Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Forkhead box protein C1

Gene

FOXC1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binding of FREAC-3 and FREAC-4 to their cognate sites results in bending of the DNA at an angle of 80-90 degrees. Regulates FOXO1 through binding to a conserved element, 5'-GTAAACAAA-3' in its promoter region, implicating FOXC1 as an important regulator of cell viability and resistance to oxidative stress in the eye.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi77 – 168Fork-headPROSITE-ProRule annotationAdd BLAST92

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000054598-MONOMER.
SignaLinkiQ12948.
SIGNORiQ12948.

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein C1
Alternative name(s):
Forkhead-related protein FKHL7
Forkhead-related transcription factor 3
Short name:
FREAC-3
Gene namesi
Name:FOXC1
Synonyms:FKHL7, FREAC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3800. FOXC1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • nuclear heterochromatin Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Axenfeld-Rieger syndrome 3 (RIEG3)12 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Features include posterior corneal embryotoxon, prominent Schwalbe line and iris adhesion to the Schwalbe line, hypertelorism, hypodontia, sensorineural deafness, redundant periumbilical skin, and cardiovascular defects such as patent ductus arteriosus and atrial septal defect. When associated with tooth anomalies, the disorder is known as Rieger syndrome.
See also OMIM:602482
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05872279P → L in RIEG3. 1 Publication1
Natural variantiVAR_05872379P → R in RIEG3. 1 Publication1
Natural variantiVAR_05872479P → T in RIEG3. 1 Publication1
Natural variantiVAR_00794482S → T in RIEG3. 1 PublicationCorresponds to variant rs104893953dbSNPEnsembl.1
Natural variantiVAR_05872586L → F in RIEG3; does not affect nuclear localization of the protein; reduces DNA binding and significantly reduces transactivation. 1 Publication1
Natural variantiVAR_00794587I → M in RIEG3. 1 PublicationCorresponds to variant rs104893954dbSNPEnsembl.1
Natural variantiVAR_05872691I → S in RIEG3. 1 Publication1
Natural variantiVAR_05872791I → T in RIEG3. 1 Publication1
Natural variantiVAR_058728115Y → S in RIEG3. 1 Publication1
Natural variantiVAR_007816126I → M in RIEG3; with glaucoma. 1 PublicationCorresponds to variant rs104893958dbSNPEnsembl.1
Natural variantiVAR_058729127R → H in RIEG3. 1 Publication1
Natural variantiVAR_058730130L → F in RIEG3; expressed at levels similar to those of wild-type protein; migrates at an apparent reduced molecular weight compared with wild-type; has significantly impaired capacity to localize to the nucleus, binds DNA and transactivates reporter genes. 1 PublicationCorresponds to variant rs121909338dbSNPEnsembl.1
Natural variantiVAR_007817131S → L in RIEG3; with glaucoma. 2 PublicationsCorresponds to variant rs104893957dbSNPEnsembl.1
Natural variantiVAR_058731149G → D in RIEG3. 1 Publication1
Natural variantiVAR_018150161M → K in RIEG3; localized correctly to the nucleus; displays reduced DNA binding ability; disrupts FOXC1's transactivation ability. 3 Publications1
Natural variantiVAR_058732161M → V in RIEG3. 1 Publication1
Natural variantiVAR_058733165G → R in RIEG3; localized correctly to the nucleus; maintains wild-type levels of DNA binding; disrupts FOXC1's transactivation ability. 1 Publication1
Natural variantiVAR_058734169R → P in RIEG3; localized correctly to the nucleus; displays reduced DNA binding ability; disrupts FOXC1's transactivation ability. 1 Publication1
Iridogoniodysgenesis anomaly (IGDA)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal dominant phenotype characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma.
See also OMIM:601631
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007815112F → S in IGDA and PETAN. 2 PublicationsCorresponds to variant rs104893951dbSNPEnsembl.1
Peters anomaly (PETAN)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionConsists 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.
See also OMIM:604229
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007815112F → S in IGDA and PETAN. 2 PublicationsCorresponds to variant rs104893951dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi86L → P: Severely disrupts the protein function. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Peters anomaly

Organism-specific databases

DisGeNETi2296.
MalaCardsiFOXC1.
MIMi601631. phenotype.
602482. phenotype.
604229. phenotype.
OpenTargetsiENSG00000054598.
Orphaneti98978. Axenfeld anomaly.
782. Axenfeld-Rieger syndrome.
708. Peters anomaly.
91483. Rieger anomaly.
PharmGKBiPA28217.

Polymorphism and mutation databases

BioMutaiFOXC1.
DMDMi13638267.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000918061 – 553Forkhead box protein C1Add BLAST553

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei235PhosphoserineCombined sources1
Modified residuei241PhosphoserineCombined sources1
Modified residuei320PhosphoserineCombined sources1
Modified residuei521PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ12948.
PeptideAtlasiQ12948.
PRIDEiQ12948.

PTM databases

iPTMnetiQ12948.
PhosphoSitePlusiQ12948.

Expressioni

Tissue specificityi

Expressed in all tissues and cell lines examined.1 Publication

Gene expression databases

BgeeiENSG00000054598.
CleanExiHS_FOXC1.
ExpressionAtlasiQ12948. baseline and differential.
GenevisibleiQ12948. HS.

Organism-specific databases

HPAiHPA040670.

Interactioni

Subunit structurei

Monomer. Interacts with C1QBP.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
C1QBPQ070216EBI-1175253,EBI-347528
FLNAP213338EBI-1175253,EBI-350432
ORFQ9Q2G43EBI-1175253,EBI-6248094From a different organism.
PBX1P404245EBI-1175253,EBI-301611
PITX2Q99697-36EBI-1175253,EBI-1175243

GO - Molecular functioni

  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108585. 47 interactors.
IntActiQ12948. 41 interactors.
STRINGi9606.ENSP00000370256.

Structurei

3D structure databases

ProteinModelPortaliQ12948.
SMRiQ12948.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi28 – 33Poly-Ala6
Compositional biasi169 – 173Poly-Arg5
Compositional biasi194 – 197Poly-Pro4
Compositional biasi262 – 272Poly-SerAdd BLAST11
Compositional biasi292 – 297Poly-Pro6
Compositional biasi375 – 382Poly-Gly8
Compositional biasi438 – 445Poly-Ser8
Compositional biasi447 – 456Poly-Gly10
Compositional biasi486 – 495Poly-Ala10

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOVERGENiHBG051640.
InParanoidiQ12948.
KOiK09396.
OMAiYSSPCSQ.
OrthoDBiEOG091G0HW9.
PhylomeDBiQ12948.
TreeFamiTF316127.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q12948-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQARYSVSSP NSLGVVPYLG GEQSYYRAAA AAAGGGYTAM PAPMSVYSHP
60 70 80 90 100
AHAEQYPGGM ARAYGPYTPQ PQPKDMVKPP YSYIALITMA IQNAPDKKIT
110 120 130 140 150
LNGIYQFIMD RFPFYRDNKQ GWQNSIRHNL SLNECFVKVP RDDKKPGKGS
160 170 180 190 200
YWTLDPDSYN MFENGSFLRR RRRFKKKDAV KDKEEKDRLH LKEPPPPGRQ
210 220 230 240 250
PPPAPPEQAD GNAPGPQPPP VRIQDIKTEN GTCPSPPQPL SPAAALGSGS
260 270 280 290 300
AAAVPKIESP DSSSSSLSSG SSPPGSLPSA RPLSLDGADS APPPPAPSAP
310 320 330 340 350
PPHHSQGFSV DNIMTSLRGS PQSAAAELSS GLLASAAASS RAGIAPPLAL
360 370 380 390 400
GAYSPGQSSL YSSPCSQTSS AGSSGGGGGG AGAAGGAGGA GTYHCNLQAM
410 420 430 440 450
SLYAAGERGG HLQGAPGGAG GSAVDDPLPD YSLPPVTSSS SSSLSHGGGG
460 470 480 490 500
GGGGGGQEAG HHPAAHQGRL TSWYLNQAGG DLGHLASAAA AAAAAGYPGQ
510 520 530 540 550
QQNFHSVREM FESQRIGLNN SPVNGNSSCQ MAFPSSQSLY RTSGAFVYDC

SKF
Length:553
Mass (Da):56,789
Last modified:April 27, 2001 - v3
Checksum:i59C6FB94303ED59A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti70 – 77QPQPKDMV → RSRSPRHG in AAK13575 (PubMed:8499623).Curated8
Sequence conflicti101L → Q in AAK13575 (PubMed:8499623).Curated1
Sequence conflicti180V → L in AAC72915 (PubMed:9792859).Curated1
Sequence conflicti199 – 202RQPP → ASPR in AAC72915 (PubMed:9792859).Curated4
Sequence conflicti426D → N in AAC18081 (PubMed:9620769).Curated1
Sequence conflicti426D → N in AAP15181 (PubMed:12592227).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05872279P → L in RIEG3. 1 Publication1
Natural variantiVAR_05872379P → R in RIEG3. 1 Publication1
Natural variantiVAR_05872479P → T in RIEG3. 1 Publication1
Natural variantiVAR_00794482S → T in RIEG3. 1 PublicationCorresponds to variant rs104893953dbSNPEnsembl.1
Natural variantiVAR_05872586L → F in RIEG3; does not affect nuclear localization of the protein; reduces DNA binding and significantly reduces transactivation. 1 Publication1
Natural variantiVAR_00794587I → M in RIEG3. 1 PublicationCorresponds to variant rs104893954dbSNPEnsembl.1
Natural variantiVAR_05872691I → S in RIEG3. 1 Publication1
Natural variantiVAR_05872791I → T in RIEG3. 1 Publication1
Natural variantiVAR_007815112F → S in IGDA and PETAN. 2 PublicationsCorresponds to variant rs104893951dbSNPEnsembl.1
Natural variantiVAR_058728115Y → S in RIEG3. 1 Publication1
Natural variantiVAR_007816126I → M in RIEG3; with glaucoma. 1 PublicationCorresponds to variant rs104893958dbSNPEnsembl.1
Natural variantiVAR_058729127R → H in RIEG3. 1 Publication1
Natural variantiVAR_058730130L → F in RIEG3; expressed at levels similar to those of wild-type protein; migrates at an apparent reduced molecular weight compared with wild-type; has significantly impaired capacity to localize to the nucleus, binds DNA and transactivates reporter genes. 1 PublicationCorresponds to variant rs121909338dbSNPEnsembl.1
Natural variantiVAR_007817131S → L in RIEG3; with glaucoma. 2 PublicationsCorresponds to variant rs104893957dbSNPEnsembl.1
Natural variantiVAR_058731149G → D in RIEG3. 1 Publication1
Natural variantiVAR_018150161M → K in RIEG3; localized correctly to the nucleus; displays reduced DNA binding ability; disrupts FOXC1's transactivation ability. 3 Publications1
Natural variantiVAR_058732161M → V in RIEG3. 1 Publication1
Natural variantiVAR_058733165G → R in RIEG3; localized correctly to the nucleus; maintains wild-type levels of DNA binding; disrupts FOXC1's transactivation ability. 1 Publication1
Natural variantiVAR_058734169R → P in RIEG3; localized correctly to the nucleus; displays reduced DNA binding ability; disrupts FOXC1's transactivation ability. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4473.1.
PIRiS51626.
RefSeqiNP_001444.2. NM_001453.2.
UniGeneiHs.348883.

Genome annotation databases

EnsembliENST00000380874; ENSP00000370256; ENSG00000054598.
GeneIDi2296.
KEGGihsa:2296.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4473.1.
PIRiS51626.
RefSeqiNP_001444.2. NM_001453.2.
UniGeneiHs.348883.

3D structure databases

ProteinModelPortaliQ12948.
SMRiQ12948.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108585. 47 interactors.
IntActiQ12948. 41 interactors.
STRINGi9606.ENSP00000370256.

PTM databases

iPTMnetiQ12948.
PhosphoSitePlusiQ12948.

Polymorphism and mutation databases

BioMutaiFOXC1.
DMDMi13638267.

Proteomic databases

PaxDbiQ12948.
PeptideAtlasiQ12948.
PRIDEiQ12948.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380874; ENSP00000370256; ENSG00000054598.
GeneIDi2296.
KEGGihsa:2296.

Organism-specific databases

CTDi2296.
DisGeNETi2296.
GeneCardsiFOXC1.
H-InvDBHIX0032962.
HGNCiHGNC:3800. FOXC1.
HPAiHPA040670.
MalaCardsiFOXC1.
MIMi601090. gene.
601631. phenotype.
602482. phenotype.
604229. phenotype.
neXtProtiNX_Q12948.
OpenTargetsiENSG00000054598.
Orphaneti98978. Axenfeld anomaly.
782. Axenfeld-Rieger syndrome.
708. Peters anomaly.
91483. Rieger anomaly.
PharmGKBiPA28217.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00760000118904.
HOVERGENiHBG051640.
InParanoidiQ12948.
KOiK09396.
OMAiYSSPCSQ.
OrthoDBiEOG091G0HW9.
PhylomeDBiQ12948.
TreeFamiTF316127.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000054598-MONOMER.
SignaLinkiQ12948.
SIGNORiQ12948.

Miscellaneous databases

GeneWikiiForkhead_box_C1.
GenomeRNAii2296.
PROiQ12948.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000054598.
CleanExiHS_FOXC1.
ExpressionAtlasiQ12948. baseline and differential.
GenevisibleiQ12948. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR018122. TF_fork_head_CS_1.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFOXC1_HUMAN
AccessioniPrimary (citable) accession number: Q12948
Secondary accession number(s): Q86UP7
, Q9BYM1, Q9NUE5, Q9UDD0, Q9UP06
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 27, 2001
Last modified: November 30, 2016
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.