bluuebunny/crossref_metadata_2025 huggingface dataset:
TRAM
Authors: Hartmann E , Rapoport T A
Published: November 2023

The TRAM protein is an integral glycosylated membrane protein of 373 amino acids having an apparant molecular weight in SDS gels of 36 kDa. It probably spans the phospholipid bilayer eight times and has a (-terminal tail of about 60 residues. It contains one N-linked carbohydrate chain. Highly homologous sequences were obtained by cDNA cloning from MDCK (canine) and from HeLa (human) cells. They are available in the GenBank under the accession numbers X63678 and X63679, respectively1. No homology to any other known sequence in the EMBUGenBank database could be detected. The TRAM protein is present in the rough ER in amounts at least equivalent to that of membrane bound ribosomes.
Signal sequence receptor (SSR) complex
Authors: Hartmann E , Rapoport T A
Published: November 2023

The $SR-complex has been purified from microsomal membranes of dog pancreas as a tetramer containing four polypeptides (SSRa, SSR . SSRy, SSRo) in stoichiometric relation (relative molecular mass 34 kDa, 22 kDa, 20 kDa, 18 kDa, respectively)1·3. Crosslinking with a bifunctional reagent indicates that the tetrameric complex exists in intact membranes. All subunits are integral membrane proteins12A- The a, . and 8-subunits span the membrane once with the (-termini located in the cytoplasm and the N-termini being translocated .
BiP
Authors: Gething M J
Published: November 2023

The nucleotide sequences of BiP cDNAs cloned from mammalian species4·7 (GenBank Accession numbers M19645 and M17169) predict a protein of 635 amino acids that includes an 18 residue N-terminal signal sequence, and a (terminal tetrapeptide (Lys-Asp-Glu-Leu or KDEL) required for retrieval of BiP molecules that leave the ER. Clusters of acidic amino acids, thought to be involved in the low affinity, high capacity ca++ binding activity of the molecule9, are found at both the N- and (-termini of the molecule. BiP proteins are highly conserved, there being 99% amino acid sequence identity between the mature proteins from human and rodent cells7 and 67% identity between the proteins from mouse cells and from the yeast, Saccharomyces cerevisiae10-12 (Kar2p; see p. 41). Comparison of the sequences of BiP proteins with those of other members of the stress-70 family reveal that the Nterminal two-thirds (-450 amino acids) are much more highly conserved than the (-terminal portions, suggesting a conserved domain followed by a more variable region13,14 (Fig. 1A).
Microsomal signal peptidase complex
Authors: Shelness G
Published: November 2023

Signal peptidase activity was first observed in vitro during cell free translation of secretory precursor mRNAs in the presence of canine pancreas rough microsomes. Preproteins expressed in this system are co-translationally translocated into microsomal vesicles and simultaneouslyprocessed to form the mature polypeptides1.
Oligosaccharide-P-P-dolichol assembly
Authors: Krag S S
Published: November 2023

phorylated family of polyisoprenols containing 17 to 21 isoprenyl groups and having the alpha isoprenyl group saturated. The early biosynthetic steps of dolichyl phosphate are identical to those for cholesterol (Figure 1). Acetyl coenzyme A (CoA) is converted to acetoacetyl CoA; one molecule of each is condensed to form 3-hydroxy-3-methylglutaryi (HMG) CoA. In an important regulatory step catalyzed by HMG-CoA reductase, HMG-CoA undergoes an NADPH-dependent reduction to form mevalonate, which is in turn converted in three ATP-requiring steps followed by loss of a carboxyl group to isopentenylpyrophosphate.
OST48
Authors: Gilmore R
Published: November 2023

The amino acid sequence of OST48 was deduced from the nucleotide sequence of a cDNA cloned from a MDCK cell cDNA library {GenBank accession number M98392)1. The OST48 cDNA clone contains an open reading frame of 445 amino acid residues1. The first 31 residues of the protein resemble a typical cleavable signal sequence for initiation of translocation across the ER membrane. The location of a signal peptidase cleavage site between residues 31 and 32 was predicted using the method of von Heijne2, and subseuently confirmed by sequence analysis of the N-terminus of canine OST48.
N-glycan terocessing in the ER
Authors: Trimbe R , Morcrnen, K , Herscovics A
Published: November 2023

N-linked oligosaccharide synthesis begins with the transfer of a precursor oligosaccharide from a dolichol-P-P-linked intermediate to Asn-X-Ser/Thr. This oligosaccharide, Glc3Man9GlcNAc2, in most cells is then trimmed by a-glucosidases and a,-mannosidases, beginning in the ER. Initial studies on the processing of newly synthesized glycoproteins reported the removal of glucose residues prior to mannose trimming reactions3.4.5. Two glucosidase activitieswere subsequently identified6·8 and termed a-glucosidase I, which removes the terminal a,-1,2-linked glucose from Glc3Man9GlcNAc2, and a-glucosidase II, which removes the remaining two a-1,3-linked glucose residues from the precursor.
Introduction
Authors: Balch W E
Published: November 2023

Export of protein from the ER involves the sequential formation (budding), targeting and fusion of carrier vesicles to the cis Golgi network (CGN), the first compartment of the central Golgi apparatus. Considerable progress has been made in identifying components involved using both biochemical and genetic approaches in yeast and mammalian cells123 While this chapter emphasizes properties unique to each protein, it is important to view their function in a more global perspective. The majority, if not all of the proteins studied to date participate in transport in the context of macromolecular protein complexes. Figure 1 illustrates the extent of these interactions as currently determined from both biochemical and genetic studies. As is readily apparent, interactions are extensive and may occur during synthesis, recycling or the differential steps involved in carrier vesicle budding, targeting and fusion.
SEC16
Authors: Kaiser B
Published: November 2023

