational modification or altered RNA processing resulting from altered splicing or other RNA modifications, are identified and characterized utilizing the protein, antibody and nucleic acid probes outlined above. Each of these new proteins and/or genes all related to DROME are then subjected to similar analyses. 
    
    
     BRIEF DESCRIPTION OF FIGURES 
     FIGS. 1A and 1B depict radiographs showing reduced expression over time of FBP mRNA. 
     FIG. 2 gives the primary structure of DROME or FUSE binding protein (FBP) cDNA sequences. 
     FIGS. 3A and 3B depict DNA binding assay radiographs showing that recombinant FBP binds specifically to the far upstream element. 
     FIG. 4 shows assays depicting recombinant FBP activated expression of a chloramphenicol acetyltransferase (CAT) gene under the control of human c-myc regulatory sequence. 
     FIGS. 5A-5C show the structural features of the primary amino acid sequence of FBP. 
     FIGS. 6A-6C illustrates a mutational analysis of the minimum DNA binding domain of recombinant FBP. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     A 70 kilodalton (kd) FUSE binding protein (FBP) has been purified from undifferentiated HL60 cells, the protein eluted from an SDS acrylamide gel and the amino acid sequence of internal peptides determined. The peptide sequences enabled the design of oligonucleotide PCR primers used to amplify cDNA template prepared from undifferentiated U937 cell total RNA. 
     Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed as described in D. Rappolee, A. Wang, D. Mark, and Z. Werb, J. Cell. Biochem. 39,1 (1989). In the RT step 5 μg total U937 RNA, 1.5 μg of random hexamer primers (Promega) and 20 μMoles of each deoxynucleotide triphosphate (dNTP) were incubated in a 40 μl reaction with Superscript Reverse Transcriptase (BRL) and the manufacturer&#39;s reaction buffer adjusted to 10 mM dithiothreitol at 45° C. for 1 hour. After ethanol precipitation and reconstitution in 40 μl dH 2  O, 2 μl of the RT reaction products were used as template in a 50 μl PCR reaction with 20 pMoles of each degenerate primer, 20 nMoles each dNTP, 1.5 units Amplitaq polymerase (Perkin Elmer Cetus) and the manufacturer&#39;s buffer adjusted to 7.5 mM MgCL 2 . Samples were incubated through 25 cycles of 94° C., 55° C., and 72° C., 2 minutes at each temperature. 
     Two amplified products contained open reading frames encoding segments identical to peptide sequences from purified FBP confirming that the authentic cDNA had been obtained. 
     The PCR fragments hybridized to a single 2.6 kilobase (kb) RNA which disappeared after DMSO induced differentiation (FIG. 1A) consistent with the loss of FUSE binding activity after DMSO treatment. Polyadenylated RNA (10 μg) from cultured cells (J. M. Chirgwin et al., Biochemistry, 18, 5294 (1979)) was separated on a 1% agarose-formaldehyde gel, transferred to nitrocellulose and hybridized with a  32  P probe from FBP, B-actin, or human c-myc cDNAs. FIG. 1A shows RNA prepared from HL60 cells grown 48 hrs. in the presence (+) or absence (-) of 1.3% Dimethyl Sulfoxide (DMSO) in RPMI medium supplemented with 10% fetal calf serum, glutamine, penicillin and streptomycin. FIG. 1B shows RNA prepared from HL60 cells cultured as indicated with or without 50 ng/ml 12-o-tetradecanohlphorbol 13-acetate (TPA) in the same medium as above. 
     As depicted in FIG. 1B, expression of the 2.6 kb transcript sharply declined after 24 hours of treatment with TPA and was undetectable at 48 hours paralleling: 1) the disappearance of the FUSE binding activity, 2) a dramatic decrease in c-myc transcriptional initiation and, 3) irreversible commitment to terminal differentiation. Hence, FBP mRNA and binding activity are shut off synchronously during differention. 
     A full length FBP cDNA sequence was assembled from overlapping clones obtained from three libraries using the PCR fragments as probes. All three cDNA libraries were prepared from poly A selected RNA and ligated into the lambda Zap II vector (Stratagene). Source RNAs were from undifferentiated HL60 cells, the B lymphoma cell line, BJAB, and PMA/PHA stimulated pooled human peripheral blood lymphocytes (PBLs). 
     The composite 2,384 bp cDNA contains 26 bp of 5&#39; untranslated sequence, 1932 bp of open reading frame, and 426 bp of 3&#39; untranslated including a poly A addition signal and 60 bp of poly A tail, as shown in FIG. 2. 
     The open box (FIG. 2) in the composite cDNA indicates the coding region, A n  the poly A tail. The position of PCR products and clones are shown, solid lines represent vertically aligned identical sequence, dashed lines represent non-homologous sequence. Clone names at left indicate source or library of origin. The nonhomologous sequences in the HL60 clones, BJAB-1, and PBL-3 most likely are from reverse transcribed, unspliced pre-mRNA or extraneous cDNA fragments ligated together during the preparation of the libraries. The open circle on clone BJAB-2 indicates the position of the 3 base pair deletion. Dideoxy sequencing (Sequenase, U.S. Biochemical) followed the manufacturer&#39;s protocol. 
     The nucleic acid sequence (SEQ ID NO:1) of the full length cDNA is as follows: 
     
         __________________________________________________________________________GCGGCAGCGG CTCTTATAGT GCAACC                ATG                   GCA                      GAC                         TAT                            TCA                               ACA                                  44CGCCGTCGCC GAGAATATCA CGTTGG                TAC                   CGT                      CTG                         ATA                            AGT                               TGTMet                  Ala                   Asp                      Tyr                         Ser                            Thr1                             5GTG   CCT CCC    CCC       TCT          TCT             GGC                TCA                   GCT                      GGT                         GGC                            GGT                               GGT                                  83CAC   GGA GGG    GGG       AGA          AGA             CCG                AGT                   CGA                      CCA                         CCG                            CCA                               CCAVal   Pro Pro    Pro       Ser          Ser             Gly                Ser                   Ala                      Gly                         Gly                            Gly                               Gly    10             15GGC   GGC GGT    GGT       GGT          GGA             GGA                GTT                   AAC                      GAC                         GCT                            TTC                               AAA                                  122CCG   CCG CCA    CCA       CCA          CCT             CCT                CAA                   TTG                      CTG                         CGA                            AAG                               TTTGly   Gly Gly    Gly       Gly          Gly             Gly                Val                   Asn                      Asp                         Ala                            Phe                               Lys20             25             30GAT   GCA CTG    CAG       AGA          GCC             CGG                CAG                   ATT                      GCA                         GCA                            AAA                               ATT                                  161CTA   CGT GAC    GTC       TCT          CGG             GCC                GTC                   TAA                      CGT                         CGT                            TTT                               TAAAsp   Ala Leu    Gln       Arg          Ala             Arg                Gln                   Ile                      Ala                         Ala                            Lys                               Ile 35             40             45GGA   GGT GAT    GCA       GGG          ACA             TCA                CTG                   AAT                      TCA                         AAT                            GAC                               TAT                                  200CCT   CCA CTA    CGT       CCC          TGT             AGT                GAC                   TTA                      AGT                         TTA                            CTG                               ATAGly   Gly Asp    Ala       Gly          Thr             Ser                Leu                   Asn                      Ser                         Asn                            Asp                               Tyr       50             55GGT   TAT GGG    GGA       CAA          AAA             AGA                CCT                   TTA                      GAA                         GAT                            GGA                               GAT                                  239CCA   ATA CCC    CCT       GTT          TTT             TCT                GGA                   AAT                      CTT                         CTA                            CCT                               CTAGly   Tyr Gly    Gly       Gln          Lys             Arg                Pro                   Leu                      Glu                         Asp                            Gly                               Asp   60             65             70CAA   CCA GAT    GCT       AAG          AAA             GTT                GCT                   CCT                      CAA                         AAT                            GAC                               TCT                                  278GTT   GGT CTA    CGA       TTC          TTT             CAA                CGA                   GGA                      GTT                         TTA                            CTG                               AGAGln   Pro Asp    Ala       Lys          Lys             Val                Ala                   Pro                      Gln                         Asn                            Asp                               Ser    75             80TTT   GGA ACA    CAG       TTA          CCA             CCG                ATG                   CAT                      CAG                         CAG                            CAA                               AGC                                  317AAA   CCT TGT    GTC       AAT          GGT             GGC                TAC                   GTA                      GTC                         GTC                            GTT                               TCGPhe   Gly Thr    Gln       Leu          Pro             Pro                Met                   His                      Gln                         Gln                            Gln                               Ser85             90             95AGA   TCT GTA    ATG       ACA          GAA             GAA                TAC                   AAA                      GTT                         CCA                            GAT                               GGA                                  356TCT   AGA CAT    TAC       TGT          CTT             CTT                ATG                   TTT                      CAA                         GGT                            CTA                               CCTArg   Ser Val    Met       Thr          Glu             Glu                Tyr                   Lys                      Val                         Pro                            Asp                               Gly 100            105            110ATG   GTT GGA    TTC       ATA          ATT             GGC                AGA                   GGA                      GGT                         GAA                            CAG                               ATC                                  395TAC   CAA CCT    AAG       TAT          TAA             CCG                TCT                   CCT                      CCA                         CTT                            GTC                               TAGMet   Val Gly    Phe       Ile          Ile             Gly                Arg                   Gly                      Gly                         Glu                            Gln                               Ile       115            120TCA   CGC ATA    CAA       CAG          GAA             TCT                GGA                   TGC                      AAA                         ATA                            CAG                               ATA                                  434AGT   GCG TAT    GTT       GTC          CTT             AGA                CCT                   ACG                      TTT                         TAT                            GTC                               TATSer   Arg Ile    Gln       Gln          Glu             Ser                Gly                   Cys                      Lys                         Ile                            Gln                               Ile   125            130            135GCT   CCT GAC    AGT       GGT          GGC             CTT                CCA                   GAA                      AGG                         TCC                            TGT                               ATG                                  473CGA   GGA CTG    TCA       CCA          CCG             GAA                GGT                   CTT                      TCC                         AGG                            ACA                               TACAla   Pro Asp    Ser       Gly          Gly             Leu                Pro                   Glu                      Arg                         Ser                            Cys                               Met    140            145TTA   ACT GGA    ACA       CCT          GAA             TCT                GTC                   CAG                      TCA                         GCA                            AAA                               CGG                                  512AAT   TGA CCT    TGT       GGA          CTT             AGA                CAG                   GTC                      AGT                         CGT                            TTT                               GCCLeu   Thr Gly    Thr       Pro          Glu             Ser                Val                   Gln                      Ser                         Ala                            Lys                               Arg150            155            160TTA   CTG GAC    CAG       ATT          GTT             GAA                AAA                   GGA                      AGA                         CCA                            GCT                               CCT                                  551AAT   GAC CTG    GTC       TAA          CAA             CTT                TTT                   CCT                      TCT                         GGT                            CGA                               GGALeu   Leu Asp    Gln       Ile          Val             Glu                Lys                   Gly                      Arg                         Pro                            Ala                               Pro 165            170            175GGC   TTC CAT    CAT       GGC          GAT             GGA                CCG                   GGA                      AAT                         GCA                            GTT                               CAA                                  590CCG   AAG GTA    GTA       CCG          CTA             CCT                GGC                   CCT                      TTA                         CGT                            CAA                               GTTGly   Phe His    His       Gly          Asp             Gly                Pro                   Gly                      Asn                         Ala                            Val                               Gln       180            185GAA   ATC ATG    ATT       CCA          GCT             AGC                AAG                   GCA                      GGA                         TTA                            GTC                               ATT                                  629CTT   TAG TAC    TAA       GGT          CGA             TCG                TTC                   CGT                      CCT                         AAT                            CAG                               TAAGlu   Ile Met    Ile       Pro          Ala             Ser                Lys                   Ala                      Gly                         Leu                            Val                               Ile   190            195            200GGA   AAA GGG    GGA       GAA          ACT             ATT                AAA                   CAG                      CTT                         CAG                            GAA                               CGG                                  668CCT   TTT CCC    CCT       CTT          TGA             TAA                TTT                   GTC                      GAA                         GTC                            CTT                               GCCGly   Lys Gly    Gly       Glu          Thr             Ile                Lys                   Gln                      Leu                         Gln                            Glu                               Arg    205            210GCT   GGA GTT    AAA       ATG          GTT             ATG                ATT                   CAA                      GAC                         GGG                            CCG                               CAG                                  707CGA   CCT CAA    TTT       TAC          CAA             TAC                TAA                   GTT                      CTG                         CCC                            GGC                               GTCAla   Gly Val    Lys       Met          Val             Met                Ile                   Gln                      Asp                         Gly                            Pro                               Gln215            220            225AAC   ACT GGT    GCT       GAC          AAA             CCT                CTT                   AGG                      ATT                         ACA                            GGA                               GAC                                  746TTG   TGA CCA    CGA       CTG          TTT             GGA                GAA                   TCC                      TAA                         TGT                            CCT                               CTGAsn   Thr Gly    Ala       Asp          Lys             Pro                Leu                   Arg                      Ile                         Thr                            Gly                               Asp 230            235            240CCA   TAT AAA    GTT       CAA          CAA             GCC                AAG                   GAA                      ATG                         GTG                            TTA                               GAG                                  785GGT   ATA TTT    CAA       GTT          GTT             CGG                TTC                   CTT                      TAC                         CAC                            AAT                               CTCPro   Tyr Lys    Val       Gln          Gln             Ala                Lys                   Glu                      Met                         Val                            Leu                               Glu       245            250TTA   ATT CGT    GAT       CAA          GGC             GGT                TTC                   AGA                      GAA                         GTT                            CGG                               AAT                                  824AAT   TAA GCA    CTA       GTT          CCG             CCA                AAG                   TCT                      CTT                         CAA                            GCC                               TTALeu   Ile Arg    Asp       Gln          Gly             Gly                Phe                   Arg                      Glu                         Val                            Arg                               Asn   255            260            265GAG   TAT GGG    TCA       AGA          ATA             GGA                GGA                   AAT                      GAA                         GGG                            ATA                               GAT                                  863CTC   ATA CCC    AGT       TCT          TAT             CCT                CCT                   TTA                      CTT                         CCC                            TAT                               CTAGlu   Tyr Gly    Ser       Arg          Ile             Gly                Gly                   Asn                      Glu                         Gly                            Ile                               Asp    270            275GTC   CCC ATT    CCA       AGA          TTT             GCT                GTT                   GGC                      ATT                         GTA                            ATA                               GGA                                  902CAG   GGG TAA    GGT       TCT          AAA             CGA                CAA                   CCG                      TAA                         CAT                            TAT                               CCTVal   Pro Ile    Pro       Arg          Phe             Ala                Val                   Gly                      Ile                         Val                            Ile                               Gly280            285            290AGA   AAT GGA    GAG       ATG          ATC             AAA                AAA                   ATA                      CAA                         AAT                            GAT                               GCT                                  941TCT   TTA CCT    CTC       TAC          TAG             TTT                TTT                   TAT                      GTT                         TTA                            CTA                               CGAArg   Asn Gly    Glu       Met          Ile             Lys                Lys                   Ile                      Gln                         Asn                            Asp                               Ala 295            300            305GGT   GTT CGC    ATT       CAG          TTT             AAG                CCA                   GAT                      GAT                         GGG                            ACA                               ACA                                  980CCA   CAA GCG    TAA       GTC          AAA             TTC                GGT                   CTA                      CTA                         CCC                            TGT                               TGTGly   Val Arg    Ile       Gln          Phe             Lys                Pro                   Asp                      Asp                         Gly                            Thr                               Thr       310            315CCC   GAA AGG    ATA       GCA          CAA             ATA                ACA                   GGA                      CCT                         CCA                            GAC                               CGA                                  1019GGG   CTT TCC    TAT       CGT          GTT             TAT                TGT                   CCT                      GGA                         GGT                            CTG                               GCTPro   Glu Arg    Ile       Ala          Gln             Ile                Thr                   Gly                      Pro                         Pro                            Asp                               Arg   320            325            330TGT   CAA CAT    GCT       GCA          GAA             ATT                ATT                   ACA                      GAC                         CTT                            CTT                               CGA                                  1058ACA   GTT GTA    CGA       CGT          CTT             TAA                TAA                   TGT                      CTG                         GAA                            GAA                               GCTCys   Gln His    Ala       Ala          Glu             Ile                Ile                   Thr                      Asp                         Leu                            Leu                               Arg    335            340AGT   GTT CAG    GCT       GGT          AAT             CCT                GGT                   GGA                      CCT                         GGA                            CCT                               GGT                                  1097TCA   CAA GTC    CGA       CCA          TTA             GGA                CCA                   CCT                      GGA                         CCT                            GGA                               CCASer   Val Gln    Ala       Gly          Asn             Pro                Gly                   Gly                      Pro                         Gly                            Pro                               Gly345            350            355GGT   CGA GGA    AGA       GGT          AGA             GGT                CAA                   GGC                      AAC                         TGG                            AAC                               ATG                                  1136CCA   GCT CCT    TCT       CCA          TCT             CCA                GTT                   CCG                      TTG                         ACC                            TTG                               TACGly   Arg Gly    Arg       Gly          Arg             Gly                Gln                   Gly                      Asn                         Trp                            Asn                               Met 360            365            370GGA   CCA CCT    GGT       GGA          TTA             CAG                GAA                   TTT                      AAT                         TTT                            ATT                               GTG                                  1175CCT   GGT GGA    CCA       CCT          AAT             GTC                CTT                   AAA                      TTA                         AAA                            TAA                               CACGly   Pro Pro    Gly       Gly          Leu             Gln                Glu                   Phe                      Asn                         Phe                            Ile                               Val       375            380CCA   ACT GGG    AAA       ACT          GGA             TTA                ATA                   ATA                      GGA                         AAA                            GGA                               GGT                                  1214GGT   TGA CCC    TTT       TGA          CCT             AAT                TAT                   TAT                      CCT                         TTT                            CCT                               CCAPro   Thr Gly    Lys       Thr          Gly             Leu                Ile                   Ile                      Gly                         Lys                            Gly                               Gly   385            390            395GAA   ACC ATA    AAA       AGC          ATA             AGC                CAG                   CAG                      TCT                         GGT                            GCA                               AGA                                  1253CTT   TGG TGT    TTT       TCG          TAT             TCG                GTC                   GTC                      AGA                         CCA                            CGT                               TCTGlu   Thr Ile    Lys       Ser          Ile             Ser                Gln                   Gln                      Ser                         Gly                            Ala                               Arg    400            405ATA   GAA CTT    CAG       AGA          AAT             CCT                CCA                   CCA                      AAT                         GCA                            GAT                               CCT                                  1292TAT   CTT GAA    GTC       TCT          TTA             GGA                GGT                   GGT                      TTA                         CGT                            CTA                               GGAIle   Glu Leu    Gln       Arg          Asn             Pro                Pro                   Pro                      Asn                         Ala                            Asp                               Pro410            415            420AAT   ATG AAG    TTA       TTT          ACA             ATT                CGT                   GGC                      ACT                         CCA                            CAA                               CAG                                  1331TTA   TAC TTC    AAT       AAA          TGT             TAA                GCA                   CCG                      TGA                         GGT                            GTT                               GTCAsn   Met Lys    Leu       Phe          Thr             Ile                Arg                   Gly                      Thr                         Pro                            Gln                               Gln 425            430            435ATA   GAC TAT    GCT       CGG          CAA             CTC                ATA                   GAA                      GAA                         AAG                            ATT                               GGT                                  1370TAT   CTG ATA    CGA       GCC          GTT             GAG                TAT                   CTT                      CTT                         TTC                            TAA                               CCAIle   Asp Tyr    Ala       Arg          Gln             Leu                Ile                   Glu                      Glu                         Lys                            Ile                               Gly       440            445GGC   CCA GTA    AAT       CCT          TTA             GGG                CCA                   CCT                      GTA                         CCC                            CAT                               GGG                                  1409CCG   GGT CAT    TTA       GGA          AAT             CCC                GGT                   GGA                      CAT                         GGG                            GTA                               CCCGly   Pro Val    Asn       Pro          Leu             Gly                Pro                   Pro                      Val                         Pro                            His                               Gly   450            455            460CCC   CAT GGT    GTC       CCA          GGC             CCC                CAT                   GGA                      CCT                         CCT                            GGG                               CCT                                  1448GGG   GTA CCA    CAG       GGT          CCG             GGG                GTA                   CCT                      GGA                         GGA                            CCC                               GGAPro   His Gly    Val       Pro          Gly             Pro                His                   Gly                      Pro                         Pro                            Gly                               Pro    465            470CCA   GGG CCT    GGA       ACT          CCA             ATG                GGA                   CCA                      TAC                         AAC                            CCT                               GCA                                  1487GGT   CCC GGA    CCT       TGA          GGT             TAC                CCT                   GGT                      ATG                         TTG                            GGA                               CGTPro   Gly Pro    Gly       Thr          Pro             Met                Gly                   Pro                      Tyr                         Asn                            Pro                               Ala475            480            485CCT   TAT AAT    CCT       GGA          CCA             CCA                GGC                   CCG                      GCT                         CCT                            CAT                               GGT                                  1526GGA   ATA TTA    GGA       CCT          GGT             GGT                CCG                   GGC                      CGA                         GGA                            GTA                               CCAPro   Tyr Asn    Pro       Gly          Pro             Pro                Gly                   Pro                      Ala                         Pro                            His                               Gly 490            495            500CCT   CCA GCC    CCA       TAT          GCT             CCC                CAG                   GGA                      TGG                         GGA                            AAT                               GCA                                  1565GGA   GGT CGG    GGT       ATA          CGA             GGG                GTC                   CCT                      ACC                         CCT                            TTA                               CGTPro   Pro Ala    Pro       Tyr          Ala             Pro                Gln                   Gly                      Trp                         Gly                            Asn                               Ala       505            510TAT   CCA CAC    TGG       CAG          CAG             CAG                GCT                   CCT                      CCT                         GAT                            CCA                               GCT                                  1604ATA   GGT GTG    ACC       GTC          GTC             GTC                CGA                   GGA                      GGA                         CTA                            GGT                               CGATyr   Pro His    Trp       Gln          Gln             Gln                Ala                   Pro                      Pro                         Asp                            Pro                               Ala   515            520            525AAG   GCA GGA    ACG       GAT          CCA             AAT                TCA                   GCA                      GCT                         TGG                            GCT                               GCT                                  1643TTC   CGT CCT    TGC       CTA          GGT             TTA                AGT                   CGT                      CGA                         ACC                            CGA                               CGALys   Ala Gly    Thr       Asp          Pro             Asn                Ser                   Ala                      Ala                         Trp                            Ala                               Ala    530            535TAT   TAC GCT    CAC       TAT          TAT             CAA                CAG                   CAA                      GCA                         CAG                            CCA                               CCA                                  1682ATA   ATG CGA    GTG       ATA          ATA             GTT                GTC                   GTT                      CGT                         GTC                            GGT                               GGTTyr   Tyr Ala    His       Tyr          Tyr             Gln                Gln                   Gln                      Ala                         Gln                            Pro                               Pro540            545            550CCA   GCA GCC    CCT       GCA          GGT             GCA                CCA                   ACT                      ACA                         ACT                            CAA                               ACT                                  1721GGT   CGT CGG    GGA       CGT          CCA             CGT                GGT                   TGA                      TGT                         TGA                            GTT                               TGAPro   Ala Ala    Pro       Ala          Gly             Ala                Pro                   Thr                      Thr                         Thr                            Gln                               Thr 555            560            565AAT   GGA CAA    GGA       GAT          CAG             CAG                AAT                   CCA                      GCC                         CCA                            GCT                               GGA                                  1760TTA   CCT GTT    CCT       CTA          GTC             GTC                TTA                   GGT                      CGG                         GGT                            CGA                               CCTAsn   Gly Gln    Gly       Asp          Gln             Gln                Asn                   Pro                      Ala                         Pro                            Ala                               Gly       570            575CAG   GTT GAT    TAT       ACC          AAG             GCT                TGG                   GAA                      GAG                         TAC                            TAC                               AAG                                  1799GTC   CAA CTA    ATA       TGG          TTC             CGA                ACC                   CTT                      CTC                         ATG                            ATG                               TTCGln   Val Asp    Tyr       Thr          Lys             Ala                Trp                   Glu                      Glu                         Tyr                            Tyr                               Lys   580            585            590AAA   ATG GGT    CAG       GCA          GTT             CCT                GCT                   CCG                      ACT                         GGG                            GCT                               CCT                                  1838TTT   TAC CCA    GTC       CGT          CAA             GGA                CGA                   GGC                      TGA                         CCC                            CGA                               GGALys   Met Gly    Gln       Ala          Val             Pro                Ala                   Pro                      Thr                         Gly                            Ala                               Pro    595            600CCA   GGT GGT    CAG       CCA          GAT             TAT                AGT                   GCA                      GCC                         TGG                            GCT                               GAG                                  1877GGT   CCA CCA    GTC       GGT          CTA             ATA                TCA                   CGT                      CGG                         ACC                            CGA                               CTCPro   Gly Gly    Gln       Pro          Asp             Tyr                Ser                   Ala                      Ala                         Trp                            Ala                               Glu605            610            615CAT   TAT AGA    CAA       CAA          GCA             GCC                TAT                   TAT                      GCC                         CAG                            ACA                               AGT                                  1916GTA   ATA TCT    GTT       GTT          CGT             CGG                ATA                   ATA                      CGG                         GTC                            TGT                               TCAHis   Tyr Arg    Gln       Gln          Ala             Ala                Tyr                   Tyr                      Ala                         Gln                            Thr                               Ser 620            625            630CCC   CAG GGA    ATG       CCA          CAG             CAT                CCT                   CCA                      GCA                         CCT                            CAG                               GGC                                  1955GGG   GTC CCT    TAC       GGT          GTC             GTA                GGA                   GGT                      CGT                         GGA                            GTC                               CCGPro   Gln Gly    Met       Pro          Gln             His                Pro                   Pro                      Ala                         Pro                            Gln                               Gly       635            640CAA   TAA TAA    GAAGTGGACA             ATACAGTATT                      TGCTTCATTG  1994GTT   ATT ATT    CTTCACCTGT             TATGTCATAA                      ACGAAGTAACGlnTGTGGGGGAA    AAAAACCTTT             GTTAAATATA                      TGGATGCAGA  2034ACACCCCCTT    TTTTTGGAAA             CAATTTATAT                      ACCTACGTCTCGACTTGATG    AAGATCTTAA             TTTTGTTTTT                      GGTTTAAAAT  2074GCTGAACTAC    TTCTAGAATT             AAAACAAAAA                      CCAAATTTTAAGTGTTTCCT    TTTTTTTTTT             TTTTTTTTTG                      AAAATGTACA  2114TCACAAAGGA    AAAAAAAAAA             AAAAAAAAAC                      TTTTACATGTAAATATCTAT    CACTACTGAT             AGGAGGTTAA                      TATTTCTGTG  2154TTTATAGATA    GTGATGACTA             TCCTCCAATT                      ATAAAGACACTAGAAATGAA    AATTGGTTTG             TTTTTAGTAT                      TTAGTGTAGA  2194ATCTTTACTT    TTAACCAAAC             AAAAATCATA                      AATCACATCTTGTACACATT    CCAGCAAATG             TATTTGCAAT                      TATGTGGTTG  2234ACATGTGTAA    GGTCGTTTAC             ATAAACGTTA                      ATACACCAACATGCTTTGTG    ATATAAATGT             ACTTTTTCAA                      TGTATACTTT  2274TACGAAACAC    TATATTTACA             TGAAAAAGTT                      ACATATGAAACACTTTCCAA    ATGCCTGTTT             TGTGCTTTAC                      AATAAATGAT  2314GTGAAAGGTT    TACGGACAAA             ACACGAAATG                      TTATTTACTAATGAAACCTC    AAAAAAAAAA             AAAAAAAAAA                      AAAAAAAAAA  2354TACTTTGGAG    TTTTTTTTTT             TTTTTTTTTT                      TTTTTTTTTTAAAAAAAAAA    AAAAAAAAAA             AAAAAAAAAA           2384TTTTTTTTTT    TTTTTTTTTT             TTTTTTTTTT__________________________________________________________________________ 
    
     Three clones from a BJAB cDNA library and three clones from an activated, human peripheral blood lymphocyte cDNA library contain the above sequence. Three clones from the same BJAB library and two clones from the activated lymphocyte library are lacking nucleotides 316, 317 and 318 (SEQ ID NO:9). The mRNA lacking these three nucleotides would encode a variant protein lacking serine 97 (SEQ ID NO:10). 
     Though the 5&#39; untranslated region of the message appears to be unusually short and contains no in-frame stop codons, the initiator methionine is contained in a nine out of ten match with the Kozak consensus. (M. Kozak, &#34;Structural features in eukaryotic mRNAs that modulate the initiation of translation&#34;. J. Biol. Chem. 266(30), 19867-19870 (1991)). The deduced polypeptide, 644 amino acids in length, has a calculated molecular weight of 67.5 kd consistent with the molecular weight of the purified protein. The amino acid sequence can be found in SEQ ID NO:2. 
