P20711 (DDC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aromatic-L-amino-acid decarboxylase
Short name=AADC
EC=4.1.1.28

Alternative name(s):
DOPA decarboxylase
Short name=DDC

Gene names

Name:	DDC
Synonyms:	AADC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	480 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine.
Catalytic activity	3,4-dihydroxy-L-phenylalanine = dopamine + CO2. 5-hydroxy-L-tryptophan = 5-hydroxytryptamine + CO2.
Cofactor	Pyridoxal phosphate.
Pathway	Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 2/2.
Subunit structure	Homodimer.
Involvement in disease	Defects in DDC are the cause of aromatic L-amino-acid decarboxylase deficiency (AADCD) [MIM:608643]. AADCD deficiency is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. It causes developmental and psychomotor delay, poor feeding, lethargy, ptosis, intermittent hypothermia, gastrointestinal disturbances. The onset is early in infancy and inheritance is autosomal recessive. Ref.3 Ref.9 Ref.12 Ref.13
Sequence similarities	Belongs to the group II decarboxylase family.

Ontologies

Keywords
Biological process	Catecholamine biosynthesis
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat
Ligand	Pyridoxal phosphate
Molecular function	Decarboxylase Lyase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular amino acid metabolic process Inferred from electronic annotation. Source: InterPro hormone biosynthetic process Traceable author statement. Source: Reactome neurotransmitter secretion Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	aromatic-L-amino-acid decarboxylase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	2	EBI-1632155,EBI-608057

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 480	480	Aromatic-L-amino-acid decarboxylase		PRO_0000146939
Regions
	Repeat	58 – 115	58	1
	Repeat	118 – 178	61	2
	Region	58 – 178	121	2 X approximate tandem repeats
Sites
	Binding site	82	1	Substrate By similarity
	Binding site	192	1	Substrate By similarity
Amino acid modifications
	Modified residue	303	1	N6-(pyridoxal phosphate)lysine
Natural variations
	Natural variant	17	1	M → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7 Ref.10 Corresponds to variant rs6264 [ dbSNP | Ensembl ].		VAR_014788
	Natural variant	47	1	P → H in AADCD. Ref.13		VAR_046137
	Natural variant	61	1	E → D. Ref.4 Corresponds to variant rs11575292 [ dbSNP | Ensembl ].		VAR_019214
	Natural variant	91	1	A → V in AADCD. Ref.9		VAR_046138
	Natural variant	102	1	G → S in AADCD. Ref.9 Ref.12		VAR_019309
	Natural variant	147	1	S → R in AADCD. Ref.9		VAR_046139
	Natural variant	210	1	P → L. Ref.4 Ref.10 Corresponds to variant rs6262 [ dbSNP | Ensembl ].		VAR_014789
	Natural variant	217	1	M → V. Ref.4 Ref.10 Corresponds to variant rs6263 [ dbSNP | Ensembl ].		VAR_014790
	Natural variant	239	1	M → I. Ref.4 Corresponds to variant rs11575377 [ dbSNP | Ensembl ].		VAR_019215
	Natural variant	239	1	M → L. Ref.4 Corresponds to variant rs11575376 [ dbSNP | Ensembl ].		VAR_019216
	Natural variant	250	1	S → F in AADCD. Ref.9 Ref.13		VAR_046140
	Natural variant	275	1	A → T in AADCD. Ref.9		VAR_046141
	Natural variant	309	1	F → L in AADCD. Ref.9		VAR_046142
	Natural variant	347	1	R → Q in AADCD. Ref.13		VAR_046143
	Natural variant	408	1	L → I in AADCD. Ref.13		VAR_046144
	Natural variant	462	1	R → Q. Ref.4 Corresponds to variant rs11575542 [ dbSNP | Ensembl ].		VAR_019217
Experimental info
	Sequence conflict	49	1	E → G in AAB59432. Ref.7
	Sequence conflict	155	1	A → P in AAD40482. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P20711 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: 0A2CFF9A39BDE298	FASTA	480	53,926
	10 20 30 40 50 60 MNASEFRRRG KEMVDYMANY MEGIEGRQVY PDVEPGYLRP LIPAAAPQEP DTFEDIINDV 70 80 90 100 110 120 EKIIMPGVTH WHSPYFFAYF PTASSYPAML ADMLCGAIGC IGFSWAASPA CTELETVMMD 130 140 150 160 170 180 WLGKMLELPK AFLNEKAGEG GGVIQGSASE ATLVALLAAR TKVIHRLQAA SPELTQAAIM 190 200 210 220 230 240 EKLVAYSSDQ AHSSVERAGL IGGVKLKAIP SDGNFAMRAS ALQEALERDK AAGLIPFFMV 250 260 270 280 290 300 ATLGTTTCCS FDNLLEVGPI CNKEDIWLHV DAAYAGSAFI CPEFRHLLNG VEFADSFNFN 310 320 330 340 350 360 PHKWLLVNFD CSAMWVKKRT DLTGAFRLDP TYLKHSHQDS GLITDYRHWQ IPLGRRFRSL 370 380 390 400 410 420 KMWFVFRMYG VKGLQAYIRK HVQLSHEFES LVRQDPRFEI CVEVILGLVC FRLKGSNKVN 430 440 450 460 470 480 EALLQRINSA KKIHLVPCHL RDKFVLRFAI CSRTVESAHV QRAWEHIKEL AADVLRAERE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase." Ichinose H., Kurosawa Y., Titani K., Fujita K., Nagatsu T. Biochem. Biophys. Res. Commun. 164:1024-1030(1989) [PubMed: 2590185] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-17. Tissue: Pheochromocytoma.
[2]	"Human dopa decarboxylase: localization to human chromosome 7p11 and characterization of hepatic cDNAs." Scherer L.J., McPherson J.D., Wasmuth J.J., Marsh L.J. Genomics 13:469-471(1992) [PubMed: 1612608] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-17.
[3]	"Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis." Sumi-Ichinose C., Ichinose H., Takahashi E., Hori T., Nagatsu T. Biochemistry 31:2229-2238(1992) [PubMed: 1540578] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISEASE, VARIANT VAL-17.
[4]	NIEHS SNPs program Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-17; ASP-61; LEU-210; VAL-217; LEU-239; ILE-239 AND GLN-462.
[5]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-17. Tissue: Lung.
[7]	"Identification of a neuron-specific promoter of human aromatic L-amino acid decarboxylase gene." Van Thai A., Coste E., Allen J.M., Palmiter R.D., Weber M.J. Brain Res. Mol. Brain Res. 17:227-238(1993) [PubMed: 8510497] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67, VARIANT VAL-17.
[8]	"Localisation of the gene for human aromatic L-amino acid decarboxylase (DDC) to chromosome 7p13-->p11 by in situ hybridisation." Craig S.P., Thai A.L., Weber M., Craig I.W. Cytogenet. Cell Genet. 61:114-116(1992) [PubMed: 1395716] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 68-105.
[9]	"Mutations in the human aromatic L-amino acid decarboxylase gene." Chang Y.T., Mues G., McPherson J.D., Bedell J., Marsh J.L., Hyland K., Courtwright K.H., Summers J.W. J. Inherit. Metab. Dis. 21:4-4(1998) Cited for: VARIANTS AADCD VAL-91; SER-102; ARG-147; PHE-250; THR-275 AND LEU-309.
[10]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANTS VAL-17; LEU-210 AND VAL-217.
[11]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[12]	"Levodopa-responsive aromatic L-amino acid decarboxylase deficiency." Chang Y.T., Sharma R., Marsh J.L., McPherson J.D., Bedell J.A., Knust A., Braeutigam C., Hoffmann G.F., Hyland K. Ann. Neurol. 55:435-438(2004) [PubMed: 14991824] [Abstract] Cited for: VARIANT AADCD SER-102.
[13]	"Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis." Pons R., Ford B., Chiriboga C.A., Clayton P.T., Hinton V., Hyland K., Sharma R., De Vivo D.C. Neurology 62:1058-1065(2004) [PubMed: 15079002] [Abstract] Cited for: VARIANTS AADCD HIS-47; PHE-250; GLN-347 AND ILE-408.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Wikipedia

Aromatic L-amino-acid decarboxylase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M76180 mRNA. Translation: AAA58437.1.
M88700 mRNA. Translation: AAA20894.1.
M84592 , M84600, M84593, M84594, M84596, M84597, M84595, M84598, M84599, M84588, M84589, M84590, M84591 Genomic DNA. Translation: AAD40482.1.
AY526322 Genomic DNA. Translation: AAS00092.1.
AC018705 Genomic DNA. Translation: AAS01995.1.
BC000485 mRNA. Translation: AAH00485.1.
BC008366 mRNA. Translation: AAH08366.1.
L05075 Genomic DNA. Translation: AAB59432.1.
S46516 Genomic DNA. Translation: AAB23675.1.

IPI

IPI00025394.

PIR

DCHUA. A33663.

RefSeq

NP_000781.1. NM_000790.3.
NP_001076440.1. NM_001082971.1.
NP_001229815.1. NM_001242886.1.
NP_001229816.1. NM_001242887.1.
NP_001229817.1. NM_001242888.1.
NP_001229818.1. NM_001242889.1.

UniGene

Hs.359698.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3RBF	X-ray	2.90	A/B	1-480	[»]
3RBL	X-ray	3.24	A/B	1-480	[»]
3RCH	X-ray	2.80	A/B	1-480	[»]

ProteinModelPortal

P20711.

SMR

P20711. Positions 1-475.

ModBase

Search...

Protein-protein interaction databases

IntAct

P20711. 4 interactions.

STRING

P20711.

PTM databases

PhosphoSite

P20711.

Polymorphism databases

DMDM

311033369.

Proteomic databases

PRIDE

P20711.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000357936; ENSP00000350616; ENSG00000132437.
ENST00000444124; ENSP00000403644; ENSG00000132437.

GeneID

1644.

KEGG

hsa:1644.

UCSC

uc003tpf.2. human.

Organism-specific databases

CTD

1644.

GeneCards

GC07M050526.

H-InvDB

HIX0006684.
HIX0020844.

HGNC

HGNC:2719. DDC.

HPA

HPA017742.

MIM

107930. gene.
608643. phenotype.

neXtProt

NX_P20711.

Orphanet

35708. Aromatic L-aminoacid decarboxylase deficiency.

PharmGKB

PA140.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17167.

HOGENOM

HBG708517.

HOVERGEN

HBG000944.

OMA

PICNKED.

OrthoDB

EOG4B8JCZ.

PhylomeDB

P20711.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000132437-MONOMER.

BRENDA

4.1.1.28. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P20711.

Bgee

P20711.

CleanEx

HS_DDC.

Genevestigator

P20711.

GermOnline

ENSG00000132437. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.40.640.10. PyrdxlP-dep_Trfase_major_sub1. 1 hit.
G3DSA:3.90.1150.10. PyrdxlP-dep_Trfase_major_sub2. 1 hit.

KO

K01593.

PANTHER

PTHR11999. Pyridoxal_deC. 1 hit.

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

DB00915. Amantadine.
DB00190. Carbidopa.
DB00875. Flupenthixol.
DB00150. L-Tryptophan.
DB01235. Levodopa.
DB01100. Pimozide.
DB00114. Pyridoxal Phosphate.
DB00409. Remoxipride.

NextBio

6762.

SOURCE

Search...

Entry information

Entry name

DDC_HUMAN

Accession

Primary (citable) accession number: P20711
Secondary accession number(s): Q16723, Q75MJ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	November 2, 2010
Last modified:	January 25, 2012
This is version 125 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.