The SEC16 gene was first identified in a screen for conditional mutants that block secretory protein transport to the cell surface. At the nonpermissive temperature, sect 6 mutations rapidly cause the accumulation of secretory protein precursors in their core-glycosylated, ER forms, implying a defect in protein transport from the ER. Moreover, by thin-section electron microscopy, sec16 mutants accumulate excess ER membrane at the nonpermissive temperature. More detailed morphological analysis shows that sec16 is in a class of ER-blocked mutants that fail to form a 50 nm vesicle intermediate in transport to the Golgi; in double-mutant epistasis tests, sec16 mutants block the vesicle accumulation that would otherwise occur in sec17, sec18, or sec22 mutants 2 (see pp. 133, 132 and 129).
SEC13
Authors: Pryer N K
Published: November 2023

Two temperature-sensitive alleles, sec13-1 and sec13-4, were isolated by a density enrichment screen1 After a shift to restrictive temperature, sec13-1 cells accumulated exaggerated ER membrane, apparent in thin-section elec tron micrographs2 Mutant cells shifted to the restrictive temperature exhibited a rapid block in secretion of secreted, plasma membrane and vacuolar proteins such as invertase, alkaline phosphatase and carboxypeptidase Y. The blocked proteins accumulated in the core-glycosylated ER form13. A third allele, sec13-5, has recently been isolated in a mutant screen for cells secreting unprocessed a factor4.
YPT1
Authors: Segev N
Published: November 2023

Analysis of the phenotype of several ypt1 mutants indicates that the Ypt1 protein plays an essential role in the secretory pathway3. First, null mutations, generated by gene disruption techniques, reveal that the YPT1 gene is essential for vegetative growth in yeast45. Second, analysis of conditional-lethal mutations suggests that the Ypt1 protein is involved in an early step of protein transport.
SLY1
Authors: Daschcr C , Schmitt H D
Published: November 2023

The null mutation of SLY1 is lethal1 A galactose-dependent conditional lethal mutant with SLY1 under transcriptional control of the regulatable GAL10 promoter grows normally on galactose but ceases growth in glucose-con-taining medium. Under restrictive conditions these mutant cells show a block in protein transport from the ER to the Golgi apparatus: Sly1p-deleted cells accumulate intracellular core-glycosylated invertase and carboxypeptidase Y as well as an excess of ER membranes2.
SEC17d
Authors: Kaiser ¾ C
Published: November 2023

The SEC17 gene was first identified in a screen for conditional mutants that block secretory protein transport to the cell surface. At the nonpermissive temperature, sec17 mutations rapidly cause the accumulation of secretory protein precursors in their core glycosylated, ER forms implying a defect in protein transport from the ER. By thin-section electron microscopy, sec17 mutants accumulate excess ER membrane at the nonpermissive temperature. More detailed morphological analysis shows that sec17 is in a class of ER-blocked mutants that accumulate 50 nm vesicles and are therefore defective in vesicle fusion with the Golgi.
SEC19
Authors: Pryer N K
Published: November 2023

A single temperature-sensitive allele, sec19-1, was isolated by a density enrichment screen. After shifting to restric-tive temperature, mutant cells accumulate a mixture of secretory organelles, including ER membrane, 80-100 nm vesicles (similar in size to mature secretory vesicles), and “Berkeley bodies”, structures thought to represent the Golgi apparatus. The sec19-1 mutant accumulates the p1 (core-glycosylated) form of the vacuolar protease carboxypeptidase Y at the restrictive temperature2 , indicating that the secretory block is imposed on transport between the ER and Golgi.
SED5
Authors: Pelham H
Published: November 2023

Deletion of the SED5 gene is lethal. When cells are depleted of Sed5 protein by repression of a GAL promoterSEDS fusion gene, transport of proteins from the ER to the Golgi is blocked and there is an accumulation of ER membranes and small vesicles1 The DNA sequence of the SED5 gene (GenBank accession number X66980) predicts a protein of 340 amino acids (39 kDa).
Coatomer
Authors: Waters M G , Beckers C J M
Published: November 2023

Coatomer was originally purified from bovine brain 1 but has also been purified from bovine liver9 with a higher yield. The original brain protocol employed precipitation of the complex with a low ionic strength acidic (pH 5.8) buffer. Although this precipitation greatly enriches the coatomer, it modifies the coatomer such that it is no longer soluble in physiological salt and must be maintained in high salt buffers. To avoid this difficulty, coatomer has been purified from bovine liver (where it is more abundant) without the precipitation step. This preparation is soluble in physiological salt.
Genes required for the maturation of N-linked carbohydrates in mammalian cells
Authors: Stanley P
Published: November 2023

N-linked glycosylation reactions that begin with the action of GlcNAc-TI are summarized in Figure 1; further information is provided in Table 1. Building of hybrid and complex oligosaccharides proceeds by the action of specific glycosyltransferases that catalyze the transfer of each sugar residue from a nucleotide-sugar to the carbohydrate acceptor in a specific glycosidic linkage. Nucleotide-sugars are synthesized for the most part in the cytoplasm and must be translocated via specific transporters into the Golgi lumen2 The N-linked structures of a glycoprotein exhibit a restricted heterogeneity dependent on several factors, including the protein conformation surrounding the glycosylation site.
Furin
Authors: Thomas F
Published: November 2023

Furin is the translation product encoded by the fur locus, which was initially identified by its proximity to the fes/fps proto-oncogene (fes/fps JJ.pstream region)3. Furin cDNAs have been isolated from several species including human, mouse, rat and Xenopus4-8. Cloning of cDNAs by PCR strategy shows that furin was the first identified member of a growing family of mammalian subtilisin-related K£X2-like endoproteases (designated KLIP’s in reference 9) that currently includes PACE-4, PC2 and PC3 (also called PC1), and PC410-17 (see PC entry p. 197).
PC2 and PC3
Authors: Smeckens S
Published: November 2023

