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O95954 (FTCD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Formimidoyltransferase-cyclodeaminase
Alternative name(s):
Formiminotransferase-cyclodeaminase
Short name=FTCD
LCHC1

Including the following 2 domains:

  1. Glutamate formimidoyltransferase
    EC=2.1.2.5
    Alternative name(s):
    Glutamate formiminotransferase
    Glutamate formyltransferase
  2. Formimidoyltetrahydrofolate cyclodeaminase
    EC=4.3.1.4
    Alternative name(s):
    Formiminotetrahydrofolate cyclodeaminase
Gene names
Name:FTCD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length541 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool.

Binds and promotes bundling of vimentin filaments originating from the Golgi By similarity.

Catalytic activity

5-formimidoyltetrahydrofolate + L-glutamate = tetrahydrofolate + N-formimidoyl-L-glutamate.

5-formyltetrahydrofolate + L-glutamate = tetrahydrofolate + N-formyl-L-glutamate.

5-formimidoyltetrahydrofolate = 5,10-methenyltetrahydrofolate + NH3.

Cofactor

Pyridoxal phosphate.

Pathway

Amino-acid degradation; L-histidine degradation into L-glutamate; L-glutamate from N-formimidoyl-L-glutamate (transferase route): step 1/1.

One-carbon metabolism; tetrahydrofolate interconversion.

Subunit structure

Homooctamer, including four polyglutamate binding sites. The subunits are arranged as a tetramer of dimers, and form a planar ring-shaped structure By similarity.

Subcellular location

Cytoplasmcytoskeletonmicrotubule organizing centercentrosomecentriole. Golgi apparatus By similarity. Note: More abundantly located around the mother centriole. Ref.5

Involvement in disease

Glutamate formiminotransferase deficiency (FIGLU-URIA) [MIM:229100]: Autosomal recessive disorder. Features of a severe phenotype, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

In the C-terminal section; belongs to the cyclodeaminase/cyclohydrolase family.

In the N-terminal section; belongs to the formiminotransferase family.

Ontologies

Keywords
   Biological processHistidine metabolism
   Cellular componentCytoplasm
Cytoskeleton
Golgi apparatus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandFolate-binding
Pyridoxal phosphate
   Molecular functionLyase
Transferase
   Technical termComplete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processcellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

folic acid-containing compound metabolic process

Traceable author statement Ref.3. Source: ProtInc

histidine catabolic process

Traceable author statement. Source: Reactome

histidine catabolic process to glutamate and formamide

Inferred from electronic annotation. Source: UniProtKB-UniPathway

histidine catabolic process to glutamate and formate

Inferred from electronic annotation. Source: UniProtKB-UniPathway

small molecule metabolic process

Traceable author statement. Source: Reactome

tetrahydrofolate interconversion

Inferred from electronic annotation. Source: UniProtKB-UniPathway

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

centriole

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Traceable author statement Ref.3. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

   Molecular_functionfolic acid binding

Inferred from electronic annotation. Source: UniProtKB-KW

formimidoyltetrahydrofolate cyclodeaminase activity

Inferred from experiment. Source: Reactome

glutamate formimidoyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: O95954-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform C (identifier: O95954-2)

The sequence of this isoform differs from the canonical sequence as follows:
     514-541: IHHRVSSLLQEAKTQAALVLDCLETRQE → PPAGSQDPGC...GTAGPSTLEG
Isoform D (identifier: O95954-3)

The sequence of this isoform differs from the canonical sequence as follows:
     421-541: EAMRLPKNTP...VLDCLETRQE → AHGGPTGGSE...QPEGHHRRGI
Isoform E (identifier: O95954-4)

The sequence of this isoform differs from the canonical sequence as follows:
     123-158: VYLYGEAARMDSRRTLPAIRAGEYEALPKKLQQADW → GLTAGLSCSLPVRRGSQDGQSPDPAGHPGRGVRGPP
     159-541: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 541541Formimidoyltransferase-cyclodeaminase
PRO_0000087359

