UniProtKB - Q12948 (FOXC1_HUMAN)
Forkhead box protein C1
FOXC1
Functioni
DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development (PubMed:11782474, PubMed:15299087, PubMed:15684392, PubMed:16492674, PubMed:27907090, PubMed:14506133, PubMed:14578375, PubMed:15277473, PubMed:16449236, PubMed:17210863, PubMed:19793056, PubMed:19279310, PubMed:25786029, PubMed:27804176).
Acts either as a transcriptional activator or repressor (PubMed:11782474).
Binds to the consensus binding site 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes (PubMed:7957066, PubMed:11782474, PubMed:12533514, PubMed:14506133, PubMed:19793056, PubMed:27804176).
Upon DNA-binding, promotes DNA bending (PubMed:7957066, PubMed:14506133).
Acts as a transcriptional coactivator (PubMed:26565916).
Stimulates Indian hedgehog (Ihh)-induced target gene expression mediated by the transcription factor GLI2, and hence regulates endochondral ossification (By similarity).
Acts also as a transcriptional coregulator by increasing DNA-binding capacity of GLI2 in breast cancer cells (PubMed:26565916).
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 (PubMed:17993506).
Cooperates with transcription factor FOXC2 in regulating expression of genes that maintain podocyte integrity (By similarity).
Promotes cell growth inhibition by stopping the cell cycle in the G1 phase through TGFB1-mediated signals (PubMed:12408963).
Involved in epithelial-mesenchymal transition (EMT) induction by increasing cell proliferation, migration and invasion (PubMed:20406990, PubMed:22991501).
Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (By similarity).
Plays a role in the gene regulatory network essential for epidermal keratinocyte terminal differentiation (PubMed:27907090).
Essential developmental transcriptional factor required for mesoderm-derived tissues, such as the somites, skin, bone and cartilage. Positively regulates CXCL12 and stem cell factor expression in bone marrow mesenchymal progenitor cells, and hence plays a role in the development and maintenance of mesenchymal niches for haematopoietic stem and progenitor cells (HSPC). Plays a role in corneal transparency by preventing both blood vessel and lymphatic vessel growth during embryonic development in a VEGF-dependent manner. Involved in chemokine CXCL12-induced endothelial cell migration through the control of CXCR4 expression (By similarity).
May function as a tumor suppressor (PubMed:12408963).
By similarity21 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 77 – 168 | Fork-headPROSITE-ProRule annotationAdd BLAST | 92 |
GO - Molecular functioni
- DNA binding Source: UniProtKB
- DNA binding, bending Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription factor binding Source: UniProtKB
- promoter-specific chromatin binding Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II-specific DNA-binding transcription factor binding Source: UniProtKB
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
- sequence-specific DNA binding Source: UniProtKB
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- anatomical structure morphogenesis Source: GO_Central
- angiogenesis Source: UniProtKB-KW
- artery morphogenesis Source: Ensembl
- blood vessel diameter maintenance Source: Ensembl
- blood vessel remodeling Source: Ensembl
- camera-type eye development Source: Ensembl
- cardiac muscle cell proliferation Source: Ensembl
- cell differentiation Source: GO_Central
- cell migration Source: UniProtKB
- cell population proliferation Source: UniProtKB
- cellular response to chemokine Source: UniProtKB
- cellular response to epidermal growth factor stimulus Source: UniProtKB
- cerebellum development Source: UniProtKB
- chemokine-mediated signaling pathway Source: UniProtKB
- collagen fibril organization Source: Ensembl
- embryonic heart tube development Source: Ensembl
- endochondral ossification Source: UniProtKB
- eye development Source: MGI
- germ cell migration Source: Ensembl
- glomerular epithelium development Source: UniProtKB