The domain structures of PC2 and PC3 are shown in Figure1. Each protein begins with a signal peptide indicating entry into the secretory pathway, followed by about a 100 residue pro-domain. In the bacterial subtilisins the pro-domain plays a role in protease folding and its removal is necessary for enzyme activation6.7. In the eukaryotic proteases, prodomain cleavage occurs at a conserved motif of basic amino acids, reflecting the substrate specificity of these proteases and suggesting that this cleavage is autocatalytic. Studies indicate that cleavage of the PC3 pro-domain occurs at an early stage during biosynthesis, perhaps in the endoplasmic reticulum.
Synaptobrevin protein family
Authors: Jahn R , Südhof T C
Published: November 2023

In mammalian species, two different synaptobrevin cDNAs have been characterized so far1,2A (GenBank accession numbers VAMP-1: M24105 and VAMP-2: M24104}. They encode two highly homologous proteins, synaptobrevin 1 (VAMP-1} and synaptobrevin 2 (VAMP-2) predicted to contain 118 and 116 amino acid residues, respectively. No evidence for a signal sequence was found. The two forms share 77% amino acid sequence identity. Comparison of the rat and human sequence revealed that each form is separately conserved, with only one and three amino acid substitutions in synaptobrevin 2 and synaptobrevin 1, respectively4. In addition, cDNA sequences of synaptobrevin homologues from Torpedo and Drosophila were reported23
SSA Hsp70 subfamily
Authors: Nelson R J , Craig E
Published: November 2023

The four SSA genes are regulated differently in response to stress and growth state. SSA1 is constitutively expressed as well as being stress-inducible, while SSA2 is constitutive and not ostensibly affected by stress. SSA3 and SSA4 are “classic” heat shock genes whose expression is stress dependent. Also, unlike any other SSA gene, SSA3 transcription is derepressed in response to nutrient limitation2·3.
VPS1
Authors: Raymond C K , Stevens T H
Published: November 2023

The overall identity between Vps1 protein and dynamin (and/or shibire, since dynamin and shibire are ∼90% identi-caI5) is 45%; however, the amino-terminal 300 residues of these proteins share 66% identity4·5. The level of similarity of Vps1 protein to the Mx proteins is -45% over the N-terminal 250 residues, and ∼30% overall1.
VPS16
Authors: Horazdosky B F , Emr S D
Published: November 2023

Cells carrying a complete deletion of the VPS16 coding region are viable, but display a temperature-sensitive growth phenotype1. vps16A cells also exhibit a severe vacuole protein localization defect (secreting >95% of the soluble vacuolar hydrolase, carboxypeptidase Y in its Golgi modified precursor form) and are completely defective in the proteolytic maturation of all vacuolar proteins examined1. In addition, cells carrying the vps16 null allele lack any identifiable vacuolar structure, but instead accumulate small vesicle-like structures typical of class C vps mutants45.
VPS21
Authors: Horazdovsky C F , Busch, G R , Emr S D
Published: November 2023

The loss of Vps21p function severely compromises the ability of yeast cells to localize both soluble and membrane associated vacuolar proteins1. Greater than 80% of two soluble hydrolases, carboxypeptidase Y (CPY) and proteinase A (PrA), are missorted in t,vps21 cells and are present as Golgi modified precursors. A small amount of mature CPY and PrA (∼15% of total) can be detected in the mutant cells.
VPS45
Authors: Piper R C , Stevens T H
Published: November 2023

Haploid cells carrying a 70% deletion of the VPS45 open reading frame (vps45A) are viable but exhibit defective growth at 37°C as observed with many other VPS mutants. vps45A cells secrete >70% of newly synthesized CPY precursors well as other vacuolar hydrolase precursors. vps45A mutants are morphologically distinguished by having large central vacuoles. Newly formed vps45A daughter cells lack vacuolar structures as determined by immunofluorescence with antibodies specific for the vacuolar membrane alkaline phosphatase or the vacuolar H+ATPase. This morphological phenotype results from a defect in vacuolar segregation from mother cells into the developing bud region (see VPS3 entry, p.231).
PEPS
Authors: Woolford C A , Jones E W
Published: November 2023

Haploid cells possessing a deletion/disruption allele of PEPS are viable. peps mutants show greatly decreased activities of the vacuolar hydrolases proteinase A (PrA), proteinase B (PrB), carboxypeptidase Y (CPY) and the repressible alkaline phosphatase2 Normal precursor forms of the proteases accumulate, as do novel forms of PrB antigen. It has been shown that in peps mutants a precursor to CPY78 and precursor and mature forms of PrA78 are mislocalized and secreted. Alpha-factor is internalized, but is not degraded4. Mutants show a growth defect on nonfermentable carbon sources4 A peps null mutant shows very slow growth at 37°C, implying that the PEPS gene product helps in extending the temperature growth range. The vacuolar morphology of peps mutants is quite aberrant.
PEP12
Authors: Bachhawat K A , Jones F W
Published: November 2023

Cells with mutations in the PEP12 gene have one unusually large vacuole. Analysis of insertion/disruption and dele-tion/disruption mutant strains has revealed that the gene product is non-essential invegetatively growing cells. The cell density of the disruption strains at stationary phase however is only -50% of wild type. Cells grown under stressful conditions, however, demonstrate growth difficulties. For example: with glucose as a carbon source, cell doubling time of a strain containing the disruption is only slightly slower than wild type at 30°C. However, at 37°C the growth is greatly slowed. Diploid strains heterozygous for the disruption allele sporulate normally while those homozygous for the disruption allele fail to sporulate.
SRP101
Authors: Ogg S C , Walter P
Published: November 2023

Although SRP101 is not an essential gene, disruption of SRP101 results in an approximate six fold reduction in the growth rate of the cells. In addition, cells which are deleted for SRP101 are unable to grow on carbon sources requiring respiration1 Yeast cells that contain the SRu gene (SRP101) under the control of the GALI promoter show impaired translocation of soluble and membrane proteins across the ER membrane after depletion of SRu1. The degree of this translocation defect varies for different proteins. Kar2p, a soluble ER resident protein, and dipeptidyl aminopeptidase-B (DPAP-B), a vacuolar integral membrane protein, showed the greatest defect.
VMA6
Authors: Bauerle B M , Stevens T H
Published: November 2023

