J. Biol. Macromol., 6 (1), 11-27 (2006)

ArticleBioinformatic study on histidine decarboxylase¶
Hiromi Okigami and Hiroshi Ueno*
Laboratory of Applied Microbiology and Biochemistry, Graduate School of Humanities and Sciences,
Nara Women’s University, Nara 630-8506, JAPAN*

Laboratory of Applied Microbiology and Biochemistry, Faculty of Human Life and Environment, Nara
Women’s University, Nara 630-8506, JAPANReceived September 17, 2005; Accepted February 20, 2006
Histidine decarboxylase (HDC) is an enzyme responsible for histamine production in living
cells.

It is of our aim to understand structure-function relationship of this enzyme in order tomanipulate enzymatic activity for clinical usages.
of species were compared.

Firstly, structural aspects of HDC from variety

Based upon the similarity of amino acid sequences, we presented theamino acid residues common among HDCs.

Secondly, we presented intron-exon relationships

based upon genomic information encoded for the enzyme.

The exon information was reflected tothe enzyme structure which was predicted based upon conformational similarity with
3,4-dihydroxyphenylalanine decarboxylase (also called aromatic amino acid decarboxylase, AroDC).
This bioinformatic study should provide insights for evolutionary construction of HDC.
Keywords:
histidine decarboxylase, histamine, intron, motif
Histamine is a multifunctional biogenic

During the past few years, some advancement

amine and primarily expressed on mast cells,

have been made in this field, including thebasophils, and histamine neurons in the brain (1-3).

generation and validation of the first

It has relevant roles in the intercellular

three-dimensional model of mammalian histidine

communication, inflammatory processes, anddecarboxylase (12); however, its structural andhighly prevalent pathologies (4-9).

functional characteristics still remain to be fully

Histaminebiosynthesis depends on a single decarboxylation

explored.

step, carried out by an HDC activity (10, 11).
________________________________________________________________________________*

Correspondence author: Phone No.: +81-742-20-3493, Fax No.: +81-742-20-3448, E-mail:hueno@cc.nara-wu.ac.jp, Abbreviations: AroDC, aromatic amino acid decarboxylase; PLP, pyridoxal
5’-phosphate; HDC, histidine decarboxylase.
¶
Preliminary results of this study was reported at the National Meeting of Japanese Science Society ofBiological Macromolecules in 2004 held in Hirakata, Osaka, Japan.

Bioinformatic study on histidine decarboxylase

12

Sandmeier et al. classified PLP (pyridoxal

exon and intron were obtained by using Ensemble

5’-phosphate)-dependent decarboxylases into four

Genome Browser (http://www.ensembl.org/).

groups based upon their evolutional origins (13).

Motif analysis - A search of homologous

They have stated that a comparison of the amino

motifs in a block of HDC gene was carried outacid sequences of nine different PLP-dependent

with InterPro program (http://www.ebi.ac.uk/

amino acid decarboxylases, subdivided into fourinterpro/).
Molecular modeling – Protein structure

different groups, seems to be evolutionarily
unrelated to each other.

Four groups are ascoordinate files were obtained from Protein Data

follows: group I is represented by glycine

Bank (http://www.rcsb.org).

Molecular modelingdecarboxylase, a component of a multi-enzyme

study was carried out with MolFeat software (ver.

system; group II comprises glutamate, histidine,

2.0.1.1, FiatLux Co., Tokyo).

tyrosine, and aromatic-L-amino-aciddecarboxylases; group III, prokaryotic ornithine

Results and Discussion
Amino acid sequences of HDC from various

and lysine decarboxylases as well as theprokaryotic biodegradative type of arginine

species were obtained by searching currently

decarboxylase; group IV, eukaryotic ornithine andavailable databases through internet, including

arginine decarboxylases as well as the prokaryotic

Swiss-Prot and EMBL.

biosynthetic type of arginine decarboxylase anddiaminopimelate decarboxylase.

There are two kinds of HDC enzymes

HDC belongs

depending upon co-enzyme requirement: thoseto group II; however, its tertiary structure is stillthat use PLP as a cofactor (13, 16, 17) and thoseundetermined.

that contain a covalently bound pyruvoyl residue

When protein structures being elucidated,(18).

In this study, we have only focused on

the relationships between protein structure

those require PLP.

modules and genetic segmentation, such as exon

pyruvoyl-dependent enzymes are clearly distinct

and intron boarder, has been recognized (14, 15).

in the evolutional tree as they located in different

It is of interests to explore the relationshipbranches.

between structures of HDC gene and protein.

sources, in which the term, number of amino acid,

The PLP-dependent andTable 1 lists 23 HDCs from different

included the pro-enzyme sequences.
Materials and Methods

Using CLUSTALW program, an evolutional

Amino acid sequences - Amino acidtree of HDC was drawn based on multiple

sequences of HDCs from different origin werealignments of amino acid sequences (Fig. 1).

obtained from the public databases via internet;

Those enzymes from animal, plants, and bacteria

the databases used are PIR and UNIPROT

were grouped together, each belongs to different(Swiss-Prot/TrEMBL/TrEMBL_new).

branches.

Multiple sequence alignment - Multiple

In order to examine the structural aspects on

sequence alignment was carried out by using

PLP-dependent HDCs, multiple alignments wereClustal W (ver. 1.83) software available to public

performed.

through GenomeNet (http://www.genome.jp/).

as marked asterisk in Fig. 2, were conserved

Exon-intron analysis - Information about

It was found that amino acid residues,

among 21 different species.

