ID KFA_HUMAN Reviewed; 303 AA. AC Q63HM1; A2RUB3; DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 22-SEP-2009, sequence version 2. DT 27-MAR-2024, entry version 139. DE RecName: Full=Kynurenine formamidase {ECO:0000255|HAMAP-Rule:MF_03014}; DE Short=KFA {ECO:0000255|HAMAP-Rule:MF_03014}; DE Short=KFase {ECO:0000255|HAMAP-Rule:MF_03014}; DE EC=3.5.1.9 {ECO:0000255|HAMAP-Rule:MF_03014}; DE AltName: Full=Arylformamidase {ECO:0000255|HAMAP-Rule:MF_03014}; DE AltName: Full=N-formylkynurenine formamidase {ECO:0000255|HAMAP-Rule:MF_03014}; DE Short=FKF {ECO:0000255|HAMAP-Rule:MF_03014}; GN Name=AFMID {ECO:0000255|HAMAP-Rule:MF_03014}; 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; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Salivary gland; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 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). CC -!- FUNCTION: Catalyzes the hydrolysis of N-formyl-L-kynurenine to L- CC kynurenine, the second step in the kynurenine pathway of tryptophan CC degradation. Kynurenine may be further oxidized to nicotinic acid, CC NAD(H) and NADP(H). Required for elimination of toxic metabolites. CC {ECO:0000255|HAMAP-Rule:MF_03014}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + N-formyl-L-kynurenine = formate + H(+) + L-kynurenine; CC Xref=Rhea:RHEA:13009, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57959, ChEBI:CHEBI:58629; EC=3.5.1.9; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03014}; CC -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via CC kynurenine pathway; L-kynurenine from L-tryptophan: step 2/2. CC {ECO:0000255|HAMAP-Rule:MF_03014}. CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03014}. CC -!- INTERACTION: CC Q63HM1; Q96D03: DDIT4L; NbExp=5; IntAct=EBI-13286382, EBI-742054; CC Q63HM1; Q9BUE0: MED18; NbExp=3; IntAct=EBI-13286382, EBI-394640; CC Q63HM1; A8MW99: MEI4; NbExp=3; IntAct=EBI-13286382, EBI-19944212; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000255|HAMAP- CC Rule:MF_03014}. Nucleus {ECO:0000255|HAMAP-Rule:MF_03014}. CC Note=Predominantly cytosolic. Some fraction is nuclear. CC {ECO:0000255|HAMAP-Rule:MF_03014}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q63HM1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q63HM1-2; Sequence=VSP_038002; CC -!- DOMAIN: The main chain amide nitrogen atoms of the second glycine and CC its adjacent residue in the HGGXW motif define the oxyanion hole, and CC stabilize the oxyanion that forms during the nucleophilic attack by the CC catalytic serine during substrate cleavage. {ECO:0000255|HAMAP- CC Rule:MF_03014}. CC -!- SIMILARITY: Belongs to the kynurenine formamidase family. CC {ECO:0000255|HAMAP-Rule:MF_03014}. 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; BX648442; CAH56149.1; -; mRNA. DR EMBL; BC132824; AAI32825.1; -; mRNA. DR CCDS; CCDS32750.2; -. [Q63HM1-1] DR CCDS; CCDS45801.1; -. [Q63HM1-2] DR RefSeq; NP_001010982.2; NM_001010982.4. [Q63HM1-1] DR RefSeq; NP_001138998.1; NM_001145526.2. [Q63HM1-2] DR AlphaFoldDB; Q63HM1; -. DR SMR; Q63HM1; -. DR BioGRID; 125914; 16. DR IntAct; Q63HM1; 5. DR MINT; Q63HM1; -. DR STRING; 9606.ENSP00000328938; -. DR ESTHER; human-AFMID; Kynurenine-formamidase. DR MEROPS; S09.977; -. DR iPTMnet; Q63HM1; -. DR PhosphoSitePlus; Q63HM1; -. DR BioMuta; AFMID; -. DR DMDM; 259016175; -. DR EPD; Q63HM1; -. DR MassIVE; Q63HM1; -. DR MaxQB; Q63HM1; -. DR PaxDb; 9606-ENSP00000328938; -. DR PeptideAtlas; Q63HM1; -. DR ProteomicsDB; 65879; -. [Q63HM1-1] DR ProteomicsDB; 65880; -. [Q63HM1-2] DR Antibodypedia; 19735; 89 antibodies from 20 providers. DR DNASU; 125061; -. DR Ensembl; ENST00000327898.9; ENSP00000328938.5; ENSG00000183077.16. [Q63HM1-2] DR Ensembl; ENST00000409257.10; ENSP00000386890.4; ENSG00000183077.16. [Q63HM1-1] DR GeneID; 125061; -. DR KEGG; hsa:125061; -. DR MANE-Select; ENST00000409257.10; ENSP00000386890.4; NM_001010982.5; NP_001010982.2. DR UCSC; uc002juz.4; human. [Q63HM1-1] DR AGR; HGNC:20910; -. DR CTD; 125061; -. DR DisGeNET; 125061; -. DR GeneCards; AFMID; -. DR HGNC; HGNC:20910; AFMID. DR HPA; ENSG00000183077; Tissue enhanced (liver). DR neXtProt; NX_Q63HM1; -. DR OpenTargets; ENSG00000183077; -. DR PharmGKB; PA134958475; -. DR VEuPathDB; HostDB:ENSG00000183077; -. DR eggNOG; KOG4627; Eukaryota. DR GeneTree; ENSGT00390000011093; -. DR HOGENOM; CLU_012494_4_7_1; -. DR InParanoid; Q63HM1; -. DR OMA; HFDIVEN; -. DR OrthoDB; 2880059at2759; -. DR PhylomeDB; Q63HM1; -. DR TreeFam; TF315112; -. DR PathwayCommons; Q63HM1; -. DR Reactome; R-HSA-71240; Tryptophan catabolism. DR SignaLink; Q63HM1; -. DR UniPathway; UPA00333; UER00454. DR BioGRID-ORCS; 125061; 12 hits in 1152 CRISPR screens. DR ChiTaRS; AFMID; human. DR GenomeRNAi; 125061; -. DR Pharos; Q63HM1; Tbio. DR PRO; PR:Q63HM1; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q63HM1; Protein. DR Bgee; ENSG00000183077; Expressed in right lobe of liver and 109 other cell types or tissues. DR ExpressionAtlas; Q63HM1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0004061; F:arylformamidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IEA:UniProtKB-UniRule. DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IBA:GO_Central. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR HAMAP; MF_03014; KFase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR013094; AB_hydrolase_3. DR InterPro; IPR027519; KFase_ver/fungi-typ. DR PANTHER; PTHR48081; AB HYDROLASE SUPERFAMILY PROTEIN C4A8.06C; 1. DR PANTHER; PTHR48081:SF34; KYNURENINE FORMAMIDASE; 1. DR Pfam; PF07859; Abhydrolase_3; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Hydrolase; Nucleus; Reference proteome; KW Tryptophan catabolism. FT CHAIN 1..303 FT /note="Kynurenine formamidase" FT /id="PRO_0000248308" FT MOTIF 95..99 FT /note="HGGXW" FT ACT_SITE 164 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03014" FT ACT_SITE 247 FT /evidence="ECO:0000255|HAMAP-Rule:MF_03014" FT ACT_SITE 279 FT /evidence="ECO:0000255|HAMAP-Rule:MF_03014" FT VAR_SEQ 260 FT /note="Q -> QVLPVQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_038002" FT CONFLICT 222 FT /note="S -> N (in Ref. 1; CAH56149)" FT /evidence="ECO:0000305" SQ SEQUENCE 303 AA; 33992 MW; 6E329218366C027D CRC64; MMDVSGVGFP SKVPWKKMSA EELENQYCPS RWVVRLGAEE ALRTYSQIGI EATTRARATR KSLLHVPYGD GEGEKVDIYF PDESSEALPF FLFFHGGYWQ SGSKDESAFM VHPLTAQGVA VVIVAYGIAP KGTLDHMVDQ VTRSVAFVQK RYPSNKGIYL CGHSAGAHLA AMMLLADWTK HGVTPNLRGF FLVSGVFDLE PIVYTSQNVA LQLTLEDAQR NSPQLKVAQA QPVDPTCRVL VVVGQFDSPE FHRQSWEFYQ TLCQGEWKAS FEELHDVDHF EIVENLTQKD NVLTQIILKT IFQ //