ACMSD_HUMAN
ID ACMSD_HUMAN Reviewed; 336 AA.
AC Q8TDX5; Q3B7X3; Q53SR5; Q96KY2;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=2-amino-3-carboxymuconate-6-semialdehyde decarboxylase {ECO:0000303|PubMed:12140278};
DE EC=4.1.1.45 {ECO:0000269|PubMed:12140278};
DE AltName: Full=Picolinate carboxylase {ECO:0000303|PubMed:12140278};
GN Name=ACMSD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:BAB86938.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CATALYTIC ACTIVITY.
RC TISSUE=Brain {ECO:0000269|PubMed:12140278};
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney, and Liver {ECO:0000312|EMBL:AAH16018.1};
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 [5]
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) IN COMPLEX WITH ZINC IONS AND DHAP,
RP FUNCTION, SUBUNIT, AND ZINC-BINDING SITES.
RX PubMed=19843166; DOI=10.1111/j.1742-4658.2009.07372.x;
RA Garavaglia S., Perozzi S., Galeazzi L., Raffaelli N., Rizzi M.;
RT "The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-
RT semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate
RT suggests a regulatory link between NAD synthesis and glycolysis.";
RL FEBS J. 276:6615-6623(2009).
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. {ECO:0000269|PubMed:19843166}.
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:12140278};
CC -!- PATHWAY: Secondary metabolite metabolism; quinolate metabolism.
CC {ECO:0000305|PubMed:12140278}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:19843166}.
CC -!- INTERACTION:
CC Q8TDX5; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-749859, EBI-10178634;
CC Q8TDX5-2; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-12809094, EBI-347538;
CC Q8TDX5-2; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-12809094, EBI-739895;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:12140278};
CC IsoId=Q8TDX5-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=Q8TDX5-2; Sequence=VSP_050622, VSP_050623;
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC ACMSD family. {ECO:0000305}.
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DR EMBL; AB071418; BAB86938.1; -; mRNA.
DR EMBL; AC016725; AAY14997.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11650.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11651.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11652.1; -; Genomic_DNA.
DR EMBL; BC016018; AAH16018.1; -; mRNA.
DR EMBL; BC107420; AAI07421.1; -; mRNA.
DR CCDS; CCDS2173.2; -. [Q8TDX5-1]
DR CCDS; CCDS77464.1; -. [Q8TDX5-2]
DR RefSeq; NP_001294912.1; NM_001307983.1. [Q8TDX5-2]
DR RefSeq; NP_612199.2; NM_138326.2. [Q8TDX5-1]
DR RefSeq; XP_005263645.1; XM_005263588.4. [Q8TDX5-2]
DR RefSeq; XP_011508894.1; XM_011510592.2. [Q8TDX5-2]
DR RefSeq; XP_016858814.1; XM_017003325.1. [Q8TDX5-2]
DR RefSeq; XP_016858815.1; XM_017003326.1. [Q8TDX5-2]
DR PDB; 2WM1; X-ray; 2.01 A; A=1-336.
DR PDB; 4IGM; X-ray; 2.39 A; A/B/C/D/E/F=1-332.
DR PDB; 4IGN; X-ray; 2.33 A; A/B/C/D/E/F=1-332.
DR PDB; 4IH3; X-ray; 2.49 A; A/B/C/D/E/F=1-332.
DR PDB; 4OFC; X-ray; 1.99 A; A/B/C/D/E/F=1-335.
DR PDBsum; 2WM1; -.
DR PDBsum; 4IGM; -.
DR PDBsum; 4IGN; -.
DR PDBsum; 4IH3; -.
DR PDBsum; 4OFC; -.
DR AlphaFoldDB; Q8TDX5; -.
DR SMR; Q8TDX5; -.
DR BioGRID; 126217; 8.
DR IntAct; Q8TDX5; 5.
DR STRING; 9606.ENSP00000348459; -.
DR BindingDB; Q8TDX5; -.
DR ChEMBL; CHEMBL4105941; -.
DR iPTMnet; Q8TDX5; -.
DR PhosphoSitePlus; Q8TDX5; -.
DR BioMuta; ACMSD; -.
DR MassIVE; Q8TDX5; -.
DR PaxDb; Q8TDX5; -.
DR PeptideAtlas; Q8TDX5; -.
DR PRIDE; Q8TDX5; -.
DR ProteomicsDB; 74359; -. [Q8TDX5-1]
DR ProteomicsDB; 74360; -. [Q8TDX5-2]
DR Antibodypedia; 2546; 119 antibodies from 20 providers.
DR DNASU; 130013; -.
DR Ensembl; ENST00000356140.10; ENSP00000348459.5; ENSG00000153086.14. [Q8TDX5-1]
DR Ensembl; ENST00000392928.5; ENSP00000376659.1; ENSG00000153086.14. [Q8TDX5-2]
DR GeneID; 130013; -.
