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Protein

Histidine decarboxylase

Gene

HDC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the biosynthesis of histamine from histidine.1 Publication

Catalytic activityi

L-histidine = histamine + CO2.1 Publication

Cofactori

pyridoxal 5'-phosphate1 Publication

Kineticsi

  1. KM=0.1 mM for histidine1 Publication
  1. Vmax=1880 nmol/min/mg enzyme1 Publication

Pathway: histamine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes histamine from L-histidine.
Proteins known to be involved in this subpathway in this organism are:
  1. Histidine decarboxylase (HDC)
This subpathway is part of the pathway histamine biosynthesis, which is itself part of Amine and polyamine biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes histamine from L-histidine, the pathway histamine biosynthesis and in Amine and polyamine biosynthesis.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei81 – 811Substrate; via amide nitrogen
Binding sitei194 – 1941Substrate

GO - Molecular functioni

  • histidine decarboxylase activity Source: UniProtKB
  • pyridoxal phosphate binding Source: InterPro

GO - Biological processi

  • catecholamine biosynthetic process Source: UniProtKB-KW
  • cellular nitrogen compound metabolic process Source: Reactome
  • histamine biosynthetic process Source: UniProtKB
  • histidine catabolic process Source: UniProtKB
  • histidine metabolic process Source: ProtInc
  • small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Decarboxylase, Lyase

Keywords - Biological processi

Catecholamine biosynthesis

Keywords - Ligandi

Pyridoxal phosphate

Enzyme and pathway databases

BioCyciMetaCyc:HS06697-MONOMER.
BRENDAi4.1.1.22. 2681.
ReactomeiREACT_1249. Histidine catabolism.
UniPathwayiUPA00822; UER00786.

Names & Taxonomyi

Protein namesi
Recommended name:
Histidine decarboxylase (EC:4.1.1.22)
Short name:
HDC
Gene namesi
Name:HDC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:4855. HDC.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi305 – 3051K → G: Loss of enzyme activity. 1 Publication
Mutagenesisi334 – 3341Y → F: Loss of enzyme activity. 1 Publication
Mutagenesisi354 – 3541S → G: Strongly decreases affinity for histidine. Strongly increases affinity for L-DOPA and confers enzyme activity toward L-DOPA. 1 Publication

Organism-specific databases

Orphaneti856. Tourette syndrome.
PharmGKBiPA29233.

Chemistry

DrugBankiDB00117. L-Histidine.

Polymorphism and mutation databases

BioMutaiHDC.
DMDMi1352220.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 662662Histidine decarboxylasePRO_0000146950Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei305 – 3051N6-(pyridoxal phosphate)lysine

Proteomic databases

PaxDbiP19113.
PRIDEiP19113.

PTM databases

PhosphoSiteiP19113.

Expressioni

Gene expression databases

BgeeiP19113.
CleanExiHS_HDC.
ExpressionAtlasiP19113. baseline and differential.
GenevisibleiP19113. HS.

Organism-specific databases

HPAiHPA038891.

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
DTX2Q4ZH493EBI-10200283,EBI-10192429
DTX2Q86UW93EBI-10200283,EBI-740376

Protein-protein interaction databases

BioGridi109317. 2 interactions.
IntActiP19113. 2 interactions.
STRINGi9606.ENSP00000267845.

Structurei

Secondary structure

1
662
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 2320Combined sources
Helixi25 – 273Combined sources
Turni36 – 394Combined sources
Helixi40 – 423Combined sources
Helixi54 – 6411Combined sources
Helixi66 – 683Combined sources
Beta strandi79 – 813Combined sources
Helixi87 – 9913Combined sources
Turni106 – 1083Combined sources
Helixi110 – 12718Combined sources
Helixi131 – 1333Combined sources
Beta strandi143 – 1486Combined sources
Helixi150 – 17223Combined sources
Helixi178 – 1825Combined sources
Beta strandi185 – 1906Combined sources
Helixi195 – 20410Combined sources
Beta strandi207 – 2115Combined sources
Helixi221 – 23313Combined sources
Beta strandi237 – 24610Combined sources
Turni248 – 2503Combined sources
Helixi256 – 26611Combined sources
Beta strandi269 – 2735Combined sources
Helixi277 – 2826Combined sources
Helixi284 – 2907Combined sources
Helixi293 – 2953Combined sources
Beta strandi297 – 3015Combined sources
Helixi303 – 3064Combined sources
Beta strandi314 – 3207Combined sources
Helixi321 – 3255Combined sources
Turni326 – 3283Combined sources
Helixi333 – 3353Combined sources
Turni338 – 3425Combined sources
Helixi346 – 3494Combined sources
Beta strandi350 – 3534Combined sources
Helixi359 – 39335Combined sources
Beta strandi406 – 41510Combined sources
Helixi417 – 43014Combined sources
Beta strandi432 – 4343Combined sources
Beta strandi436 – 4405Combined sources
Beta strandi443 – 4497Combined sources
Helixi457 – 47519Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4E1OX-ray1.80A/B/C/D/E/F2-477[»]
ProteinModelPortaliP19113.
SMRiP19113. Positions 2-477.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the group II decarboxylase family.Curated

Phylogenomic databases

eggNOGiCOG0076.
GeneTreeiENSGT00760000119205.
HOGENOMiHOG000121941.
HOVERGENiHBG000944.
InParanoidiP19113.
KOiK01590.
OMAiPEHFLHH.
OrthoDBiEOG75B851.
PhylomeDBiP19113.
TreeFamiTF313863.

Family and domain databases

Gene3Di3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProiIPR010977. 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]
PfamiPF00282. Pyridoxal_deC. 1 hit.
[Graphical view]
PRINTSiPR00800. YHDCRBOXLASE.
SUPFAMiSSF53383. SSF53383. 1 hit.
PROSITEiPS00392. DDC_GAD_HDC_YDC. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19113-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMEPEEYRER GREMVDYICQ YLSTVRERRV TPDVQPGYLR AQLPESAPED
60 70 80 90 100
PDSWDSIFGD IERIIMPGVV HWQSPHMHAY YPALTSWPSL LGDMLADAIN
110 120 130 140 150
CLGFTWASSP ACTELEMNVM DWLAKMLGLP EHFLHHHPSS QGGGVLQSTV
160 170 180 190 200
SESTLIALLA ARKNKILEMK TSEPDADESC LNARLVAYAS DQAHSSVEKA
210 220 230 240 250
GLISLVKMKF LPVDDNFSLR GEALQKAIEE DKQRGLVPVF VCATLGTTGV
260 270 280 290 300
CAFDCLSELG PICAREGLWL HIDAAYAGTA FLCPEFRGFL KGIEYADSFT
310 320 330 340 350
FNPSKWMMVH FDCTGFWVKD KYKLQQTFSV NPIYLRHANS GVATDFMHWQ
360 370 380 390 400
IPLSRRFRSV KLWFVIRSFG VKNLQAHVRH GTEMAKYFES LVRNDPSFEI
410 420 430 440 450
PAKRHLGLVV FRLKGPNCLT ENVLKEIAKA GRLFLIPATI QDKLIIRFTV
460 470 480 490 500
TSQFTTRDDI LRDWNLIRDA ATLILSQHCT SQPSPRVGNL ISQIRGARAW
510 520 530 540 550
ACGTSLQSVS GAGDDPVQAR KIIKQPQRVG AGPMKRENGL HLETLLDPVD
560 570 580 590 600
DCFSEEAPDA TKHKLSSFLF SYLSVQTKKK TVRSLSCNSV PVSAQKPLPT
610 620 630 640 650
EASVKNGGSS RVRIFSRFPE DMMMLKKSAF KKLIKFYSVP SFPECSSQCG
660
LQLPCCPLQA MV
Length:662
Mass (Da):74,141
Last modified:February 1, 1996 - v2
Checksum:iD7611CFAAD60F469
GO
Isoform 2 (identifier: P19113-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     348-380: Missing.

Note: No experimental confirmation available.
Show »
Length:629
Mass (Da):70,059
Checksum:i72BDB69D63CE7606
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti118 – 1181N → M no nucleotide entry (PubMed:1425659).Curated
Sequence conflicti148 – 1481S → Q in CAA38196 (PubMed:2216786).Curated
Sequence conflicti148 – 1481S → Q no nucleotide entry (PubMed:1425659).Curated
Sequence conflicti500 – 5001W → M no nucleotide entry (PubMed:1425659).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti31 – 311T → M.1 Publication
Corresponds to variant rs17740607 [ dbSNP | Ensembl ].
VAR_048873
Natural varianti49 – 491E → V in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036470
Natural varianti285 – 2851E → K in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036471
Natural varianti553 – 5531F → L.
Corresponds to variant rs16963486 [ dbSNP | Ensembl ].
VAR_048874
Natural varianti644 – 6441E → D.
Corresponds to variant rs2073440 [ dbSNP | Ensembl ].
VAR_033846

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei348 – 38033Missing in isoform 2. 1 PublicationVSP_056296Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54297 mRNA. Translation: CAA38196.1.
M60445 mRNA. Translation: AAC41698.1.
D16583 Genomic DNA. Translation: BAA04015.1.
AC009753 Genomic DNA. No translation available.
AC022087 Genomic DNA. No translation available.
BC130527 mRNA. Translation: AAI30528.1.
BC144173 mRNA. Translation: AAI44174.1.
CCDSiCCDS10134.1. [P19113-1]
PIRiA49882.
RefSeqiNP_002103.2. NM_002112.3. [P19113-1]
UniGeneiHs.1481.