The VMA6 gene was cloned using a reverse genetic strategy. Peptide sequence data from tryptic fragments of gel purified 36 kDa polypeptide was used to design corresponding “sense” and “antisense” oligonucleotides. Pairs of degenerate oligonucleotides were used as primers to amplify sequences from yeast genomic DNA by PCR, and the PCR fragment was used to obtain the intact VMA6 gene. The DNA sequence of VMA6 (GenBank accession # L11584) contains an open reading frame that is predicted to encode a polypeptide of 345 amino acids with a molecular mass of 39.8 kDa. All five of the originally determined internal peptide sequences of the 36 kDa polypeptide were found within the open reading frame. The predicted polypeptide is hydrophilic overall, with many acidic charged residues dispersed throughout the sequence.
CHG1
Authors: Payne H S , Lemmon S K
Published: November 2023

Depending on the genetic background, deletions of CHC1 may result in slow-growing viable haploid cells or inviable haploid cells (see Genetic interaction section below)1·4. Viable mutants grow at rates roughly 2-6 times slower than wild-type cells. chc1-!l cells display genetic instability that can result from increases in genome copy number2A. In cultures of chc1-!l strains, cells with multiple nuclei can be present at levels approaching 1% of the population.
END3,END4
Authors: Raths S , Reizman- H
Published: November 2023

The mutant, end3, was identified by screening an ethylmethanesulfonate (EMS) mutagenized bank of Saccharomyces cerevisiae for strains that bind but fail to internalize 35S-a-factor. This mutation is recessive and renders cells unable to grow at temperatures of 37°C. end3 strains, however, can bind but not internalize a-factor at permissive (24°C) and restrictive temperatures (37°(). Lucifer yellow, a fluid phase endocytic marker, is also not accumulated in the vacuole of end3 mutants at either temperature. Other vesicle-mediated processes seem to be normal in end3 as invertase secretion and carboxypeptidase Y maturation proceed unimpaired. The end3 gene was cloned by complementation of the temperature-sensitive growth defect of the end3 mutant.
Clathrin-associated protein complexes (APs)
Authors: Kirchhausen T
Published: November 2023

= - - =

Clathrin-associated proteins are also referred to as assem bly proteins and adaptors. The term “associated proteins” is a general term used to indicate that their in vivo function is still not completely understood. “Assembly proteins” refers to the in vitro property that under physiological ionic conditions APs interact with clathrin and assemble with it into small coats1 The term “adaptor”2 was introduced to indicate that a possible role of the APs is to interact with clathrin and with the cytoplasmic tails of some membrane proteins, leading to their selection and concentration into coated pits and coated vesicles2,3.
End3
Authors: Draper R K
Published: November 2023

This complementation group contains one mutant, termed G.7.1, isolated by exposing mutagenized Chinese hamster ovary cells to both diphtheria toxin and the plant toxin modeccin1. At the restrictive temperature, G.7.1 cells are defective in endosomal, but not lysosomal, acidification13. The acidification of endosomes prepared from mutant cells harvested at the permissive temperature is hypersensitive to thermal inactivation in vitro, demonstrating that a thermosensitive component is a resident of vesicles from the mutant cells. Coated vesicle preparations made from G.7.1 cells grown at the permissive temperature have a thermolabile acidification activity and a thermolabile proton-translocating ATPase activity.
End4
Authors: Draper R K
Published: November 2023

This complementation group was originally defined in genetic studies with mutant V.24.1, isolated by exposing Chinese hamster ovary cells to diphtheria toxin1 Two other Chinese hamster ovary cell mutants, DS28-6 and HRP-1, have recently been added to the group by complementation analysis2. DS28-6 was isolated by Nakano et al. using a replica-plating technique to rescue temperaturesensitive mutants defective in secretion3 HRP-1 was isolated by Wang et al. using a new procedure to obtain mutants defective in fluid-phase endocytosis2.
Rab4
Authors: Mellman I
Published: November 2023

Rab4 was first localized to early endosomes by screening subcellular fractions prepared from CHO cells using the original panel of polyclonal anti-rab antibodies prepared by Bruno Goud3 Free-flow electrophoresis fractions were analyzed by immunoblotting, and only antibody to rab4 was found to yield a clear signal in the anodally-shifted fractions that co-migrated with transferrin receptor. This localization was confirmed by immunofluorescence performed on cells (Hela, CHO) stably or transiently transfected with wild type rab4a cDNAs. lmmunoelectron microscopy (immuno-EM) on frozen thin sections is also consistent with an early endosome/recycling vesicle localization4; very little rab4 is detectable on the plasma membrane. Since rab5 has also been localized by immunofluorescence, cell fractionation, and immune-EM to early endocytic compartments (see rab5 entry, p. 295), it has been presumed that rab4 and rab5 are themselves co-localized.
Bet2p
Authors: Ferro-Novick Susan
Published: November 2023

The DNA sequence of BET2 predicts a hydrophilic protein of-36 500 daltons (Peterson-Bjorn et al. 1990; Rossi et al. 1991). Antibody raised to this protein has confirmed this prediction (Jiang et al. 1993). Bet2 shares 56.6% similarity and 34% identity with Dpr1 (Ram1), an essential component of a protein prenyltransferase that adds farnesyl (a 15 carbon lipid) to the COCH-terminus of Ras and the yeast mating pheromone afactor (Schafer et al. 1990; Goodman et al. 1990; He et al. 1991).8ET2wasalsofoundto be the same as ORF2, an essential yeast gene of unknown function (Peterson-Bjorn et al. 1990; Rossi et al. 1991). The DNA sequences of BET2 andORF2 are identical with one exception that results in a conserved amino acid change (asparagine in Orf2 and lysine in Bet2 at position 22) in the protein. This change may be attributable to differences in strain backgrounds.
Dras2
Authors: III John G Bishop , Corces Victor G
Published: November 2023

Dras2 was identified by cross-homology with the Harvey murine sarcoma virus (Neuman-Silbergerg et al. 1984; Mozer et al. 1985). It maps to chromosomal subdivision 64B on Drosophila polytene chromosomes. The nucleotide sequence of Dras2 is shown in Fig. 1. This sequence differs from that reported initially from sequence analysis of genomic clones (Neuman-Silberberg etal. 1984; Mozer et al. 1985), and was obtained by sequencing full-length cDNA clones (Bishop and Corces 1988). The nucleotide sequence of Dras2 is deposited in the GenBank database with accession numbers M10759 and M10803; the sequence of the promoter region is under accession number X12558, and the updated sequence of the exon2/exon3 borders is under X12559.
Sevenless
Authors: Mlodzik Marek
Published: November 2023

The rescue fragment contains a single 8.2-kb transcript (Hafen et al. 1987). The complete nucleotide sequence of the 12 kb rescue fragment has been determined (Basler and Hafen 1988; Bowtell et al. 1988). The GenBank accession numbers are J03158 and Y00218, respectively.ProteinIn comparison to other known tyrosine kinases, the sev gene product is unique in size and structure. The nucleotide sequence predicts a protein of 2554 amino acids with two transmembrane segments (Basler and Hafen 1988; Bowtell et al. 1988).
Dm Gapl
Authors: Gaul Ulrike
Published: November 2023

Mutations in Gap1 have been obtained by P enhancer trap insertion and chemical mutagenesis (Buckles et al. 1992; Gaul etal. 1992; Rogge etal. 1992). Gap1 was identified by screening cDNA libraries using genomic sequences flanking the P insertion (Gaul et al. 1992). The P enhancer trap is inserted into the open reading frame (ORF) of the Gap1 transcript, which is the cause of its mutagenicity. The DNA sequence of Drosophila Gap1 (Gaul etal. 1992) is shown in Fig. 1. The GenBank accession number is M86655.
Bcl2
Authors: Bischoff James R , Fernandez-Sarabia Maria Jose
Published: November 2023

Probes for the IgH locus were used to clone t(14; 18) breakpoint DNAs. These DNAs allowed the identification of a transcriptional unit on chromosome 18, which was named bc!2. The bcl2 gene is transcribed by alternative splicing into three mRNAs of different sizes. bcl2 contains two exons and encodes two proteins that only differ at their C-terminal regions (Tsujimoto and Croce 1986). The open reading frame of the human bcl2 gene and its amino acid sequence is shown in Fig. 1. The accession number for the genomic sequence is M13994.
Rsr lp
Authors: Bender Alan , Pringle John R
Published: November 2023

RSR1 was identified both as a multicopy suppressor of a cdc24ts mutation (Bender and Pringle 1989) and on the basis of a mutation (bud1) that randomized bud position (Chant and Herskowitz 1991). Its nucleotide and predicted amino acid sequences (Bender and Pringle 1989; GenBank accession number M26928) are shown in Fig. 1.
Ira 2p
Authors: Powers Scott
Published: November 2023

The Ira2 gene was cloned from a yeast DNA expression library by searching for genes that when overexpressed could suppress the heat-shock sensitivity of an ira1-1 mutant (Tanaka et al. 1990b). The GenBank accession number is M33779.
Rho2p
Authors: Madaule Pascal , Myers Alan
Published: November 2023

The RHO2 gene was identified by a low stringency screen of a Saccharomyces cerevisiae genomic library, using as a probe a Rho cDNA from Aplysia californica (Madaule and Axel 1985; Madaule et al. 1987). RHO2 is not an essential gene. GenBank accession number is M15190.
Cdc24p
Authors: Bender Alan , Pringle John R
Published: November 2023

CDC24 was identified both during a screen for temperature-sensitive (Ts_) cell-division-cycle mutants that fail to initiate bud emergence but can initiate the nuclear-division cycle (Hartwell et al. 1973, 1974) and during a screen for mutants that are sensitive to high levels of Ca2+ in the medium (Ohya etal. 1986a, b). Its nucleotide and predicted amino acid sequences (Miyamoto et al. 1987, 1991; GenBank accession number M16809) are shown in Fig. 1.
Rab proteins
Authors: Zerial Marino
Published: November 2023

The intracellular localization of Rab proteins has provided a first clue into their function. Rab proteins are present in two intracellular pools, one minor, cytosolic, and another major, membrane-bound. A characteristic feature of the members of this subfamily is their intracellular compartmentalization. A number of organelles of the exocytic and endocytic transport pathways contain a characteristic set of membrane-associated Rab proteins. Figure 1 and Table 1 summarise the subcellular localization of these proteins. This distribution is consistent with a function of Rab proteins in distinct intracellular transport processes.
RabSc
Authors: Kikuchi Akira , Takai Yoshimi
Published: November 2023

Bovine Rab3c cDNA was isolated from a bovine brain cDNA library using oligonucleotide probes of Rab3a (Matsui etal. 1988). The nucleotide sequence of bovine Rab3c and its deduced amino acid sequence are shown in Fig. 1. The GenBank accession number is J03943.
Ypt52p
Authors: Singer-Kruger Birgit
Published: November 2023

Sequence analysis of chromosome XI of S. cerevisiae in the yeast genome sequence project of the European community led to the identification of a small GTPase that contained 55%/70% sequence identity/homology to Rab5a, and 54%/71% and 51%/66% identity/homology to Ypt51p and Ypt53p, respectively (Singer-Kruger et al. 1994). Due to the close phylogenetic relationship of these proteins and their functional similarities, this gene was named YPT52 and its gene product Ypt52p (Fig. 1).
Gdilp/Secl9p
Authors: Garrett Michelle D , Novick Peter
Published: November 2023