Significant numbers

H. Okigami and H. Ueno

Table I

13

Lists of HDC found in the databases

SpeciesClass

ID

AccessingnumberNo. of
amino
acid

1

Drosophila melanogaster (Fruit fly)Insecta

sp:DCHS_DROME1)

Q05733847

2Enterobacter aerogenes (Aerobacteraerogenes)

Bacteria

sp:DCHS_ENTAE

P28577377

3Homo sapiens (Human)

Mammalia

sp:DCHS_HUMAN

P19113662

Bacteria

sp:DCHS_KLEPL

P28578377

Spermatophyta

sp:DCHS_LYCES

P54772413

4
5

Klebsiella planticola(Raoultella planticola)
Lycopersicon esculentum (Tomato)

6

Morganella morganii(Proteus morganii)

Bacteria

sp:DCHS_MORMO

P05034377

7Mus musculus (Mouse)

Mammalia

sp:DCHS_MOUSE

P23738662

8Pseudomonas fluorescens.

Bacteria

sp:DCHS_PSEFL

P95477405

9Rattus norvegicus (Rat)

Mammalia

sp:DCHS_RAT

P16453656

Bacteria

sp:DCHS_RHILO

Q98A07369

Bacteria

sp:DCHS_VIBAN

Q56581

386

Archaea

tr:Q9YF282)

Q9YF28362

Metazoa;

tr:Q86BW8

Q86BW8926

Spermatophyta

tr:Q7XHE6Q7XHE6467

Spermatophyta

tr:Q9MA74

Q9MA74

482

10
11
12
13
14
15

Rhizobium loti
(Mesorhizobium loti)
Vibrio anguillarum(Listonella anguillarum)
Aeropyrum pernix.
Aplysia californica(California sea hare)
Oryza sativa(japonica cultivar-group)
Arabidopsis thaliana(Mouse-ear cress)

16

Oryza sativa (Rice)

Spermatophyta

tr:Q8RV06

Q8RV06467

17Vibrio anguillarum(Listonella anguillarum)

Bacteria

tr:Q6W4S7Q6W4S740018Photobacterium phosphoreum

Bacteria

tr:Q846V2

Q846V2380

19

Gloeobacter violaceus

Bacteria

tr:Q7NIG4Q7NIG4382

20

Clostridium tetani

Bacteria

tr:Q894Q7

Q894Q7575

21Mus musculus (Mouse)

Mammalia

tr:Q7TMW5Q7TMW5662

22

Vibrio anguillarum(Listonella anguillarum)

Bacteria

trnew:AAR125333)

AAR12533

400

trnew:AAO92385

AAO92385

386

Vibrio anguillarum
Bacteria(Listonella anguillarum)
Database: UniProt
1)
Sp:SWISS-PROT protein sequence database2)
Tr:TrEMBL protein sequence database3)
Trnew:TrEMBL_new protein sequence database23

Bioinformatic study on histidine decarboxylase

14of the conserved amino acid residues were foundcrystals of HDC is still difficult due to thein the range of 298-319, which number correlates

instability of HDC protein, especially in the highly

the human HDC sequence number (19).

purified preparations (21, 22).

To

However,elucidate the significance of the conserved amino

crystalline structure for pig AroDC was reportedacid residues in the evolutional process, we have

(12, 23).

explored exon/intron sequence of the enzyme.

homology to mammalian HDCs; thus, it is quite

Fig. 2 also shows group of exons based uponlikely to predict three-dimensional model structureexon/intron searches carried out at genomic DNA

for human HDC by overlaying the amino acidlevel.

sequence of HDC over AroDC (21).

Exon 8 of human enzyme has a typicalmotif for PLP-dependent decarboxylases, whichcontains the active site Lys residue.

The ε-amino

Pig AroDC exhibits high sequence

We have employed the method described byRodriguez-Caso et al. (21) to predict the humangroup of the active site Lys binds to PLP to form

HDC structure, and result is shown in Fig. 3

an internal Schiff base.

(http://www-cryst.bioc.cam.ac.uk/~jiye/evoltrace/

PLP-dependent decarboxylase motif is also

evoltrace.html).

Each exons as indicated in Fig.

found in other decarboxylases, such as

2 are color coded as described in Fig. 2.

3,4-dihydroxyphenylalanine (also called aromatic

apparent that PLP molecule is situated justamino acid ) decarboxylase (AroDC), glutamate

adjacent to Exon 8 (pink colored), which isdecarboxylase (GAD), and tyrosine decarboxylasetranslated into two helical structures that contain a(YDC).

typical motif for the active site sequence of group

Because having similar motifs, thoseIt isdecarboxylases are grouped as group II (16, 17,

II decarboxylases.

20).

PLP-dependent enzyme, situates an active site Lys
As of now, there is no solved crystal structure

for any PLP-dependent HDC.

Obtaining stable

HDC, as a typicalresidue (Lys-305) in the helical region derived
from Exon 8.

Fig. 1 Evolutionary tree of PLP-dependent HDCs.
correspond to those of Table I.

This Lys residue forms a covalent

Numbers indicatedH. Okigami and H. Ueno
3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

15

1
15
---------- ---------- --------MM EPEEYRER-- -----GREMV---------- ---------- --------MM EPCEYREYRE YYRARGKEMV---------- ---------- --------MM EPCEYREYRE YYRARGKEMV---------- ---------- --------MM EPSEYHEY-- --QARGKEMV---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------MVGSLESDQT LSMATLIEKL DILSDDFDPT AVVTEPLPPP VTNGIGADKG---------- ---------- ---MVLLNSE EVSCNDHHQV DVVAAAGLQC---------- ---------- ---MVLLNSE EVSCNDHHQV DVVAAAGLQC---------- ---------- ---------- ---------- ------------------- --------MA EDLLSEQCKS SLPPGGMTVE EYRKRGKEMV---------- ---------- ---------- ------MDFK EYRQRGKEMV---------- ---------- ---------- ---------- ---------M---------- ---------- ---------- ---------- ---------Exon1

