DDC_RAT
ID DDC_RAT Reviewed; 480 AA.
AC P14173; Q6LEG4;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Aromatic-L-amino-acid decarboxylase;
DE Short=AADC;
DE EC=4.1.1.28 {ECO:0000269|PubMed:11358515, ECO:0000269|PubMed:8889823};
DE AltName: Full=DOPA decarboxylase {ECO:0000303|PubMed:2813383};
DE Short=DDC {ECO:0000303|PubMed:8889823};
GN Name=Ddc {ECO:0000303|PubMed:8889823, ECO:0000312|RGD:2494};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2813383; DOI=10.1073/pnas.86.20.8142;
RA Tanaka T., Horio Y., Taketoshi M., Imamura I., Ando-Yamamoto M.,
RA Kangawa K., Matsuo H., Kurodo M., Wada H.;
RT "Molecular cloning and sequencing of a cDNA of rat dopa decarboxylase:
RT partial amino acid homologies with other enzymes synthesizing
RT catecholamines.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8142-8146(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67.
RC STRAIN=Sprague-Dawley;
RX PubMed=1465439; DOI=10.1073/pnas.89.24.12053;
RA Albert V.R., Lee M.R., Bolden A.H., Wurzburger R.J., Aguanno A.;
RT "Distinct promoters direct neuronal and nonneuronal expression of rat
RT aromatic L-amino acid decarboxylase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:12053-12057(1992).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, MUTAGENESIS OF HIS-192; ASP-252;
RP ASP-271; SER-296; LYS-303; TYR-332 AND ARG-355, AND COFACTOR.
RX PubMed=8889823; DOI=10.1093/oxfordjournals.jbchem.a021422;
RA Ishii S., Mizugichi H., Nishino J., Hayashi H., Kagamiyama H.;
RT "Functionally important residues of aromatic L-amino acid decarboxylase
RT probed by sequence alignment and site-directed mutagenesis.";
RL J. Biochem. 120:369-376(1996).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF HIS-192; ASP-271;
RP ASN-300 AND HIS-302.
RX PubMed=11358515; DOI=10.1046/j.1432-1327.2001.02187.x;
RA Bertoldi M., Castellani S., Bori Voltattorni C.;
RT "Mutation of residues in the coenzyme binding pocket of Dopa decarboxylase.
RT Effects on catalytic properties.";
RL Eur. J. Biochem. 268:2975-2981(2001).
CC -!- FUNCTION: Catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine
CC (DOPA) to dopamine and L-5-hydroxytryptophan to serotonin.
CC {ECO:0000269|PubMed:11358515, ECO:0000269|PubMed:8889823}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-dopa = CO2 + dopamine; Xref=Rhea:RHEA:12272,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57504,
CC ChEBI:CHEBI:59905; EC=4.1.1.28;
CC Evidence={ECO:0000269|PubMed:11358515, ECO:0000269|PubMed:8889823};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12273;
CC Evidence={ECO:0000269|PubMed:11358515, ECO:0000269|PubMed:8889823};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-hydroxy-L-tryptophan + H(+) = CO2 + serotonin;
CC Xref=Rhea:RHEA:18533, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:58266, ChEBI:CHEBI:350546; EC=4.1.1.28;
CC Evidence={ECO:0000269|PubMed:11358515, ECO:0000269|PubMed:8889823};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18534;
CC Evidence={ECO:0000269|PubMed:11358515, ECO:0000269|PubMed:8889823};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000269|PubMed:8889823};
CC -!- PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine
CC from L-tyrosine: step 2/2. {ECO:0000269|PubMed:11358515,
CC ECO:0000269|PubMed:8889823}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P20711}.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L33001; AAA40646.1; -; Genomic_DNA.
DR EMBL; L32989; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32990; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32991; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32992; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32993; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32994; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32995; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32996; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32997; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L33003; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L32999; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; L33000; AAA40646.1; JOINED; Genomic_DNA.
DR EMBL; M27716; AAA41087.1; -; mRNA.
DR EMBL; BC087032; AAH87032.1; -; mRNA.
DR EMBL; L03417; AAA99905.1; -; Genomic_DNA.
DR PIR; A33994; DCRTA.
DR RefSeq; NP_001257781.1; NM_001270852.1.
DR RefSeq; NP_001257782.1; NM_001270853.1.
DR RefSeq; NP_036677.1; NM_012545.4.
DR RefSeq; XP_006251537.1; XM_006251475.3.
DR RefSeq; XP_008768474.1; XM_008770252.2.
DR AlphaFoldDB; P14173; -.
DR SMR; P14173; -.
DR BioGRID; 246491; 1.
DR CORUM; P14173; -.
DR IntAct; P14173; 1.
DR STRING; 10116.ENSRNOP00000064520; -.
DR iPTMnet; P14173; -.
DR PhosphoSitePlus; P14173; -.
DR jPOST; P14173; -.
DR PaxDb; P14173; -.
DR PRIDE; P14173; -.
DR GeneID; 24311; -.
DR KEGG; rno:24311; -.
DR UCSC; RGD:2494; rat.
DR CTD; 1644; -.
DR RGD; 2494; Ddc.
DR VEuPathDB; HostDB:ENSRNOG00000004327; -.
DR eggNOG; KOG0628; Eukaryota.
DR HOGENOM; CLU_011856_3_1_1; -.
DR InParanoid; P14173; -.
DR OMA; NPGFNWS; -.
DR OrthoDB; 856958at2759; -.
DR PhylomeDB; P14173; -.
DR TreeFam; TF313863; -.
DR BioCyc; MetaCyc:MON-15070; -.
DR BRENDA; 4.1.1.28; 5301.
DR Reactome; R-RNO-209905; Catecholamine biosynthesis.
DR Reactome; R-RNO-209931; Serotonin and melatonin biosynthesis.
DR SABIO-RK; P14173; -.
DR UniPathway; UPA00747; UER00734.
DR PRO; PR:P14173; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000004327; Expressed in duodenum and 16 other tissues.
DR ExpressionAtlas; P14173; baseline and differential.
DR Genevisible; P14173; RN.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0036467; F:5-hydroxy-L-tryptophan decarboxylase activity; IEA:RHEA.
DR GO; GO:0016597; F:amino acid binding; IDA:RGD.
DR GO; GO:0004058; F:aromatic-L-amino-acid decarboxylase activity; IDA:RGD.
DR GO; GO:0016831; F:carboxy-lyase activity; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0036468; F:L-dopa decarboxylase activity; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IDA:RGD.
DR GO; GO:0015842; P:aminergic neurotransmitter loading into synaptic vesicle; IDA:RGD.
DR GO; GO:0042423; P:catecholamine biosynthetic process; TAS:RGD.
DR GO; GO:0006584; P:catecholamine metabolic process; IBA:GO_Central.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IEA:InterPro.
DR GO; GO:0071312; P:cellular response to alkaloid; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0042416; P:dopamine biosynthetic process; IDA:RGD.
DR GO; GO:0042417; P:dopamine metabolic process; TAS:RGD.
DR GO; GO:0033076; P:isoquinoline alkaloid metabolic process; IEP:RGD.
DR GO; GO:0010259; P:multicellular organism aging; IEP:RGD.
DR GO; GO:0052314; P:phytoalexin metabolic process; IEP:RGD.
DR GO; GO:0046684; P:response to pyrethroid; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; ISO:RGD.
DR GO; GO:0042427; P:serotonin biosynthetic process; IDA:RGD.
DR Gene3D; 3.40.640.10; -; 1.
DR Gene3D; 3.90.1150.10; -; 1.
DR InterPro; IPR010977; Aromatic_deC.
DR InterPro; IPR002129; PyrdxlP-dep_de-COase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR015422; PyrdxlP-dep_Trfase_small.
DR InterPro; IPR021115; Pyridoxal-P_BS.