- glycosaminoglycan metabolic process Source: Ensembl
- heart development Source: MGI
- in utero embryonic development Source: Ensembl
- kidney development Source: UniProtKB
- lacrimal gland development Source: Ensembl
- lymph vessel development Source: Ensembl
- maintenance of lens transparency Source: UniProtKB
- mesenchymal cell development Source: UniProtKB
- negative regulation of angiogenesis Source: UniProtKB
- negative regulation of apoptotic process involved in outflow tract morphogenesis Source: Ensembl
- negative regulation of lymphangiogenesis Source: UniProtKB
- negative regulation of mitotic cell cycle Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- neural crest cell development Source: Ensembl
- Notch signaling pathway Source: Ensembl
- odontogenesis of dentin-containing tooth Source: UniProtKB
- ovarian follicle development Source: Ensembl
- paraxial mesoderm formation Source: Ensembl
- positive regulation of core promoter binding Source: UniProtKB
- positive regulation of DNA binding Source: UniProtKB
- positive regulation of epithelial to mesenchymal transition Source: UniProtKB
- positive regulation of gene expression Source: Ensembl
- positive regulation of hematopoietic progenitor cell differentiation Source: UniProtKB
- positive regulation of hematopoietic stem cell differentiation Source: UniProtKB
- positive regulation of keratinocyte differentiation Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- regulation of organ growth Source: Ensembl
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- somitogenesis Source: Ensembl
- ureteric bud development Source: UniProtKB
- vascular endothelial growth factor receptor signaling pathway Source: Ensembl
- vascular endothelial growth factor signaling pathway Source: UniProtKB
- ventricular cardiac muscle tissue morphogenesis Source: Ensembl
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding, Repressor |
Biological process | Angiogenesis, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q12948 |
SignaLinki | Q12948 |
SIGNORi | Q12948 |
Names & Taxonomyi
Protein namesi | Recommended name: Forkhead box protein C1Alternative name(s): Forkhead-related protein FKHL7 Forkhead-related transcription factor 3 Short name: FREAC-3 |
Gene namesi | Name:FOXC1 Synonyms:FKHL7, FREAC3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3800, FOXC1 |
MIMi | 601090, gene |
neXtProti | NX_Q12948 |
VEuPathDBi | HostDB:ENSG00000054598 |
Subcellular locationi
Nucleus
- Nucleus 13 Publications
Note: Colocalizes with PITX2 isoform 3 in the nucleus at subnuclear chromatine regions (PubMed:16449236). Colocalizes with CBX5 to a heterochromatin-rich region of the nucleus (PubMed:15684392). Colocalizes with GLI2 in the nucleus (By similarity).By similarity2 Publications
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- chromatin Source: NTNU_SB
- heterochromatin Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Axenfeld-Rieger syndrome 3 (RIEG3)20 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058722 | 79 | P → L in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_058723 | 79 | P → R in RIEG3. 1 Publication | 1 | |
Natural variantiVAR_058724 | 79 | P → T in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_007944 | 82 | S → T in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 3 PublicationsCorresponds to variant dbSNP:rs104893953EnsemblClinVar. | 1 | |
Natural variantiVAR_078501 | 85 | A → P in RIEG3; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_058725 | 86 | L → F in RIEG3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 PublicationCorresponds to variant dbSNP:rs886039568EnsemblClinVar. | 1 | |
Natural variantiVAR_007945 | 87 | I → M in RIEG3; loss of protein stability. 2 PublicationsCorresponds to variant dbSNP:rs104893954EnsemblClinVar. | 1 | |
Natural variantiVAR_058726 | 91 | I → S in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_058727 | 91 | I → T in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_007815 | 112 | F → S in ASGD3 and RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 4 PublicationsCorresponds to variant dbSNP:rs104893951EnsemblClinVar. | 1 | |
Natural variantiVAR_058728 | 115 | Y → S in RIEG3. 1 Publication | 1 | |
Natural variantiVAR_007816 | 126 | I → M in ASGD3 and RIEG3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 3 PublicationsCorresponds to variant dbSNP:rs104893958EnsemblClinVar. | 1 | |
Natural variantiVAR_078503 | 126 | I → S in RIEG3; hypomorphic mutation; decreased protein abundance; decreased protein stability; changed post-translational phosphorylation; decreased location at the nucleus; novel location at the cytoplasm; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 PublicationCorresponds to variant dbSNP:rs483352810EnsemblClinVar. | 1 | |
Natural variantiVAR_058729 | 127 | R → H in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 3 PublicationsCorresponds to variant dbSNP:rs1085307884EnsemblClinVar. | 1 | |
Natural variantiVAR_078504 | 127 | R → L in RIEG3. 1 PublicationCorresponds to variant dbSNP:rs1085307884EnsemblClinVar. | 1 | |
Natural variantiVAR_078505 | 128 | H → R in RIEG3; no effect on protein abundance; increased protein stability; decreased location at nucleus; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_058730 | 130 | L → F in RIEG3; no effect on protein abundance; changed post-translational phosphorylation; novel location at aggresome, aggregation correspond to microtubule-dependent inclusion bodies; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 2 PublicationsCorresponds to variant dbSNP:rs121909338EnsemblClinVar. | 1 | |
Natural variantiVAR_007817 | 131 | S → L in RIEG3 and ASGD3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 5 PublicationsCorresponds to variant dbSNP:rs104893957EnsemblClinVar. | 1 | |
Natural variantiVAR_078507 | 135 | C → Y in RIEG3; decreased protein abundance; decreased protein stability; decreased location at nucleus; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_058731 | 149 | G → D in RIEG3. 1 Publication | 1 | |
Natural variantiVAR_018150 | 161 | M → K in RIEG3 and ASGD3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 4 Publications | 1 | |
Natural variantiVAR_058732 | 161 | M → V in RIEG3; no effect on protein abundance; no effect on protein stability; no effect on location at nucleus; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 2 Publications | 1 | |
Natural variantiVAR_058733 | 165 | G → R in RIEG3; no change in location at the nucleus; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_058734 | 169 | R → P in RIEG3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_078510 | 170 | R → W in RIEG3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1581373890EnsemblClinVar. | 1 |
Anterior segment dysgenesis 3 (ASGD3)6 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078502 | 109 | M → V in ASGD3. 1 PublicationCorresponds to variant dbSNP:rs917382067Ensembl. | 1 | |
Natural variantiVAR_007815 | 112 | F → S in ASGD3 and RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 4 PublicationsCorresponds to variant dbSNP:rs104893951EnsemblClinVar. | 1 | |
Natural variantiVAR_007816 | 126 | I → M in ASGD3 and RIEG3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 3 PublicationsCorresponds to variant dbSNP:rs104893958EnsemblClinVar. | 1 | |
Natural variantiVAR_007817 | 131 | S → L in RIEG3 and ASGD3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 5 PublicationsCorresponds to variant dbSNP:rs104893957EnsemblClinVar. | 1 | |
Natural variantiVAR_078506 | 131 | S → W in ASGD3. 1 Publication | 1 | |
Natural variantiVAR_078508 | 138 | K → E in ASGD3. 1 Publication | 1 | |
Natural variantiVAR_078509 | 152 | W → G in ASGD3; no change in protein abundance; changed post-translational phosphorylation; changed protein structure; decreased location at the nucleus; novel location at the cytoplasm; increased protein aggregation, aggregation do not correspond to microtubule-dependent inclusion bodies; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_018150 | 161 | M → K in RIEG3 and ASGD3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 4 Publications | 1 | |
Natural variantiVAR_078511 | 297 | P → S in ASGD3; no effect on protein abundance; increased protein stability; no effect on nuclear location; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 PublicationCorresponds to variant dbSNP:rs79691946EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 68 | T → A: No effect on protein stability. No effect on transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 79 | P → A: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 79 | P → E: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 79 | P → K: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 86 | L → A: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 86 | L → E: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 86 | L → K: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 86 | L → P: Severely disrupts the protein function. 1 Publication | 1 | |
Mutagenesisi | 87 | I → A, E or K: Loss of protein stability. 1 Publication | 1 | |
Mutagenesisi | 91 | I → A: Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 91 | I → E: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 91 | I → K: Decreased nuclear localization. No effect on DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 126 | I → A: Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 126 | I → E: Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 126 | I → K: Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 127 | R → A: Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 127 | R → E: Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 127 | R → K: Decreased nuclear localization. Decreased DNA-binding activity. Decreased transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 241 | S → A: Decreased protein stability. No effect on transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 259 | S → A: No effect on protein stability. No effect on transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 272 | S → A: Decreased protein stability. Decreased transcriptional activity. 1 Publication | 1 |
Keywords - Diseasei
Deafness, Disease variant, Peters anomalyOrganism-specific databases
DisGeNETi | 2296 |
MalaCardsi | FOXC1 |
MIMi | 601631, phenotype 602482, phenotype |
OpenTargetsi | ENSG00000054598 |
Orphaneti | 98978, Axenfeld anomaly 782, Axenfeld-Rieger syndrome 250923, Isolated aniridia 708, Peters anomaly 91483, Rieger anomaly |
PharmGKBi | PA28217 |
Miscellaneous databases
Pharosi | Q12948, Tbio |
Genetic variation databases
BioMutai | FOXC1 |
DMDMi | 13638267 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000091806 | 1 – 553 | Forkhead box protein C1Add BLAST | 553 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 235 | PhosphoserineCombined sources | 1 | |
Modified residuei | 241 | PhosphoserineCombined sources | 1 | |
Modified residuei | 272 | Phosphoserine1 Publication | 1 | |
Modified residuei | 320 | PhosphoserineCombined sources | 1 | |
Modified residuei | 521 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q12948 |
jPOSTi | Q12948 |
MassIVEi | Q12948 |
PaxDbi | Q12948 |
PeptideAtlasi | Q12948 |
PRIDEi | Q12948 |
ProteomicsDBi | 59043 |
PTM databases
GlyGeni | Q12948, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q12948 |
PhosphoSitePlusi | Q12948 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000054598, Expressed in parotid gland and 234 other tissues |
ExpressionAtlasi | Q12948, baseline and differential |
Genevisiblei | Q12948, HS |
Organism-specific databases
HPAi | ENSG00000054598, Tissue enriched (salivary) |
Interactioni
Subunit structurei
Monomer.
Interacts with C1QBP (PubMed:18676636).
Interacts (via N-terminus) with GLI2 (via C-terminal internal region); this interaction is direct and increases GLI2 DNA-binding and transcriptional activity through a smoothened (SMO)-independent Hedgehog (Hh) signaling pathway (PubMed:26565916).
Interacts (via C-terminus domain) with PITX2 isoform 3 (via homeobox domain) (PubMed:16449236).
Interacts with FLNA and PBX1 (PubMed:15684392).
4 PublicationsBinary interactionsi
Q12948
GO - Molecular functioni
- DNA-binding transcription factor binding Source: UniProtKB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 108585, 72 interactors |
IntActi | Q12948, 76 interactors |
MINTi | Q12948 |
STRINGi | 9606.ENSP00000370256 |
Miscellaneous databases
RNActi | Q12948, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 51 | Required for transcriptional activation1 PublicationAdd BLAST | 51 | |
Regioni | 173 – 310 | DisorderedSequence analysisAdd BLAST | 138 | |
Regioni | 215 – 366 | Required for transcriptional inhibition1 PublicationAdd BLAST | 152 | |
Regioni | 356 – 387 | DisorderedSequence analysisAdd BLAST | 32 | |
Regioni | 414 – 465 | DisorderedSequence analysisAdd BLAST | 52 | |
Regioni | 466 – 553 | Required for transcriptional activation1 PublicationAdd BLAST | 88 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 78 – 93 | Nuclear localization signal 1 (NLS 1)1 PublicationAdd BLAST | 16 | |
Motifi | 168 – 176 | Nuclear localization signal 2 (NLS 2)1 Publication | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 178 – 194 | Basic and acidic residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 195 – 221 | Pro residuesSequence analysisAdd BLAST | 27 | |
Compositional biasi | 257 – 278 | Polar residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 288 – 302 | Pro residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 356 – 375 | Polar residuesSequence analysisAdd BLAST | 20 | |
Compositional biasi | 433 – 447 | Polar residuesSequence analysisAdd BLAST | 15 |
Phylogenomic databases
eggNOGi | KOG2294, Eukaryota |
GeneTreei | ENSGT00940000162303 |
HOGENOMi | CLU_035722_3_0_1 |
InParanoidi | Q12948 |
OMAi | HCNLQAM |
OrthoDBi | 1270467at2759 |
PhylomeDBi | Q12948 |
TreeFami | TF316127 |
Family and domain databases
CDDi | cd00059, FH, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR001766, Fork_head_dom IPR033067, FoxC1 IPR018122, TF_fork_head_CS_1 IPR030456, TF_fork_head_CS_2 IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR11829:SF68, PTHR11829:SF68, 1 hit |
Pfami | View protein in Pfam PF00250, Forkhead, 1 hit |
PRINTSi | PR00053, FORKHEAD |
SMARTi | View protein in SMART SM00339, FH, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00657, FORK_HEAD_1, 1 hit PS00658, FORK_HEAD_2, 1 hit PS50039, FORK_HEAD_3, 1 hit |
i Sequence
Sequence statusi: Complete.
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 70 – 77 | QPQPKDMV → RSRSPRHG in AAK13575 (PubMed:8499623).Curated | 8 | |
Sequence conflicti | 101 | L → Q in AAK13575 (PubMed:8499623).Curated | 1 | |
Sequence conflicti | 180 | V → L in AAC72915 (PubMed:9792859).Curated | 1 | |
Sequence conflicti | 199 – 202 | RQPP → ASPR in AAC72915 (PubMed:9792859).Curated | 4 | |
Sequence conflicti | 426 | D → N in AAC18081 (PubMed:9620769).Curated | 1 | |
Sequence conflicti | 426 | D → N in AAP15181 (PubMed:12592227).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_058722 | 79 | P → L in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_058723 | 79 | P → R in RIEG3. 1 Publication | 1 | |
Natural variantiVAR_058724 | 79 | P → T in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_007944 | 82 | S → T in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 3 PublicationsCorresponds to variant dbSNP:rs104893953EnsemblClinVar. | 1 | |
Natural variantiVAR_078501 | 85 | A → P in RIEG3; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_058725 | 86 | L → F in RIEG3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 PublicationCorresponds to variant dbSNP:rs886039568EnsemblClinVar. | 1 | |
Natural variantiVAR_007945 | 87 | I → M in RIEG3; loss of protein stability. 2 PublicationsCorresponds to variant dbSNP:rs104893954EnsemblClinVar. | 1 | |
Natural variantiVAR_058726 | 91 | I → S in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_058727 | 91 | I → T in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity; no change on DNA bending activity. 2 Publications | 1 | |
