KFA_HUMAN
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 03-AUG-2022, entry version 130.
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; 15.
DR IntAct; Q63HM1; 4.
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; Q63HM1; -.
DR PeptideAtlas; Q63HM1; -.
DR PRIDE; Q63HM1; -.
DR ProteomicsDB; 65879; -. [Q63HM1-1]
DR ProteomicsDB; 65880; -. [Q63HM1-2]
DR Antibodypedia; 19735; 82 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 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; WSHRMAA; -.
DR OrthoDB; 992858at2759; -.
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 1076 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 107 other 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; -; 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 Pfam; PF07859; Abhydrolase_3; 1.
DR SUPFAM; SSF53474; SSF53474; 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