DR Pfam; PF00282; Pyridoxal_deC; 1.
DR PRINTS; PR00800; YHDCRBOXLASE.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00392; DDC_GAD_HDC_YDC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Catecholamine biosynthesis; Decarboxylase; Lyase;
KW Pyridoxal phosphate; Reference proteome; Repeat.
FT CHAIN 1..480
FT /note="Aromatic-L-amino-acid decarboxylase"
FT /id="PRO_0000146942"
FT REPEAT 58..115
FT /note="1"
FT REPEAT 118..178
FT /note="2"
FT REGION 58..178
FT /note="2 X approximate tandem repeats"
FT BINDING 82
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P80041"
FT BINDING 148
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P20711"
FT BINDING 149
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P20711"
FT BINDING 192
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P80041"
FT BINDING 246
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P20711"
FT BINDING 300
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:P20711"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P80041"
FT MOD_RES 303
FT /note="N6-(pyridoxal phosphate)lysine"
FT MUTAGEN 192
FT /note="H->A: Abolishes decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:11358515,
FT ECO:0000269|PubMed:8889823"
FT MUTAGEN 192
FT /note="H->Q: Reduces decarboxylase activity by 96%."
FT /evidence="ECO:0000269|PubMed:11358515,
FT ECO:0000269|PubMed:8889823"
FT MUTAGEN 252
FT /note="D->A,E: Abolishes decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:8889823"
FT MUTAGEN 271
FT /note="D->A: Abolishes decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:11358515,
FT ECO:0000269|PubMed:8889823"
FT MUTAGEN 271
FT /note="D->E: Reduces decarboxylase activity by 65%."
FT /evidence="ECO:0000269|PubMed:11358515,
FT ECO:0000269|PubMed:8889823"
FT MUTAGEN 296
FT /note="S->A: Abolishes decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:8889823"
FT MUTAGEN 300
FT /note="N->A: Reduces decarboxylase activity by 75%."
FT /evidence="ECO:0000269|PubMed:11358515"
FT MUTAGEN 302
FT /note="H->Q: Reduces decarboxylase activity by 99.8%."
FT /evidence="ECO:0000269|PubMed:11358515"
FT MUTAGEN 303
FT /note="K->A,R: Abolishes decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:8889823"
FT MUTAGEN 332
FT /note="Y->A,F: Abolishes decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:8889823"
FT MUTAGEN 355
FT /note="R->A: Abolishes decarboxylase activity."
FT /evidence="ECO:0000269|PubMed:8889823"
FT MUTAGEN 355
FT /note="R->K: No effect."
FT /evidence="ECO:0000269|PubMed:8889823"
SQ SEQUENCE 480 AA; 54053 MW; 1E1D077488704574 CRC64;
MDSREFRRRG KEMVDYIADY LDGIEGRPVY PDVEPGYLRA LIPTTAPQEP ETYEDIIRDI
EKIIMPGVTH WHSPYFFAYF PTASSYPAML ADMLCGAIGC IGFSWAASPA CTELETVMMD
WLGKMLELPE AFLAGRAGEG GGVIQGSASE ATLVALLAAR TKMIRQLQAA SPELTQAALM
EKLVAYTSDQ AHSSVERAGL IGGVKIKAIP SDGNYSMRAA ALREALERDK AAGLIPFFVV
VTLGTTSCCS FDNLLEVGPI CNQEGVWLHI DAAYAGSAFI CPEFRYLLNG VEFADSFNFN
PHKWLLVNFD CSAMWVKKRT DLTEAFNMDP VYLRHSHQDS GLITDYRHWQ IPLGRRFRSL
KMWFVFRMYG VKGLQAYIRK HVKLSHEFES LVRQDPRFEI CTEVILGLVC FRLKGSNQLN
ETLLQRINSA KKIHLVPCRL RDKFVLRFAV CSRTVESAHV QLAWEHIRDL ASSVLRAEKE