     To create the full length cDNA, pools of degenerate oligonucleotides were synthesized to correspond to the amino acid sequence of the peptide encoded by nucleotides 843 to 860 and used as primers in a PCR reaction. The oligo sequences (SEQ ID NO:3) are: 
     5&#39;-CAGAATTCGGIGGIAAYGARGGIANCG-3&#39; where I indicates an inosine residue, and Y is either T or C, R is either A or G, and N is either I or T. 
     Degenerate oligonucleotides were also synthesized to correspond to the peptide encoded by nucleotides 957 to 971 and used together with the above primer (SEQ ID NO:3) in a PCR reaction which amplified the PCR product encoded by nucleotides 861 to 956 from human cDNA. The sequences (SEQ ID NO:4) of this degenerate oligo pool are: 
     5&#39;-GAGTCGACRTCRTCRTCIGGYTTRAA-3&#39; where R is either A or G, and Y is either C or T. 
     The full length cDNA sequence has features which suggest multiple modes of FBP regulation. There is an unusual codon bias. For every amino acid with a degenerate codon, except glutamine, the FBP sequence avoids the codons preferred in a survey of 2,681 human genes (K-n. Wada, Y. Wada, F. Ishibashi, T. Gojobori and T. Ikemura. Codon usage tabulated from the GenBank genetic sequence data. Nucleic Acids Res. 20(supplement), 2111-2118 (1992)) suggesting translational regulation. The existence of alternate isoforms of FBP generated by regulation of RNA processing is suggested by multiple independent clones, half of which exhibit a precise deletion of 3 nucleotides at basepair 316, 317 and 318, removing serine 97 (see FIG. 2B). The surrounding sequence is consistent with an alternate splice acceptor site (S. M. Mount, Nuc. Acids Res. 10,459 (1982)) which could generate this deletion. 
     Other variations of the cDNA sequence and encoded protein were found in separate clones. In a clone labeled &#34;25-1&#34; an A residue was found at nucleic acid position 473, which resulted in a complementary base T and a codon specifying an isoleucine at amino acid 149. 
     The clone from an HL60 cDNA library labeled &#34;3-1&#34; contains 10 basepairs of 5&#39; untranslated sequence, followed by an open reading frame comprised of the nucleotides from position 858 to position 1561 shown above in SEQ ID NO:1 and a unique 3&#39; end cDNA sequence of 25 base pairs, followed by two adjacent stop codons and additional 3&#39; untranslated sequence. The sequence of clone 3-1 is as follows (SEQ ID NO: 5): 
     
         __________________________________________________________________________GGAATTCCGG    ATA       GAT          GTC             CCC                ATT                   CCA                      AGA                         TTT                            GCT                               GTT                                  40CCTTAAGGCC    TAT       CTA          CAG             GGG                TAA                   GGT                      TCT                         AAA                            CGA                               CAA    Ile       Asp          Val             Pro                Ile                   Pro                      Arg                         Phe                            Ala                               Val    1           5              10GGC   ATT GTA    ATA       GGA          AGA             AAT                GGA                   GAG                      ATG                         ATC                            AAA                               AAA                                  79CCG   TAA CAT    TAT       CCT          TCT             TTA                CCT                   CTC                      TAC                         TAG                            TTT                               TTTGly   Ile Val    Ile       Gly          Arg             Asn                Gly                   Glu                      Met                         Ile                            Lys                               Lys       15             20ATA   CAA AAT    GAT       GCT          GGT             GTT                CGC                   ATT                      CAG                         TTT                            AAG                               CCA                                  118TAT   GTT TTA    CTA       CGA          CCA             CAA                GCG                   TAA                      GTC                         AAA                            TTC                               GGTIle   Gln Asn    Asp       Ala          Gly             Val                Arg                   Ile                      Gln                         Phe                            Lys                               Pro   25             30             35GAT   GAT GGG    ACA       ACA          CCC             GAA                AGG                   ATA                      GCA                         CAA                            ATA                               ACA                                  157CTA   CTA CCC    TGT       TGT          GGG             CTT                TCC                   TAT                      CGT                         GTT                            TAT                               TGTAsp   Asp Gly    Thr       Thr          Pro             Glu                Arg                   Ile                      Ala                         Gln                            Ile                               Thr    40             45GGA   CCT CCA    GAC       CGA          TGT             CAA                CAT                   GCT                      GCA                         GAA                            ATT                               ATT                                  196CCT   GGA GGT    CTG       GCT          ACA             GTT                GTA                   CGA                      CGT                         CTT                            TAA                               TAAGly   Pro Pro    Asp       Arg          Cys             Gln                His                   Ala                      Ala                         Glu                            Ile                               Ile50             55             60ACA   GAC CTT    CTT       CGA          AGT             GTT                CAG                   GCT                      GGT                         AAT                            CCT                               GGT                                  235TGT   CTG GAA    GAA       GCT          TCA             CAA                GTC                   CGA                      CCA                         TTA                            GGA                               CCAThr   Asp Leu    Leu       Arg          Ser             Val                Gln                   Ala                      Gly                         Asn                            Pro                               Gly 65             70             75GGA   CCT GGA    CCT       GGT          GGT             CGA                GGA                   AGA                      GGT                         AGA                            GGT                               CAA                                  274CCT   GGA CCT    GGA       CCA          CCA             GCT                CCT                   TCT                      CCA                         TCT                            CCA                               GTTGly   Pro Gly    Pro       Gly          Gly             Arg                Gly                   Arg                      Gly                         Arg                            Gly                               Gln       80             85GGC   AAC TGG    AAC       ATG          GGA             CCA                CCT                   GGT                      GGA                         TTA                            CAG                               GAA                                  313CCG   TTG ACC    TTG       TAC          CCT             GGT                GGA                   CCA                      CCT                         AAT                            GTC                               CTTGly   Asn Trp    Asn       Met          Gly             Pro                Pro                   Gly                      Gly                         Leu                            Gln                               Glu   90             95             100TTT   AAT TTT    ATT       GTG          CCA             ACT                GGG                   AAA                      ACT                         GGA                            TTA                               ATA                                  352AAA   TTA AAA    TAA       CAC          GGT             TGA                CCC                   TTT                      TGA                         CCT                            AAT                               TATPhe   Asn Phe    Ile       Val          Pro             Thr                Gly                   Lys                      Thr                         Gly                            Leu                               Ile    105            110ATA   GGA AAA    GGA       GGT          GAA             ACC                ATA                   AAA                      AGC                         ATA                            AGC                               CAG                                  391TAT   CCT TTT    CCT       CCA          CTT             TGG                TGT                   TTT                      TCG                         TAT                            TCG                               GTCIle   Gly Lys    Gly       Gly          Glu             Thr                Ile                   Lys                      Ser                         Ile                            Ser                               Gln115            120            125CAG   TCT GGT    GCA       AGA          ATA             GAA                CTT                   CAG                      AGA                         AAT                            CCT                               CCA                                  430GTC   AGA CCA    CGT       TCT          TAT             CTT                GAA                   GTC                      TCT                         TTA                            GGA                               GGTGln   Ser Gly    Ala       Arg          Ile             Glu                Leu                   Gln                      Arg                         Asn                            Pro                               Pro 130            135            140CCA   AAT GCA    GAT       CCT          AAT             ATG                AAG                   TTA                      TTT                         ACA                            ATT                               CGT                                  469GGT   TTA CGT    CTA       GGA          TTA             TAC                TTC                   AAT                      AAA                         TGT                            TAA                               GCAPro   Asn Ala    Asp       Pro          Asn             Met                Lys                   Leu                      Phe                         Thr                            Ile                               Arg       145            150GGC   ACT CCA    CAA       CAG          ATA             GAC                TAT                   GCT                      CGG                         CAA                            CTC                               ATA                                  508CCG   TGA GGT    GTT       GTC          TAT             CTG                ATA                   CGA                      GCC                         GTT                            GAG                               TATGly   Thr Pro    Gln       Gln          Ile             Asp                Tyr                   Ala                      Arg                         Gln                            Leu                               Ile   155            160            165GAA   GAA AAG    ATT       GGT          GGC             CCA                GTA                   AAT                      CCT                         TTA                            GGG                               CCA                                  547CTT   CTT TTC    TAA       CCA          CCG             GGT                CAT                   TTA                      GGA                         AAT                            CCC                               GGTGlu   Glu Lys    Ile       Gly          Gly             Pro                Val                   Asn                      Pro                         Leu                            Gly                               Pro    170            175CCT   GTA CCC    CAT       GGG          CCC             CAT                GGT                   GTC                      CCA                         GGC                            CCC                               CAT                                  586GGA   CAT GGG    GTA       CCC          GGG             GTA                CCA                   CAG                      GGT                         CCG                            GGG                               GTAPro   Val Pro    His       Gly          Pro             His                Gly                   Val                      Pro                         Gly                            Pro                               His180            185            190GGA   CCT CCT    GGG       CCT          CCA             GGG                CCT                   GGA                      ACT                         CCA                            ATG                               GGA                                  625CCT   GGA GGA    CCC       GGA          GGT             CCC                GGA                   CCT                      TGA                         GGT                            TAC                               CCTGly   Pro Pro    Gly       Pro          Pro             Gly                Pro                   Gly                      Thr                         Pro                            Met                               Gly 195            200            205CCA   TAC AAC    CCT       GCA          CCT             TAT                AAT                   CCT                      GGA                         CCA                            CCA                               GGC                                  664GGT   ATG TTG    GGA       CGT          GGA             ATA                TTA                   GGA                      CCT                         GGT                            GGT                               CCGPro   Tyr Asn    Pro       Ala          Pro             Tyr                Asn                   Pro                      Gly                         Pro                            Pro                               Gly       210            215CCG   GCT CCT    CAT       GGT          CCT             CCA                GCC                   CCA                      TAT                         GCT                            CCC                               CAG                                  703GGC   CGA GGA    GTA       CCA          GGA             GGT                CGG                   GGT                      ATA                         CGA                            GGG                               GTCPro   Ala Pro    His       Gly          Pro             Pro                Ala                   Pro                      Tyr                         Ala                            Pro                               Gln   220            225            230GGA   TGG GGA    AAG       GAA          ATT             GAG                CAG                   AAG                      GTA                         CAG                            GAG                               TAA                                  742CCT   ACC CCT    TTC       CTT          TAA             CTC                GTC                   TTC                      CAT                         GTC                            CTC                               ATTGly   Trp Gly    Lys       Glu          Ile             Glu                Gln                   Lys                      Val                         Gln                            Glu    235            240TAG   CAATTCCCTG       TAGCTCTCAA                AGCAAATTTT                         GAGCTCATTT                                  785ATC   GTTAAGGGAC       ATCGAGAGTT                TCGTTTAAAA                         CTCGAGTAAATTCTTTTTCT    GCAAGCTCAG             CAGCAGAATG                      CCCAGAGTCT  825AAGAAAAAGA    CGTTCGAGTC             GTCGTCTTAC                      GGGTCTCAGATCCCTGGTAG    ATGCAGGTTC             CATAGCGACG                      TTCTCCTGCA  865AGGGACCATC    TACGTCCAAG             GTATCGCTGC                      AAGAGGACGTATGCACGCTG    GTATTCTGCA             ATAGCAGGCC                      ATGTTTTCCT  905TACGTGCGAC    CATAAGACGT             TATCGTCCGG                      TACAAAAGGATGAGCCTGGA    TGCTTTGGAG             CCAAGCTTTC                      GTCCCATGCA  945ACTCGGACCT    ACGAAACCTC             GGTTCGAAAG                      CAGGGTACGTAGGGAAACAA    CCACTTCTGG             GATGTCCGCT                      GCAATCTGCT  985TCCCTTTGTT    GGTGAAGACC             CTACAGGCGA                      CGTTAGACGACCGGGGCTGC    AGCAACCTCA             TCAGCTCTCT                      TGCCTGGAGT  1025GGCCCCGACG    TCGTTGGAGT             AGTCGAGAGA                      ACGGACCTCAGGCTCAGCCT    GGCCTGCAGG             GCCACCAGGA                      GAATGGCAGC  1065CCGAGTCGGA    CCGGACGTCC             CGGTGGTCCT                      CTTACCGTCGAAGGATGGCG    AGGGTCCTCA             TGGCTGGAAT                      TC          1097TTCCTACCGC    TCCCAGGAGT             ACCGACCTTA                      AG__________________________________________________________________________ 
    
     The amino acid sequence for the protein encoded by the cDNA sequence for clone 3-1 can be found in SEQ ID NO:6. 
     In addition, the clone from an activated, human peripheral blood lymphocyte cDNA library labeled &#34;31-10&#34; contains 24 basepairs of 5&#39; untranslated sequence, followed by an open reading frame comprised of the basepairs from position 135 to position 1991 of the DROME sequence given in SEQ ID NO:1 with two exceptions. Clone 31-10 contains 63 nucleotides inserted at position 238 in the DROME cDNA sequence which probably result from an intron which had not been spliced out in the DROME mRNA molecule that gave rise to the 31-10 clone. The inserted nucleotides remain in the open reading frame and are translated into an alternate form of the DROME protein. 
     The 31-10 clone also deviates in that nucleotides from position 1807 to 1952 in the DROME cDNA sequence are deleted. This deletion shifts out of frame the stop codons which would terminate translation in the other clones. When the mRNA represented by the 31-10 cDNA is translated, additional amino acids must be added to the C-terminal end of the DROME protein. 
     The sequence of clone 31-10 is as follows (SEQ ID NO:7): 
     
         __________________________________________________________________________GAATTCCGGA    CGACAGCGGC             TCTG                 AGA                    GCC                       CGG                          CAG                             ATT                                GCA                                   42CTTAAGGCCT    GCTGTCGCCG             AGAC                 TCT                    CGG                       GCC                          GTC                             TAA                                CGT                 Arg                    Ala                       Arg                          Gln                             Ile                                Ala                 1           5GCA   AAA ATT    GGA       GGT          GAT             GCA GGG                    ACA                       TCA                          CTG                             AAT                                TCA                                   81CGT   TTT TAA    CCT       CCA          CTA             CGT CCC                    TGT                       AGT                          GAC                             TTA                                AGTAla   Lys Ile    Gly       Gly          Asp             Ala Gly                    Thr                       Ser                          Leu                             Asn                                Ser    10              15AAT   GAC TAT    GGT       TAT          GGG             GGA CAA                    AAA                       AGA                          CCT                             TTA                                GAA                                   120TTA   CTG ATA    CCA       ATA          CCC             CCT GTT                    TTT                       TCT                          GGA                             AAT                                CTTAsn   Asp Tyr    Gly       Tyr          Gly             Gly Gln                    Lys                       Arg                          Pro                             Leu                                Glu20             25              30GAT   GGA GAT    GGC       TCT          TGG             ACA AGT                    CCG                       AGC                          AGT                             ACA                                ACA                                   159CTA   CCT CTA    CCG       AGA          ACC             TGT TCA                    GGC                       TCG                          TCA                             TGT                                TGTAsp   Gly Asp    Gly       Ser          Trp             Thr Ser                    Pro                       Ser                          Ser                             Thr                                Thr 35              40             45CAC   TGG GAG    GGA       ATG          CCC             TCT CCT                    TTT                       AAA                          GAT                             CAA                                CCA                                   198GTG   ACC CTC    CCT       TAC          GGG             AGA GGA                    AAA                       TTT                          CTA                             GTT                                GGTHis   Trp Glu    Gly       Met          Pro             Ser Pro                    Phe                       Lys                          Asp                             Gln                                Pro       50              55GAT   GCT AAG    AAA       GTT          GCT             CCT CAA                    AAT                       GAC                          TCT                             TTT                                GGA                                   237CTA   CGA TTC    TTT       CAA          CGA             GGA GTT                    TTA                       CTG                          AGA                             AAA                                CCTAsp   Ala Lys    Lys       Val          Ala             Pro Gln                    Asn                       Asp                          Ser                             Phe                                Gly   60             65              70ACA   CAG TTA    CCA       CCG          ATG             CAT CAG                    CAG                       CAA                          AGA                             TCT                                GTA                                   276TGT   GTC AAT    GGT       GGC          TAC             GTA GTC                    GTC                       GTT                          TCT                             AGA                                CATThr   Gln Leu    Pro       Pro          Met             His Gln                    Gln                       Gln                          Arg                             Ser                                Val    75              80ATG   ACA GAA    GAA       TAC          AAA             GTT CCA                    GAT                       GGA                          ATG                             GTT                                GGA                                   315TAC   TGT CTT    CTT       ATG          TTT             CAA GGT                    CTA                       CCT                          TAC                             CAA                                CCTMet   Thr Glu    Glu       Tyr          Lys             Val Pro                    Asp                       Gly                          Met                             Val                                Gly85             90              95TTC   ATA ATT    GGC       AGA          GGA             GGT GAA                    CAG                       ATC                          TCA                             CGC                                ATA                                   354AAG   TAT TAA    CCG       TCT          CCT             CCA CTT                    GTC                       TAG                          AGT                             GCG                                TATPhe   Ile Ile    Gly       Arg          Gly             Gly Glu                    Gln                       Ile                          Ser                             Arg                                Ile 100             105            110CAA   CAG GAA    TCT       GGA          TGC             AAA ATA                    CAG                       ATA                          GCT                             CCT                                GAC                                   393GTT   GTC CTT    AGA       CCT          ACG             TTT TAT                    GTC                       TAT                          CGA                             GGA                                CTGGln   Gln Glu    Ser       Gly          Cys             Lys Ile                    Gln                       Ile                          Ala                             Pro                                Asp       115             120AGT   GGT GGC    CTT       CCA          GAA             AGG TCC                    TGT                       ATG                          TTA                             ACT                                GGA                                   432TCA   CCA CCG    GAA       GGT          CTT             TCC AGG                    ACA                       TAC                          AAT                             TGA                                CCTSer   Gly Gly    Leu       Pro          Glu             Arg Ser                    Cys                       Met                          Leu                             Thr                                Gly   125            130             135ACA   CCT GAA    TCT       GTC          CAG             TCA GCA                    AAA                       CGG                          TTA                             CTG                                GAC                                   471TGT   GGA CTT    AGA       CAG          GTC             AGT CGT                    TTT                       GCC                          AAT                             GAC                                CTGThr   Pro Glu    Ser       Val          Gln             Ser Ala                    Lys                       Arg                          Leu                             Leu                                Asp    140             145CAG   ATT GTT    GAA       AAA          GGA             AGA CCA                    GCT                       CCT                          GGC                             TTC                                CAT                                   510GTC   TAA CAA    CTT       TTT          CCT             TCT GGT                    CGA                       GGA                          CCG                             AAG                                GTAGln   Ile Val    Glu       Lys          Gly             Arg Pro                    Ala                       Pro                          Gly                             Phe                                His150            155             160CAT   GGC GAT    GGA       CCG          GGA             AAT GCA                    GTT                       CAA                          GAA                             ATC                                ATG                                   549GTA   CCG CTA    CCT       GGC          CCT             TTA CGT                    CAA                       GTT                          CTT                             TAG                                TACHis   Gly Asp    Gly       Pro          Gly             Asn Ala                    Val                       Gln                          Glu                             Ile                                Met 165             170            175ATT   CCA GCT    AGC       AAG          GCA             GGA TTA                    GTC                       ATT                          GGA                             AAA                                GGG                                   588TAA   GGT CGA    TCG       TTC          CGT             CCT AAT                    CAG                       TAA                          CCT                             TTT                                CCCIle   Pro Ala    Ser       Lys          Ala             Gly Leu                    Val                       Ile                          Gly                             Lys                                Gly       180             185GGA   GAA ACT    ATT       AAA          CAG             CTT CAG                    GAA                       CGG                          GCT                             GGA                                GTT                                   627CCT   CTT TGA    TAA       TTT          GTC             GAA GTC                    CTT                       GCC                          CGA                             CCT                                CAAGly   Glu Thr    Ile       Lys          Gln             Leu Gln                    Glu                       Arg                          Ala                             Gly                                Val   190            195             200AAA   ATG GTT    ATG       ATT          CAA             GAC GGG                    CCG                       CAG                          AAC                             ACT                                GGT                                   666TTT   TAC CAA    TAC       TAA          GTT             CTG CCC                    GGC                       GTC                          TTG                             TGA                                CCALys   Met Val    Met       Ile          Gln             Asp Gly                    Pro                       Gln                          Asn                             Thr                                Gly    205             210GCT   GAC AAA    CCT       CTT          AGG             ATT ACA                    GGA                       GAC                          CCA                             TAT                                AAA                                   705CGA   CTG TTT    GGA       GAA          TCC             TAA TGT                    CCT                       CTG                          GGT                             ATA                                TTTAla   Asp Lys    Pro       Leu          Arg             Ile Thr                    Gly                       Asp                          Pro                             Tyr                                Lys215            220             225GTT   CAA CAA    GCC       AAG          GAA             ATG GTG                    TTA                       GAG                          TTA                             ATT                                CGT                                   744CAA   GTT GTT    CGG       TTC          CTT             TAC CAC                    AAT                       CTC                          AAT                             TAA                                GCAVal   Gln Gln    Ala       Lys          Glu             Met Val                    Leu                       Glu                          Leu                             Ile                                Arg 230             235            240GAT   CAA GGC    GGT       TTC          AGA             GAA GTT                    CGG                       AAT                          GAG                             TAT                                GGG                                   783CTA   GTT CCG    CCA       AAG          TCT             CTT CAA                    GCC                       TTA                          CTC                             ATA                                CCCAsp   Gln Gly    Gly       Phe          Arg             Glu Val                    Arg                       Asn                          Glu                             Tyr                                Gly       245             250TCA   AGA ATA    GGA       GGA          AAT             GAA GGG                    ATA                       GAT                          GTC                             CCC                                ATT                                   822AGT   TCT TAT    CCT       CCT          TTA             CTT CCC                    TAT                       CTA                          CAG                             GGG                                TAASer   Arg Ile    Gly       Gly          Asn             Glu Gly                    Ile                       Asp                          Val                             Pro                                Ile   255            260             265CCA   AGA TTT    GCT       GTT          GGC             ATT GTA                    ATA                       GGA                          AGA                             AAT                                GGA                                   861GGT   TCT AAA    CGA       CAA          CCG             TAA CAT                    TAT                       CCT                          TCT                             TTA                                CCTPro   Arg Phe    Ala       Val          Gly             Ile Val                    Ile                       Gly                          Arg                             Asn                                Gly    270             275GAG   ATG ATC    AAA       AAA          ATA             CAA AAT                    GAT                       GCT                          GGT                             GTT                                CGC                                   900CTC   TAC TAG    TTT       TTT          TAT             GTT TTA                    CTA                       CGA                          CCA                             CAA                                GCGGlu   Met Ile    Lys       Lys          Ile             Gln Asn                    Asp                       Ala                          Gly                             Val                                Arg280            285             290ATT   CAG TTT    AAG       CCA          GAT             GAT GGG                    ACA                       ACA                          CCC                             GAA                                AGG                                   939TAA   GTC AAA    TTC       GGT          CTA             CTA CCC                    TGT                       TGT                          GGG                             CTT                                TCCIle   Gln Phe    Lys       Pro          Asp             Asp Gly                    Thr                       Thr                          Pro                             Glu                                Arg 295             300            305ATA   GCA CAA    ATA       ACA          GGA             CCT CCA                    GAC                       CGA                          TGT                             CAA                                CAT                                   978TAT   CGT GTT    TAT       TGT          CCT             GGA GGT                    CTG                       GCT                          ACA                             GTT                                GTAIle   Ala Gln    Ile       Thr          Gly             Pro Pro                    Asp                       Arg                          Cys                             Gln                                His       310             315GCT   GCA GAA    ATT       ATT          ACA             GAC CTT                    CTT                       CGA                          AGT                             GTT                                CAG                                   1017CGA   CGT CTT    TAA       TAA          TGT             CTG GAA                    GAA                       GCT                          TCA                             CAA                                GTCAla   Ala Glu    Ile       Ile          Thr             Asp Leu                    Leu                       Arg                          Ser                             Val                                Gln   320            325             330GCT   GGT AAT    CCT       GGT          GGA             CCT GGA                    CCT                       GGT                          GGT                             CGA                                GGA                                   1056CGA   CCA TTA    GGA       CCA          CCT             GGA CCT                    GGA                       CCA                          CCA                             GCT                                CCTAla   Gly Asn    Pro       Gly          Gly             Pro Gly                    Pro                       Gly                          Gly                             Arg                                Gly    335             340AGA   GGT AGA    GGT       CAA          GGC             AAC TGG                    AAC                       ATG                          GGA                             CCA                                CCT                                   1095TCT   CCA TCT    CCA       GTT          CCG             TTG ACC                    TTG                       TAC                          CCT                             GGT                                GGAArg   Gly Arg    Gly       Gln          Gly             Asn Trp                    Asn                       Met                          Gly                             Pro                                Pro345            350             355GGT   GGA TTA    CAG       GAA          TTT             AAT TTT                    ATT                       GTG                          CCA                             ACT                                GGG                                   1134CCA   CCT AAT    GTC       CTT          AAA             TTA AAA                    TAA                       CAC                          GGT                             TGA                                CCCGly   Gly Leu    Gln       Glu          Phe             Asn Phe                    Ile                       Val                          Pro                             Thr                                Gly 360             365            370AAA   ACT GGA    TTA       ATA          ATA             GGA AAA                    GGA                       GGT                          GAA                             ACC                                ATA                                   1173TTT   TGA CCT    AAT       TAT          TAT             CCT TTT                    CCT                       CCA                          CTT                             TGG                                TGTLys   Thr Gly    Leu       Ile          Ile             Gly Lys                    Gly                       Gly                          Glu                             Thr                                Ile       375             380AAA   AGC ATA    AGC       CAG          CAG             TCT GGT                    GCA                       AGA                          ATA                             GAA                                CTT                                   1212TTT   TCG TAT    TCG       GTC          GTC             AGA CCA                    CGT                       TCT                          TAT                             CTT                                GAALys   Ser Ile    Ser       Gln          Gln             Ser Gly                    Ala                       Arg                          Ile                             Glu                                Leu   385            390             395CAG   AGA AAT    CCT       CCA          CCA             AAT GCA                    GAT                       CCT                          AAT                             ATG                                AAG                                   1251GTC   TCT TTA    GGA       GGT          GGT             TTA CGT                    CTA                       GGA                          TTA                             TAC                                TTCGln   Arg Asn    Pro       Pro          Pro             Asn Ala                    Asp                       Pro                          Asn                             Met                                Lys    400             405TTA   TTT ACA    ATT       CGT          GGC             ACT CCA                    CAA                       CAG                          ATA                             GAC                                TAT                                   1290AAT   AAA TGT    TAA       GCA          CCG             TGA GGT                    GTT                       GTC                          TAT                             CTG                                ATALeu   Phe Thr    Ile       Arg          Gly             Thr Pro                    Gln                       Gln                          Ile                             Asp                                Tyr410            415             420GCT   CGG CAA    CTC       ATA          GAA             GAA AAG                    ATT                       GGT                          GGC                             CCA                                GTA                                   1329CGA   GCC GTT    GAG       TAT          CTT             CTT TTC                    TAA                       CCA                          CCG                             GGT                                CATAla   Arg Gln    Leu       Ile          Glu             Glu Lys                    Ile                       Gly                          Gly                             Pro                                Val 425             430            435AAT   CCT TTA    GGG       CCA          CCT             GTA CCC                    CAT                       GGG                          CCC                             CAT                                GGT                                   1368TTA   GGA AAT    CCC       GGT          GGA             CAT GGG                    GTA                       CCC                          GGG                             GTA                                CCAAsn   Pro Leu    Gly       Pro          Pro             Val Pro                    His                       Gly                          Pro                             His                                Gly       440             445GTC   CCA GGC    CCC       CAT          GGA             CCT CCT                    GGG                       CCT                          CCA                             GGG                                CCT                                   1407CAG   GGT CCG    GGG       GTA          CCT             GGA GGA                    CCC                       GGA                          GGT                             CCC                                GGAVal   Pro Gly    Pro       His          Gly             Pro Pro                    Gly                       Pro                          Pro                             Gly                                Pro   450            455             460GGA   ACT CCA    ATG       GGA          CCA             TAC AAC                    CCT                       GCA                          CCT                             TAT                                AAT                                   1446CCT   TGA GGT    TAC       CCT          GGT             ATG TTG                    GGA                       CGT                          GGA                             ATA                                TTAGly   Thr Pro    Met       Gly          Pro             Tyr Asn                    Pro                       Ala                          Pro                             Tyr                                Asn    465             470CCT   GGA CCA    CCA       GGC          CCG             GCT CCT                    CAT                       GGT                          CCT                             CCA                                GCC                                   1485GGA   CCT GGT    GGT       CCG          GGC             CGA GGA                    GTA                       CCA                          GGA                             GGT                                CGGPro   Gly Pro    Pro       Gly          Pro             Ala Pro                    His                       Gly                          Pro                             Pro                                Ala475            480             485CCA   TAT GCT    CCC       CAG          GGA             TGG GGA                    AAT                       GCA                          TAT                             CCA                                CAC                                   1524GGT   ATA CGA    GGG       GTC          CCT             ACC CCT                    TTA                       CGT                          ATA                             GGT                                GTGPro   Tyr Ala    Pro       Gln          Gly             Trp Gly                    Asn                       Ala                          Tyr                             Pro                                His 490             495            500TGG   CAG CAG    CAG       GCT          CCT             CCT GAT                    CCA                       GCT                          AAG                             GCA                                GGA                                   1563ACC   GTC GTC    GTC       CGA          GGA             GGA CTA                    GGT                       CGA                          TTC                             CGT                                CCTTrp   Gln Gln    Gln       Ala          Pro             Pro Asp                    Pro                       Ala                          Lys                             Ala                                Gly       505             510ACG   GAT CCA    AAT       TCA          GCA             GCT TGG                    GCT                       GCT                          TAT                             TAC                                GCT                                   1602TGC   CTA GGT    TTA       AGT          CGT             CGA ACC                    CGA                       CGA                          ATA                             ATG                                CGAThr   Asp Pro    Asn       Ser          Ala             Ala Trp                    Ala                       Ala                          Tyr                             Tyr                                Ala   515            520             525CAC   TAT TAT    CAA       CAG          CAA             GCA CAG                    CCA                       CCA                          CCA                             GCA                                GCC                                   1641GTG   ATA ATA    GTT       GTC          GTT             CGT GTC                    GGT                       GGT                          GGT                             CGT                                CGGHis   Tyr Tyr    Gln       Gln          Gln             Ala Gln                    Pro                       Pro                          Pro                             Ala                                Ala    530             535CCT   GCA GGT    GCA       CCA          ACT             ACA ACT                    CAA                       ACT                          AAT                             GGA                                CAA                                   1680GGA   CGT CCA    CGT       GGT          TGA             TGT TGA                    GTT                       TGA                          TTA                             CCT                                GTTPro   Ala Gly    Ala       Pro          Thr             Thr Thr                    Gln                       Thr                          Asn                             Gly                                Gln540            545             550GGA   GAT CAG    CAG       AAT          CCA             GCC CCA                    GCT                       GGA                          CAG                             GTT                                GAT                                   1719CCT   CTA GTC    GTC       TTA          GGT             CGG GGT                    CGA                       CCT                          GTC                             CAA                                CTAGly   Asp Gln    Gln       Asn          Pro             Ala Pro                    Ala                       Gly                          Gln                             Val                                Asp 555             560            565TAT   ACC AAG    GCT       TGG          GAA             GAG TAC                    TAC                       AAG                          AAA                             ATG                                GGG                                   1758ATA   TGG TTC    CGA       ACC          CTT             CTC ATG                    ATG                       TTC                          TTT                             TAC                                CCCTyr   Thr Lys    Ala       Trp          Glu             Glu Tyr                    Tyr                       Lys                          Lys                             Met                                Gly       570             575CCA   ATA ATA    AGA       AGT          GGA             CAA TAC                    AGT                       ATT                          TGC                             TTC   1794GGT   TAT TAT    TCT       TCA          CCT             GGT ATG                    TCA                       TAA                          ACG                             AAGPro   Ile Ile    Arg       Ser          Gly             Gln Tyr                    Ser                       Ile                          Cys                             Phe   580            585             590AGGAATTCC                              1803TCCTTAAGG__________________________________________________________________________ 
    
     The amino acid sequence for the protein encoded by the cDNA sequence for clone 31-10 can be found in SEQ ID NO:8. 
     The following examples are for illustration only, and should not be used to limit the scope of the invention. 
     EXAMPLE 1 
     The cloned cDNA encodes a protein with FUSE binding activity, referred to as DROME or FUSE binding protein (&#34;FBP&#34;). The coding region contained in the HL60 clones was expressed as a fusion protein in bacteria, purified from extracts and tested with electrophoretic mobility shift assays (EMSAs) for binding to an oligonucleotide containing the FUSE site. Recombinant fusion protein (GST-FBP) bound effectively to the FUSE oligonucleotide. 
     The open reading frame present in the HL60-1 and HL60-2 clones (amino acid residues 145 to 511) was expressed as a Glutathione-S-transferase fusion protein (GST-FBP) in the pGEX system. The inserts from the HL60-1 and HL60-2 clones were spliced together and the open reading frame region subcloned into the Sma I site of the pGEX-2T plasmid (AMARAD Corp.; D. B. Smith and K. S. Johnson, Gene. 67,31 (1988)) to express a GST-FBP fusion protein. Recombinant protein was purified from E. coli extracts on a glutathione-agarose matrix (Sigma Chemical Co.), GST alone was prepared from a pGEX-2T plasmid with no insert in a similar manner. Fusion proteins were eluted with 20 mM glutathione, checked for purity, correct size and concentration with SDS PAGE. 
     Purified recombinant proteins were incubated with double stranded,  32  P labeled, oligonucleotide (Probe) in the presence or absence of the indicated quantity of unlabeled, double stranded oligonucleotide as competitor, and subjected to EMSA. (M. Fried and D. M. Crothers, Nucleic Acids Res. 9, 6505 (1981)). 
     DNA binding assays were performed with an equivalent amount of GST-FBP or GST alone incubated in 25 mM Tris, 200 mM Glycine, 1mM EDTA, 0.5 mg/ml BSA, 0.1% Tween20, 10% glycerol, 100 μg/ml poly(dI:dC), and 0.2 ng of labeled probe. The probe was prepared by annealing two complementary synthetic oligonucleotides and 5&#39; end labeling with T 4  polynucleotide kinase in the presence of γ- 32  P-ATP. The top strand of the FUSE oligonucleotide was 5&#39;-GATCACAAAATAAAAATCCCGAGGGAATATAG-3&#39; (SEQ ID NO:11). The top strand of Mut A was 5&#39;-GATCACAAAAAATCCGAGGAATATAG-3&#39; (SEQ ID NO:12) (lower case indicates changes from FUSE oligomer sequence). The top strand of CRE was 5&#39;-GATCTGACGTCATGACTGACGTCATGACTGACGTCATCA-3&#39; (SEQ ID NO:13). The top strand of CTE was 5&#39;-AATTCTCCTCCCCACCTTCCCCACCTCCCCA-3&#39; (SEQ ID NO:14). Reaction mixtures were incubated 30 minutes at room temperature and protein-DNA complexes resolved by electrophoresis on a 4.2% acrylamide gel in 25 mM Tris, 200 mM Glycine, 1 mM EDTA buffer. 
     Radioactive DNA and DNA-protein complexes were visualized by autoradiography (FIG. 3A). Glutathione-S-transferase (GST) alone did not bind to the probe. Competitor oligonucleotides were as follows: Mut A, a mutant FUSE oligonucleotide with 17 residues covering the binding site changed; CRE, CAMP response element; CTE, CT element in c-myc 5&#39; flanking region. 
     Recombinant FBP and purified human FBP were also demonstrated to display similar DNA binding specificity. Full length GST-FBP and human FBP purified from HL60 cells by oligo-affinity chromatography were assayed for FUSE binding using EMSA. The DNA-protein complexes formed by human FBP in the presence of 25ng of the indicated non-radioactive competitors, visualized by autoradiography, are shown in the upper panel of FIG. 3B. The lower panel of FIG. 3B shows recombinant GST-FBP binding the FUSE probe in the presence of 25 ng of the same competitors. Competitor oligonucleotides are the same as in (A) with the addition of Mut B and Mut C, each with a different mutation in the FUSE sequence. The top strand of Mut B was 5&#39;-GATCACAAAATAAAAAATggacgccGAATATAG-3&#39; (SEQ ID NO:15) and the top strand of Mut C was 5&#39; AATTCTCCTCCCACCTCCCACCTCCCA-GATCACAActacgtgctaggCGAGGGAATATAG-3&#39; (SEQ ID NO:16). 
     Recombinant fusion protein also failed to bind to the nonhomologous oligonucleotides when they were used as radioactive probes. The full length recombinant protein, and purified human FBP shared the same DNA binding specificity as indicated by challenging their binding to FUSE with a panel of competitors (FIG. 3B). An excess of cold FUSE significantly reduced binding of human and recombinant FBP to the radioactive probe; the same amount of the Mut B oligo which has minor changes in the FUSE sequence, bound both as well; but more divergent oligonucleotides did not significantly compete for binding to either protein. 
     EXAMPLE 2 
     Recombinant FBP activated expression of a chloramphenicol acetyltransferase (CAT) gene under the control of human c-myc regulatory sequence was tested in co-transection experiments (FIG. 4). 
     Full length FBP was inserted into an expression vector downstream from the cytomegalovirus enhancer/promoter in both the sense and anti-sense orientations. These plasmids or the expression vector alone were transfected into U937 cells with another vector containing a CAT gene under the control of myc regulator sequence (myc-CAT) or the reporter plasmid with the FUSE site deleted (ΔFUSE myc-CAT). The myc-CAT and ΔFUSE myc-CAT reporter plasmids are derivatives of pMP CAT (M. Avigan, B. Strober, and D. Levens, J. Biol. Chem., 265,18538 (1990)) with the deletion of a 580 bp Nsi I fragment from position -669 to -1249 relative to the myc P1 promoter. The Nsi I deletion results in more consistent CAT expression without disrupting FUSE mediated activation. The ΔFUSE myc-CAT plasmid was produced from pMP CAT by cutting the parent plasmid at the Ava I site located in the FUSE element, partial digestion with mung bean exonuclease (Bethesda Research Labs) and religation. The DNA sequence of the deleted plasmid revealed that 68 nucleotides between position -1493 and -1561 relative to myc P1 were removed, completely deleting the FUSE element. 
     U937 cells (5×10 6 ) were electroporated (Cell-porator, BRL, 200V, 1180 μF) with 10 μg of each plasmid in 250 μl of RPMI supplemented with 10% fetal calf serum. Transfected cells were added to 8 ml additional medium and incubated 48 hours before harvesting for CAT assays. (C. M. Gorman, L. F. Moffat, B. H. Howard, Mol. Cell. Biol. 2, 1044 (1982)). The same quantity of protein (Bradford method) was assayed for each extract. Two independent transfections are shown for each plasmid combination. 
     In the presence of the FBP expression plasmid (FBP-sense), the FUSE containing myc-CAT plasmid (myc-CAT) gave a 5-fold higher level of CAT activity than in the presence of the expression vector alone. In contrast, this level of stimulation did not occur when the reporter plasmid had a 68 bp deletion that eliminated the FUSE site (ΔFUSE myc-CAT) nor when the expression plasmid contained the FBP cDNA in the reverse orientation (FBP-antisense). The minor increase in the ΔFUSE myc-CAT expression with FBP co-transection could be due to secondary binding sites present in the myc regulatory sequence. 
     FBP shows no significant homology to known DNA binding motifs in a search against the GenBank databases, however the primary amino acid sequence of FBP has distinct structural features which could constitute a DNA binding domain, as well as other features with potential functional significance. 
     EXAMPLE 3 
     A Pustell matrix self-comparison of FBP revealed three domains in the primary amino acid sequence, each containing internally repeated sequences. 
     The Pustell matrix (J. Pustell, F. C. Kafatos, N. A. R. 10, 4765 (1982); W. R. Pearson, Meth. Enzymol. 183, 63 (1990); MacVector software, International Biotechnologies, Inc.) revealed the repeated sequences in the three domains of FBP. The repeated glycines in the N-terminal domain, the four copies of the FBP repeat in the central domain, the proline/glycine rich segment and the WAAYY (where W is Trp, A is Ala and Y is Tyr) repeat in the C-terminal domain all score as diagonals. A window size of 20 residues and a minimum score of 35% were used for this analysis. The diagram above the box in FIG. 5A symbolizes the structures in FBP: striped fill indicates glycine rich segments, the solid boxes indicate the FBP repeats, and the shaded boxes represent amphipathic helices. 
     The amino-terminal domain is comprised of 106 amino acids featuring a string of 11 repeated glycine residues and the first of 5 predicted amphipathic alpha helices found in FBP. Following the helix, residues 63 to 106 are enriched for glutamine (16%) relative to the whole protein (9%). 
     The central and largest FBP domain contains structures sufficient for sequence specific binding because a recombinant protein comprised of only this domain bound DNA specifically. The central domain is made up of four evenly spaced units each unit containing (1) a highly conserved 30 residue segment termed here the FBP repeat (FIG. 5B), followed by (2) a potential amphipathic alpha helix (FIG. 5C). Each FBP repeat is comprised of three structures in sequential order: a region of predicted β-sheet, separated by a turn at conserved glycines 13 and 14, from a segment of alpha-helix as predicted by Chou-Fasman and Robson-Garnier analysis. (P. Y. Chou and G. D. Fasman, &#34;Prediction of the secondary structure of proteins from their amino acid sequence.&#34; Adv. Enzymol. Relat. Areas Mol. Biol. 47:45-148 (1978); B. Robson and E. Suzuki, &#34;Conformational properties of amino acid residues in globular proteins.&#34; J. Mol. Biol. 107:327-356 (1976); J. Garnier, D. J. Osguthorpe, and B. Robson, &#34;Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins.&#34; J. Mol. Biol. 120:97-120 (1978). Analysis was performed with MacVector Software (International Biotechnologies, Inc.)). The FBP repeats are found at amino acid positions 107-136, 192-221, 282-311 and 383-412. 
     The invariant glycine at position 25 may not disrupt helix formation due to the hydrophilic character of neighboring residues in the predicted helix. (L. Serrano, J. L. Neira, J. Sancho, and A. R. Fersht, &#34;Effect of alanine versus glycine in alpha-helices on protein stability.&#34; Nature, 356:453-455 (1992)). This sheet-turn-helix pattern evokes the DNA-binding domain of the papilloma virus E2 protein. (R. S. Hegde, S. R. Grossman, L. A. Laimins, and P. Sigler, &#34;Crystal structure at 1.7 A of the bovine papillomavirus-1 E2 DNA-binding domain bound to its DNA target.&#34; Nature 359:505-512 (1992)). An amphipathic helix follows each repeat after a spacer of 18-21 residues. The amphipathic helices are found at amino acid positions 155-170, 242-258, 330-347 and 434-447. The amphipathic character of the four central domain helices extends uniformly over their 16-18 residue lengths with the exception of hydrophilic residues at position 2 (FIG. 5C). The lack of a hydrophobic residue at this position deviates from the heptad repeat pattern shown to be important in coiled-coiled interactions. (F. H. C. Crick, Nature. 170, 882 (1952)). The helices are not flanked by basic regions as in basic-coiled-coil (S. C. Harrison, &#34;Structural taxonomy of DNA-binding proteins.&#34; Nature, 353:715-719 (1991); W. H. Landschulz, P. F. Johnson, and S. L. McKnight. Science, 240:1759-1764 (1988)) or helix-loop-helix motifs. (C. Murre, P. Schonleber McCaw, and D. Baltimore, &#34;A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins.&#34; Cell 56:777-783 (1989)). Thus the repeat-helix unit found in the central domain of FBP does not resemble known DNA binding motifs. 