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

16
65
DYICQYLSTV RERRVTPDVQ PGYLRAQLPE SAPEDPDSWD SIFGDIERIIDYISQYLSTV RERQVTPNVQ PGYLRAQLPA SAPEEPDSWD SIFGDIERVIDYISQYLSTV RERQVTPNVQ PGYLRAQLPA SAPEEPDSWD SIFGDIERVIDYICQYLSTV RERQVTPNVK PGYLRAQIPS SAPEEPDSWD SIFGDIEQII---------- ---------- ---------- --SLSIADQN KLDAFWSYCV---------- ---------- ---------- --TLSISDQN KLDSFWSYCV---------- ---------- ---------- --TLSINDQN KLDAFWAYCV---------- ---------- ---------- -MTLSIENQN KLDEFWAYCV---------- ---------- ---------- -MTLSPADQS KLEGFWQHCV---------- -------MLF SPFRQRLIGN VMKLSNEDLC KLNKFWLYCE---------- -------MLF SPFRQRLIGN VMKLSNEDLC KLNKFWLYCE---------- ---------- ---------- -MKLSNEDLC KLNKFWLYCE---------- ---------- ---------- -MKLSNEDLC KLNKFWLYCE---------- ---------- ---------- --MLEPQDQK KLDELFSSMQ---------- ---------- ----MESDIK NETSFQELDM ILTQYLETLS
GGGGEREMVL GRNIHTTSLA VTEPEVNDEF TGDKEAYMAS VLARYRKTLVSGDMLGDKQL VSQVILEGLE IEEPPADEME AAEKKAGISR LMAGYVQHLQSGDMLGDKQL VSQVILEGLE IEEPPADEME AAEKKAGISR LMAGYVQHLQ---------- ---------- --------MS TAGIRASVAD ELVTYGLSLDDYIADYFLDI RSRRVFPDVQ PGYMQALVPD RAPEEPNKWE DIFADVERVIDYIADYLENI RERRVFPDVS PGYMRQLLPE SAPIEGEPWP KIFSDVERIVKNPMTQPTKD PNTVYPKVPG IDYDKFKLSE DKMTSKQIND ALEELHNYIS---------- ---------- ---------- ---------- MAIILGGMVP
Exon2

Fig. 2 Homology alignment of HDCs. CLUSTAL W (1.83) multiple sequence alignment was
employed. '*' indicates a fully conserved residue. ':' indicates a residue having
Gonnet Pam250 matrix score > 0.5, i.e., STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY,
FYW. '.' indicates the score =< 0.5, i.e., CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK,NEQHRK, FVLIM, HFY.

16

Bioinformatic study on histidine decarboxylase

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

66
113
MPGVVHWQSP HMHAYYPALT SWPSLLG--D MLADAINCLG FTWASSPACTMPGVVHWQSP HMHAYYPALT SWPSLLG--D MLADAINCLG FTWASSPACTMPGVVHWQSP HMHAYYPALT SWPSLLG--D MLADAINCLG FTWASSPACTMPGVVHWQSP HMHAYYPALT SWPSLLG--D MLADAINCLG FTWASSPACTKNRYFNIGYP ESADFDYT-M LERFLR---F SINNCGDWG- EYCNYLLNSF
KNQYFNIGYP ESADFDYT-I LERFMR---F SINNCGDWG- EYCNYLLNSF
KNQYFNIGYP ESADFDYT-N LERFLR---F SINNCGDWG- EYCNYLLNSF
KNQYFNIGYP ESADFDYT-I LERFMR---F SINNCGDWA- EYCNYLLNSF
THQYFNIGYP ESADFDYS-Q LHRFLQ---F SINNLLGTGN EYSNYLLNSF
ENQYFNVGYP ESAAFDYS-I LEKFMK---F SINNCGDWR- EESNYKLNSF
ENQYFNVGYP ESAAFDYS-I LEKFMK---F SINNCGDWR- EESNYKLNSF
ENQYFNVGYP ESAAFDYS-I LEKFMK---F SINNCGDWR- EESNYKLNSF
ENQYFNVGYP ESAAFDYS-I LEKFMK---F SINNCGDWR- EESNYKLNSF
EANGCFLGYP FAKDFDYE-P LWRFMS---L TGNNLGDPF- EPGTYRVNSHERKKYHIGYP INMCYEHHAT LAPLLQ---F HLNNCGDPF- TQHPTDFHSKERTKNHLGYP YNLDFDYG-A LGQLQH---F SINNLGDPF- IESNYGVHSRHRSAYHLGYP LNFDYDFS-P LAPFLN---F SLNNAGDPF- AKVNNSVHSRHRSAYHLGYP LNFDYDFS-P LAPFLN---F SLNNAGDPF- AKVNNSVHSRIHKRNHLGYP FCLKYDHAEQ LAETIQDQRY TLINIGDPF- SSPIYQISSLMPGVTHWQSP RMHAYFPALT SYPSLLG--D MLADAVSCLG FTWASSPACTMPGITHWQSP HMHAYFPALN SMPSLLG--D MLADAINCLG FTWASSPACT
NQQINFLGYQ INQSFNYMKD LKEYLN---V HMNNIGDPF- VSGNFTVNTKRPPWKYRLLA AIHAHR---- ---------- ---NAGDPGA DPLVRRAVER.
: .

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

114
156
ELEMNVMDWL AKMLGLPEHF LHHHPSSQ-- ----GGGVLQ STV-SESTLIELEMNIMDWL AKMLGLPEYF LHHHPSSR-- ----GGGVLQ STV-SESTLIELEMNIMDWL AKMLGLPEYF LHHHPSSR-- ----GGGVLQ STV-SESTLIELEMNIMDWL AKMLGLPDFF LHHHPSSQ-- ----GGGVLQ RTV-SESTLIDFEKEVMEYF SGIFKIPFAE S--------- -----WGYVT NGG-TESNMFDFEKEVMEYF AQLFKIPFEE S--------- -----WGYVT NGG-TEGNMF
DFEKEVMEYF ADLFKIPFEQ S--------- -----WGYVT NGG-TEGNMF
DFEKEVMEYF ADLFKIPFED S--------- -----WGYVT NGG-TESNMFDFEKDVMTYF AELFNIALED S--------- -----WGYVT NGG-TEGNMF
EFEKEVMRFF SQLFKIPYND S--------- -----WGYIS NGG-TEGNMF
EFEKEVMRFF SQLFKIPYND S--------- -----WGYIS NGG-TEGNMF
EFEKEVMRFF SQLFKIPYND S--------- -----WGYIS NGG-TEGNMF
EFEKEVMRFF SQLFKIPYND S--------- -----WGYIS NGG-TEGNMF
AFECDVVDFF ARLFRACSCE V--------- -----WGYVT NGG-TEGNIYDFEVAVLDWF AQLWEIEKDE ---------- ----YWGYIT SGG-TEGNLHPFEVGVLDWF ARLWEIERDD ---------- ----YWGYIT NCG-TEGNLHQFEVAVLNWF ANFWDVQRDQ ---------- ----FWGYIT SGG-TEGNLYQFEVAVLNWF ANFWDVQRDQ ---------- ----FWGYIT SGG-TEGNLY
EYERQVLGFF AELFGLDRQP RP-------- ----WWGYIG SCG-TEGNLYELETIVMDWL GKMLELPESF LHGEKGSR-- --SLGGGCIQ TTA-SDCTFVELEIIVMNWL GKMIGLPDAF LHLSSQSQ-- ----GGGVLQ TTA-SEATLVFLERAVLDYF ASLWNAQWPH ESKGDSNTND WKNSYWGYVV SMGSTEANFFLVAVTSRVVF GVEK------ ---------- -----PGWIT SGA-SEGNLL
: .
* :
:: .:

Exon3

Exon4

Fig. 2 (continued)

Exon5

H. Okigami and H. Ueno

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

17

157
185
ALLAARKNKI LEMKTSEPDA DESCLNARL- ---------- ---------ALLAARKNKI LAMTACEPDA NESSLNARL- ---------- ---------ALLAARKNKI LAMKACEPDA NESSLNARL- ---------- ---------ALLAARKNKI LEMKAHEPNA DESSLNARL- ---------- ---------GCYLG----- ---------- --RELFPEG- ---------- ---------GCYLG----- ---------- --REIFPNG- ---------- ---------GCYLG----- ---------- --REIFPDG- ---------- ---------GCYLG----- ---------- --RELFPDG- ---------- ---------GCYLG----- ---------- --RELFPDG- ---------- ---------SCYLA----- ---------- --REIFPTA- ---------- ---------SCYLA----- ---------- --REIFPTA- ---------- ---------SCYLA----- ---------- --REIFPTA- ---------- ---------SCYLA----- ---------- --REIFPTA- ---------- ---------GLYLA----- ---------- --RELYPNA- ---------- ---------GFWLGR---- ---------- --RELLPNG- ---------- ---------GILVG----- ---------- --REMFPDG- ---------- ---------GLLVG----- ---------- --RELFPDG- ---------- ---------GLLVG----- ---------- --RELFPDG- ---------- ---------GLLLG----- ---------- --RLAQPEG- ---------- ---------TLLAARTDAI ARYKAIHPDK DEAWINGRL- ---------- ---------CLLAGRTRAI QRFHERHPGY QDAEINARL- ---------- ---------GIWNARDYLS GKALLLDTST HKRAKSASIN GNPQSVEPRV LNYQAKSLEDALYTLR---- ---------- --EEGYRR-- ---------- ---------Exon5

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

186
209-------VAY ASDQAHSSVE KAGLISLVKM K--------- ----------------VAY TSDQAHSSVE KAGLISLVKI R--------- ----------------VAY TSDQAHSSVE KAGLISLVKI R--------- ----------------VAY ASDQAHSSVE KAGLISLVKI K--------- ----------------TLY YSKDTHYSVA KIVKLLRIKS Q--------- ----------------TLY YSKDTHYSVA KIVKLLRIKS T--------- ----------------TLY YSKDTHYSVA KIVKLLRIKS Q--------- ----------------TLY YSKDTHYSVA KIVKLLRIKS Q--------- ----------------TLY YSKDTHYSVA KIVKLLRIKC R--------- ----------------YIY YSEETHYSVD KIVRLLNIPA R--------- ----------------YIY YSEETHYSVD KIVRLLNIPA R--------- ----------------YIY YSEETHYSVD KIVRLLNIPA R--------- ----------------YIY YSEETHYSVD KIVRLLNIPA R--------- ----------------VAY FSQDTHYSVS KGVRLLRLEH S--------- ----------------YLY ASKDSHYSIF KAARMYRMEL Q--------- ----------------ILY ASRESHYSVF KAARMYRMEC E--------- ----------------ILY ASNDSHYSVF KAAKMYRVKC I--------- ----------------ILY ASNDSHYSVF KAAKMYRVKC I--------- ----------------ILY FSEAAHYSVG KAARMFRMPY R--------- ----------------IGY CSDQAHSSVE KAGLIGLVKM R--------- ----------------VAY CSDQAHSSVE KAALIGLVRM R--------- ---------NPNMYTPIAF YSQDTHYSII KGMRILNFTT FNEAGSGKFE CPLKYPEDYP--------VV AFDTSHYSIK KSALTLSMEL D--------- ---------:* *: *
.
Exon5

Exon6

Fig. 2 (continued)

18

Bioinformatic study on histidine decarboxylase

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

210242---------- -----FLPVD DNFSLRGEAL QKAIEEDKQR GLVPVF--VC---------- -----FLPVD DNFSLRGEAL QKAIEEDKQQ GLVPVF--VC---------- -----FLPVD DNFSLRGEAL QKAIEEDKQQ GLVPVF--VC---------- -----FLPVD DNFSLRGEAL QKAIEEDKQQ GLVPVF--VC---------- -----LVESQ PDGEMDYDDL INKIRTSGER HPIIFA--NI---------- -----LVESQ PNGEMDYADL IKKIKRDNEK HPIIFA--NI---------- -----VVESQ PNGEIDYDDL MKKIADDKEA HPIIFA--NI---------- -----LVESL PNGEIDYDDL IAKIKQDDEK HPIIFA--NI---------- -----AVESL PNGEIDYDDL MAKITADQER HPIIFA--NI---------- -----KIRSL PSGEIDYQNL VDQIQKDKQK NPIIFA--NI---------- -----KIRSL PSGEIDYQNL VDQIQKDKQK NPIIFA--NI---------- -----KIRSL PSGEIDYQNL VDQIQKDKQK NPIIFA--NI---------- -----KIRSL PSGEIDYQNL VDQIQKDKQK NPIIFA--NI---------- -----VVRSQ SNGEINYDDL AQKATRYRTR PAVVVA--NI---------- -----TINTL VNGEIDYEDL QSKLLVNKNK PAIINI--NI---------- -----KVDTL MSGEIDCDDL RKKLLANKDK PAILNV--NI---------- -----RIATT VSGEMNYADL KSKLQHNTNS PAIINA--NI---------- -----RIATT VSGEMNYADL KSKLQHNTNS PAIINA--NI---------- -----KVRSQ ASGEMDYAHL AEIVESG̶ Q PVIINL--TL---------- -----FLPSD ENLSLRGSTL QEAVSKDRER GFIPFY--VC---------- -----YIEAD EDLAMRGKLL REAIEDDIKQ GLVPFW--VC
KGFSINYLDE NGWPFEVPSN NDGSVFIPAL KKLVEAFASK GYPIFVNFNY---------- ------LLPT HGGRPRLDLL ERRITPDSVV VATVGT---T:.
*

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

243
271
ATLGTTGVCA FDCLSELGP- ---------- --------IC AREG--LWLH
ATLGTTGVCA FDRLSELGP- ---------- --------IC ASEG--LWLH
ATLGTTGVCA FDRPSELGP- ---------- --------IC ASEG--LWLH
ATLGTTGVCA FDKLSELGP- ---------- --------IC AREG--LWLH
GTTVRGAVDN IAEIQKRIA- ---------- --------AL GIPREDYYLHGTTVRGAIDN IAIIQQSIS- ---------- --------EL GIERKDYYLHGTTVRGAIDD IAEIQKRLK- ---------- --------AA GIKREDYYLHGTTVRGAIDD ISKIQAMIG- ---------- --------EL GIKREDYYIHGTTMRGALDN IVTIQQRLQ- ---------- --------QA GIARHDYYLH
GTTMRGATDN IQRIQQDLA- ---------- --------SI GLERNDYYIHGTTMRGATDN IQRIQQDLA- ---------- --------SI GLERNDYYIHGTTMRGATDN IQRIQQDLA- ---------- --------SI GLERNDYYIHGTTMRGATDN IQRIQQDLA- ---------- --------SI GLERNDYYIHGTTMKEGKDD TLKIRAVLH- ---------- --------DV GIS--AIYVHGTTFKGAIDD LDFVIQTLE- ---------- --------NC GYSNDNYYIHGTTVKGAVDD LDLVIKTLE- ---------- --------EC GFSHDRFYIHGTTFKGAVDD IDQIISTLE- ---------- --------KC GFQN-RYYIHGTTFKGAVDD IDQIISTLE- ---------- --------KC GFQN-RYYIHGTTFTGAVDE IGRTVEALT- ---------- --------GR GIGLDQVYIHATLGTTGACA FDNLAEIGP- ---------- --------VC RSEK--LWLH
ATLGTTGSCS FDNLEEIGI- ---------- --------VC AEHH--LWLH
GTTFKGSYDN VEKAIDELVP ILKKYNLYER EIIFDKNNKN SDTRTGFWFH
QEGLVDPVEE IAGVAESVG- ---------- ---------- ------AAVH
.*

Exon6

Exon7

Fig. 2 (continued)

Exon8

H. Okigami and H. Ueno

19

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

272
314
IDAAYAGTAF LCPEFRGFLK -------GIE YADSFTFNPS KWMMVHFDCTVDAAYAGTAF LCPELRGFLE -------GIE YADSFTFNPS KWMMVHFDCTVDAAYAGTAF LCPELRGFLE -------GIE YADSSTFNPS KWMMVHFDCTVDAAYAGTAF LRPELRGFLK -------GIE YADSFTFNPS KWMMVHFDCTADAALSGMIL PFVEDPQPFT -------FAD GIDSIGVSGH KMIGSPIPCGADAALSGMIL PFVDNPQPFN -------FAD GIDSIGVSGH KMIGSPIPCGADAALSGMIL PFVDDAQPFT -------FAD GIDSIGVSGH KMIGSPIPCGADAALSGMIL PFVDEPQGFN -------FAD GIDSIGVSGH KMIGSPIPCGADAALSGMIL PFVDHPQPFS -------FAD GIDSICVSGH KMIGSPIPCGADAALSGMIM PFVEQPHPYS -------FED GIDSISVSGH KMIGSPIPCGADAALSGMIM PFVEQPHPYS -------FED GIDSISVSGH KMIGSPIPCGADAALSGMIM PFVEQPHPYS -------FED GIDSISVSGH KMIGSPIPCGADAALSGMIM PFVEQPHPYS -------FED GIDSISVSGH KMIGSPIPCGSDAALCGPYA PLLNPKPAFD -------FAD GADSITLSGH KFLGAPMPCGCDRALCGLIL PFIKHAKKIT -------FKK PIGSISISGH KFLGCPMSCGCDGALFGLMM PFVKRAPKVT -------FNK PIGSVSVSGH KFVGCPMPCGCDSALSGMMT PFMKQAPKVS -------FKK PIGSISVSGH KFLGCPMPCGCDSALSGMMT PFMKQAPKVS -------FKK PIGSISVSGH KFLGCPMPCGVDAALGGMIA CYIR-PELIS -------FDW PIGSLAISGH KFIGCPHPCGLDAAYAGSAF ICPEFRSWMA -------GIE FSDSFAFNPS KWLMVHFDCS
VDAAYAGSAF ICPEFRTWLR -------GIE RADSIAFNPS KWLMVHFDATVDGALGAAYM PFLEMTTDNE DFPVFDFRLK DVHSISMSGH KWIGVPWPCG
VDAAYGGYIA RFLTGKARFR -------LEP PVMTVVVDAH KIPEAPPPAG* * .
: .. *.

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

315361
GFWVKDKYKL QQ̶ TFSVNP IYLRH-ANSG VATDFMHWQI PLSRRFRSVKGFWVKDKYKL QQ̶ TFSVNP IYLRH-ANSG AATDFMHWQI PLSRRFRSIKGFWVKDKYKL QQ̶ TFSVNP IYLRH-ANSG AATDFMHWQI PLSRCFRSIKGFWVKDKYKL QQ̶ TFSVNP IYLRH-ANSG VATDFMHWQI PLSRRFRSIKIVVAKKANVD R----ISVEI DYISA-HDKT ISGSRN---- ----GHTPLMIVVAKKKNVD R----ISVEI DYISA-HDKT ISGSRN---- ----GHTPLMIVVAKKENVD R----ISVEI DYISA-HDKT ITGSRN---- ----GHTPLMIVVAKKRNVD A----ISVEI DYISA-HDKT ITGSRN---- ----GHTPLMIVVAKRNNVA R----ISVEV DYIRA-HDKT ISGSRN---- ----GHTPLMIVLAKRHMVD Q----ISVEV DYISS-RDQT ISGSRN---- ----GHSALFIVLAKRHMVD Q----ISVEV DYISS-RDQT ISGSRN---- ----GHSALFIVLAKRHMVD Q----ISVEV DYISS-RDQT ISGSRN---- ----GHSALFIVLAKRHMVD Q----ISVEV DYISS-RDQT ISGSRN---- ----GHSALF
VVLSHKLHVQ R----VMRNI DYIGS-SDTT LSGSRN---- ----AFTPIIVQITRRSYVS ----TLS-KI EYINS-ADAT ISGSRN---- ----GFTPIFVQITRMEHIK ----VLSSNV EYLAS-RDAT IMGSRN---- ----GHAPLF
VVITRLEHAE ----VLSTDI EYIAS-RDST ITGSRN---- ----GHAPIFVVITRLEHAE ----VLSTDI EYIAS-RDST ITGSRN---- ----GHAPIFVVLTYKETAD RFSSEISAEV EYIGS-TDLT IMGSRN---- ----GHTPLYAMWVKDARAL HR̶ TFNVEP LYLQH-ENSG AAIDYMHWQI ALSRRFRALKALWVRDSTAV HR̶ TFNVEP LYLQH-ENSG VAVDFMHWQI PLSRRFRALKIYMSKIKYQL LP----PDNP NYIGS-PDST FAGSRN---- ----AFSSLIVILASKQKLL DN---LWFES PYIPTGRQFG ILGTRP---- ----GGPIVA
.
*:
:
:

Exon8

Exon9

Fig. 2 (continued)

Exon1020

Bioinformatic study on histidine decarboxylase

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

362
405
LWFVIRSFGV KNLQAHVRHG TEMAKYFESL VRND------ PSFEIPAKRH
LWFVIRSFGV KNLQAHVRHG TEMAKYFESL VRSD------ PSFEIPAKRH
LWFVIRSFGV KNLQAHVRHG TEMAKYFESL VRSD------ PSFEIPAKRH
LWFVIRSFGV KNLQAHVRHG TDMAKYFESL VRSD------ PVFEIPAERHMWAAVRSHTD AEWHRRIGHS LNMAKYAVDR FKAA------ GIDALCHKNSMWEAIRSHSW EEWRRRIERS LNMAQYAVDR FQSA------ GIDAWRNKNSLWEAIRSHST EEWKRRITRS LDMAQYAVDR MQKA------ GINAWRNKNSMWCAVKSHTH EDFKRRINRS LDLAQHAVQR LQSA------ GINAWCNKNSMWAALRSYSW AEWRHRIKHS LDTAQYAVDR FQAS------ GIDAWRNENSMWTAIKSHSF VDWQGKVNQC LNMAEYTVQR FQEV------ GINAWRNKNSMWTAIKSHSF VDWQGKVNQC LNMAEYTVQR FQEV------ GINAWRNKNSMWTAIKSHSF VDWQGKVNQC LNMAEYTVQR FQEV------ GINAWRNKNSMWTAIKSHSF VDWQGKVNQC LNMAEYTVQR FQEV------ GINAWRNKNSLWYAIRSLGI EGIKQTFQQC ERLAAYTADE LNVR------ GVSAWRNPNALWYCLSKKGH ARLQQDSITC IENARYLKDR LLEA------ GISVMLNDFSLWYTLNRKGY KGFQKEVQKC LRNAHYLKDR LREA------ GISAMLNELSLWYTLSKKGY KGLLKEVHIC MGNARYLEVL LKQV------ GISASCNTLS
LWYTLSKKGY KGLLKEVHIC MGNARYLEVL LKQV------ GISASCNTLS
LWAEIQRR-K STFHLEAEAI VDKARFLHQK LSDQ------ GLPALLNPLSLWFVLRSFGV SGLQRHIRRG VELAQMFENL VQAD------ LRFEVTAPRWVWFVLRSYGI KGLQRHIREG VRLAQKFEAL VLAD------ HRFELPAKRHLWYYIATHSY EDCKNMILDC QDTAKYTVEK LNELSKKLGI DLWVEYSSKSAWRRVEDLER NPGFPRLASI LMRRLRKTLK ALER-----L GYETPVTPDL* :Exon103̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

Exon11406
448
LGLVVFRLKG PNCLTE---- ---NVLKEIA KAGRLFLIPA TIQDKLIIRFLGLVVFRLKG PNCLTE---- ---SVLKEIA KAGQLFLIPA TIQDKLIIRFLGLVVFRLKG PNCLTE---- ---SVLKEIA KAGQLFLIPA TIQDKLIIRFLGLVVFRLKG PNCLTE---- ---SVLKEIA KTGQVFLIPA TIQDKLIIRF
ITVVFPKP-S EWVWKK---- ---HCLATSG NVAHLITTAH HLDSSRIDAL
ITVVFPCP-S EAVWKK---- ---HCLATSG DIAHLIATAH HLDSSKIDAL
ITVVFPCP-S ERVWRE---- ---HCLATSG DVAHLITTAH HLDTVQIDKLITVVFPCP-S EAVWKK---- ---HCLATSG GQAHLITTAH HLDASKVDAL
ITVVFPCP-S ERIATK---- ---YCLATSG NSAHLITTPH HHDCSMIDAL
NTVVFPCP-S EPVWRK---- ---HSLANSG SVAHIITMPH LDGPDKLDPLNTVVFPCP-S EPVWRK---- ---HSLANSG SVAHIITMPH LDGPDKLDPLNTVVFPCP-S EPVWRK---- ---HSLANSG SVAHIITMPH LDGPDKLDPLNTVVFPCP-S EPVWRK---- ---HSLANSG SVAHIITMPH LDGPDKLDPLLTVVLPPV-E DSIKTK---- ---WQIAT-Q DVSHLVVTPG TT-KQQADALITVVFERPCD HKFIRR---- ---WNLCCLR GMAHVVIMPG ITRETIDSFF
STVVFERPKD EEFVRR---- ---WQLACQG DIAHVVVMPS VTIEKLDNFL
NIVVFERPKD ERIVCR---- ---WQLACEG NLAHIVVMPN VTFEKLTVFV
NIVVFERPKD ERIVCR---- ---WQLACEG NLAHIVVMPN VTFEKLTVFVSTVVFPRP-P QPVIAK---- ---YQLAVQV DQAHAVIMQQ HSYELLEEFALGMVVFRLVG PNELTE---- ---ALLKRLN KEGKVHMVPA SLKGKYVIRFLGLVVFRIRG DNEITE---- ---KLLKRLN HRGNLHCIPS SLKGQYVIRF
LTIRFKEANP DIVFKYSLSG EILYVNGEKR AYSHIYIMPH VTKDLIDKFIPVACATHPRL GEVLER---- ---LKASGVR VYRCRSPKPC LHVTNYGRLC
Exon11

Exon12

Fig. 2 (continued)

Exon12

H. Okigami and H. Ueno

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

449
478
TVTSQFTTRD DILRDWNLIR DAATLILSQH ---------- ---------TVTSQFTTKE DILRDWHLIQ EAANLVLSQH ---------- ---------TVTSQFTTKE DILRDWHLIQ EAANLVLSQH ---------- ---------TVTSQFTTKD DILRDWNLIR EAANLVLSQH ---------- ---------IDDVIADLAQ RAA------- ---------- ---------- ---------IDDVIADLKK QAA------- ---------- ---------- ---------IDDVIADFNL HAA------- ---------- ---------- ---------IDDVIKDANG ETIAA----- ---------- ---------- ---------IDEVVAEAQL NTLRSKRAFT EQTVVERLPA ASFNLRTHY- ---------IEDVIYDLLP NYNILNVSGQ N--------- ---------- ---------IEDVIYDLLP NYNILNVSGQ N--------- ---------- ---------IEDVIYDLLP NYNILNVSGQ N--------- ---------- ---------IEDVIYDLLP NYNILNVSGQ N--------- ---------- ---------IETISNRNR- ---------- ---------- ---------- ---------KDLMQERNYK WYQDVKALPP CLADDLALNC MCSNKKMHN- ---------KDLVKHR-LI WYEDGSQPPC LASEVGTNNC ICPAHK---- ---------EELAEKRKDW YQDKGFDIPC LAVDIGKENC YCNLHAKKLR IPKM-----EELAEKRKDW YQDKGFDIPC LAVDIGKENC YCNLHAKKLR IPKM-----GVLGTCLG-- ---------- ---------- ---------- ---------TVTSQFTLES DIEKDWITIT DMASKILIEA GEQADESIEE NDEEDDDTSE
TITSTHTTLD DIVKDWMEIR QVASTVLEEM NITISNRVYL KETKEKNEAFKDLSKPGAFP EQVSHLEKDG VNFNSNSHKG IYVPQIGRGF K--------RARLGSSRSP RGCLRKPLGA SLGNPGVTGL GL-----------------Exon123̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------AETTQMSTNS NKEEPPTLQR VPRKNAARSN GLTNGEAHLC RPRPLPHPLP
GSSLLLSNSP LSPKVVNGSF AAIFDADEFL AKTYAG---- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ----------

Fig. 2 (continued)

21

22

Bioinformatic study on histidine decarboxylase

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------HAKTASLRRK EFGISLLLSN VPMSPKVVNG SFAALYDDND VGLEQLAGQL---------- ---------- ---------- ---------- ----VRIAHQ---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ----------

