Q99958 (FOXC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 127.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Forkhead box protein C2 Alternative name(s): Forkhead-related protein FKHL14 Mesenchyme fork head protein 1 Short name=MFH-1 protein Transcription factor FKH-14 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) [Reference 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. |
| 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 | Lymphedema, hereditary, 2 (LMPH2) [MIM:153200]: 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. Lymphedema-yellow nails (LYYN) [MIM:153300]: A disorder 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. Lymphedema-distichiasis (LYD) [MIM:153400]: A disorder 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). Drooping of the upper eyelid (ptosis) is a variable feature of the lymphedema-distichiasis syndrome, occurring in about 30% of patients. |
| Sequence similarities | Contains 1 fork-head DNA-binding domain. |
Ontologies
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 | 215 | 1 | Phosphoserine Ref.9 | ||||||||||||||||||||
| Modified residue | 219 | 1 | Phosphoserine Ref.8 Ref.9 | ||||||||||||||||||||
| Modified residue | 232 | 1 | Phosphoserine Ref.9 Ref.10 | ||||||||||||||||||||
| Modified residue | 235 | 1 | Phosphoserine Ref.7 | ||||||||||||||||||||
| Modified residue | 240 | 1 | Phosphoserine Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 | ||||||||||||||||||||
| Modified residue | 288 | 1 | Phosphoserine Ref.9 | ||||||||||||||||||||
Natural variations | |||||||||||||||||||||||
| Natural variant | 125 | 1 | S → L in LYD. Ref.13 | VAR_018418 | |||||||||||||||||||
| Natural variant | 191 | 1 | S → F. Ref.2 | VAR_060950 | |||||||||||||||||||
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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION. |
| [2] | NIEHS SNPs program Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-191. |
| [3] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [4] | "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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LMPH2. |
| [5] | "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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN LYMPHEDEMA SYNDROMES. |
| [6] | "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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-240, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-235 AND SER-240, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-219; SER-232; SER-240 AND SER-288, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [10] | "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232 AND SER-240, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [11] | "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-240, MASS SPECTROMETRY. |
| [12] | "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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 70-162. |
| [13] | "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] [Europe PMC] [Abstract] Cited for: VARIANT LYD LEU-125. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | Y08223 Genomic DNA. Translation: CAA69400.1. GQ282998 Genomic DNA. Translation: ACS83751.1. BC113437 mRNA. Translation: AAI13438.1. BC113439 mRNA. Translation: AAI13440.1. | ||||||||||||
| IPI | IPI00019155. | ||||||||||||
| RefSeq | NP_005242.1. NM_005251.2. | ||||||||||||
| UniGene | Hs.740701. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | Q99958. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q99958. 1 interaction. | ||||||||||||
| STRING | 9606.ENSP00000326371. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q99958. | ||||||||||||
Polymorphism databases | |||||||||||||
| DMDM | 3024149. | ||||||||||||
Proteomic databases | |||||||||||||
| PaxDb | Q99958. | ||||||||||||
| PRIDE | Q99958. | ||||||||||||
Protocols and materials databases | |||||||||||||
| DNASU | 2303. | ||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000320354; ENSP00000326371; ENSG00000176692. | ||||||||||||
| GeneID | 2303. | ||||||||||||
| KEGG | hsa:2303. | ||||||||||||
| UCSC | uc002fjq.3. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 2303. | ||||||||||||
| GeneCards | GC16P086600. | ||||||||||||
| HGNC | HGNC:3801. FOXC2. | ||||||||||||
| MIM | 153200. phenotype. 153300. phenotype. 153400. phenotype. 602402. gene+phenotype. | ||||||||||||
| neXtProt | NX_Q99958. | ||||||||||||
| Orphanet | 33001. Lymphedema - distichiasis. 662. Yellow nail syndrome. | ||||||||||||
| PharmGKB | PA28218. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | COG5025. | ||||||||||||
| HOGENOM | HOG000007939. | ||||||||||||
| HOVERGEN | HBG051640. | ||||||||||||
| InParanoid | Q99958. | ||||||||||||
| KO | K09396. | ||||||||||||
| OMA | LNHLPGH. | ||||||||||||
| OrthoDB | EOG4MCX19. | ||||||||||||
| PhylomeDB | Q99958. | ||||||||||||
Gene expression databases | |||||||||||||
| Bgee | Q99958. | ||||||||||||
| CleanEx | HS_FOXC2. | ||||||||||||
| Genevestigator | Q99958. | ||||||||||||
| GermOnline | ENSG00000176692. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| Gene3D | 1.10.10.10. 1 hit. | ||||||||||||
| InterPro | IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_DNA-bd_dom. [Graphical view] | ||||||||||||
| Pfam | PF00250. Fork_head. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR00053. FORKHEAD. | ||||||||||||
| 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 | |||||||||||||
| EvolutionaryTrace | Q99958. | ||||||||||||
| GenomeRNAi | 2303. | ||||||||||||
| NextBio | 9351. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | FOXC2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q99958 Secondary accession number(s): C6KMR9, Q14DA6 | ||||||||
| Entry history |
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| Entry status | 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. | ||||||||
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
