Reviewed,
UniProtKB/Swiss-Prot Q99958 (FOXC2_HUMAN)
Last modified
July 7, 2009.
Version 85.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Forkhead box protein C2 Alternative name(s): Forkhead-related protein FKHL14 Transcription factor FKH-14 Mesenchyme fork head protein 1 Short name=MFH-1 protein | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 501 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Transcriptional activator. Might be involved in the formation of special mesenchymal tissues. Ref.1 |
| Subcellular location | Nucleus Probable. |
| Involvement in disease | Defects in FOXC2 are the cause of lymphedema hereditary type 2 (LYH2) [MIM:153200]; also known as Meige lymphedema. Hereditary lymphedema is a chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections, and physical impairment. Ref.3 Defects in FOXC2 are a cause of lymphedema-yellow nails (LYYN) [MIM:153300]. LYYN is characterized by yellow, dystrophic, thick and slowly growing nails, associated with lymphedema and respiratory involvement. Lymphedema occurs more often in the lower limbs. It can appear at birth or later in life. Onset generally follows the onset of ungual abnormalities. Defects in FOXC2 are a cause of lymphedema-distichiasis syndrome (LYD) [MIM:153400]. LYD is characterized by primary limb lymphedema usually starting at puberty (but in some cases later or at birth) and associated with distichiasis (double rows of eyelashes, with extra eyelashes growing from the Meibomian gland orifices). Ref.11 |
| Sequence similarities | Contains 1 fork-head DNA-binding domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Nucleus |
| Disease | Disease mutation |
| Ligand | DNA-binding |
| Molecular function | Activator Developmental protein |
| PTM | Phosphoprotein |
| Technical term | 3D-structure Complete proteome |
| Gene Ontology (GO) | |
| Biological process | insulin receptor signaling pathway Inferred from direct assay. Source: UniProtKB lymphangiogenesisInferred from mutant phenotype. Source: UniProtKB transcriptionInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | nucleus Ref.1 Inferred from direct assay. Source: UniProtKB |
| Molecular function | chromatin DNA binding Inferred from direct assay. Source: UniProtKB sequence-specific DNA bindingInferred from direct assay. Source: UniProtKB transcription activator activity Ref.1Inferred from direct assay. Source: UniProtKB |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||
Molecule processing | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 501 | 501 | Forkhead box protein C2 | PRO_0000091808 | |||||||||||||||||||
Regions | |||||||||||||||||||||||
| DNA binding | 71 – 162 | 92 | Fork-head | ||||||||||||||||||||
| Compositional bias | 163 – 167 | 5 | Poly-Arg | ||||||||||||||||||||
| Compositional bias | 387 – 396 | 10 | His-rich | ||||||||||||||||||||
| Compositional bias | 397 – 421 | 25 | Ala/Pro-rich | ||||||||||||||||||||
| Compositional bias | 400 – 408 | 9 | Poly-Pro | ||||||||||||||||||||
| Compositional bias | 416 – 422 | 7 | Poly-Ala | ||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||
| Modified residue | 36 | 1 | Phosphoserine Ref.9 | ||||||||||||||||||||
| Modified residue | 215 | 1 | Phosphoserine Ref.9 | ||||||||||||||||||||
| Modified residue | 219 | 1 | Phosphoserine Ref.9 Ref.6 Ref.8 | ||||||||||||||||||||
| Modified residue | 232 | 1 | Phosphoserine Ref.9 Ref.5 Ref.7 | ||||||||||||||||||||
| Modified residue | 235 | 1 | Phosphoserine Ref.7 | ||||||||||||||||||||
| Modified residue | 240 | 1 | Phosphoserine Ref.9 Ref.5 Ref.7 | ||||||||||||||||||||
| Modified residue | 281 | 1 | Phosphoserine Ref.9 Ref.7 | ||||||||||||||||||||
| Modified residue | 288 | 1 | Phosphoserine Ref.9 | ||||||||||||||||||||
Natural variations | |||||||||||||||||||||||
| Natural variant | 125 | 1 | S → L in LYD. Ref.11 | VAR_018418 | |||||||||||||||||||
Secondary structure | |||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||
| Helix | 77 – 86 | 10 | |||||||||||||||||||||
| Beta strand | 89 – 93 | 5 | |||||||||||||||||||||
| Helix | 95 – 105 | 11 | |||||||||||||||||||||
| Helix | 108 – 111 | 4 | |||||||||||||||||||||
| Helix | 116 – 126 | 11 | |||||||||||||||||||||
| Beta strand | 128 – 132 | 5 | |||||||||||||||||||||
| Beta strand | 146 – 148 | 3 | |||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures." Miura N., Iida K., Kakinuma H., Yang X.-L., Sugiyama T. Genomics 41:489-492(1997) [PubMed: 9169153] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION. |
| [2] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [3] | "Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome." Fang J., Dagenais S.L., Erickson R.P., Arlt M.F., Glynn M.W., Gorski J.L., Seaver L.H., Glover T.W. Am. J. Hum. Genet. 67:1382-1388(2000) [PubMed: 11078474] [Abstract] Cited for: INVOLVEMENT IN LYH2. |
| [4] | "Truncating mutations in FOXC2 cause multiple lymphedema syndromes." Finegold D.N., Kimak M.A., Lawrence E.C., Levinson K.L., Cherniske E.M., Pober B.R., Dunlap J.W., Ferrell R.E. Hum. Mol. Genet. 10:1185-1189(2001) [PubMed: 11371511] [Abstract] Cited for: INVOLVEMENT IN LYMPHEDEMA SYNDROMES. |
| [5] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232 AND SER-240, MASS SPECTROMETRY. Tissue: Epithelium. |
| [6] | "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, MASS SPECTROMETRY. Tissue: Epithelium. |
| [7] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232; SER-235; SER-240 AND SER-281, MASS SPECTROMETRY. |
| [8] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, MASS SPECTROMETRY. |
| [9] | "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-36; SER-215; SER-219; SER-232; SER-240; SER-281 AND SER-288, MASS SPECTROMETRY. |
| [10] | "Solution structure and dynamics of the DNA-binding domain of the adipocyte-transcription factor FREAC-11." van Dongen M.J., Cederberg A., Carlsson P., Enerback S., Wikstrom M. J. Mol. Biol. 296:351-359(2000) [PubMed: 10669593] [Abstract] Cited for: STRUCTURE BY NMR OF 70-162. |
| [11] | "Analysis of lymphoedema-distichiasis families for FOXC2 mutations reveals small insertions and deletions throughout the gene." Bell R., Brice G., Child A.H., Murday V.A., Mansour S., Sandy C.J., Collin J.R.O., Brady A.F., Callen D.F., Burnand K., Mortimer P., Jeffery S. Hum. Genet. 108:546-551(2001) [PubMed: 11499682] [Abstract] Cited for: VARIANT LYD LEU-125. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y08223 Genomic DNA. Translation: CAA69400.1. BC113437 mRNA. Translation: AAI13438.1. BC113439 mRNA. Translation: AAI13440.1. | |||||||||||||
| IPI | IPI00019155. | ||||||||||||
| RefSeq | NP_005242.1. | ||||||||||||
| UniGene | Hs.436448 | ||||||||||||
3D structure databases | |||||||||||||
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| ModBase | Search... | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q99958. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | Q99958. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENSG00000176692. Homo sapiens. [Contig view] | ||||||||||||
| GeneID | 2303. | ||||||||||||
| KEGG | hsa:2303. | ||||||||||||
| UCSC | uc002fjq.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| GeneCards | GC16P085158. | ||||||||||||
| H-InvDB | HIX0038664. | ||||||||||||
| HGNC | HGNC:3801. FOXC2. | ||||||||||||
| MIM | 153200. phenotype. 153300. phenotype. 153400. phenotype. 602402. gene+phenotype. | ||||||||||||
| Orphanet | 33001. Lymphedema - distichiasis. 2419. Lymphedema - ptosis. 662. Yellow nail syndrome. | ||||||||||||
| PharmGKB | PA28218. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| HOGENOM | Q99958. | ||||||||||||
| HOVERGEN | Q99958. | ||||||||||||
| OMA | Q99958. QQTFPNV. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q99958. | ||||||||||||
| Bgee | Q99958. | ||||||||||||
| CleanEx | HS_FOXC2. | ||||||||||||
| GermOnline | ENSG00000176692. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. Wing_hlx_DNA_bd. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit. | ||||||||||||
| 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 | 9351. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | FOXC2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q99958 Secondary accession number(s): Q14DA6 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 16 Human chromosome 16: 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 |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