     The C-terminal domain is separated from the central domain by a highly flexible, proline-glycine rich segment. This domain is also glutamine rich (22/140=15.7% from amino acid 505 to the C-terminal) and tyrosine rich (13/140=9.3%) including repeated tyrosine dyad motifs some of which conform to a tyrosine phosphorylation recognition site. (J. A. Cooper, F. S. Esch, S. S. Taylor, and T. Hunter, &#34;Phosphorylation sites in enolase and lactate dehydrogenase utilized by tyrosine protein kinases in vivo and in vitro.&#34; J. Biol. Chem. 259:7835-7841 (1984)). 
     EXAMPLE 4 
     To define a minimum DNA binding motif within the central domain, further truncations were constructed as well as short insertions to disrupt the predicted structures. Mutant constructs were expressed as bacterial fusion proteins, purified and tested for DNA binding to the FUSE oligonucleotide. 
     The plasmid which encodes the 278-511 mutant was constructed by inserting an EcoR I-Sac I fragment from the HL60-2 clone into the pGEX-1 vector. The fusion protein contains amino acids 278-511 of FBP plus the residues KEIEQKVQE (SEQ ID NO:17) (where K is Lys, E is Glu, I is Ile, Q is Gln, and V is Val) at the carboxyterminal end stopping at a termination codon unique to the HL60-2 clone. The 278-474 encoding plasmid was constructed from the 278-511 plasmid by inserting a 12 bp double stranded oligonucleotide with the sequence TTAGTTAACTAA (SEQ ID NO:18) into an Sfi I site. This oligonucleotide encodes stop codons in all 3 reading frames so that a truncated protein is produced. The 278-372 encoding plasmid was similarly constructed by inserting the termination oligonucleotide into a Dra III site. The 298-511 encoding plasmid was constructed from the 278-511 plasmid by deleting a fragment between the BamH I site in the pGEX vector and a Bcl I in the FBP cDNA. 
     The ability of each construct to bind (+) or failure to bind (-) the FUSE DNA sequence is indicated at the right in FIG. 6A. The open boxes labeled &#34;GST&#34; indicate the glutathione-S-transferase fragment present in the fusion proteins. Other symbols are the same as in FIG. 5A. 
     The truncated protein containing the third and fourth units of the central domain and the proline/glycine rich region (278-511, FIG. 6A) bound DNA with the same specificity as full length DROME or FPB (FIG. 6C). A truncation mutant lacking a portion of the proline-glycine rich region (278-474) still bound DNA. In contrast, the removal of FBP repeat 4 and the rest of the C-terminus in a mutant with a larger truncation (278-372) or removal of the NH2-terminal portion of repeat 3 (298-511) abrogated binding. These truncations suggest that at least two intact FBP repeat-helix units are required to constitute a DNA binding domain and that at least half of the Pro-Gly region is not required. 
     EXAMPLE 5 
     Insertion mutants further demonstrated the importance of two repeat-helix units for DNA binding. Three to six amino acids were introduced at eight positions throughout the 278-511 construct (FIG. 6B) without altering the reading frame. 
     The insertion mutants were constructed by cutting the 278-511 plasmid at restriction sites, treating the ends with the large fragment of DNA polymerase I (if not already blunt) and inserting linkers of 8, 10 or 12 base pairs. The appropriate length was chosen to insert a small number of amino acids but restore the original reading frame leaving the rest of the sequence unchanged. Insertion mutant 1 had the amino acids ArgIleArg added between GST and the FBP polypeptide. Mutant 2 had residues IleGlySerArgIleArg (SEQ ID NO:19) added after the Met at position 297 in FBP, mutant 3 had IleArgIleArg (SEQ ID NO:20) added after Met297. Mutant 4 had ProArgIleArgGlu (SEQ ID NO:21) added while deleting Gln at amino acid 333. Mutant 5 had GlyIlePro added after amino acid 336. Mutant 6 had GlyIleProArg (SEQ ID NO:22) added after amino acid 343. Mutant 7 ArgIleArg added after amino acid 373. Mutant 8 had ArgAspProAla (SEQ ID NO:23) added while deleting GlnSer after amino acid 404. Mutant 9 had ArgGlySerGly (SEQ ID NO:24) inserted while deleting Pro after amino acid 475. All constructs were confirmed by DNA sequencing. The DNA binding property of each insertion mutant is indicated by a +, - or R (reduced binding) below the insertion site. 
     An insertion at the junction between GST and the FBP sequence (insertion mutant number 1) does not effect binding. Neither do insertions into the region between helix 4 and repeat 4 (number 7) or the Pro-Gly region (number 9). In contrast, insertions 2 and 3 in repeat three, insertions 4 and 5 in helix four, and insertion 8 in repeat four all resulted in mutant proteins failing to bind DNA. Insertion number 6, near the end of helix four, reduced but did not eliminate binding. 
     The combined evidence from RNA expression, DNA binding specificity and transection experiments indicate the presence of a human FUSE binding protein (referred to as FBP or DROME) that activates myc expression. FBP binds DNA through a novel, repeated motif. The presence of four sets of the repeat-helix unit in FBP, when only two are required for FUSE binding, suggests that this protein has the potential to form at least two binding sites. A dual binding capability may be important for its cellular function. For example, binding of FBP could facilitate DNA looping which stimulates the interaction of distant elements, a mechanism consistent with the far upstream location and the requirement for additional regulatory sequence to observe the stimulatory effect of the FUSE site. 
     EXAMPLE 6 
     The purified FUSE binding protein is also useful in the production of monoclonal antibodies. Thus, a mouse is injected with purified FUSE binding protein, or a fragment thereof, which activates a number of B-lymphocytes in the mouse which produce antibodies against the protein. The mouse is sacrificed and spleen lymphoid cells, containing large quantities of these B-lymphocytes, are isolated and tested to assure production of antibody to FUSE binding protein. The lymphocytes producing antibody to FUSE binding protein are then fused with mouse plasmacytoma cells, ensuring a reproducible source of monoclonal antibody (Kohler, G. and Milstein, C. Nature, 256:495-97 (1975)). These antibodies, or fragments thereof, can then be used to detect and quantitate the FUSE binding protein. 
     EXAMPLE 7 
     The anti-sense sequence for the FUSE binding protein cDNA is useful therapeutically to arrest cell development in a target area of uncontrolled cell growth. An expression vector or oligonucleotide is constructed incorporating the anti-sense sequence of the FUSE binding protein cDNA. The oligonucleotide or vector is then incorporated into the cells of the target area, and acts to antagonize or block expression of the FUSE binding protein, inhibiting cell division and proliferation. 
     This is effective, for example, in arresting tumor cell growth, or an unwarranted immune response (i.e., arresting B- or T-lymphocytes). 
     The invention has been described in detail with particular reference to a preferred embodiment thereof, but it will be understood that the invention is capable of other and different embodiments. As is readily apparent to those skilled in the art, variations and modifications can be effected within the spirit and scope of the invention. Accordingly, the foregoing disclosure, description, and figures are for illustrative purposes only, and do not in any way limit the invention, which is defined only by the claims. 
     
         __________________________________________________________________________SEQUENCE LISTING(1) GENERAL INFORMATION:(iii) NUMBER OF SEQUENCES: 24(2) INFORMATION FOR SEQ ID NO: 1:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 2384(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: cDNA(iii) HYPOTHETICAL: No(iv) ANTI-SENSE: YES(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(H) CELL LINE: HL60(ix) FEATURE:(D) OTHER INFORMATION: 473 bpvariable region where R is A or G.(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1:GCGGCAGCGGCTCTTATAGTGCAACCATGGCAGACTATTCAACA44GTGCCTCCCCCCTCTTCTGGCTCAGCTGGTGGCGGTGGT83GGCGGCGGTGGTGGTGGAGGAGTTAACGACGCTTTCAAA122GATGCACTGCAGAGAGCCCGGCAGATTGCAGCAAAAATT161GGAGGTGATGCAGGGACATCACTGAATTCAAATGACTAT200GGTTATGGGGGACAAAAAAGACCTTTAGAAGATGGAGAT239CAACCAGATGCTAAGAAAGTTGCTCCTCAAAATGACTCT278TTTGGAACACAGTTACCACCGATGCATCAGCAGCAAAGC317AGATCTGTAATGACAGAAGAATACAAAGTTCCAGATGGA356ATGGTTGGATTCATAATTGGCAGAGGAGGTGAACAGATC395TCACGCATACAACAGGAATCTGGATGCAAAATACAGATA434GCTCCTGACAGTGGTGGCCTTCCAGAAAGGTCCTGTATR473TTAACTGGAACACCTGAATCTGTCCAGTCAGCAAAACGG512TTACTGGACCAGATTGTTGAAAAAGGAAGACCAGCTCCT551GGCTTCCATCATGGCGATGGACCGGGAAATGCAGTTCAA590GAAATCATGATTCCAGCTAGCAAGGCAGGATTAGTCATT629GGAAAAGGGGGAGAAACTATTAAACAGCTTCAGGAACGG668GCTGGAGTTAAAATGGTTATGATTCAAGACGGGCCGCAG707AACACTGGTGCTGACAAACCTCTTAGGATTACAGGAGAC746CCATATAAAGTTCAACAAGCCAAGGAAATGGTGTTAGAG785TTAATTCGTGATCAAGGCGGTTTCAGAGAAGTTCGGAAT824GAGTATGGGTCAAGAATAGGAGGAAATGAAGGGATAGAT863GTCCCCATTCCAAGATTTGCTGTTGGCATTGTAATAGGA902AGAAATGGAGAGATGATCAAAAAAATACAAAATGATGCT941GGTGTTCGCATTCAGTTTAAGCCAGATGATGGGACAACA980CCCGAAAGGATAGCACAAATAACAGGACCTCCAGACCGA1019TGTCAACATGCTGCAGAAATTATTACAGACCTTCTTCGA1058AGTGTTCAGGCTGGTAATCCTGGTGGACCTGGACCTGGT1097GGTCGAGGAAGAGGTAGAGGTCAAGGCAACTGGAACATG1136GGACCACCTGGTGGATTACAGGAATTTAATTTTATTGTG1175CCAACTGGGAAAACTGGATTAATAATAGGAAAAGGAGGT1214GAAACCATAAAAAGCATAAGCCAGCAGTCTGGTGCAAGA1253ATAGAACTTCAGAGAAATCCTCCACCAAATGCAGATCCT1292AATATGAAGTTATTTACAATTCGTGGCACTCCACAACAG1331ATAGACTATGCTCGGCAACTCATAGAAGAAAAGATTGGT1370GGCCCAGTAAATCCTTTAGGGCCACCTGTACCCCATGGG1409CCCCATGGTGTCCCAGGCCCCCATGGACCTCCTGGGCCT1448CCAGGGCCTGGAACTCCAATGGGACCATACAACCCTGCA1487CCTTATAATCCTGGACCACCAGGCCCGGCTCCTCATGGT1526CCTCCAGCCCCATATGCTCCCCAGGGATGGGGAAATGCA1565TATCCACACTGGCAGCAGCAGGCTCCTCCTGATCCAGCT1604AAGGCAGGAACGGATCCAAATTCAGCAGCTTGGGCTGCT1643TATTACGCTCACTATTATCAACAGCAAGCACAGCCACCA1682CCAGCAGCCCCTGCAGGTGCACCAACTACAACTCAAACT1721AATGGACAAGGAGATCAGCAGAATCCAGCCCCAGCTGGA1760CAGGTTGATTATACCAAGGCTTGGGAAGAGTACTACAAG1799AAAATGGGTCAGGCAGTTCCTGCTCCGACTGGGGCTCCT1838CCAGGTGGTCAGCCAGATTATAGTGCAGCCTGGGCTGAG1877CATTATAGACAACAAGCAGCCTATTATGCCCAGACAAGT1916CCCCAGGGAATGCCACAGCATCCTCCAGCACCTCAGGGC1955CAATAATAAGAAGTGGACAATACAGTATTTGCTTCATTG1994TGTGGGGGAAAAAAACCTTTGTTAAATATATGGATGCAGA2034CGACTTGATGAAGATCTTAATTTTGTTTTTGGTTTAAAAT2074AGTGTTTCCTTTTTTTTTTTTTTTTTTTTGAAAATGTACA2114AAATATCTATCACTACTGATAGGAGGTTAATATTTCTGTG2154TAGAAATGAAAATTGGTTTGTTTTTAGTATTTAGTGTAGA2194TGTACACATTCCAGCAAATGTATTTGCAATTATGTGGTTG2234ATGCTTTGTGATATAAATGTACTTTTTCAATGTATACTTT2274CACTTTCCAAATGCCTGTTTTGTGCTTTACAATAAATGAT2314ATGAAACCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA2354AAAAAAAAAAAAAAAAAAAAAAAAAAAAAA2384(2) INFORMATION