FTCD_HUMAN
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 03-AUG-2022, entry version 190.
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(+) = 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}.
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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; 8.
DR IntAct; O95954; 6.
DR STRING; 9606.ENSP00000291670; -.
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; O95954; -.
DR PeptideAtlas; O95954; -.
DR PRIDE; O95954; -.
DR ProteomicsDB; 51142; -. [O95954-1]
DR ProteomicsDB; 51143; -. [O95954-2]
DR ProteomicsDB; 51144; -. [O95954-3]
DR ProteomicsDB; 51145; -. [O95954-4]
DR Antibodypedia; 4293; 652 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 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; VGQPECV; -.
DR OrthoDB; 1063278at2759; -.
DR PhylomeDB; O95954; -.
DR TreeFam; TF333892; -.
DR BioCyc; MetaCyc:HS08479-MON; -.
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 1071 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 124 other tissues.
DR ExpressionAtlas; O95954; baseline and differential.
DR Genevisible; O95954; HS.
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; -; 1.
DR Gene3D; 3.30.70.670; -; 1.
DR Gene3D; 3.30.990.10; -; 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 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; SSF101262; SSF101262; 1.
DR SUPFAM; SSF55116; SSF55116; 2.
DR TIGRFAMs; TIGR02024; FtcD; 1.
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