DR KEGG; hsa:130013; -.
DR MANE-Select; ENST00000356140.10; ENSP00000348459.5; NM_138326.3; NP_612199.2.
DR UCSC; uc002ttz.4; human. [Q8TDX5-1]
DR CTD; 130013; -.
DR DisGeNET; 130013; -.
DR GeneCards; ACMSD; -.
DR HGNC; HGNC:19288; ACMSD.
DR HPA; ENSG00000153086; Group enriched (kidney, liver).
DR MIM; 608889; gene.
DR neXtProt; NX_Q8TDX5; -.
DR OpenTargets; ENSG00000153086; -.
DR PharmGKB; PA134973312; -.
DR VEuPathDB; HostDB:ENSG00000153086; -.
DR eggNOG; KOG4245; Eukaryota.
DR GeneTree; ENSGT00490000043417; -.
DR HOGENOM; CLU_039329_1_2_1; -.
DR InParanoid; Q8TDX5; -.
DR OMA; TTNYKAI; -.
DR OrthoDB; 941496at2759; -.
DR PhylomeDB; Q8TDX5; -.
DR TreeFam; TF313232; -.
DR BioCyc; MetaCyc:HS14455-MON; -.
DR BRENDA; 4.1.1.45; 2681.
DR PathwayCommons; Q8TDX5; -.
DR Reactome; R-HSA-71240; Tryptophan catabolism.
DR SignaLink; Q8TDX5; -.
DR UniPathway; UPA00270; -.
DR BioGRID-ORCS; 130013; 4 hits in 1057 CRISPR screens.
DR EvolutionaryTrace; Q8TDX5; -.
DR GenomeRNAi; 130013; -.
DR Pharos; Q8TDX5; Tchem.
DR PRO; PR:Q8TDX5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q8TDX5; protein.
DR Bgee; ENSG00000153086; Expressed in kidney epithelium and 108 other tissues.
DR ExpressionAtlas; Q8TDX5; baseline and differential.
DR Genevisible; Q8TDX5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0001760; F:aminocarboxymuconate-semialdehyde decarboxylase activity; IDA:ParkinsonsUK-UCL.
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; IDA:ParkinsonsUK-UCL.
DR GO; GO:1904985; P:negative regulation of quinolinate biosynthetic process; IDA:UniProtKB.
DR GO; GO:1905004; P:picolinic acid biosynthetic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:1905012; P:regulation of 'de novo' NAD biosynthetic process from tryptophan; TAS:ParkinsonsUK-UCL.
DR GO; GO:0019748; P:secondary metabolic process; IBA:GO_Central.
DR GO; GO:0006569; P:tryptophan catabolic process; TAS:ParkinsonsUK-UCL.
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 3D-structure; Alternative splicing; Decarboxylase; Lyase; Metal-binding;
KW Reference proteome; Zinc.
FT CHAIN 1..336
FT /note="2-amino-3-carboxymuconate-6-semialdehyde
FT decarboxylase"
FT /id="PRO_0000190979"
FT BINDING 6
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19843166"
FT BINDING 8
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19843166"
FT BINDING 47
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:19843166"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19843166"
FT BINDING 291
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19843166"
FT VAR_SEQ 1..58
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_050622"
FT VAR_SEQ 59..83
FT /note="RIREMDQKGVTVQALSTVPVMFSYW -> MGKSSEWCERIAGIQKFVLEKWT
FT KK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_050623"
FT STRAND 3..8
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 17..21
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 27..33
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 51..53
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 56..66
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 86..106
FT /evidence="ECO:0007829|PDB:4OFC"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 111..115
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 122..134
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 139..147
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 158..167
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 189..192
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 194..207
FT /evidence="ECO:0007829|PDB:4OFC"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 229..242
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 244..247
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 261..265
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 271..281
FT /evidence="ECO:0007829|PDB:4OFC"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 303..307
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 313..320
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 322..328
FT /evidence="ECO:0007829|PDB:4OFC"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:4OFC"
SQ SEQUENCE 336 AA; 38035 MW; 892B01D2A77C35A5 CRC64;
MKIDIHSHIL PKEWPDLKKR FGYGGWVQLQ HHSKGEAKLL KDGKVFRVVR ENCWDPEVRI
REMDQKGVTV QALSTVPVMF SYWAKPEDTL NLCQLLNNDL ASTVVSYPRR FVGLGTLPMQ
APELAVKEME RCVKELGFPG VQIGTHVNEW DLNAQELFPV YAAAERLKCS LFVHPWDMQM
DGRMAKYWLP WLVGMPAETT IAICSMIMGG VFEKFPKLKV CFAHGGGAFP FTVGRISHGF
SMRPDLCAQD NPMNPKKYLG SFYTDALVHD PLSLKLLTDV IGKDKVILGT DYPFPLGELE
PGKLIESMEE FDEETKNKLK AGNALAFLGL ERKQFE