Natural variantiVAR_078502 | 109 | M → V in ASGD3. 1 PublicationCorresponds to variant dbSNP:rs917382067Ensembl. | 1 | |
Natural variantiVAR_007815 | 112 | F → S in ASGD3 and RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 4 PublicationsCorresponds to variant dbSNP:rs104893951EnsemblClinVar. | 1 | |
Natural variantiVAR_058728 | 115 | Y → S in RIEG3. 1 Publication | 1 | |
Natural variantiVAR_007816 | 126 | I → M in ASGD3 and RIEG3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 3 PublicationsCorresponds to variant dbSNP:rs104893958EnsemblClinVar. | 1 | |
Natural variantiVAR_078503 | 126 | I → S in RIEG3; hypomorphic mutation; decreased protein abundance; decreased protein stability; changed post-translational phosphorylation; decreased location at the nucleus; novel location at the cytoplasm; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 PublicationCorresponds to variant dbSNP:rs483352810EnsemblClinVar. | 1 | |
Natural variantiVAR_058729 | 127 | R → H in RIEG3; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 3 PublicationsCorresponds to variant dbSNP:rs1085307884EnsemblClinVar. | 1 | |
Natural variantiVAR_078504 | 127 | R → L in RIEG3. 1 PublicationCorresponds to variant dbSNP:rs1085307884EnsemblClinVar. | 1 | |
Natural variantiVAR_078505 | 128 | H → R in RIEG3; no effect on protein abundance; increased protein stability; decreased location at nucleus; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_058730 | 130 | L → F in RIEG3; no effect on protein abundance; changed post-translational phosphorylation; novel location at aggresome, aggregation correspond to microtubule-dependent inclusion bodies; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 2 PublicationsCorresponds to variant dbSNP:rs121909338EnsemblClinVar. | 1 | |
Natural variantiVAR_007817 | 131 | S → L in RIEG3 and ASGD3; with glaucoma; decreased location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 5 PublicationsCorresponds to variant dbSNP:rs104893957EnsemblClinVar. | 1 | |
Natural variantiVAR_078506 | 131 | S → W in ASGD3. 1 Publication | 1 | |
Natural variantiVAR_078507 | 135 | C → Y in RIEG3; decreased protein abundance; decreased protein stability; decreased location at nucleus; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_078508 | 138 | K → E in ASGD3. 1 Publication | 1 | |
Natural variantiVAR_058731 | 149 | G → D in RIEG3. 1 Publication | 1 | |
Natural variantiVAR_078509 | 152 | W → G in ASGD3; no change in protein abundance; changed post-translational phosphorylation; changed protein structure; decreased location at the nucleus; novel location at the cytoplasm; increased protein aggregation, aggregation do not correspond to microtubule-dependent inclusion bodies; loss of transcription regulatory region DNA binding; loss of sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_018150 | 161 | M → K in RIEG3 and ASGD3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 4 Publications | 1 | |
Natural variantiVAR_058732 | 161 | M → V in RIEG3; no effect on protein abundance; no effect on protein stability; no effect on location at nucleus; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 2 Publications | 1 | |
Natural variantiVAR_058733 | 165 | G → R in RIEG3; no change in location at the nucleus; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_058734 | 169 | R → P in RIEG3; no change in location at the nucleus; decreased transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 Publication | 1 | |
Natural variantiVAR_078510 | 170 | R → W in RIEG3; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1581373890EnsemblClinVar. | 1 | |
Natural variantiVAR_078511 | 297 | P → S in ASGD3; no effect on protein abundance; increased protein stability; no effect on nuclear location; no effect on transcription regulatory region DNA binding; decreased sequence-specific DNA binding transcription factor activity. 1 PublicationCorresponds to variant dbSNP:rs79691946EnsemblClinVar. | 1 | |
Natural variantiVAR_078512 | 368 | T → N No effect on protein abundance; no effect on protein stability; no effect on nuclear location; no effect on transcription regulatory region DNA binding; no effect on sequence-specific DNA binding transcription factor activity. 1 Publication | 1 |
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 No translation available. L12143 mRNA Translation: AAK13575.1 U13221 mRNA Translation: AAA92038.1 |
CCDSi | CCDS4473.1 |
PIRi | S51626 |
RefSeqi | NP_001444.2, NM_001453.2 |
Genome annotation databases
Ensembli | ENST00000645831.2; ENSP00000493906.1; ENSG00000054598.9 |
GeneIDi | 2296 |
KEGGi | hsa:2296 |
MANE-Selecti | ENST00000645831.2; ENSP00000493906.1; NM_001453.3; NP_001444.2 |
Similar proteinsi
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 No translation available. L12143 mRNA Translation: AAK13575.1 U13221 mRNA Translation: AAA92038.1 |
CCDSi | CCDS4473.1 |
PIRi | S51626 |
RefSeqi | NP_001444.2, NM_001453.2 |
3D structure databases
AlphaFoldDBi | Q12948 |
SMRi | Q12948 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108585, 72 interactors |
IntActi | Q12948, 76 interactors |
MINTi | Q12948 |
STRINGi | 9606.ENSP00000370256 |
PTM databases
GlyGeni | Q12948, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q12948 |
PhosphoSitePlusi | Q12948 |
Genetic variation databases
BioMutai | FOXC1 |
DMDMi | 13638267 |
Proteomic databases
EPDi | Q12948 |
jPOSTi | Q12948 |
MassIVEi | Q12948 |
PaxDbi | Q12948 |
PeptideAtlasi | Q12948 |
PRIDEi | Q12948 |
ProteomicsDBi | 59043 |
Protocols and materials databases
Antibodypediai | 9213, 428 antibodies from 41 providers |
DNASUi | 2296 |
Genome annotation databases
Ensembli | ENST00000645831.2; ENSP00000493906.1; ENSG00000054598.9 |
GeneIDi | 2296 |
KEGGi | hsa:2296 |
MANE-Selecti | ENST00000645831.2; ENSP00000493906.1; NM_001453.3; NP_001444.2 |
Organism-specific databases
CTDi | 2296 |
DisGeNETi | 2296 |
GeneCardsi | FOXC1 |
HGNCi | HGNC:3800, FOXC1 |
HPAi | ENSG00000054598, Tissue enriched (salivary) |
MalaCardsi | FOXC1 |
MIMi | 601090, gene 601631, phenotype 602482, phenotype |
neXtProti | NX_Q12948 |
OpenTargetsi | ENSG00000054598 |
Orphaneti | 98978, Axenfeld anomaly 782, Axenfeld-Rieger syndrome 250923, Isolated aniridia 708, Peters anomaly 91483, Rieger anomaly |
PharmGKBi | PA28217 |
VEuPathDBi | HostDB:ENSG00000054598 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2294, Eukaryota |
GeneTreei | ENSGT00940000162303 |
HOGENOMi | CLU_035722_3_0_1 |
InParanoidi | Q12948 |
OMAi | HCNLQAM |
OrthoDBi | 1270467at2759 |
PhylomeDBi | Q12948 |
TreeFami | TF316127 |
Enzyme and pathway databases
PathwayCommonsi | Q12948 |
SignaLinki | Q12948 |
SIGNORi | Q12948 |
Miscellaneous databases
BioGRID-ORCSi | 2296, 26 hits in 1092 CRISPR screens |
ChiTaRSi | FOXC1, human |
GeneWikii | Forkhead_box_C1 |
GenomeRNAii | 2296 |
Pharosi | Q12948, Tbio |
PROi | PR:Q12948 |
RNActi | Q12948, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000054598, Expressed in parotid gland and 234 other tissues |
ExpressionAtlasi | Q12948, baseline and differential |
Genevisiblei | Q12948, HS |
Family and domain databases
CDDi | cd00059, FH, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR001766, Fork_head_dom IPR033067, FoxC1 IPR018122, TF_fork_head_CS_1 IPR030456, TF_fork_head_CS_2 IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR11829:SF68, PTHR11829:SF68, 1 hit |
Pfami | View protein in Pfam PF00250, Forkhead, 1 hit |
PRINTSi | PR00053, FORKHEAD |
SMARTi | View protein in SMART SM00339, FH, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit |
PROSITEi | View protein in PROSITE PS00657, FORK_HEAD_1, 1 hit PS00658, FORK_HEAD_2, 1 hit PS50039, FORK_HEAD_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FOXC1_HUMAN | |
Accessioni | Q12948Primary (citable) accession number: Q12948 Secondary accession number(s): Q86UP7 Q9UP06 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | April 27, 2001 | |
Last modified: | May 25, 2022 | |
This is version 206 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot