ACMSD_RAT
ID ACMSD_RAT Reviewed; 336 AA.
AC Q8R5M5;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=2-amino-3-carboxymuconate-6-semialdehyde decarboxylase {ECO:0000305};
DE EC=4.1.1.45 {ECO:0000269|PubMed:11802786};
DE AltName: Full=Picolinate carboxylase;
GN Name=Acmsd {ECO:0000312|RGD:620868};
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 {ECO:0000312|EMBL:BAB84692.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-20 AND 136-152, TISSUE
RP SPECIFICITY, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=Wistar {ECO:0000312|EMBL:BAB84692.1};
RC TISSUE=Liver {ECO:0000312|EMBL:BAB84692.1};
RX PubMed=11802786; DOI=10.1042/0264-6021:3610567;
RA Tanabe A., Egashira Y., Fukuoka S., Shibata K., Sanada H.;
RT "Purification and molecular cloning of rat 2-amino-3-carboxymuconate-6-
RT semialdehyde decarboxylase.";
RL Biochem. J. 361:567-575(2002).
RN [2] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=12140278; DOI=10.1074/jbc.m200819200;
RA Fukuoka S., Ishiguro K., Yanagihara K., Tanabe A., Egashira Y., Sanada H.,
RA Shibata K.;
RT "Identification and expression of a cDNA encoding human alpha-amino-beta-
RT carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD). A key enzyme
RT for the tryptophan-niacine pathway and 'quinolinate hypothesis'.";
RL J. Biol. Chem. 277:35162-35167(2002).
CC -!- FUNCTION: Converts alpha-amino-beta-carboxymuconate-epsilon-
CC semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can
CC be converted non-enzymatically to quinolate (QA), a key precursor of
CC NAD, and a potent endogenous excitotoxin of neuronal cells which is
CC implicated in the pathogenesis of various neurodegenerative disorders.
CC In the presence of ACMSD, ACMS is converted to AMS, a benign
CC catabolite. ACMSD ultimately controls the metabolic fate of tryptophan
CC catabolism along the kynurenine pathway.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-amino-3-carboxymuconate 6-semialdehyde + H(+) = 2-
CC aminomuconate 6-semialdehyde + CO2; Xref=Rhea:RHEA:16557,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:77634,
CC ChEBI:CHEBI:77803; EC=4.1.1.45;
CC Evidence={ECO:0000269|PubMed:11802786};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16558;
CC Evidence={ECO:0000305|PubMed:11802786};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6. {ECO:0000269|PubMed:11802786};
CC Temperature dependence:
CC Optimum temperature is 40 degrees Celsius.
CC {ECO:0000269|PubMed:11802786};
CC -!- PATHWAY: Secondary metabolite metabolism; quinolate metabolism.
CC {ECO:0000305|PubMed:11802786}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Liver and kidney. Very low levels detected in
CC brain. {ECO:0000269|PubMed:11802786, ECO:0000269|PubMed:12140278}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC ACMSD family. {ECO:0000305}.
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DR EMBL; AB069781; BAB84692.1; -; mRNA.
DR RefSeq; NP_599199.1; NM_134372.1.
DR AlphaFoldDB; Q8R5M5; -.
DR SMR; Q8R5M5; -.
DR STRING; 10116.ENSRNOP00000005206; -.
DR iPTMnet; Q8R5M5; -.
DR PhosphoSitePlus; Q8R5M5; -.
DR PaxDb; Q8R5M5; -.
DR DNASU; 171385; -.
DR Ensembl; ENSRNOT00000109111; ENSRNOP00000081182; ENSRNOG00000003884.
DR GeneID; 171385; -.
DR KEGG; rno:171385; -.
DR UCSC; RGD:620868; rat.
DR CTD; 130013; -.
DR RGD; 620868; Acmsd.
DR eggNOG; KOG4245; Eukaryota.
DR GeneTree; ENSGT00490000043417; -.
DR InParanoid; Q8R5M5; -.
DR OrthoDB; 941496at2759; -.
DR PhylomeDB; Q8R5M5; -.
DR BRENDA; 4.1.1.45; 5301.
DR UniPathway; UPA00270; -.
DR PRO; PR:Q8R5M5; -.
DR Proteomes; UP000002494; Chromosome 13.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0001760; F:aminocarboxymuconate-semialdehyde decarboxylase activity; IDA:RGD.
DR GO; GO:0016831; F:carboxy-lyase activity; IBA:GO_Central.
DR GO; GO:0016787; F:hydrolase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IDA:RGD.
DR GO; GO:1904985; P:negative regulation of quinolinate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019748; P:secondary metabolic process; IBA:GO_Central.
DR GO; GO:0006569; P:tryptophan catabolic process; IDA:RGD.
DR InterPro; IPR032465; ACMSD.
DR InterPro; IPR006680; Amidohydro-rel.
DR InterPro; IPR032466; Metal_Hydrolase.
DR PANTHER; PTHR21240; PTHR21240; 1.
DR Pfam; PF04909; Amidohydro_2; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
PE 1: Evidence at protein level;
KW Decarboxylase; Direct protein sequencing; Lyase; Metal-binding;
KW Reference proteome; Zinc.
FT CHAIN 1..336
FT /note="2-amino-3-carboxymuconate-6-semialdehyde
FT decarboxylase"
FT /id="PRO_0000190982"
FT BINDING 6
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 8
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 47
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 291
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
SQ SEQUENCE 336 AA; 38091 MW; 4030A54E93DDD04B CRC64;
MKIDIHTHIL PKEWPDLEKR FGYGGWVQLQ QQGKGEAKMM KDGKVFRVIQ QNCWDPEVRI
REMNQKGVTV QALSTVPVMF SYWAKPKDTL ELCQFLNNDL AATVARYPRR FVGLGTLPMQ
APGLAVEEME RCVKELGFPG IQIGSHINMW DLNDPELFPI YTAAERLNCS LFVHPWDMQM
DGRMAKYWLP WLVGMPSETT TAICSMIMGG VFEKFPKLKV CFAHGGGAFP FTIGRIAHGF
NMRPDLCARD NSSDPRKYLG SFYTDSLVHD PLSLKLLTDV IGKDRVILGT DYPFPLGEQE
PGKLIESMAD FDEETKDKLT AGNALTFLGL ERKLFE