Complementation and linkage analysis indicates that GDI1 is allelic to sec19-1, a temperature-sensitive, conditionally lethal mutant isolated by a density enrichment protocol (Novick et al. 1980; Garrett et al. 1994). At the restrictive temperature of 37C, the sec19-1 cells are blocked for the transport of invertase and acid phosphatase; they accumulate the p1 form of the vacuolar protease carboxypeptidase Y, and are defective for the uptake of the fluid phase marker, Lucifer yellow (Novick et al. 1980; Stevens et al.
Yptl (Schizosaccharomyces pombe)
Authors: Armstrong John
Published: November 2023

The ypt1 gene was isolated fortuitously by hybridizing a S. pombe genomic library with a probe from the sec4 gene of 5. cerevisiae (Fawell et al. 1989) and independently with a ypt3 probe (Miyake and Yamamoto 1990). The sequence, including four introns, is given in Fig. 1(A). Note that, due to the presence of an unusual splice junction, the extreme N-terminus was originally assigned incorrectly. The correct splice pattern was determined by Northern blotting (Miyakeand Yamamoto 1990) and polymerase chain reaction (PCR) of cDNA (Newman etal. 1992). The EMBL accession numbers are X15082, X52099.
Arf2
Authors: Kahn Richard A
Published: November 2023

Bovine Arf2 was cloned by screening a bovine retinal cDNA library with a degenerate oligonucleotide probe, derived from partial protein sequencing of purified protein (Price etal. 1988; accession number P16500).
Ran/TC4
Authors: Bischoff F Ralf , Coutavas Elias , Ponstingl Peter D’Eustachio. Herwig , Ren Mindong , Rush Mark
Published: November 2023

Ran/TC4 was originally identified by screening a human teratocarcinoma cDNA library with degenerate oligonucleotides based on the conserved DTAGQE sequence of Ras family members (Drivas etal. 1990). The DNA sequence of Ran/TC4 (Ren et al. 1993) and its predicted open reading frame are shown in Fig. 1 (GenBank accession number M31469). To date, the coding sequences for several other Ran subfamily members have been identified in mouse (Coutavas et al. 1994),
Interleukin-4 (IL-4)
Authors: Howard M , Harada N
Published: November 2023

The nucleotide sequences of IL-4 cDNAs cloned from mouse and man (GenBank accession numbers M13238 and M13982) predict a protein of 153 (human) or 140 (mouse) amino acids, each containing a 20-amino-acid leader sequence (Lee et al. 1986; Noma et al. 1986; Yokota et al. 1986). These proteins are approximately 50 per cent homologous at the amino acid level, and there is no cross-reaction either biologically or at the receptor level between the two species of cytokine.
Interleukin-6 (IL-6)
Authors: Narazaki M , Kishimoto T
Published: November 2023

B cell stimulatory factor 2 (BSF-2), B cell differentiation factor (BCDF), interferon-P2 (IFN/J2), 26-kDa protein, hybridoma growth factor (HGF), hepatocyte-stimulating factor (HSF). Human IL-6 consists of 212 amino acids including a 28 amino acid signal peptide (Hirano et al. 1986) (GenBank accession number X04602), whereas mouse and rat IL-6 consist of 211 amino acids with a 24-amino-acid signal peptide (Van Snick et al. 1988; Northemann et al. 1989) (GenBank accession number X06203 for mouse IL-6, M26744 for rat IL-6). Comparison ofthe amino acid sequence of human IL-6 with that of mouse IL-6 shows a homology of only 42 per cent, although the mouse and rat protein sequence are 93 per cent identical. Human IL-6 acts on murine cells with the same biological activity as mouse IL-6, but not vice versa. The central portion of IL-6 is more conserved (57 per cent for the region spanning residues 42-102) and contains the four cysteine residues of the protein in perfect alignment.
Receptors for Interleukin-8 (IL-8)
Authors: Horuk R
Published: November 2023

Recently, cDNA clones encoding two human IL-8 receptors were isolated and characterized (Holmes et al. 1991; Murphy and Tiffany 1991). One receptor, termed the IL-BRA, was isolated (Holmes et al. 1991) from a human neutrophil cDNA library by expression cloning, using binding to 1251-IL-8 as the method of detection. The IL-8RA is a 350-aminoacid protein (GenBank accession number M68932) with five potential N-linked glycosylation sites and seven hydrophobic membrane-spanning stretches characteristic of the G-protein-linked family of molecules (Strosberg 1991). The receptor is glycosylated since the translated molecular size of the receptor is around 40 kDa, which is considerably smaller than the reported size of 55 to 69 kDa based on cross-linking oft he neutrophil receptor (Holmes et al. 1991; Samanta et al. 1989).
Tumour Necrosis Factor Receptor
Authors: Aggarwal B B , Reddy S
Published: November 2023

The p80 form of the TNF receptor contains 461 amino acid residues consisting of an extracellular domain (ECD), a single transmembrane domain, and a cytoplasmic domain of 235, 30, and 174 amino acid residues, respectively. In contrast, the p60 form of the TNF receptor contains 455 amino acid residues consisting of extracellular, transmembrane, and cytoplasmic domains of 182, 21, and 223 amino acid residues, respectively. The ECD of the p80 receptor has two potential N-linked and several O-linked glycosylation sites, whereas the p60 receptor has only three N-linked sites. The ECD of the p60 and p80 receptors have 24 and 22 cysteine residues, respectively, organized into four cysteine-rich domains. The theoretical molecular masses of p60 and p80 receptor protein are 47 526 and 46 000 Da, respectively. Both receptors have one net positive charge. The ECD of both are highly susceptible to cleavage by proteases activated by kinases and phosphatase inhibitors. The soluble form of both the p60 and p80 receptors, consisting primarily of the ECD, has been detected in cell-conditioned media, urine, serum, amniotic fluids, and synovial fluids.
Receptors for Leukaemia Inhibitory Factor (LIF) and Oncostatin M (OSM)
Authors: Gearing D P
Published: November 2023

The a-subunit of the human LIF receptor is produced as a 1097 amino acid precursor with a predicted 44-amino-acid leader sequence (Gearing et al. 1991). There is a single predicted transmembrane segment of 26 amino acids, an extracellular domain of 789 amino acids and a relatively long cytoplasmic domain of 238 amino acids. The predicted molecular weight of the protein is 111 000 Da but the observed molecular weight on 5D5-PAGE gels is 200000 Da due to extensive N-glycosylation at several of the predicted20 N-glycosylation sites. Distal to the transmembrane region the extracellular region comprises two haemapoietin receptor domains separated by an immunoglobulin-like domain and three membrane-proximal fibronectin type Ill domains.
Neu Differentiation Factor (NDF) and the Neuregulin (NRG) Family
Authors: Yarden Y , Wen D
Published: November 2023

The heat-stable rodent factor and its human homologue (named HRG) are secreted proteins that were purified by heparin-chromatography from the media conditioned by cancer cells (Peles et al. 1992; Holmes et al. 1992). NDF is sensitive to reduction but resists extremes of pH. N- and O-linked sugars account for approximately one-quarter of the mass of the mature 44 kDa glycoprotein, but they are not required for receptor recognition.
Neu/ErbB-2 Receptor
Authors: Yarden Y , Levy R B
Published: November 2023

The rodent 185 kD glycoprotein consists of 1260 amino acids (Bargmann et a/. 1986) (GenBank accession number X03662), whereas the human protein is 1255 amino acids long (Coussens eta/. 1985; Yamamoto et al. 1986) (GenBank accession number M11730). An insect homologue of neu has been identified in Drosophila melanogaster (Livneh et al. 1985). The protein is bisected by a single hydrophobic stretch that functions as a transmembrane domain and separates the extracellular ligand-binding portion from the cytoplasm-facing tyrosine kinase domain (Fig. 1). Neu is related in its molecular architecture and amino acid sequence to three other receptor tyrosine kinases. These are the receptor for EGF, erbB-3/HER3 (Kraus et al. 1989; Plowman et al. 1990) and erbB-4/HER-4 (Plowman et al. 1993).
Receptors for Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
Authors: Nicola N A
Published: November 2023

The a-chain of the human GM-CSF receptor is produced as a 400-amino-acid precursor with a predicted 22-amino-acid leader sequence (GenBank accession numbers M73832 and M64445} (Fig. 1}. There is a single predicted transmembrane segment of 26 amino acids, an extracellular domain of 298 amino acids and a short cytoplasmic domain of 54 amino acids. The predicted molecular weight of the protein is 44000 but the observed molecular weight on SDS-PAGE gels is 75 000-85000 due to N-glycosylation at several of the predicted eleven N-glycosylation sites (Gearing et al. 1989}. The 200 amino acids proximal to the transmembrane region (on the extracellular side) form a haemopoietin receptor domain that is presumed to bind GM-CSF and which is homologous in many cytokine receptors (see Introductory chapters).
Hepatocyte Growth Factor
Authors: Comoglio P M , Graziani A
Published: November 2023

Scatter factor (SF), human lung fibroblast-derived mitogen, hepatopoietin A, hepatotrophin, tumour cytotoxic factor. HGF is a disulphide-linked heterodimer of a heavy (a) subunit of 60 kDa and a light (/J) subunit of 32 or 36 kDa, originating from proteolytic cleavage of a single 92 kDa precursor (Fig. 1) (Miyazawa et al. 1989; Nakamura et al. 1989; Weidner et al. 1991; Rubin et al. 1991).
Growth Hormone/Prolactin Receptors
Authors: Clackson T
Published: November 2023

The mature human GH receptor cloned from liver comprises 620 amino acids (aa) and is expressed with a signal sequence of 18 aa (GenBank accession number X06562). A 246-aa extracellular domain containing seven cysteine residues is followed by a transmembrane domain of 24 residues and a 350-aa intracellular domain. The extracellular domain (residues 1-238) is found in serum as a GH-binding protein (hGHbp) (Leung et al. 1987). In rodents the soluble binding protein bears a short (17 or 27 aa) (-terminal extension not present in the membrane receptor (Mathews 1991; Kelly et al. 1993).
Platelet-derived Growth Factor (PDGF)
Authors: Heldin C -H , Westermark B
Published: November 2023

cDNAs for human PDGF A-chain (Betsholtz et al. 1986) and B-chain (Josephs et al. 1984) have been cloned (GenBank accession numbers X03795 and M12782, respectively). The PDGFA-chains have also been cloned from mouse (Rorsman et al. 1992) and Xenopus (Mercola et al. 1988) and the B-chain from mouse (Bonthron eta/. 1991) and cat (Van den Ouweland et al. 1987); the conservation of the sequences between different species is very high. The human B-chain sequence predicts a 241-amino-acid polypeptide including a 20-amino-acid long leader sequence (Fig. 1). The A-chain occurs in two forms as a result of differential splicing.
Receptors for Platelet-derived Growth Factor (PDGF)
Authors: Heldin C -H , Claesson-Welsh L
Published: November 2023

The human a-receptor has 1089 amino acids including a 23-amino-acid leader sequence (GenBank accession number M22734 and M21574}, and the p-receptor has 1106 amino acids including a 32-amino-acid leader (GenBank accession number M21616 and JO3278) (Fig. 1). The mouse a-and p-receptors have also been cloned (GenBank accession numbers 540407 and X04367, respectively). The predicted molecular weight of the human a-receptor is 120 000 and of the /I-receptor 121 000; however, the receptors run as components of apparent molecular weights 170000 and 180000 in SDS-gel electrophoresis, respectively, due to glycosylation and other post-translational modifications. Each receptor has five immunoglobulin-like domains in the extracellular part; the amino acid sequence similarity between the receptors is 30 per cent in this region.
Three-dimensional strudure of Hsc70
Authors: Wilbanks S
Published: November 2023

The X-ray crystal structure of the isolated ATPase domain (residues 1-384) of bovine Hsc70 (Swiss Protein Accession # Hs7c_Bovin) has been solved (Flaherty et al., 1990). The secondary structural elements of a recombinant peptide binding fragment (residues 385-543) of rat Hsc70 (Swiss Protein Accession # Hs7c_Rat).
Three-dimensional structure of the peptide-binding domain of E.coli DnaK
Authors: Gething M -J
Published: November 2023

HSP70 proteins contain two major. domains - an N-terminal domain that contains the ATPase catalytic site, a (-terminal substrate binding domain - that com municate to regulate the affinity, duration of (poly)peptide binding (reviewed by McKay et al., 1993). The 3-dimensional structure of the isolated ATPase domain of the constitutively-expressed bovine cytosolic Hsc70 was reported some time ago (Flaherty et al., 1990), but the determination of the structure of the (-terminal domain of an HSP70 protein remained elusive. Intriguingly, two totally indepent approaches using struc ture prediction algorithms suggested that the peptide binding domain might resemble that of MHC class I anti gens (Flajnik et al., 1991; Rippmann et al., 1991).
Saccharomyces cerevisiae Ssb proteins
Authors: Ziegelhoffer T , Craig Christine Pfund, E A
Published: November 2023

The SSB1, SSB2 genes (initially known as YG101, YG103) were isolated by virtue of their high degree of similarity to Drosophila HSP70 genes (Ingolia et al., 1982; Craig, Jacobsen, 1985).
Mammalian a-Crystallins
Authors: Jong W W de , Boelens W C
Published: November 2023

α-Crystallin, comprising up to one-third of total lens protein in mammals, can be isolated in large quantities by gel filtration of aqueous lens extracts (Groenen et al., 1994). Lenticular a-crystallin is composed of acidic aA, more basic aB subunits, generally in a ratio of about 3:1. These can be separated by ion exchange chromatography under denaturing conditions, or by reverse-phase HPLC. The amino acid sequences of calf lens aA, aB, determined in the early 1970s, are 57% identical. aA, aB are 173, 175 residues in length, appear on SDS-PAGE as 20, 22 kDa bands, respectively. Both proteins are N-terminally acetylated.
Schizosaccharomyces pombe BiP
Authors: Armstrong J
Published: November 2023

A homologue of the BiP/Kar2p proteins of mammalian cells, budding yeast was identified in the fission yeast Schizosaccharomyces pombe (Pidoux, Armstrong, 1992). A portion of the gene was recovered by polymerase chain reaction using primers designed from sequences conserved between mammalian, 5. cerevisiae BiP. This fragment was used to isolate the complete gene by hybridization. A further S. pombe HSP70 homologue, which is probably located in the endoplasmic reticulum, has been identified from genome sequencing (protein accession number e212000) but no studies of this gene have been reported.
Mammalian thioredoxin
Authors: Nakamura H , Bjornstedt M , Holmgren A
Published: November 2023

Mammalian thioredoxin has been purified from several sources including rat Novikoff hepatoma, calf liver, rat liver, rabbit bone marrow, human placenta (Holmgren, 1985; Holmgren, Bjornstedt, 1995). A protein that was purified from the conditioned medium of human T cell lymphotropic virus type-l (HTLV-l)-trans-formed T cells, Epstein-Barr virus-transformed B cells.
Mammalian ERp72
Authors: Ferrari D , Soling H -D
Published: November 2023

ERp72 DNA/protein sequences have been reported from several sources [EMBL/SWISS-PROT accession numbers J05016/P13667 (human), S59335/P38659 (rat), J05186/ P15841 (mouse), L15188/P34329 (Caenorhabditis elegans)]. The DNA sequences are c. 1.9 kb long, encode an N-terminal signal sequence of around 20 amino acids that is cleaved to generate a highly conserved c. 625 amino acids protein (Mazzarella et a!.,
Escherichia coli cydophilins
Authors: Takahashi N
Published: November 2023

Although the peptidyl-prolyl cis-trans isomerase (PPIase) activities of most cyclophilins originating from eukaryotic cells are inhibited by the immunosuppressive drug cyclosporin A (CsA), the activity of Escherichia coli cyclophilins is essentially not sensitive to CsA. No definitive evidence for the physiological role of cyclophilins was identified in E. coli cells; however, they are believed to be involved in protein folding in the cell.
Saccharomyces cerevisiae cydophilin B /Cpr2/Cyp2
Authors: Cafferkey R , Stan R , Freeman K , Livi G P
Published: November 2023

Cyclophilin B belongs to the family of yeast cyclophilin-related peptidyl-prolyl cis-trans isomerases (PPIases), enzymes that catalyse the isomerization of prolyl-peptide bonds in vitro. The protein was originally identified as the deduced translation product of a gene cloned as a homolog of a human cyclophilin A-encoding cDNA. Yeast cyclophilin B is directed to the ER/secretory pathway by a 20 amino acid hydrophobic signal sequence, where it may function to catalyse the folding of secretory proteins. Cyclophilin B is also involved in the heat shock response. Although purified recombinant cyclophilin B protein possesses cyclosporin A (CsA)-sensitive PPIase activity in vitro, cyclophilin B does not play a role in CsA cytotoxicity in yeast, which is mediated instead by cytosolic cyclophilin A.
Saccharomyces cerevisiae mitochondrial cydophilin Cpr3
Authors: Matouschek A
Published: November 2023

CYP3 (McLaughlin et al., 1992), cyclophilin C (see Cafferkey et al. p. 373). The yeast mitochondrial cyclophilin gene was isolated as CPR3 from a S. cerevisiae genomic library by hybridization with a rat cyclophilin cDNA probe (Davis etal., 1992). Independently, yeast mitochondrial cyclophilin protein was purified from yeast extracts following cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase activity (McLaughlin etal., 1992). The corresponding gene (CYP3) was then isolated from S. cerevisiae genomic libraries by hybridization with a probe derived from the N-terminal protein sequence.