Genome annotation databases

EnsembliENST00000267845; ENSP00000267845; ENSG00000140287. [P19113-1]
ENST00000543581; ENSP00000440252; ENSG00000140287. [P19113-2]
GeneIDi3067.
KEGGihsa:3067.
UCSCiuc001zxy.3. human. [P19113-1]
uc010uff.2. human.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54297 mRNA. Translation: CAA38196.1.
M60445 mRNA. Translation: AAC41698.1.
D16583 Genomic DNA. Translation: BAA04015.1.
AC009753 Genomic DNA. No translation available.
AC022087 Genomic DNA. No translation available.
BC130527 mRNA. Translation: AAI30528.1.
BC144173 mRNA. Translation: AAI44174.1.
CCDSiCCDS10134.1. [P19113-1]
PIRiA49882.
RefSeqiNP_002103.2. NM_002112.3. [P19113-1]
UniGeneiHs.1481.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4E1OX-ray1.80A/B/C/D/E/F2-477[»]
ProteinModelPortaliP19113.
SMRiP19113. Positions 2-477.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109317. 2 interactions.
IntActiP19113. 2 interactions.
STRINGi9606.ENSP00000267845.

Chemistry

DrugBankiDB00117. L-Histidine.
GuidetoPHARMACOLOGYi1274.

PTM databases

PhosphoSiteiP19113.

Polymorphism and mutation databases

BioMutaiHDC.
DMDMi1352220.

Proteomic databases

PaxDbiP19113.
PRIDEiP19113.

Protocols and materials databases

DNASUi3067.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000267845; ENSP00000267845; ENSG00000140287. [P19113-1]
ENST00000543581; ENSP00000440252; ENSG00000140287. [P19113-2]
GeneIDi3067.
KEGGihsa:3067.
UCSCiuc001zxy.3. human. [P19113-1]
uc010uff.2. human.

Organism-specific databases

CTDi3067.
GeneCardsiGC15M050534.
HGNCiHGNC:4855. HDC.
HPAiHPA038891.
MIMi142704. gene.
neXtProtiNX_P19113.
Orphaneti856. Tourette syndrome.
PharmGKBiPA29233.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0076.
GeneTreeiENSGT00760000119205.
HOGENOMiHOG000121941.
HOVERGENiHBG000944.
InParanoidiP19113.
KOiK01590.
OMAiPEHFLHH.
OrthoDBiEOG75B851.
PhylomeDBiP19113.
TreeFamiTF313863.

Enzyme and pathway databases

UniPathwayiUPA00822; UER00786.
BioCyciMetaCyc:HS06697-MONOMER.
BRENDAi4.1.1.22. 2681.
ReactomeiREACT_1249. Histidine catabolism.

Miscellaneous databases

GeneWikiiHistidine_decarboxylase.
GenomeRNAii3067.
NextBioi12133.
PROiP19113.
SOURCEiSearch...

Gene expression databases

BgeeiP19113.
CleanExiHS_HDC.
ExpressionAtlasiP19113. baseline and differential.
GenevisibleiP19113. HS.

Family and domain databases

Gene3Di3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProiIPR010977. 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]
PfamiPF00282. Pyridoxal_deC. 1 hit.
[Graphical view]
PRINTSiPR00800. YHDCRBOXLASE.
SUPFAMiSSF53383. SSF53383. 1 hit.
PROSITEiPS00392. DDC_GAD_HDC_YDC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 1).
  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] (ISOFORM 1).
  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] (ISOFORM 1), 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. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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] (ISOFORMS 1 AND 2), VARIANT MET-31.
  7. "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.
  8. Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-49 AND LYS-285.

Entry informationi

Entry nameiDCHS_HUMAN
AccessioniPrimary (citable) accession number: P19113
Secondary accession number(s): A1L4G0, B7ZM01
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: February 1, 1996
Last modified: June 24, 2015
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.