FOR SEQ ID NO: 2:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 644(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(iii) HYPOTHETICAL: No(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(H) CELL LINE: HL60(ix) FEATURE:(D) OTHER INFORMATION:Amino Acid 149 (Xaa) is Met or Ile(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2:MetAlaAspTyrSerThrValProProProSerSerGly1510SerAlaGlyGlyGlyGlyGlyGlyGlyGlyGlyGlyGly152025ValAsnAspAlaPheLysAspAlaLeuGlnArgAlaArg3035GlnIleAlaAlaLysIleGlyGlyAspAlaGlyThrSer404550LeuAsnSerAsnAspTyrGlyTyrGlyGlyGlnLysArg556065ProLeuGluAspGlyAspGlnProAspAlaLysLysVal7075AlaProGlnAsnAspSerPheGlyThrGlnLeuProPro808590MetHisGlnGlnGlnSerArgSerValMetThrGluGlu95100TyrLysValProAspGlyMetValGlyPheIleIleGly105110115ArgGlyGlyGluGlnIleSerArgIleGlnGlnGluSer120125130GlyCysLysIleGlnIleAlaProAspSerGlyGlyLeu135140ProGluArgSerCysXaaLeuThrGlyThrProGluSer145150155ValGlnSerAlaLysArgLeuLeuAspGlnIleValGlu160165LysGlyArgProAlaProGlyPheHisHisGlyAspGly170175180ProGlyAsnAlaValGlnGluIleMetIleProAlaSer185190195LysAlaGlyLeuValIleGlyLysGlyGlyGluThrIle200205LysGlnLeuGlnGluArgAlaGlyValLysMetValMet210215220IleGlnAspGlyProGlnAsnThrGlyAlaAspLysPro225230LeuArgIleThrGlyAspProTyrLysValGlnGlnAla235240245LysGluMetValLeuGluLeuIleArgAspGlnGlyGly250255260PheArgGluValArgAsnGluTyrGlySerArgIleGly265270GlyAsnGluGlyIleAspValProIleProArgPheAla275280285ValGlyIleValIleGlyArgAsnGlyGluMetIleLys290295LysIleGlnAsnAspAlaGlyValArgIleGlnPheLys300305310ProAspAspGlyThrThrProGluArgIleAlaGlnIle315320325ThrGlyProProAspArgCysGlnHisAlaAlaGluIle330335IleThrAspLeuLeuArgSerValGlnAlaGlyAsnPro340345350GlyGlyProGlyProGlyGlyArgGlyArgGlyArgGly355360GlnGlyAsnTrpAsnMetGlyProProGlyGlyLeuGln365370375GluPheAsnPheIleValProThrGlyLysThrGlyLeu380385390IleIleGlyLysGlyGlyGluThrIleLysSerIleSer395400GlnGlnSerGlyAlaArgIleGluLeuGlnArgAsnPro405410415ProProAsnAlaAspProAsnMetLysLeuPheThrIle420425ArgGlyThrProGlnGlnIleAspTyrAlaArgGlnLeu430435440IleGluGluLysIleGlyGlyProValAsnProLeuGly445450455ProProValProHisGlyProHisGlyValProGlyPro460465HisGlyProProGlyProProGlyProGlyThrProMet470475480GlyProTyrAsnProAlaProTyrAsnProGlyProPro485490GlyProAlaProHisGlyProProAlaProTyrAlaPro495500505GlnGlyTrpGlyAsnAlaTyrProHisTrpGlnGlnGln510515520AlaProProAspProAlaLysAlaGlyThrAspProAsn525530SerAlaAlaTrpAlaAlaTyrTyrAlaHisTyrTyrGln535540545GlnGlnAlaGlnProProProAlaAlaProAlaGlyAla550555ProThrThrThrGlnThrAsnGlyGlnGlyAspGlnGln560565570AsnProAlaProAlaGlyGlnValAspTyrThrLysAla575580585TrpGluGluTyrTyrLysLysMetGlyGlnAlaValPro590595AlaProThrGlyAlaProProGlyGlyGlnProAspTyr600605610SerAlaAlaTrpAlaGluHisTyrArgGlnGlnAlaAla615620TyrTyrAlaGlnThrSerProGlnGlyMetProGlnHis625630635ProProAlaProGlnGlyGln640(2) INFORMATION FOR SEQ ID NO:3:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 27(B) TYPE: Nucleic acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: cDNA(iii) HYPOTHETICAL: No(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(ix) FEATURE:(A) NAME/KEY:(B) LOCATION:(C) IDENTIFICATION METHOD:(D) OTHER INFORMATION: N at positions11, 14, and 23 is inosine (I);Y is either T or C; R is eitherA or G; N at position 25 is eitherI or T.(ix) SEQUENCE DESCRIPTION: SEQ ID NO: 3:CAGAATTCGGNGGNAAYGARGGNANCG27(2) INFORMATION FOR SEQ ID NO:4:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 26(B) TYPE: Nucleic acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: cDNA(iii) HYPOTHETICAL: No(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(ix) FEATURE:(D) OTHER INFORMATION: N is inosine;R is either A or G; Y iseither C or T.(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4:GAGTCGACRTCRTCRTCNGGYTTRAA26(2) INFORMATION FOR SEQ ID NO: 5:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 1097(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: cDNA(iii) HYPOTHETICAL: No(iv) ANTI-SENSE: YES(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(H) CELL LINE: HL60(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5:GGAATTCCGGATAGATGTCCCCATTCCAAGATTTGCTGTT40GGCATTGTAATAGGAAGAAATGGAGAGATGATCAAAAAA79ATACAAAATGATGCTGGTGTTCGCATTCAGTTTAAGCCA118GATGATGGGACAACACCCGAAAGGATAGCACAAATAACA157GGACCTCCAGACCGATGTCAACATGCTGCAGAAATTATT196ACAGACCTTCTTCGAAGTGTTCAGGCTGGTAATCCTGGT235GGACCTGGACCTGGTGGTCGAGGAAGAGGTAGAGGTCAA274GGCAACTGGAACATGGGACCACCTGGTGGATTACAGGAA313TTTAATTTTATTGTGCCAACTGGGAAAACTGGATTAATA352ATAGGAAAAGGAGGTGAAACCATAAAAAGCATAAGCCAG391CAGTCTGGTGCAAGAATAGAACTTCAGAGAAATCCTCCA430CCAAATGCAGATCCTAATATGAAGTTATTTACAATTCGT469GGCACTCCACAACAGATAGACTATGCTCGGCAACTCATA508GAAGAAAAGATTGGTGGCCCAGTAAATCCTTTAGGGCCA547CCTGTACCCCATGGGCCCCATGGTGTCCCAGGCCCCCAT586GGACCTCCTGGGCCTCCAGGGCCTGGAACTCCAATGGGA625CCATACAACCCTGCACCTTATAATCCTGGACCACCAGGC664CCGGCTCCTCATGGTCCTCCAGCCCCATATGCTCCCCAG703GGATGGGGAAAGGAAATTGAGCAGAAGGTACAGGAGTAA742TAGCAATTCCCTGTAGCTCTCAAAGCAAATTTTGAGCTCATTT785TTCTTTTTCTGCAAGCTCAGCAGCAGAATGCCCAGAGTCT825TCCCTGGTAGATGCAGGTTCCATAGCGACGTTCTCCTGCA865ATGCACGCTGGTATTCTGCAATAGCAGGCCATGTTTTCCT905TGAGCCTGGATGCTTTGGAGCCAAGCTTTCGTCCCATGCA945AGGGAAACAACCACTTCTGGGATGTCCGCTGCAATCTGCT985CCGGGGCTGCAGCAACCTCATCAGCTCTCTTGCCTGGAGT1025GGCTCAGCCTGGCCTGCAGGGCCACCAGGAGAATGGCAGC1065AAGGATGGCGAGGGTCCTCATGGCTGGAATTC1097(2) INFORMATION FOR SEQ ID NO: 6:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 243(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(iii) HYPOTHETICAL: No(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(G) CELL TYPE: HL60(ix) SEQUENCE DESCRIPTION: SEQ ID NO: 6:IleAspValProIleProArgPheAlaVal1510GlyIleValIleGlyArgAsnGlyGluMetIleLysLys1520IleGlnAsnAspAlaGlyValArgIleGlnPheLysPro253035AspAspGlyThrThrProGluArgIleAlaGlnIleThr4045GlyProProAspArgCysGlnHisAlaAlaGluIleIle505560ThrAspLeuLeuArgSerValGlnAlaGlyAsnProGly657075GlyProGlyProGlyGlyArgGlyArgGlyArgGlyGln8085GlyAsnTrpAsnMetGlyProProGlyGlyLeuGlnGlu9095100PheAsnPheIleValProThrGlyLysThrGlyLeuIle105110IleGlyLysGlyGlyGluThrIleLysSerIleSerGln115120125GlnSerGlyAlaArgIleGluLeuGlnArgAsnProPro130135140ProAsnAlaAspProAsnMetLysLeuPheThrIleArg145150GlyThrProGlnGlnIleAspTyrAlaArgGlnLeuIle155160165GluGluLysIleGlyGlyProValAsnProLeuGlyPro170175ProValProHisGlyProHisGlyValProGlyProHis180185190GlyProProGlyProProGlyProGlyThrProMetGly195200205ProTyrAsnProAlaProTyrAsnProGlyProProGly210215ProAlaProHisGlyProProAlaProTyrAlaProGln220225230GlyTrpGlyLysGluIleGluGlnLysValGlnGlu235240(2) INFORMATION FOR SEQ ID NO: 7:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 1803(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: cDNA(iii) HYPOTHETICAL: No(iv) ANTI-SENSE: YES(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(H) CELL LINE: HL60(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7:GAATTCCGGACGACAGCGGCTCTGAGAGCCCGGCAGATTGCA42GCAAAAATTGGAGGTGATGCAGGGACATCACTGAATTCA81AATGACTATGGTTATGGGGGACAAAAAAGACCTTTAGAA120GATGGAGATGGCTCTTGGACAAGTCCGAGCAGTACAACA159CACTGGGAGGGAATGCCCTCTCCTTTTAAAGATCAACCA198GATGCTAAGAAAGTTGCTCCTCAAAATGACTCTTTTGGA237ACACAGTTACCACCGATGCATCAGCAGCAAAGATCTGTA276ATGACAGAAGAATACAAAGTTCCAGATGGAATGGTTGGA315TTCATAATTGGCAGAGGAGGTGAACAGATCTCACGCATA354CAACAGGAATCTGGATGCAAAATACAGATAGCTCCTGAC393AGTGGTGGCCTTCCAGAAAGGTCCTGTATGTTAACTGGA432ACACCTGAATCTGTCCAGTCAGCAAAACGGTTACTGGAC471CAGATTGTTGAAAAAGGAAGACCAGCTCCTGGCTTCCAT510CATGGCGATGGACCGGGAAATGCAGTTCAAGAAATCATG549ATTCCAGCTAGCAAGGCAGGATTAGTCATTGGAAAAGGG588GGAGAAACTATTAAACAGCTTCAGGAACGGGCTGGAGTT627AAAATGGTTATGATTCAAGACGGGCCGCAGAACACTGGT666GCTGACAAACCTCTTAGGATTACAGGAGACCCATATAAA705GTTCAACAAGCCAAGGAAATGGTGTTAGAGTTAATTCGT744GATCAAGGCGGTTTCAGAGAAGTTCGGAATGAGTATGGG783TCAAGAATAGGAGGAAATGAAGGGATAGATGTCCCCATT822CCAAGATTTGCTGTTGGCATTGTAATAGGAAGAAATGGA861GAGATGATCAAAAAAATACAAAATGATGCTGGTGTTCGC900ATTCAGTTTAAGCCAGATGATGGGACAACACCCGAAAGG939ATAGCACAAATAACAGGACCTCCAGACCGATGTCAACAT978GCTGCAGAAATTATTACAGACCTTCTTCGAAGTGTTCAG1017GCTGGTAATCCTGGTGGACCTGGACCTGGTGGTCGAGGA1056AGAGGTAGAGGTCAAGGCAACTGGAACATGGGACCACCT1095GGTGGATTACAGGAATTTAATTTTATTGTGCCAACTGGG1134AAAACTGGATTAATAATAGGAAAAGGAGGTGAAACCATA1173AAAAGCATAAGCCAGCAGTCTGGTGCAAGAATAGAACTT1212CAGAGAAATCCTCCACCAAATGCAGATCCTAATATGAAG1251TTATTTACAATTCGTGGCACTCCACAACAGATAGACTAT1290GCTCGGCAACTCATAGAAGAAAAGATTGGTGGCCCAGTA1329AATCCTTTAGGGCCACCTGTACCCCATGGGCCCCATGGT1368GTCCCAGGCCCCCATGGACCTCCTGGGCCTCCAGGGCCT1407GGAACTCCAATGGGACCATACAACCCTGCACCTTATAAT1446CCTGGACCACCAGGCCCGGCTCCTCATGGTCCTCCAGCC1485CCATATGCTCCCCAGGGATGGGGAAATGCATATCCACAC1524TGGCAGCAGCAGGCTCCTCCTGATCCAGCTAAGGCAGGA1563ACGGATCCAAATTCAGCAGCTTGGGCTGCTTATTACGCT1602CACTATTATCAACAGCAAGCACAGCCACCACCAGCAGCC1641CCTGCAGGTGCACCAACTACAACTCAAACTAATGGACAA1680GGAGATCAGCAGAATCCAGCCCCAGCTGGACAGGTTGAT1719TATACCAAGGCTTGGGAAGAGTACTACAAGAAAATGGGG1758CCAATAATAAGAAGTGGACAATACAGTATTTGCTTC1794AGGAATTCC1803(2) INFORMATION FOR SEQ ID NO: 8:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 590(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(iii) HYPOTHETICAL: No(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(H) CELL LINE: HL60(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8:ArgAlaArgGlnIleAla15AlaLysIleGlyGlyAspAlaGlyThrSerLeuAsnSer1015AsnAspTyrGlyTyrGlyGlyGlnLysArgProLeuGlu202530AspGlyAspGlySerTrpThrSerProSerSerThrThr354045HisTrpGluGlyMetProSerProPheLysAspGlnPro5055AspAlaLysLysValAlaProGlnAsnAspSerPheGly606570ThrGlnLeuProProMetHisGlnGlnGlnArgSerVal7580MetThrGluGluTyrLysValProAspGlyMetValGly859095PheIleIleGlyArgGlyGlyGluGlnIleSerArgIle100105110GlnGlnGluSerGlyCysLysIleGlnIleAlaProAsp115120SerGlyGlyLeuProGluArgSerCysMetLeuThrGly125130135ThrProGluSerValGlnSerAlaLysArgLeuLeuAsp140145GlnIleValGluLysGlyArgProAlaProGlyPheHis150155160HisGlyAspGlyProGlyAsnAlaValGlnGluIleMet165170175IleProAlaSerLysAlaGlyLeuValIleGlyLysGly180185GlyGluThrIleLysGlnLeuGlnGluArgAlaGlyVal190195200LysMetValMetIleGlnAspGlyProGlnAsnThrGly205210AlaAspLysProLeuArgIleThrGlyAspProTyrLys215220225ValGlnGlnAlaLysGluMetValLeuGluLeuIleArg230235240AspGlnGlyGlyPheArgGluValArgAsnGluTyrGly245250SerArgIleGlyGlyAsnGluGlyIleAspValProIle255260265ProArgPheAlaValGlyIleValIleGlyArgAsnGly270275GluMetIleLysLysIleGlnAsnAspAlaGlyValArg280285290IleGlnPheLysProAspAspGlyThrThrProGluArg295300305IleAlaGlnIleThrGlyProProAspArgCysGlnHis310315AlaAlaGluIleIleThrAspLeuLeuArgSerValGln320325330AlaGlyAsnProGlyGlyProGlyProGlyGlyArgGly335340ArgGlyArgGlyGlnGlyAsnTrpAsnMetGlyProPro345350355GlyGlyLeuGlnGluPheAsnPheIleValProThrGly360365370LysThrGlyLeuIleIleGlyLysGlyGlyGluThrIle375380LysSerIleSerGlnGlnSerGlyAlaArgIleGluLeu385390395GlnArgAsnProProProAsnAlaAspProAsnMetLys400405LeuPheThrIleArgGlyThrProGlnGlnIleAspTyr410415420AlaArgGlnLeuIleGluGluLysIleGlyGlyProVal425430435AsnProLeuGlyProProValProHisGlyProHisGly440445ValProGlyProHisGlyProProGlyProProGlyPro450455460GlyThrProMetGlyProTyrAsnProAlaProTyrAsn465470ProGlyProProGlyProAlaProHisGlyProProAla475480485ProTyrAlaProGlnGlyTrpGlyAsnAlaTyrProHis490495500TrpGlnGlnGlnAlaProProAspProAlaLysAlaGly505510ThrAspProAsnSerAlaAlaTrpAlaAlaTyrTyrAla515520525HisTyrTyrGlnGlnGlnAlaGlnProProProAlaAla530535ProAlaGlyAlaProThrThrThrGlnThrAsnGlyGln540545550GlyAspGlnGlnAsnProAlaProAlaGlyGlnValAsp555560565TyrThrLysAlaTrpGluGluTyrTyrLysLysMetGly570575ProIleIleArgSerGlyGlnTyrSerIleCysPhe580585590(2) INFORMATION FOR SEQ ID NO: 9:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 2381(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: cDNA(iii) HYPOTHETICAL: No(iv) ANTI-SENSE: YES(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(H) CELL LINE: HL60(ix) FEATURE:(D) OTHER INFORMATION: 470 bp variableregion where R is A or G.