Regions

Region1 – 181181Formiminotransferase N-subdomain By similarity
Region182 – 326145Formiminotransferase C-subdomain By similarity
Region327 – 3348Linker By similarity
Region335 – 541207Cyclodeaminase/cyclohydrolase By similarity

Sites

Active site821For formimidoyltransferase activity By similarity
Active site4121For cyclodeaminase activity By similarity

Natural variations

Alternative sequence123 – 15836VYLYG…QQADW → GLTAGLSCSLPVRRGSQDGQ SPDPAGHPGRGVRGPP in isoform E.
VSP_004257
Alternative sequence159 – 541383Missing in isoform E.
VSP_004258
Alternative sequence421 – 541121EAMRL…ETRQE → AHGGPTGGSEAGSLCAADAG GDGGLAVAGAAGTGPVWEPG LPVRPPGGGQSPGDGRVWRI FQRAHQPEGHHRRGI in isoform D.
VSP_004259
Alternative sequence514 – 54128IHHRV…ETRQE → PPAGSQDPGCTGAGLLGDPA GVTVREASPGSVAPPSPIPR GQSCDLETPGTAGPSTLEG in isoform C.
VSP_004260
Natural variant1351R → C in FIGLU-URIA; mild phenotype; 61% wild-type activity. Ref.6
Corresponds to variant rs28941768 [ dbSNP | Ensembl ].
VAR_015887
Natural variant2991R → P in FIGLU-URIA; mild phenotype; 57% wild-type activity. Ref.6
VAR_015888
Natural variant4381A → E. Ref.6
VAR_015889

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: C6CFEBFC6DC2ED68

FASTA54158,927
        10         20         30         40         50         60 
MSQLVECVPN FSEGKNQEVI DAISGAITQT PGCVLLDVDA GPSTNRTVYT FVGPPECVVE 

        70         80         90        100        110        120 
GALNAARVAS RLIDMSRHQG EHPRMGALDV CPFIPVRGVS VDECVLCAQA FGQRLAEELD 

       130        140        150        160        170        180 
VPVYLYGEAA RMDSRRTLPA IRAGEYEALP KKLQQADWAP DFGPSSFVPS WGATATGARK 

       190        200        210        220        230        240 
FLIAFNINLL GTKEQAHRIA LNLREQGRGK DQPGRLKKVQ GIGWYLDEKN LAQVSTNLLD 

       250        260        270        280        290        300 
FEVTALHTVY EETCREAQEL SLPVVGSQLV GLVPLKALLD AAAFYCEKEN LFILEEEQRI 

       310        320        330        340        350        360 
RLVVSRLGLD SLCPFSPKER IIEYLVPERG PERGLGSKSL RAFVGEVGAR SAAPGGGSVA 

       370        380        390        400        410        420 
AAAAAMGAAL GSMVGLMTYG RRQFQSLDTT MRRLIPPFRE ASAKLTTLVD ADAEAFTAYL 

       430        440        450        460        470        480 
EAMRLPKNTP EEKDRRTAAL QEGLRRAVSV PLTLAETVAS LWPALQELAR CGNLACRSDL 

       490        500        510        520        530        540 
QVAAKALEMG VFGAYFNVLI NLRDITDEAF KDQIHHRVSS LLQEAKTQAA LVLDCLETRQ 


E 

« Hide

Isoform C [UniParc].

Checksum: 487A7518726BF2DF
Show »

FASTA57261,276
Isoform D [UniParc].

Checksum: 2A1ECD587F8E8882
Show »

FASTA49552,765
Isoform E [UniParc].

Checksum: E03CA7F616A1023A
Show »

FASTA15816,503

References

« Hide 'large scale' references
[1]"Cloning and characterization of human FTCD on 21q22.3, a candidate gene for glutamate formiminotransferase deficiency."
Solans A., Estivill X., de la Luna S.
Cytogenet. Cell Genet. 88:43-49(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; C; D AND E).
Tissue: Kidney.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
Tissue: Liver.
[3]"Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis."
Lapierre P., Hajoui O., Homberg J.-C., Alvarez F.
Gastroenterology 116:643-649(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 396-541.
[4]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[5]"Localization of Golgi 58K protein (formiminotransferase cyclodeaminase) to the centrosome."
Hagiwara H., Tajika Y., Matsuzaki T., Suzuki T., Aoki T., Takata K.
Histochem. Cell Biol. 126:251-259(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CENTRIOLE ASSOCIATION.
[6]"The molecular basis of glutamate formiminotransferase deficiency."
Hilton J.F., Christensen K.E., Watkins D., Raby B.A., Renaud Y., De La Luna S., Estivill X., MacKenzie R.E., Hudson T.J., Rosenblatt D.S.
Hum. Mutat. 22:67-73(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS FIGLU-URIA CYS-135 AND PRO-299, VARIANT GLU-438.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF169017 mRNA. Translation: AAF15558.1.
AF289021 mRNA. Translation: AAG01852.1.
AF289022 mRNA. Translation: AAG01853.1.
AF289023 mRNA. Translation: AAG01854.1.
AF289024 mRNA. Translation: AAG01855.1.
BC052248 mRNA. Translation: AAH52248.2.
BC136383 mRNA. Translation: AAI36384.1.
BC136395 mRNA. Translation: AAI36396.1.
U91541 mRNA. Translation: AAD15627.1.
RefSeqNP_006648.1. NM_006657.2.
NP_996848.1. NM_206965.1.
UniGeneHs.415846.

3D structure databases

ProteinModelPortalO95954.
SMRO95954. Positions 2-541.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116053. 2 interactions.
STRING9606.ENSP00000291670.

Chemistry

DrugBankDB00142. L-Glutamic Acid.
DB00114. Pyridoxal Phosphate.
DB00116. Tetrahydrofolic acid.

PTM databases

PhosphoSiteO95954.

Proteomic databases

PaxDbO95954.
PRIDEO95954.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000291670; ENSP00000291670; ENSG00000160282. [O95954-1]
ENST00000359679; ENSP00000352707; ENSG00000160282. [O95954-2]
ENST00000397746; ENSP00000380854; ENSG00000160282. [O95954-1]
ENST00000397748; ENSP00000380856; ENSG00000160282. [O95954-2]
GeneID10841.
KEGGhsa:10841.
UCSCuc002zif.3. human. [O95954-1]
uc002zig.3. human. [O95954-2]

Organism-specific databases

CTD10841.
GeneCardsGC21M047556.
HGNCHGNC:3974. FTCD.
HPACAB016409.
HPA020073.
HPA030929.
MIM229100. phenotype.
606806. gene.
neXtProtNX_O95954.
Orphanet51208. Formiminoglutamic aciduria.
PharmGKBPA28391.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3404.
HOVERGENHBG000168.
KOK13990.
OMACEKENLF.
OrthoDBEOG7N63MS.
PhylomeDBO95954.
TreeFamTF333892.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00193.
UPA00379; UER00555.

Gene expression databases

ArrayExpressO95954.
BgeeO95954.
CleanExHS_FTCD.
GenevestigatorO95954.

Family and domain databases

Gene3D3.30.70.670. 1 hit.
3.30.990.10. 1 hit.
InterProIPR007044. Cyclodeamin/CycHdrlase.
IPR013802. Formiminotransferase_C.
IPR004227. Formiminotransferase_cat.
IPR012886. Formiminotransferase_N.
IPR022384. FormiminoTrfase_N/C_subdom.
[Graphical view]
PfamPF02971. FTCD. 1 hit.
PF04961. FTCD_C. 1 hit.
PF07837. FTCD_N. 1 hit.
[Graphical view]
SUPFAMSSF101262. SSF101262. 1 hit.
SSF55116. SSF55116. 2 hits.
TIGRFAMsTIGR02024. FtcD. 1 hit.
ProtoNetSearch...

Other

ChiTaRSFTCD. human.
GenomeRNAi10841.
NextBio41160.
PROO95954.
SOURCESearch...

Entry information

Entry nameFTCD_HUMAN
AccessionPrimary (citable) accession number: O95954
Secondary accession number(s): B9EGD0 expand/collapse secondary AC list , Q86V03, Q9HCT4, Q9HCT5, Q9HCT6, Q9UHJ2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: April 16, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM