ID FTCD_HUMAN Reviewed; 541 AA. AC O95954; B9EGD0; Q86V03; Q9HCT4; Q9HCT5; Q9HCT6; Q9UHJ2; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 27-MAR-2024, entry version 199. DE RecName: Full=Formimidoyltransferase-cyclodeaminase {ECO:0000305|PubMed:12815595}; DE AltName: Full=Formiminotransferase-cyclodeaminase; DE Short=FTCD; DE AltName: Full=LCHC1; DE Includes: DE RecName: Full=Glutamate formimidoyltransferase {ECO:0000305|PubMed:12815595}; DE EC=2.1.2.5 {ECO:0000269|PubMed:12815595}; DE AltName: Full=Glutamate formiminotransferase; DE AltName: Full=Glutamate formyltransferase; DE Includes: DE RecName: Full=Formimidoyltetrahydrofolate cyclodeaminase {ECO:0000250|UniProtKB:P53603}; DE EC=4.3.1.4 {ECO:0000250|UniProtKB:P53603}; DE AltName: Full=Formiminotetrahydrofolate cyclodeaminase; GN Name=FTCD; 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 [MRNA] (ISOFORMS A; C; D AND E). RC TISSUE=Kidney; RX PubMed=10773664; DOI=10.1159/000015483; RA Solans A., Estivill X., de la Luna S.; RT "Cloning and characterization of human FTCD on 21q22.3, a candidate gene RT for glutamate formiminotransferase deficiency."; RL Cytogenet. Cell Genet. 88:43-49(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 396-541. RX PubMed=10029623; DOI=10.1016/s0016-5085(99)70186-1; RA Lapierre P., Hajoui O., Homberg J.-C., Alvarez F.; RT "Formiminotransferase cyclodeaminase is an organ-specific autoantigen RT recognized by sera of patients with autoimmune hepatitis."; RL Gastroenterology 116:643-649(1999). RN [4] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [5] RP SUBCELLULAR LOCATION, AND CENTRIOLE ASSOCIATION. RX PubMed=16534631; DOI=10.1007/s00418-006-0166-5; RA Hagiwara H., Tajika Y., Matsuzaki T., Suzuki T., Aoki T., Takata K.; RT "Localization of Golgi 58K protein (formiminotransferase cyclodeaminase) to RT the centrosome."; RL Histochem. Cell Biol. 126:251-259(2006). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316 AND SER-386, RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-549 (ISOFORM C), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [7] RP VARIANTS FIGLU-URIA CYS-135 AND PRO-299, VARIANT GLU-438, INVOLVEMENT IN RP FIGLU, CHARACTERIZATION OF VARIANTS FIGLU-URIA CYS-135 AND PRO-299, RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=12815595; DOI=10.1002/humu.10236; RA Hilton J.F., Christensen K.E., Watkins D., Raby B.A., Renaud Y., RA De La Luna S., Estivill X., MacKenzie R.E., Hudson T.J., Rosenblatt D.S.; RT "The molecular basis of glutamate formiminotransferase deficiency."; RL Hum. Mutat. 22:67-73(2003). CC -!- FUNCTION: Folate-dependent enzyme, that displays both transferase and CC deaminase activity. Serves to channel one-carbon units from CC formiminoglutamate to the folate pool. {ECO:0000269|PubMed:12815595}. CC -!- FUNCTION: Binds and promotes bundling of vimentin filaments originating CC from the Golgi. {ECO:0000250|UniProtKB:O88618}. CC -!- CATALYTIC ACTIVITY: CC Reaction=5-formimidoyltetrahydrofolate + L-glutamate = (6S)-5,6,7,8- CC tetrahydrofolate + N-formimidoyl-L-glutamate; Xref=Rhea:RHEA:15097, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:57453, ChEBI:CHEBI:57456, CC ChEBI:CHEBI:58928; EC=2.1.2.5; CC Evidence={ECO:0000269|PubMed:12815595}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15099; CC Evidence={ECO:0000305|PubMed:12815595}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5-formimidoyltetrahydrofolate + 2 H(+) = (6R)-5,10- CC methenyltetrahydrofolate + NH4(+); Xref=Rhea:RHEA:22736, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:57455, CC ChEBI:CHEBI:57456; EC=4.3.1.4; CC Evidence={ECO:0000250|UniProtKB:P53603}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22737; CC Evidence={ECO:0000250|UniProtKB:P53603}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC Vmax=10.2 umol/min/mg enzyme for the glutamate formimidoyltransferase CC activity {ECO:0000269|PubMed:12815595}; CC -!