Reviewed, UniProtKB/Swiss-Prot Q12948 (FOXC1_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	553 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	DNA-binding
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	negative regulation of mitotic cell cycle Inferred from direct assay. Source: UniProtKB odontogenesis of dentine-containing tooth Ref.8 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	nuclear heterochromatin Inferred from direct assay. Source: UniProtKB
Molecular function	DNA bending activity Ref.6 Inferred from direct assay. Source: UniProtKB sequence-specific DNA binding Ref.6 Inferred from direct assay. Source: UniProtKB transcription activator activity Ref.5 Non-traceable author statement. Source: UniProtKB transcription factor binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PITX2	Q99697-3	2	EBI-1175253,EBI-1175243

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 553	553	Forkhead box protein C1		PRO_0000091806
Regions
	DNA binding	77 – 168	92	Fork-head
	Compositional bias	28 – 33	6	Poly-Ala
	Compositional bias	169 – 173	5	Poly-Arg
	Compositional bias	194 – 197	4	Poly-Pro
	Compositional bias	262 – 272	11	Poly-Ser
	Compositional bias	292 – 297	6	Poly-Pro
	Compositional bias	375 – 382	8	Poly-Gly
	Compositional bias	438 – 445	8	Poly-Ser
	Compositional bias	447 – 456	10	Poly-Gly
	Compositional bias	486 – 495	10	Poly-Ala
Amino acid modifications
	Modified residue	235	1	Phosphoserine
	Modified residue	241	1	Phosphoserine
Natural variations
	Natural variant	82	1	S → T in ARS.		VAR_007944
	Natural variant	87	1	I → M in ARS.		VAR_007945
	Natural variant	112	1	F → S in IGDA and Peters anomaly.		VAR_007815
	Natural variant	126	1	I → M in ARS; with glaucoma.		VAR_007816
	Natural variant	131	1	S → L in ARS; with glaucoma.		VAR_007817
	Natural variant	161	1	M → K		VAR_018150
Experimental info
	Sequence conflict	70 – 77	8	QPQPKDMV → RSRSPRHG in AAK13575. Ref.5
	Sequence conflict	101	1	L → Q in AAK13575. Ref.5
	Sequence conflict	180	1	V → L in AAC72915. Ref.2
	Sequence conflict	199 – 202	4	RQPP → ASPR in AAC72915. Ref.2
	Sequence conflict	426	1	D → N Ref.1 Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q12948-1 [UniParc]. Last modified April 27, 2001. Version 3. Checksum: 59C6FB94303ED59A	FASTA	553	56,789
	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

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
PIR	S51626.
RefSeq	NP_001444.2.
UniGene	Hs.348883
3D structure databases
HSSP	HSSP built from PDB template 1D5V based on UniProtKB Q99958.
SMR	Q12948. Positions 76-168.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q12948.
PTM databases
PhosphoSite	Q12948.
Genome annotation databases
Ensembl	ENSG00000054598. Homo sapiens. [Contig view]
GeneID	2296.
KEGG	hsa:2296.
Organism-specific databases
HGNC	HGNC:3800. FOXC1.
MIM	601090. gene. 601631. phenotype. 604229. phenotype.
Orphanet	1220. Axenfeld-Rieger anomaly - hydrocephaly - skeletal abnormalities. 708. Peters anomaly. 91483. Rieger-Axenfeld anomaly.
PharmGKB	PA28217.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q12948.
HOVERGEN	Q12948.
Gene expression databases
ArrayExpress	Q12948.
CleanEx	HS_FOXC1.
GermOnline	ENSG00000054598. Homo sapiens.
Family and domain databases
InterPro	IPR001766. TF_Fork_head. [Graphical view]
PANTHER	PTHR11829. Fork_box_protein. 1 hit.
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
ProDom	PD000425. TF_Fork_head. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00339. FH. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	9319.
SOURCE	Search...

Entry information

Entry name

FOXC1_HUMAN

Accession

Primary (citable) accession number: Q12948
Secondary accession number(s): Q86UP7 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)