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) [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	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	L-dopa = 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	Aromatic L-amino-acid decarboxylase deficiency (AADCD) [MIM:608643]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. 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
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	catecholamine biosynthetic process Traceable author statement. Source: Reactome cellular amino acid metabolic process Inferred from electronic annotation. Source: InterPro cellular response to alkaloid Inferred from electronic annotation. Source: Compara cellular response to drug Inferred from electronic annotation. Source: Compara cellular response to growth factor stimulus Inferred from electronic annotation. Source: Compara circadian rhythm Inferred from electronic annotation. Source: Compara dopamine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway indolalkylamine biosynthetic process Traceable author statement. Source: Reactome isoquinoline alkaloid metabolic process Inferred from electronic annotation. Source: Compara multicellular organismal aging Inferred from electronic annotation. Source: Compara phytoalexin metabolic process Inferred from electronic annotation. Source: Compara response to pyrethroid Inferred from electronic annotation. Source: Compara serotonin biosynthetic process Inferred from electronic annotation. Source: Compara synaptic vesicle amine transport Inferred from electronic annotation. Source: Compara
Cellular_component	axon Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome neuronal cell body Inferred from electronic annotation. Source: Compara synaptic vesicle Inferred from electronic annotation. Source: Compara
Molecular_function	amino acid binding Inferred from electronic annotation. Source: Compara aromatic-L-amino-acid decarboxylase activity Inferred from direct assay PubMed 16338639. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
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

1

1

N-acetylmethionine By similarity

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

Secondary structure

1

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480

Helix Strand Turn

Details...

Helix

3 – 22

20

Helix

24 – 26

3

Helix

39 – 41

3

Helix

53 – 62

10

Helix

65 – 67

3

Helix

86 – 98

13

Helix

109 – 125

17

Helix

130 – 132

3

Beta strand

135 – 137

3

Beta strand

141 – 146

6

Helix

148 – 169

22

Helix

176 – 180

5

Beta strand

183 – 188

6

Helix

193 – 202

10

Beta strand

205 – 209

5

Helix

219 – 231

13

Beta strand

235 – 244

10

Turn

246 – 248

3

Helix

254 – 263

10

Beta strand

267 – 271

5

Helix

275 – 280

6

Turn

282 – 284

3

Helix

285 – 288

4

Helix

291 – 293

3

Beta strand

295 – 299

5

Helix

301 – 305

5

Beta strand

312 – 317

6

Turn

319 – 321

3

Helix

359 – 393

35

Beta strand

398 – 400

3

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 – 476

20

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [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], 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
AH005280 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 1-480.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-40563N.

IntAct

P20711. 4 interactions.

STRING

9606.ENSP00000350616.

PTM databases

PhosphoSite

P20711.

Polymorphism databases

DMDM

311033369.

Proteomic databases

PaxDb

P20711.

PRIDE

P20711.

Protocols and materials databases

DNASU

1644.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

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

GeneID

1644.

KEGG

hsa:1644.

Organism-specific databases

CTD

1644.

GeneCards

GC07M050526.

H-InvDB

HIX0006684.

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

COG0076.

HOGENOM

HOG000121941.

HOVERGEN

HBG000944.

KO

K01593.

OMA

PRFEVCA.

OrthoDB

EOG4B8JCZ.

Enzyme and pathway databases

BioCyc

MetaCyc:HS05635-MONOMER.

BRENDA

4.1.1.28. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00747; UER00734.

Gene expression databases

ArrayExpress

P20711.

Bgee

P20711.

CleanEx

HS_DDC.

Genevestigator

P20711.

GermOnline

ENSG00000132437. 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

ChEMBL

CHEMBL1843.

DrugBank

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

GenomeRNAi

1644.

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:	May 1, 2013
This is version 139 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.