- PATHWAY: Amino-acid degradation; L-histidine degradation into L- CC glutamate; L-glutamate from N-formimidoyl-L-glutamate (transferase CC route): step 1/1. {ECO:0000269|PubMed:12815595}. CC -!- SUBUNIT: Homooctamer, including four polyglutamate binding sites. The CC subunits are arranged as a tetramer of dimers, and form a planar ring- CC shaped structure. {ECO:0000250|UniProtKB:O88618}. CC -!- INTERACTION: CC O95954; O95994: AGR2; NbExp=3; IntAct=EBI-10192648, EBI-712648; CC O95954; G5E9W6: CCDC183; NbExp=3; IntAct=EBI-10192648, EBI-17212717; CC O95954; O14964: HGS; NbExp=3; IntAct=EBI-10192648, EBI-740220; CC O95954; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-10192648, EBI-749265; CC O95954; Q9NPJ6: MED4; NbExp=3; IntAct=EBI-10192648, EBI-394607; CC O95954; Q8N3R9: PALS1; NbExp=3; IntAct=EBI-10192648, EBI-2513978; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:Q9YH58}. Golgi apparatus CC {ECO:0000250|UniProtKB:Q9YH58}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome, centriole {ECO:0000269|PubMed:16534631}. CC Note=More abundantly located around the mother centriole. CC {ECO:0000269|PubMed:16534631}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=A; CC IsoId=O95954-1; Sequence=Displayed; CC Name=C; CC IsoId=O95954-2; Sequence=VSP_004260; CC Name=D; CC IsoId=O95954-3; Sequence=VSP_004259; CC Name=E; CC IsoId=O95954-4; Sequence=VSP_004257, VSP_004258; CC -!- DISEASE: Glutamate formiminotransferase deficiency (FIGLU-URIA) CC [MIM:229100]: Autosomal recessive disorder. Features of a severe CC phenotype, include elevated levels of formiminoglutamate (FIGLU) in the CC urine in response to histidine administration, megaloblastic anemia, CC and intellectual disability. Features of a mild phenotype include high CC urinary excretion of FIGLU in the absence of histidine administration, CC mild developmental delay, and no hematological abnormalities. CC {ECO:0000269|PubMed:12815595}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform E]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: In the C-terminal section; belongs to the CC cyclodeaminase/cyclohydrolase family. {ECO:0000305}. CC -!- SIMILARITY: In the N-terminal section; belongs to the CC formiminotransferase family. {ECO:0000305}. 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; AF169017; AAF15558.1; -; mRNA. DR EMBL; AF289021; AAG01852.1; -; mRNA. DR EMBL; AF289022; AAG01853.1; -; mRNA. DR EMBL; AF289023; AAG01854.1; -; mRNA. DR EMBL; AF289024; AAG01855.1; -; mRNA. DR EMBL; BC052248; AAH52248.2; -; mRNA. DR EMBL; BC136383; AAI36384.1; -; mRNA. DR EMBL; BC136395; AAI36396.1; -; mRNA. DR EMBL; U91541; AAD15627.1; -; mRNA. DR CCDS; CCDS13731.1; -. [O95954-1] DR CCDS; CCDS82684.1; -. [O95954-2] DR RefSeq; NP_001307341.1; NM_001320412.1. [O95954-2] DR RefSeq; NP_006648.1; NM_006657.2. [O95954-1] DR RefSeq; NP_996848.1; NM_206965.1. [O95954-1] DR AlphaFoldDB; O95954; -. DR SMR; O95954; -. DR BioGRID; 116053; 9. DR IntAct; O95954; 22. DR STRING; 9606.ENSP00000380856; -. DR DrugBank; DB03256; (6R)-Folinic acid. DR DrugBank; DB00142; Glutamic acid. DR DrugBank; DB00116; Tetrahydrofolic acid. DR iPTMnet; O95954; -. DR PhosphoSitePlus; O95954; -. DR BioMuta; FTCD; -. DR EPD; O95954; -. DR jPOST; O95954; -. DR MassIVE; O95954; -. DR MaxQB; O95954; -. DR PaxDb; 9606-ENSP00000291670; -. DR PeptideAtlas; O95954; -. DR ProteomicsDB; 51142; -. [O95954-1] DR ProteomicsDB; 51143; -. [O95954-2] DR ProteomicsDB; 51144; -. [O95954-3] DR ProteomicsDB; 51145; -. [O95954-4] DR Antibodypedia; 4293; 733 antibodies from 39 providers. DR DNASU; 10841; -. DR Ensembl; ENST00000291670.9; ENSP00000291670.5; ENSG00000160282.15. [O95954-1] DR Ensembl; ENST00000397746.8; ENSP00000380854.3; ENSG00000160282.15. [O95954-1] DR Ensembl; ENST00000397748.5; ENSP00000380856.1; ENSG00000160282.15. [O95954-2] DR GeneID; 10841; -. DR KEGG; hsa:10841; -. DR MANE-Select; ENST00000397746.8; ENSP00000380854.3; NM_206965.2; NP_996848.1. DR UCSC; uc002zif.3; human. [O95954-1] DR AGR; HGNC:3974; -. DR CTD; 10841; -. DR DisGeNET; 10841; -. DR GeneCards; FTCD; -. DR HGNC; HGNC:3974; FTCD. DR HPA; ENSG00000160282; Tissue enriched (liver). DR MalaCards; FTCD; -. DR MIM; 229100; phenotype. DR MIM; 606806; gene. DR neXtProt; NX_O95954; -. DR OpenTargets; ENSG00000160282; -. DR Orphanet; 51208; Formiminoglutamic aciduria. DR PharmGKB; PA28391; -. DR VEuPathDB; HostDB:ENSG00000160282; -. DR eggNOG; ENOG502QQBY; Eukaryota. DR GeneTree; ENSGT00390000005581; -. DR HOGENOM; CLU_040037_1_0_1; -. DR InParanoid; O95954; -. DR OMA; GWYIDEY; -. DR OrthoDB; 5388914at2759; -. DR PhylomeDB; O95954; -. DR TreeFam; TF333892; -. DR BioCyc; MetaCyc:HS08479-MONOMER; -. DR BRENDA; 2.1.2.5; 2681. DR BRENDA; 4.3.1.4; 2681. DR PathwayCommons; O95954; -. DR Reactome; R-HSA-70921; Histidine catabolism. DR SignaLink; O95954; -. DR UniPathway; UPA00379; UER00555. DR BioGRID-ORCS; 10841; 20 hits in 1147 CRISPR screens. DR ChiTaRS; FTCD; human. DR GenomeRNAi; 10841; -. DR Pharos; O95954; Tbio. DR PRO; PR:O95954; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; O95954; Protein. DR Bgee; ENSG00000160282; Expressed in right lobe of liver and 126 other cell types or tissues. DR ExpressionAtlas; O95954; baseline and differential. DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL. DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISS:BHF-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:BHF-UCL. DR GO; GO:0000139; C:Golgi membrane; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0030868; C:smooth endoplasmic reticulum membrane; IDA:BHF-UCL. DR GO; GO:0005542; F:folic acid binding; IEA:UniProtKB-KW. DR GO; GO:0030412; F:formimidoyltetrahydrofolate cyclodeaminase activity; ISS:BHF-UCL. DR GO; GO:0030409; F:glutamate formimidoyltransferase activity; IDA:UniProtKB. DR GO; GO:0008017; F:microtubule binding; IDA:BHF-UCL. DR GO; GO:0007010; P:cytoskeleton organization; IEA:Ensembl. DR GO; GO:0006760; P:folic acid-containing compound metabolic process; TAS:ProtInc. DR GO; GO:0019556; P:histidine catabolic process to glutamate and formamide; IEA:UniProtKB-UniPathway. DR GO; GO:0019557; P:histidine catabolic process to glutamate and formate; IEA:UniProtKB-UniPathway. DR Gene3D; 1.20.120.680; Formiminotetrahydrofolate cyclodeaminase monomer, up-and-down helical bundle; 1. DR Gene3D; 3.30.70.670; Formiminotransferase, C-terminal subdomain; 1. DR Gene3D; 3.30.990.10; Formiminotransferase, N-terminal subdomain; 1. DR InterPro; IPR007044; Cyclodeamin/CycHdrlase. DR InterPro; IPR013802; Formiminotransferase_C. DR InterPro; IPR037070; Formiminotransferase_C_sf. DR InterPro; IPR004227; Formiminotransferase_cat. DR InterPro; IPR012886; Formiminotransferase_N. DR InterPro; IPR037064; Formiminotransferase_N_sf. DR InterPro; IPR022384; FormiminoTrfase_cat_dom_sf. DR InterPro; IPR036178; Formintransfe-cycloase-like_sf. DR NCBIfam; TIGR02024; FtcD; 