Reviewed, UniProtKB/Swiss-Prot P20711 (DDC_HUMAN)

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) [Complete proteome]

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.
Sequence processing	The displayed sequence is not processed.
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	Complete proteome
Gene Ontology (GO)
Biological process	carboxylic acid metabolic process Inferred from electronic annotation. Source: InterPro catecholamine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	aromatic-L-amino-acid decarboxylase activity Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AR	P10275	1	EBI-1632155,EBI-608057
Ar	P15207	1	EBI-1632155,EBI-1632225	From a different organism.

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	V → M: dbSNP rs6264. Ref.5 Ref.10		VAR_014788
	Natural variant	47	1	P → H in AADCD. Ref.13		VAR_046137
	Natural variant	61	1	E → D: dbSNP rs11575292. Ref.4		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: dbSNP rs6262. Ref.10 Ref.4		VAR_014789
	Natural variant	217	1	M → V: dbSNP rs6263. Ref.10 Ref.4		VAR_014790
	Natural variant	239	1	M → I: dbSNP rs11575377. Ref.4		VAR_019215
	Natural variant	239	1	M → L: dbSNP rs11575376. Ref.4		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: dbSNP rs11575542. Ref.4		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)
	P20711-1 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: 898FD4B99A96C13E	FASTA	480	53,894
	10 20 30 40 50 60 MNASEFRRRG KEMVDYVANY 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]. 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].
[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.
[4]	NIEHS SNPs program Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS 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], VARIANT MET-17.
[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]. 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.
[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 MET-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
EMBLGenBankDDBJ	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. NP_001076440.1.
UniGene	Hs.359698
3D structure databases
SMR	P20711. Positions 1-475.
ModBase	Search...
Protein-protein interaction databases
IntAct	P20711. 2 interactions.
STRING	P20711.
Proteomic databases
PRIDE	P20711.
Genome annotation databases
Ensembl	ENST00000357936; ENSP00000350616; ENSG00000132437; Homo sapiens. [Genome view] ENST00000444124; ENSP00000403644; ENSG00000132437; Homo sapiens. [Genome view]
GeneID	1644.
KEGG	hsa:1644.
UCSC	uc003tpf.2. human.
Organism-specific databases
CTD	1644.
GeneCards	GC07M050493.
H-InvDB	HIX0006684. HIX0020844.
HGNC	HGNC:2719. DDC.
HPA	HPA017742.
MIM	107930. gene. 608643. phenotype.
Orphanet	35708. Aromatic L-aminoacid decarboxylase deficiency.
PharmGKB	PA140.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P20711.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000132437-MON.
BRENDA	4.1.1.28. 247.
Reactome	REACT_13685. Synaptic Transmission. REACT_15314. Hormone biosynthesis.
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. IPR015421. PyrdxlP-dep_Trfase_major_sub1. IPR015422. PyrdxlP-dep_Trfase_major_sub2. [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.
PANTHER	PTHR11999. Pyridoxal_deC. 1 hit.
Pfam	PF00282. Pyridoxal_deC. 1 hit. [Graphical view]
PRINTS	PR00800. YHDCRBOXLASE.
PROSITE	PS00392. DDC_GAD_HDC_YDC. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	February 1, 1991
Last modified:	November 24, 2009
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.