KFA_MOUSE
ID KFA_MOUSE Reviewed; 305 AA.
AC Q8K4H1; B1AQK9; Q80XP3; Q8R1K6;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, 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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 16-29; 35-53;
RP 150-160 AND 224-242, AND FUNCTION.
RC STRAIN=Swiss Webster; TISSUE=Liver;
RX PubMed=12007602; DOI=10.1016/s0167-4838(02)00232-7;
RA Pabarcus M.K., Casida J.E.;
RT "Kynurenine formamidase: determination of primary structure and modeling-
RT based prediction of tertiary structure and catalytic triad.";
RL Biochim. Biophys. Acta 1596:201-211(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INDUCTION,
RP AND TISSUE SPECIFICITY.
RX PubMed=12411446; DOI=10.1074/jbc.m204843200;
RA Schuettengruber B., Doetzlhofer A., Kroboth K., Wintersberger E.,
RA Seiser C.;
RT "Alternate activation of two divergently transcribed mouse genes from a
RT bidirectional promoter is linked to changes in histone modification.";
RL J. Biol. Chem. 278:1784-1793(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Kidney, and Liver;
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 DISRUPTION PHENOTYPE.
RX PubMed=15866519; DOI=10.1016/j.bbagen.2005.03.010;
RA Dobrovolsky V.N., Bowyer J.F., Pabarcus M.K., Heflich R.H., Williams L.D.,
RA Doerge D.R., Arvidsson B., Bergquist J., Casida J.E.;
RT "Effect of arylformamidase (kynurenine formamidase) gene inactivation in
RT mice on enzymatic activity, kynurenine pathway metabolites and phenotype.";
RL Biochim. Biophys. Acta 1724:163-172(2005).
RN [6]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF SER-162; ASP-247 AND
RP HIS-279.
RX PubMed=15935693; DOI=10.1016/j.pep.2005.04.013;
RA Pabarcus M.K., Casida J.E.;
RT "Cloning, expression, and catalytic triad of recombinant arylformamidase.";
RL Protein Expr. Purif. 44:39-44(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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, ECO:0000269|PubMed:12007602}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.18 mM for N-formyl-L-kynurenine {ECO:0000269|PubMed:15935693};
CC Vmax=42 umol/min/mg enzyme {ECO:0000269|PubMed:15935693};
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 -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000255|HAMAP-
CC Rule:MF_03014, ECO:0000269|PubMed:12411446}. Nucleus
CC {ECO:0000255|HAMAP-Rule:MF_03014, ECO:0000269|PubMed:12411446}.
CC Note=Predominantly cytosolic. Some fraction is nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8K4H1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K4H1-2; Sequence=VSP_020237;
CC -!- TISSUE SPECIFICITY: Highly expressed in liver. Expressed in kidney.
CC Weakly or not expressed in other tissues.
CC {ECO:0000269|PubMed:12411446}.
CC -!- INDUCTION: Down-regulated upon IL2-mediated activation. Transcriptional
CC activation correlates with reduced histone acetylation.
CC {ECO:0000269|PubMed:12411446}.
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 -!- PTM: The N-terminus is blocked.
CC -!- DISRUPTION PHENOTYPE: Mice display sclerosis of kidney glomeruli,
CC possibly due to failures in the elimination of toxic metabolites.
CC {ECO:0000269|PubMed:15866519}.
CC -!- MISCELLANEOUS: The Afmid gene shares a bidirectional promoter region
CC with Tk1 gene.
CC -!- SIMILARITY: Belongs to the kynurenine formamidase family.
CC {ECO:0000255|HAMAP-Rule:MF_03014}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH24452.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF399717; AAM62284.1; -; mRNA.
DR EMBL; AY099479; AAM44406.1; -; mRNA.
DR EMBL; AL591433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC024452; AAH24452.1; ALT_INIT; mRNA.
DR EMBL; BC043309; AAH43309.1; -; mRNA.
DR EMBL; BC066780; AAH66780.1; -; mRNA.
DR CCDS; CCDS25693.1; -. [Q8K4H1-1]
DR RefSeq; NP_082103.1; NM_027827.3. [Q8K4H1-1]
DR RefSeq; XP_006534309.1; XM_006534246.1.
DR AlphaFoldDB; Q8K4H1; -.
DR SMR; Q8K4H1; -.
DR STRING; 10090.ENSMUSP00000073102; -.
DR ESTHER; mouse-KFA; Kynurenine-formamidase.
DR MEROPS; S09.977; -.
DR iPTMnet; Q8K4H1; -.
DR PhosphoSitePlus; Q8K4H1; -.
DR jPOST; Q8K4H1; -.
DR MaxQB; Q8K4H1; -.
DR PaxDb; Q8K4H1; -.
DR PRIDE; Q8K4H1; -.
DR ProteomicsDB; 263431; -. [Q8K4H1-1]
DR ProteomicsDB; 263432; -. [Q8K4H1-2]
DR Antibodypedia; 19735; 82 antibodies from 20 providers.
DR DNASU; 71562; -.
DR Ensembl; ENSMUST00000073388; ENSMUSP00000073102; ENSMUSG00000017718. [Q8K4H1-1]
DR GeneID; 71562; -.
DR KEGG; mmu:71562; -.
DR UCSC; uc007moa.2; mouse. [Q8K4H1-2]
DR UCSC; uc007mob.2; mouse. [Q8K4H1-1]
DR CTD; 125061; -.
DR MGI; MGI:2448704; Afmid.
DR VEuPathDB; HostDB:ENSMUSG00000017718; -.
DR eggNOG; KOG4627; Eukaryota.
DR GeneTree; ENSGT00390000011093; -.
DR HOGENOM; CLU_012494_4_7_1; -.
DR InParanoid; Q8K4H1; -.
DR OMA; WSHRMAA; -.
DR OrthoDB; 992858at2759; -.
DR PhylomeDB; Q8K4H1; -.
DR TreeFam; TF315112; -.
DR BioCyc; MetaCyc:MON-15003; -.
DR BRENDA; 3.5.1.9; 3474.
DR SABIO-RK; Q8K4H1; -.
DR UniPathway; UPA00333; UER00454.
DR BioGRID-ORCS; 71562; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Afmid; mouse.
DR PRO; PR:Q8K4H1; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q8K4H1; protein.
DR Bgee; ENSMUSG00000017718; Expressed in right kidney and 96 other tissues.
DR ExpressionAtlas; Q8K4H1; baseline and differential.
DR Genevisible; Q8K4H1; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004061; F:arylformamidase activity; TAS:Reactome.
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; IDA:MGI.
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; Direct protein sequencing; Hydrolase;
KW Nucleus; Reference proteome; Tryptophan catabolism.
FT CHAIN 1..305
FT /note="Kynurenine formamidase"
FT /id="PRO_0000248309"
FT MOTIF 93..97
FT /note="HGGXW"
FT ACT_SITE 162
FT /note="Nucleophile"
FT /evidence="ECO:0000305"
FT ACT_SITE 247
FT /evidence="ECO:0000305"
FT ACT_SITE 279
FT /evidence="ECO:0000305"
FT VAR_SEQ 296..305
FT /note="IILKTVFQKL -> VGLTPTTVFLNGQRGSHAHTWAWPGRQEQRERLAVPRW
FT KSQSRLHRRACGECLLFIIVVAETMSHCITLAGLGLKI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020237"
FT MUTAGEN 162
FT /note="S->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:15935693"
FT MUTAGEN 247
FT /note="D->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:15935693"
FT MUTAGEN 279
FT /note="H->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:15935693"
FT CONFLICT 33
FT /note="H -> R (in Ref. 4; AAH43309/AAH24452)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 305 AA; 34229 MW; 898000A577132A52 CRC64;
MAFPSLSAGQ NPWRNLSSEE LEKQYSPSRW VIHTKPEEVV GNFVQIGSQA TQKARATRRN
QLDVPYGDGE GEKLDIYFPD EDSKAFPLFL FLHGGYWQSG SKDDSAFMVN PLTAQGIVVV
IVAYDIAPKG TLDQMVDQVT RSVVFLQRRY PSNEGIYLCG HSAGAHLAAM VLLARWTKHG
VTPNLQGFLL VSGIYDLEPL IATSQNDPLR MTLEDAQRNS PQRHLDVVPA QPVAPACPVL
VLVGQHDSPE FHRQSKEFYE TLLRVGWKAS FQQLRGVDHF DIIENLTRED DVLTQIILKT
VFQKL
