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Reviewed, UniProtKB/Swiss-Prot Q12948 (FOXC1_HUMAN)

Last modified November 25, 2008. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Forkhead box protein C1
Alternative name(s):
    Forkhead-related protein FKHL7
    Forkhead-related transcription factor 3
      Short name=FREAC-3
Gene names
Name: FOXC1
Synonyms: FKHL7, FREAC3
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length553 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Binding of FREAC-3 and FREAC-4 to their cognate sites results in bending of the DNA at an angle of 80-90 degrees.

Subunit structure

Monomer.

Subcellular location

Nucleus.

Tissue specificity

Expressed in all tissues and cell lines examined.

Involvement in disease

Defects in FOXC1 are a cause of Axenfeld-Rieger syndrome (ARS) [MIM:601090]; also known as Axenfeld syndrome or Axenfeld anomaly. It is characterized by posterior corneal embryotoxon, prominent Schwalbe line and iris adhesion to the Schwalbe line. Other features may be hypertelorism (wide spacing of the eyes), hypoplasia of the malar bones, congenital absence of some teeth and mental retardation. When associated with tooth anomalies, the disorder is known as Rieger syndrome. Glaucoma is a progressive blinding condition that occurs in approximately half of patients with Axenfeld-Rieger malformations.

Defects in FOXC1 are the cause of iridogoniodysgenesis anomaly (IGDA) [MIM:601631]. IGDA is an autosomal dominant phenotype characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma.

Defects in FOXC1 are a cause of Peters anomaly [MIM:604229]. Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea.

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PITX2Q99697-32EBI-1175253,EBI-1175243

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 553553Forkhead box protein C1
PRO_0000091806

Regions

DNA binding77 – 16892Fork-head
Compositional bias28 – 336Poly-Ala
Compositional bias169 – 1735Poly-Arg
Compositional bias194 – 1974Poly-Pro
Compositional bias262 – 27211Poly-Ser
Compositional bias292 – 2976Poly-Pro
Compositional bias375 – 3828Poly-Gly
Compositional bias438 – 4458Poly-Ser
Compositional bias447 – 45610Poly-Gly
Compositional bias486 – 49510Poly-Ala

Amino acid modifications

Modified residue2351Phosphoserine
Modified residue2411Phosphoserine

Natural variations

Natural variant821S → T in ARS.
VAR_007944
Natural variant871I → M in ARS.
VAR_007945
Natural variant1121F → S in IGDA and Peters anomaly.
VAR_007815
Natural variant1261I → M in ARS; with glaucoma.
VAR_007816
Natural variant1311S → L in ARS; with glaucoma.
VAR_007817
Natural variant1611M → K
VAR_018150

Experimental info

Sequence conflict70 – 778QPQPKDMV → RSRSPRHG in AAK13575. Ref.5
Sequence conflict1011L → Q in AAK13575. Ref.5
Sequence conflict1801V → L in AAC72915. Ref.2
Sequence conflict199 – 2024RQPP → ASPR in AAC72915. Ref.2
Sequence conflict4261D → N Ref.1 Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q12948-1 [UniParc].

Last modified April 27, 2001. Version 3.
Checksum: 59C6FB94303ED59A

FASTA55356,789
        10         20         30         40         50         60 
MQARYSVSSP NSLGVVPYLG GEQSYYRAAA AAAGGGYTAM PAPMSVYSHP AHAEQYPGGM 

        70         80         90        100        110        120 
ARAYGPYTPQ PQPKDMVKPP YSYIALITMA IQNAPDKKIT LNGIYQFIMD RFPFYRDNKQ 

       130        140        150        160        170        180 
GWQNSIRHNL SLNECFVKVP RDDKKPGKGS YWTLDPDSYN MFENGSFLRR RRRFKKKDAV 

       190        200        210        220        230        240 
KDKEEKDRLH LKEPPPPGRQ PPPAPPEQAD GNAPGPQPPP VRIQDIKTEN GTCPSPPQPL 

       250        260        270        280        290        300 
SPAAALGSGS AAAVPKIESP DSSSSSLSSG SSPPGSLPSA RPLSLDGADS APPPPAPSAP 

       310        320        330        340        350        360 
PPHHSQGFSV DNIMTSLRGS PQSAAAELSS GLLASAAASS RAGIAPPLAL GAYSPGQSSL 

       370        380        390        400        410        420 
YSSPCSQTSS AGSSGGGGGG AGAAGGAGGA GTYHCNLQAM SLYAAGERGG HLQGAPGGAG 

       430        440        450        460        470        480 
GSAVDDPLPD YSLPPVTSSS SSSLSHGGGG GGGGGGQEAG HHPAAHQGRL TSWYLNQAGG 

       490        500        510        520        530        540 
DLGHLASAAA AAAAAGYPGQ QQNFHSVREM FESQRIGLNN SPVNGNSSCQ MAFPSSQSLY 

       550 
RTSGAFVYDC SKF 

« Hide

References

« Hide 'large scale' references
[1]"The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25."
Nishimura D.Y., Swiderski R.E., Alward W.L.M., Searby C.C., Patil S.R., Bennet S.R., Kanis A.B., Gastier J.M., Stone E.M., Sheffield V.C.
Nat. Genet. 19:140-147(1998) [PubMed: 9620769] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-112; MET-126 AND LEU-131.
[2]"Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly."
Mears A.J., Jordan T., Mirzayans F., Dubois S., Kume T., Parlee M., Ritch R., Koop B., Kuo W.-L., Collins C., Marshall J., Gould D.B., Pearce W., Carlsson P., Enerbaeck S., Morissette J., Bhattacharya S., Hogan B., Raymond V., Walter M.A.
Am. J. Hum. Genet. 63:1316-1328(1998) [PubMed: 9792859] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARS THR-82 AND MET-87.
[3]"Human FOXC1 gene."
Komatireddy S., Chakrabarti S., Mandal A.K., Reddy A.B., Sampath S., Panicker S.G., Balasubramanian D.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-161.
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed: 14574404] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Drosophila forkhead homologues are expressed in a lineage-restricted manner in human hematopoietic cells."
Hromas R., Moore J., Johnston T., Socha C., Klemsz M.
Blood 81:2854-2859(1993) [PubMed: 8499623] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 68-177, TISSUE SPECIFICITY.
Tissue: Erythroleukemia.
[6]"Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending."
Pierrou S., Hellqvist M., Samuelsson L., Enerbaeck S., Carlsson P.
EMBO J. 13:5002-5012(1994) [PubMed: 7957066] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-178.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-235 AND SER-241, MASS SPECTROMETRY.
[8]"A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene."
Honkanen R.A., Nishimura D.Y., Swiderski R.E., Bennett S.R., Hong S., Kwon Y.H., Stone E.M., Sheffield V.C., Alward W.L.M.
Am. J. Ophthalmol. 135:368-375(2003) [PubMed: 12614756] [Abstract]
Cited for: VARIANT PETERS ANOMALY SER-112.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

AF048693 Genomic DNA. Translation: AAC18081.1.
AF078096 Genomic DNA. Translation: AAC72915.1.
AY228704 Genomic DNA. Translation: AAP15181.1.
AL034344 Genomic DNA. Translation: CAB81658.1.
L12143 mRNA. Translation: AAK13575.1.
U13221 mRNA. Translation: AAA92038.1.
PIRS51626.
RefSeqNP_001444.2.
UniGeneHs.348883

3D structure databases

HSSPHSSP built from PDB template 1D5V based on UniProtKB Q99958.
SMRQ12948. Positions 76-168.
ModBaseSearch...

Protein-protein interaction databases

IntActQ12948.

PTM databases

PhosphoSiteQ12948.

Genome annotation databases

EnsemblENSG00000054598. Homo sapiens. [Contig view]
GeneID2296.
KEGGhsa:2296.

Organism-specific databases

HGNCHGNC:3800. FOXC1.
MIM601090. gene.
601631. phenotype.
604229. phenotype.
Orphanet1220. Axenfeld-Rieger anomaly - hydrocephaly - skeletal abnormalities.
708. Peters anomaly.
91483. Rieger-Axenfeld anomaly.
PharmGKBPA28217.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOGENOMQ12948.
HOVERGENQ12948.

Gene expression databases

ArrayExpressQ12948.
CleanExHS_FOXC1.
GermOnlineENSG00000054598. Homo sapiens.

Family and domain databases

InterProIPR001766. TF_Fork_head.
[Graphical view]
PANTHERPTHR11829. Fork_box_protein. 1 hit.
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
ProDomPD000425. TF_Fork_head. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio9319.
SOURCESearch...

Entry information

Entry nameFOXC1_HUMAN
AccessionPrimary (citable) accession number: Q12948
Secondary accession number(s): Q86UP7 expand/collapse secondary AC list , Q9BYM1, Q9NUE5, Q9UDD0, Q9UP06
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 27, 2001
Last modified: November 25, 2008
This is version 85 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents