P19113 (DCHS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histidine decarboxylase
Short name=HDC
EC=4.1.1.22

Gene names

Name:

HDC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	662 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the biosynthesis of histamine from histidine. Ref.6
Catalytic activity	L-histidine = histamine + CO2. Ref.6
Cofactor	Pyridoxal phosphate. Ref.6
Pathway	Amine and polyamine biosynthesis; histamine biosynthesis; histamine from L-histidine: step 1/1.
Subunit structure	Homodimer. Ref.6
Sequence similarities	Belongs to the group II decarboxylase family.
Biophysicochemical properties	Kinetic parameters: KM=0.1 mM for histidine Ref.6 Vmax=1880 nmol/min/mg enzyme

Ontologies

Keywords
Biological process	Catecholamine biosynthesis
Coding sequence diversity	Polymorphism
Ligand	Pyridoxal phosphate
Molecular function	Decarboxylase Lyase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	catecholamine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW histamine biosynthetic process Inferred from direct assay Ref.6. Source: UniProtKB histidine catabolic process Inferred from direct assay Ref.6. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	histidine decarboxylase activity Inferred from direct assay Ref.6. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 662

662

Histidine decarboxylase

PRO_0000146950

Sites

Binding site

81

1

Substrate; via amide nitrogen

Binding site

194

1

Substrate

Amino acid modifications

Modified residue

305

1

N6-(pyridoxal phosphate)lysine

Natural variations

Natural variant

31

1

T → M. Ref.5
Corresponds to variant rs17740607 [ dbSNP | Ensembl ].

VAR_048873

Natural variant

49

1

E → V in a colorectal cancer sample; somatic mutation. Ref.7

VAR_036470

Natural variant

285

1

E → K in a colorectal cancer sample; somatic mutation. Ref.7

VAR_036471

Natural variant

553

1

F → L.
Corresponds to variant rs16963486 [ dbSNP | Ensembl ].

VAR_048874

Natural variant

644

1

E → D.
Corresponds to variant rs2073440 [ dbSNP | Ensembl ].

VAR_033846

Experimental info

Mutagenesis

305

1

K → G: Loss of enzyme activity. Ref.6

Mutagenesis

334

1

Y → F: Loss of enzyme activity. Ref.6

Mutagenesis

354

1

S → G: Strongly decreases affinity for histidine. Strongly increases affinity for L-DOPA and confers enzyme activity toward L-DOPA. Ref.6

Sequence conflict

118

1

N → M no nucleotide entry Ref.3

Sequence conflict

148

1

S → Q in CAA38196. Ref.1

Sequence conflict

148

1

S → Q no nucleotide entry Ref.3

Sequence conflict

500

1

W → M no nucleotide entry Ref.3

Secondary structure

1

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662

Helix Strand Turn

Details...