(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:GCGGCAGCGGCTCTTATAGTGCAACCATGGCAGACTATTCAACA44GTGCCTCCCCCCTCTTCTGGCTCAGCTGGTGGCGGTGGT83GGCGGCGGTGGTGGTGGAGGAGTTAACGACGCTTTCAAA122GATGCACTGCAGAGAGCCCGGCAGATTGCAGCAAAAATT161GGAGGTGATGCAGGGACATCACTGAATTCAAATGACTAT200GGTTATGGGGGACAAAAAAGACCTTTAGAAGATGGAGAT239CAACCAGATGCTAAGAAAGTTGCTCCTCAAAATGACTCT278TTTGGAACACAGTTACCACCGATGCATCAGCAGCAA314AGATCTGTAATGACAGAAGAATACAAAGTTCCAGATGGA353ATGGTTGGATTCATAATTGGCAGAGGAGGTGAACAGATC392TCACGCATACAACAGGAATCTGGATGCAAAATACAGATA431GCTCCTGACAGTGGTGGCCTTCCAGAAAGGTCCTGTATR470TTAACTGGAACACCTGAATCTGTCCAGTCAGCAAAACGG509TTACTGGACCAGATTGTTGAAAAAGGAAGACCAGCTCCT548GGCTTCCATCATGGCGATGGACCGGGAAATGCAGTTCAA587GAAATCATGATTCCAGCTAGCAAGGCAGGATTAGTCATT626GGAAAAGGGGGAGAAACTATTAAACAGCTTCAGGAACGG665GCTGGAGTTAAAATGGTTATGATTCAAGACGGGCCGCAG704AACACTGGTGCTGACAAACCTCTTAGGATTACAGGAGAC743CCATATAAAGTTCAACAAGCCAAGGAAATGGTGTTAGAG782TTAATTCGTGATCAAGGCGGTTTCAGAGAAGTTCGGAAT821GAGTATGGGTCAAGAATAGGAGGAAATGAAGGGATAGAT860GTCCCCATTCCAAGATTTGCTGTTGGCATTGTAATAGGA899AGAAATGGAGAGATGATCAAAAAAATACAAAATGATGCT938GGTGTTCGCATTCAGTTTAAGCCAGATGATGGGACAACA977CCCGAAAGGATAGCACAAATAACAGGACCTCCAGACCGA1016TGTCAACATGCTGCAGAAATTATTACAGACCTTCTTCGA1055AGTGTTCAGGCTGGTAATCCTGGTGGACCTGGACCTGGT1094GGTCGAGGAAGAGGTAGAGGTCAAGGCAACTGGAACATG1133GGACCACCTGGTGGATTACAGGAATTTAATTTTATTGTG1172CCAACTGGGAAAACTGGATTAATAATAGGAAAAGGAGGT1211GAAACCATAAAAAGCATAAGCCAGCAGTCTGGTGCAAGA1250ATAGAACTTCAGAGAAATCCTCCACCAAATGCAGATCCT1289AATATGAAGTTATTTACAATTCGTGGCACTCCACAACAG1328ATAGACTATGCTCGGCAACTCATAGAAGAAAAGATTGGT1367GGCCCAGTAAATCCTTTAGGGCCACCTGTACCCCATGGG1406CCCCATGGTGTCCCAGGCCCCCATGGACCTCCTGGGCCT1445CCAGGGCCTGGAACTCCAATGGGACCATACAACCCTGCA1484CCTTATAATCCTGGACCACCAGGCCCGGCTCCTCATGGT1523CCTCCAGCCCCATATGCTCCCCAGGGATGGGGAAATGCA1562TATCCACACTGGCAGCAGCAGGCTCCTCCTGATCCAGCT1601AAGGCAGGAACGGATCCAAATTCAGCAGCTTGGGCTGCT1640TATTACGCTCACTATTATCAACAGCAAGCACAGCCACCA1679CCAGCAGCCCCTGCAGGTGCACCAACTACAACTCAAACT1718AATGGACAAGGAGATCAGCAGAATCCAGCCCCAGCTGGA1757CAGGTTGATTATACCAAGGCTTGGGAAGAGTACTACAAG1796AAAATGGGTCAGGCAGTTCCTGCTCCGACTGGGGCTCCT1835CCAGGTGGTCAGCCAGATTATAGTGCAGCCTGGGCTGAG1874CATTATAGACAACAAGCAGCCTATTATGCCCAGACAAGT1913CCCCAGGGAATGCCACAGCATCCTCCAGCACCTCAGGGC1952CAATAATAAGAAGTGGACAATACAGTATTTGCTTCATTG1991TGTGGGGGAAAAAAACCTTTGTTAAATATATGGATGCAGA2031CGACTTGATGAAGATCTTAATTTTGTTTTTGGTTTAAAAT2071AGTGTTTCCTTTTTTTTTTTTTTTTTTTTGAAAATGTACA2111AAATATCTATCACTACTGATAGGAGGTTAATATTTCTGTG2151TAGAAATGAAAATTGGTTTGTTTTTAGTATTTAGTGTAGA2191TGTACACATTCCAGCAAATGTATTTGCAATTATGTGGTTG2231ATGCTTTGTGATATAAATGTACTTTTTCAATGTATACTTT2271CACTTTCCAAATGCCTGTTTTGTGCTTTACAATAAATGAT2311ATGAAACCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA2351AAAAAAAAAAAAAAAAAAAAAAAAAAAAAA2381(2) INFORMATION FOR SEQ ID NO: 10:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 643(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(iii) HYPOTHETICAL: No(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(H) CELL LINE: HL60(ix) FEATURE:(D) OTHER INFORMATION:Amino Acid 148 (Xaa) is Met or Ile(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10:MetAlaAspTyrSerThrValProProProSerSerGly1510SerAlaGlyGlyGlyGlyGlyGlyGlyGlyGlyGlyGly152025ValAsnAspAlaPheLysAspAlaLeuGlnArgAlaArg3035GlnIleAlaAlaLysIleGlyGlyAspAlaGlyThrSer404550LeuAsnSerAsnAspTyrGlyTyrGlyGlyGlnLysArg556065ProLeuGluAspGlyAspGlnProAspAlaLysLysVal7075AlaProGlnAsnAspSerPheGlyThrGlnLeuProPro808590MetHisGlnGlnGlnArgSerValMetThrGluGlu95100TyrLysValProAspGlyMetValGlyPheIleIleGly105110115ArgGlyGlyGluGlnIleSerArgIleGlnGlnGluSer120125GlyCysLysIleGlnIleAlaProAspSerGlyGlyLeu130135140ProGluArgSerCysXaaLeuThrGlyThrProGluSer145150155ValGlnSerAlaLysArgLeuLeuAspGlnIleValGlu160165LysGlyArgProAlaProGlyPheHisHisGlyAspGly170175180ProGlyAsnAlaValGlnGluIleMetIleProAlaSer185190LysAlaGlyLeuValIleGlyLysGlyGlyGluThrIle195200205LysGlnLeuGlnGluArgAlaGlyValLysMetValMet210215220IleGlnAspGlyProGlnAsnThrGlyAlaAspLysPro225230LeuArgIleThrGlyAspProTyrLysValGlnGlnAla235240245LysGluMetValLeuGluLeuIleArgAspGlnGlyGly250255PheArgGluValArgAsnGluTyrGlySerArgIleGly260265270GlyAsnGluGlyIleAspValProIleProArgPheAla275280285ValGlyIleValIleGlyArgAsnGlyGluMetIleLys290295LysIleGlnAsnAspAlaGlyValArgIleGlnPheLys300305310ProAspAspGlyThrThrProGluArgIleAlaGlnIle315320ThrGlyProProAspArgCysGlnHisAlaAlaGluIle325330335IleThrAspLeuLeuArgSerValGlnAlaGlyAsnPro340345350GlyGlyProGlyProGlyGlyArgGlyArgGlyArgGly355360GlnGlyAsnTrpAsnMetGlyProProGlyGlyLeuGln365370375GluPheAsnPheIleValProThrGlyLysThrGlyLeu380385IleIleGlyLysGlyGlyGluThrIleLysSerIleSer390395400GlnGlnSerGlyAlaArgIleGluLeuGlnArgAsnPro405410415ProProAsnAlaAspProAsnMetLysLeuPheThrIle420425ArgGlyThrProGlnGlnIleAspTyrAlaArgGlnLeu430435440IleGluGluLysIleGlyGlyProValAsnProLeuGly445450ProProValProHisGlyProHisGlyValProGlyPro455460465HisGlyProProGlyProProGlyProGlyThrProMet470475480GlyProTyrAsnProAlaProTyrAsnProGlyProPro485490GlyProAlaProHisGlyProProAlaProTyrAlaPro495500505GlnGlyTrpGlyAsnAlaTyrProHisTrpGlnGlnGln510515AlaProProAspProAlaLysAlaGlyThrAspProAsn520525530SerAlaAlaTrpAlaAlaTyrTyrAlaHisTyrTyrGln535540545GlnGlnAlaGlnProProProAlaAlaProAlaGlyAla550555ProThrThrThrGlnThrAsnGlyGlnGlyAspGlnGln560565570AsnProAlaProAlaGlyGlnValAspTyrThrLysAla575580TrpGluGluTyrTyrLysLysMetGlyGlnAlaValPro585590595AlaProThrGlyAlaProProGlyGlyGlnProAspTyr600605610SerAlaAlaTrpAlaGluHisTyrArgGlnGlnAlaAla615620TyrTyrAlaGlnThrSerProGlnGlyMetProGlnHis625630635ProProAlaProGlnGlyGln640(2) INFORMATION FOR SEQ ID NO: 11:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: DNA(vi) ORIGINAL SOURCE:(A) ORGANISM: Human(ix) FEATURE:(D) OTHER INFORMATION: FUSEoligonucleotide(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11:GATCACAAAATAAAAAATCCCGAGGGAATATAG33(2) INFORMATION FOR SEQ ID NO: 12:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: DNA(iii) HYPOTHETICAL: YES(ix) FEATURE:(D) OTHER INFORMATION: Mut A(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12:GATCACAACTACGTGCTAGGACGCCGAATATAG33(2) INFORMATION FOR SEQ ID NO: 13:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 39(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: DNA(iii) HYPOTHETICAL: No(ix) FEATURE:(D) OTHER INFORMATION: cAMP responseelement(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13:GATCTGACGTCATGACTGACGTCATGACTGACGTCATCA39(2) INFORMATION FOR SEQ ID NO: 14:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 32(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: DNA(iii) HYPOTHETICAL: NO(ix) FEATURE:(D) OTHER INFORMATION: CT element in c-myc5&#39;- flanking region (&#34;CTE&#34;)(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14:AATTCTCCTCCCCACCTTCCCCACCCTCCCCA32(2) INFORMATION FOR SEQ ID NO: 15:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: DNA(iii) HYPOTHETICAL: YES(ix) FEATURE:(D) OTHER INFORMATION: Mut B(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15:GATCACAAAATAAAAAATGGACGCCGAATATAG33(2) INFORMATION FOR SEQ ID NO: 16:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 33(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: DNA(iii) HYPOTHETICAL: YES(ix) FEATURE:(D) OTHER INFORMATION: Mut C(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16:GATCACAACTACGTGCTAGGCGAGGGAATATAG33(2) INFORMATION FOR SEQ ID NO: 17:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 9(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(iii) HYPOTHETICAL: No(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17:LysGluIleGluGlnLysValGlnGlu15(2) INFORMATION FOR SEQ ID NO: 18:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 12(B) TYPE: Nucleic acid(C) STRANDEDNESS: Double(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: DNA(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18:TTAGTTAACTAA12(2) INFORMATION FOR SEQ ID NO: 19:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 6(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(ix) FEATURE:(D) OTHER INFORMATION: Mutant 2(ix) SEQUENCE DESCRIPTION: SEQ ID NO: 19:IleGlySerArgIleArg15(2) INFORMATION FOR SEQ ID NO: 20:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 4(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(ix) FEATURE:(D) OTHER INFORMATION: Mutant 3(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20:IleArgIleArg15(2) INFORMATION FOR SEQ ID NO: 21:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 5(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(ix) FEATURE:(D) OTHER INFORMATION: Mutant 4(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21:ProArgIleArgGlu15(2) INFORMATION FOR SEQ ID NO: 22:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 4(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(ix) FEATURE:(D) OTHER INFORMATION: Mutant 6(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22:GlyIleProArg15(2) INFORMATION FOR SEQ ID NO: 23:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 4(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(ix) FEATURE:(D) OTHER INFORMATION: Mutant 8(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23:ArgAspProAla15(2) INFORMATION FOR SEQ ID NO: 24:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 4(B) TYPE: Amino Acid(C) STRANDEDNESS: Single(D) TOPOLOGY: Unknown(ii) MOLECULE TYPE: Peptide/Protein(ix) FEATURE:(D) OTHER INFORMATION: Mutant 9(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24:ArgGlySerGly15__________________________________________________________________________

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