FOXC2

Protein identityUniProt · HPA

UniProt accession

Q99958

Gene

FOXC2

Ensembl

ENSG00000176692

Chromosome

16

Canonical length

501 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Nuclear bodies

OverviewNCBI Gene

This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the development of mesenchymal tissues. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

501 residues, UniProt reviewed canonical sequence.

>Q99958|FOXC2
     1  MQARYSVSDP NALGVVPYLS EQNYYRAAGS YGGMASPMGV YSGHPEQYSA GMGRSYAPYH
    61  HHQPAAPKDL VKPPYSYIAL ITMAIQNAPE KKITLNGIYQ FIMDRFPFYR ENKQGWQNSI
   121  RHNLSLNECF VKVPRDDKKP GKGSYWTLDP DSYNMFENGS FLRRRRRFKK KDVSKEKEER
   181  AHLKEPPPAA SKGAPATPHL ADAPKEAEKK VVIKSEAASP ALPVITKVET LSPESALQGS
   241  PRSAASTPAG SPDGSLPEHH AAAPNGLPGF SVENIMTLRT SPPGGELSPG AGRAGLVVPP
   301  LALPYAAAPP AAYGQPCAQG LEAGAAGGYQ CSMRAMSLYT GAERPAHMCV PPALDEALSD
   361  HPSGPTSPLS ALNLAAGQEG ALAATGHHHQ HHGHHHPQAP PPPPAPQPQP TPQPGAAAAQ
   421  AASWYLNHSG DLNHLPGHTF AAQQQTFPNV REMFNSHRLG IENSTLGESQ VSGNASCQLP
   481  YRSTPPLYRH AAPYSYDCTK Y

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FOXC2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.65

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FOXC2.

Disease | AllUniProt

Conditions FOXC2 is implicated in, by any mechanism.

• Lymphedema-distichiasis syndrome (LPHDST) MIM:153400

Disease | GeneticClinVar

58 pathogenic / likely-pathogenic of 305 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Distichiasis-lymphedema syndrome
• FOXC2-related disorder
• Non-immune hydrops fetalis
• Inborn genetic diseases
• LYMPHEDEMA-DISTICHIASIS SYNDROME WITH RENAL DISEASE AND DIABETES MELLITUS

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.79

gnomAD pLI

0.13

gnomAD missense Z

-0.25

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anatomical structure morphogenesis
• apoptotic process involved in outflow tract morphogenesis
• artery morphogenesis
• blood vessel diameter maintenance
• blood vessel remodeling
• branching involved in blood vessel morphogenesis
• camera-type eye development
• cardiac muscle cell proliferation
• cell differentiation
• collagen fibril organization
• embryonic heart tube development
• embryonic viscerocranium morphogenesis
• glomerular endothelium development
• glomerular mesangial cell development
• heart development
• insulin receptor signaling pathway
• lymphangiogenesis
• mesoderm development
• metanephros development
• negative regulation of apoptotic process involved in outflow tract morphogenesis
• negative regulation of cold-induced thermogenesis
• negative regulation of transcription by RNA polymerase II
• neural crest cell development
• Notch signaling pathway
• ossification
• paraxial mesodermal cell fate commitment
• podocyte differentiation
• positive regulation of cell adhesion mediated by integrin
• positive regulation of cell migration involved in sprouting angiogenesis
• positive regulation of DNA-templated transcription
• positive regulation of endothelial cell migration
• positive regulation of transcription by RNA polymerase II
• positive regulation of vascular wound healing
• regulation of organ growth
• regulation of transcription by RNA polymerase II
• response to hormone
• somitogenesis
• ureteric bud development
• vascular endothelial growth factor receptor signaling pathway
• ventricular cardiac muscle tissue morphogenesis

Molecular functions

• chromatin DNA binding
• DNA-binding transcription activator activity
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• identical protein binding
• promoter-specific chromatin binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• transcription cis-regulatory region binding

Cellular components

• chromatin
• nuclear body
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Fork head domain
• Fork head domain conserved site1
• Fork head domain conserved site 2
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Forkhead box protein C1/C2-like, forkhead domain
• Forkhead box domain-containing protein
• Forkhead domain

KeywordsUniProt

• Activator
• Developmental protein
• DNA-binding
• Isopeptide bond
• Methylation
• Nucleus
• Phosphoprotein
• Transcription
• Transcription regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of FOXC2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ESR1