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

479
499---------- ---------- -------CTS QPSPRVGNLI SQIRG--ARA---------- ---------- -------CTS QPSPRAKNVI PPPPG-------------- ---------- -------CTS QPSPRAKNVI PPPPG-------------- ---------- -------CTS QPSPRAKNLI PPPVTRDSKD---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------SVGGEFIRLS PRKRGKLSEK DRQRSLDCSF LAYRRDNPIK MKMMGSLDSKESPSMRRRVR GILMSGKQFS LDSHMDVVVQ TTLDAGNGAT RTSTTNSYGH---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------Exon12

Fig. 2 (continued)

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

H. Okigami and H. Ueno
500
549
WACGTSLQSV SGAGDDPVQA RKIIKQPQRV GAGPMKRENG LHLETLLDPV-TRGLSLESV SEGGDDPAQA RKIIKQPGAS LA---RREGG SDLETMPDPF-TRGLSLESV SEGGDDPAQA RKIIKQPGAS LA---RREGG SDLETMPDPF
LTNGLSLESV NEGGDDPVQV RKIFRLP--- ---------G DSLETTMDPF---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------IDDILEMGSK VAGGGDDSDG ETAEGRKEKD KEEDDRREGK GKVDEEGKEVTTSAAQANSE RQASIQEDNE ESPEETELLS LCRTSNVPSP EHAHSLSTPS---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------Exon123̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

550
571
DDCFSEEAPD ATKHKLSSFL FS-------- ---------- ---------DDCFSEEAPN TTKHKLSSFL FS-------- ---------- ---------DDCFSEEAPN TTKHKLSSFL FS-------- ---------- ---------DDCFSEEASD TTKHKLSSFL FS-------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------DQAEEAESNE KSFSEKNVVG AKKGRVIEVP AVTKVKVKMS NGGLVKGEGTRSCSSSSHSL THSLTQSSAR SSPVNQFRHI TLCAVPSQSH LSMPLAMPLP---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------Exon12

Fig. 2 (continued)

23

24

Bioinformatic study on histidine decarboxylase

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

572
610---------- -YLSVQTKKK TVRSLSCNSV PVSAQKPLPT EASVKNGGSS---------- -YLSVQNRRK TTRSLSCNSV PMSAQKSLPA DASLKNGGSF---------- -YLSVQNRRK TTRSLSCNSV PMSAQKSLPA DASLKNGGSF---------- -YLSVQNKKK TMRSLSCNSM PMSAQKSPPP DASVKHGGFF---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------SLEGRVLEQE RWDTGHRGQK GKKSQTGQEK DTGVKNNEIA KVASAGKNSPNRNVTVSVDS LLNPVTTCNV YHGKRFLEPL ENLAQTSASF SSSIFRLPTP---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------Exon123̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

611
649
RVRIFSRFPE DMMMLKKSAF KKLIKFYSVP SFPECSSQC- ---------RARIFSGFPE QMMMMKKGAF KKLIKFYSVP SFPECSSQC- ---------RARIFSGFPE QMMMMKKGAF KKLIKFYSVP SFPECSSQC- ---------RARIFSGFPE EMMMMKKGGF KKLIKFYSVP SFPECSSQCG ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------QKRDQKSNTA SENQNSVGDH KMVLKASKSS ELPTKSKNSV GGSNPDAGGT
MATPTRESPE DPDWPAKTFS QLLLERYSSQ SQSLGNNSST ESSSLSGGAT---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------Exon12

Fig. 2 (continued)

H. Okigami and H. Ueno

3̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

25

650 657---------- ---------- ---------- ---------- --GLQLPCCP---------- ---------- ---------- ---------- --ARQLPCCP---------- ---------- ---------- ---------- --ARQLPCCP---------- ---------- ---------- ---------- --TLQLPCCP---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------GGRYMMELSK AVCSKVKEAL LTLPGSGGGN STPAAMAGDG DGDECCPCCG
PTPTPMSSLD ELVTPLLLSF ASPSQPMLSA HGIGEGQRER GSDSDATVCS---------- ---------- ---------- ---------- ------------------- ---------- ---------- ---------- ---------Exon123̲HomoSapiens
7̲MusMusculus
21̲MusMusculus
9̲RattusNorvegicus
2̲EnterobacterAerogenes
4̲KlebsiellaPlanticola
6̲MorganellaMorganii
18̲Photobacterium
8̲PseudomonasFluorescens
17̲VibrioAnguillarum
22̲VibrioAnguillarum
11̲VibrioAnguillarum
23̲VibrioAnguillarum
10̲RhizobiumLoti
5̲LycopersiconEsculentum
15̲ArabidopsisThaliana
14̲OryzaSativa
16̲OryzaSativa
19̲GloeobacterViolaceus
13̲AplysiaCalifornica
1̲DrosophilaMelanogaster
20̲ClostridiumTetani
12̲AeropyrumPernix

658
LQAMV---LEAMV---LEAMV---LQAMV---------------------------------------------------------------------------------------------------------------------------RELPSSLLSTTSSMESL-----------------

Fig. 2 (continued)

Bioinformatic study on histidine decarboxylase

26

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Ohtsu, H., Tanaka, S., Terui, T., Hori, Y.,
Makabe-Kobayashi, Y., Pejler, G.,
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Falus, A., Watanabe, T., and Nagy, A., FEBS

Fig. 3. Three-dimensional orientation of exonsin histidine decarboxylase structure predictedfrom AroDC structure (1JS3.pdb (21)). Exon
1-11 are colored as indicated in Fig. 2. Exon
12 is not shown here because HDC has extra
150 amino acids in its C-terminal region ascompared to AroDC and it was not possible toconstruct the structure for Exon 12.

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HDC.

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Communicated by Masatake Ohnishi