Helix

4 – 23

20

Helix

25 – 27

3

Turn

36 – 39

4

Helix

40 – 42

3

Helix

54 – 64

11

Helix

66 – 68

3

Beta strand

79 – 81

3

Helix

87 – 99

13

Turn

106 – 108

3

Helix

110 – 127

18

Helix

131 – 133

3

Beta strand

143 – 148

6

Helix

150 – 172

23

Helix

178 – 182

5

Beta strand

185 – 190

6

Helix

195 – 204

10

Beta strand

207 – 211

5

Helix

221 – 233

13

Beta strand

237 – 246

10

Turn

248 – 250

3

Helix

256 – 266

11

Beta strand

269 – 273

5

Helix

277 – 282

6

Helix

284 – 290

7

Helix

293 – 295

3

Beta strand

297 – 301

5

Helix

303 – 306

4

Beta strand

314 – 320

7

Helix

321 – 325

5

Turn

326 – 328

3

Helix

333 – 335

3

Turn

338 – 342

5

Helix

346 – 349

4

Beta strand

350 – 353

4

Helix

359 – 393

35

Beta strand

406 – 415

10

Helix

417 – 430

14

Beta strand

432 – 434

3

Beta strand

436 – 440

5

Beta strand

443 – 449

7

Helix

457 – 475

19

Sequences

	Sequence		Length	Mass (Da)
	P19113 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: D7611CFAAD60F469	FASTA	662	74,141
	10 20 30 40 50 60 MMEPEEYRER GREMVDYICQ YLSTVRERRV TPDVQPGYLR AQLPESAPED PDSWDSIFGD 70 80 90 100 110 120 IERIIMPGVV HWQSPHMHAY YPALTSWPSL LGDMLADAIN CLGFTWASSP ACTELEMNVM 130 140 150 160 170 180 DWLAKMLGLP EHFLHHHPSS QGGGVLQSTV SESTLIALLA ARKNKILEMK TSEPDADESC 190 200 210 220 230 240 LNARLVAYAS DQAHSSVEKA GLISLVKMKF LPVDDNFSLR GEALQKAIEE DKQRGLVPVF 250 260 270 280 290 300 VCATLGTTGV CAFDCLSELG PICAREGLWL HIDAAYAGTA FLCPEFRGFL KGIEYADSFT 310 320 330 340 350 360 FNPSKWMMVH FDCTGFWVKD KYKLQQTFSV NPIYLRHANS GVATDFMHWQ IPLSRRFRSV 370 380 390 400 410 420 KLWFVIRSFG VKNLQAHVRH GTEMAKYFES LVRNDPSFEI PAKRHLGLVV FRLKGPNCLT 430 440 450 460 470 480 ENVLKEIAKA GRLFLIPATI QDKLIIRFTV TSQFTTRDDI LRDWNLIRDA ATLILSQHCT 490 500 510 520 530 540 SQPSPRVGNL ISQIRGARAW ACGTSLQSVS GAGDDPVQAR KIIKQPQRVG AGPMKRENGL 550 560 570 580 590 600 HLETLLDPVD DCFSEEAPDA TKHKLSSFLF SYLSVQTKKK TVRSLSCNSV PVSAQKPLPT 610 620 630 640 650 660 EASVKNGGSS RVRIFSRFPE DMMMLKKSAF KKLIKFYSVP SFPECSSQCG LQLPCCPLQA MV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of the cDNA encoding L-histidine decarboxylase derived from human basophilic leukemia cell line, KU-812-F." Yamauchi K., Ruriko S., Ohkawara Y., Tanno Y., Maeyama K., Watanabe T., Satoh K., Yoshizawa M., Shibahara S., Takishima T. Nucleic Acids Res. 18:5891-5891(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of the cDNA encoding human histidine decarboxylase from an erythroleukemia cell line and mapping of the gene locus to chromosome 15." Zahnow C.A., Yi H.F., McBride O.W., Joseph D.R. DNA Seq. 1:395-400(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Functional analysis of alternatively spliced transcripts of the human histidine decarboxylase gene and its expression in human tissues and basophilic leukemia cells." Mamune-Sato R., Yamauchi K., Tanno Y., Ohkawara Y., Ohtsu H., Katayose D., Maeyama K., Watanabe T., Shibahara S., Takishima T. Eur. J. Biochem. 209:533-539(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Leukemia.
[4]	"Structure of the L-histidine decarboxylase gene." Yatsunami K., Ohtsu H., Tsuchikawa M., Higuchi T., Ishibashi K., Shida A., Shima Y., Nakagawa S., Yamauchi K., Yamamoto M., Hayashi N., Watanabe T., Ichikawa A. J. Biol. Chem. 269:1554-1559(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-31.
[6]	"Structural study reveals that Ser-354 determines substrate specificity on human histidine decarboxylase." Komori H., Nitta Y., Ueno H., Higuchi Y. J. Biol. Chem. 287:29175-29183(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 2-477 IN COMPLEX WITH HISTIDINE METHYL ESTER AND PYRIDOXAL PHOSPHATE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-305; TYR-334 AND SER-354.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-49 AND LYS-285.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X54297 mRNA. Translation: CAA38196.1.
M60445 mRNA. Translation: AAC41698.1.
D16583 Genomic DNA. Translation: BAA04015.1.
BC130527 mRNA. Translation: AAI30528.1.

IPI

IPI00290368.

PIR

A49882.

RefSeq

NP_002103.2. NM_002112.3.

UniGene

Hs.1481.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4E1O	X-ray	1.80	A/B/C/D/E/F	2-477	[»]

ProteinModelPortal

P19113.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000267845.

PTM databases

PhosphoSite

P19113.

Polymorphism databases

DMDM

1352220.

Proteomic databases

PaxDb

P19113.

PRIDE

P19113.

Protocols and materials databases

DNASU

3067.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000267845; ENSP00000267845; ENSG00000140287.

GeneID

3067.

KEGG

hsa:3067.

UCSC

uc001zxy.3. human.

Organism-specific databases

CTD

3067.

GeneCards

GC15M050534.

HGNC

HGNC:4855. HDC.

HPA

HPA038891.

MIM

142704. gene.

neXtProt

NX_P19113.

PharmGKB

PA29233.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0076.

HOGENOM

HOG000121941.

HOVERGEN

HBG000944.

InParanoid

P19113.

KO

K01590.

OMA

DVQPGYM.

OrthoDB

EOG4DV5M4.

Enzyme and pathway databases

BRENDA

4.1.1.22. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00822; UER00786.

Gene expression databases

ArrayExpress

P19113.

Bgee

P19113.

CleanEx

HS_HDC.

Genevestigator

P19113.

GermOnline

ENSG00000140287. Homo sapiens.

Family and domain databases

Gene3D

3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.

InterPro

IPR010977. Aromatic_deC.
IPR002129. PyrdxlP-dep_de-COase.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR015422. PyrdxlP-dep_Trfase_major_sub2.
IPR021115. Pyridoxal-P_BS.
[Graphical view]

Pfam

PF00282. Pyridoxal_deC. 1 hit.
[Graphical view]

PRINTS

PR00800. YHDCRBOXLASE.

SUPFAM

SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.

PROSITE

PS00392. DDC_GAD_HDC_YDC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00117. L-Histidine.
DB00114. Pyridoxal Phosphate.

GenomeRNAi

3067.

NextBio

12133.

SOURCE

Search...

Entry information

Entry name

DCHS_HUMAN

Accession

Primary (citable) accession number: P19113
Secondary accession number(s): A1L4G0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.