1. DR PANTHER; PTHR12234:SF0; FORMIMIDOYLTRANSFERASE-CYCLODEAMINASE; 1. DR PANTHER; PTHR12234; FORMIMINOTRANSFERASE-CYCLODEAMINASE; 1. DR Pfam; PF02971; FTCD; 1. DR Pfam; PF04961; FTCD_C; 1. DR Pfam; PF07837; FTCD_N; 1. DR SMART; SM01221; FTCD; 1. DR SMART; SM01222; FTCD_N; 1. DR SUPFAM; SSF55116; Formiminotransferase domain of formiminotransferase-cyclodeaminase; 2. DR SUPFAM; SSF101262; Methenyltetrahydrofolate cyclohydrolase-like; 1. DR Genevisible; O95954; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Cytoskeleton; Disease variant; KW Folate-binding; Golgi apparatus; Histidine metabolism; Lyase; KW Multifunctional enzyme; Phosphoprotein; Reference proteome; Transferase. FT CHAIN 1..541 FT /note="Formimidoyltransferase-cyclodeaminase" FT /id="PRO_0000087359" FT REGION 1..181 FT /note="Formiminotransferase N-subdomain" FT /evidence="ECO:0000250" FT REGION 182..326 FT /note="Formiminotransferase C-subdomain" FT /evidence="ECO:0000250" FT REGION 327..334 FT /note="Linker" FT /evidence="ECO:0000250" FT REGION 335..541 FT /note="Cyclodeaminase/cyclohydrolase" FT /evidence="ECO:0000250" FT ACT_SITE 82 FT /note="For formimidoyltransferase activity" FT /evidence="ECO:0000250" FT ACT_SITE 412 FT /note="For cyclodeaminase activity" FT /evidence="ECO:0000250" FT MOD_RES 316 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 386 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 520 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88618" FT VAR_SEQ 123..158 FT /note="VYLYGEAARMDSRRTLPAIRAGEYEALPKKLQQADW -> GLTAGLSCSLPV FT RRGSQDGQSPDPAGHPGRGVRGPP (in isoform E)" FT /evidence="ECO:0000303|PubMed:10773664" FT /id="VSP_004257" FT VAR_SEQ 159..541 FT /note="Missing (in isoform E)" FT /evidence="ECO:0000303|PubMed:10773664" FT /id="VSP_004258" FT VAR_SEQ 421..541 FT /note="EAMRLPKNTPEEKDRRTAALQEGLRRAVSVPLTLAETVASLWPALQELARCG FT NLACRSDLQVAAKALEMGVFGAYFNVLINLRDITDEAFKDQIHHRVSSLLQEAKTQAAL FT VLDCLETRQE -> AHGGPTGGSEAGSLCAADAGGDGGLAVAGAAGTGPVWEPGLPVRP FT PGGGQSPGDGRVWRIFQRAHQPEGHHRRGI (in isoform D)" FT /evidence="ECO:0000303|PubMed:10773664" FT /id="VSP_004259" FT VAR_SEQ 514..541 FT /note="IHHRVSSLLQEAKTQAALVLDCLETRQE -> PPAGSQDPGCTGAGLLGDPA FT GVTVREASPGSVAPPSPIPRGQSCDLETPGTAGPSTLEG (in isoform C)" FT /evidence="ECO:0000303|PubMed:10773664" FT /id="VSP_004260" FT VARIANT 135 FT /note="R -> C (in FIGLU-URIA; mild phenotype; decreased FT glutamate formimidoyltransferase activity; 61% of wild-type FT activity; dbSNP:rs28941768)" FT /evidence="ECO:0000269|PubMed:12815595" FT /id="VAR_015887" FT VARIANT 299 FT /note="R -> P (in FIGLU-URIA; mild phenotype; decreased FT glutamate formimidoyltransferase activity; 57% wild-type FT activity; dbSNP:rs119469015)" FT /evidence="ECO:0000269|PubMed:12815595" FT /id="VAR_015888" FT VARIANT 438 FT /note="A -> E" FT /evidence="ECO:0000269|PubMed:12815595" FT /id="VAR_015889" FT MOD_RES O95954-2:549 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" SQ SEQUENCE 541 AA; 58927 MW; C6CFEBFC6DC2ED68 CRC64; MSQLVECVPN FSEGKNQEVI DAISGAITQT PGCVLLDVDA GPSTNRTVYT FVGPPECVVE GALNAARVAS RLIDMSRHQG EHPRMGALDV CPFIPVRGVS VDECVLCAQA FGQRLAEELD VPVYLYGEAA RMDSRRTLPA IRAGEYEALP KKLQQADWAP DFGPSSFVPS WGATATGARK FLIAFNINLL GTKEQAHRIA LNLREQGRGK DQPGRLKKVQ GIGWYLDEKN LAQVSTNLLD FEVTALHTVY EETCREAQEL SLPVVGSQLV GLVPLKALLD AAAFYCEKEN LFILEEEQRI RLVVSRLGLD SLCPFSPKER IIEYLVPERG PERGLGSKSL RAFVGEVGAR SAAPGGGSVA AAAAAMGAAL GSMVGLMTYG RRQFQSLDTT MRRLIPPFRE ASAKLTTLVD ADAEAFTAYL EAMRLPKNTP EEKDRRTAAL QEGLRRAVSV PLTLAETVAS LWPALQELAR CGNLACRSDL QVAAKALEMG VFGAYFNVLI NLRDITDEAF KDQIHHRVSS LLQEAKTQAA LVLDCLETRQ E //