Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q99958

- FOXC2_HUMAN

UniProt

Q99958 - FOXC2_HUMAN

Protein

Forkhead box protein C2

Gene

FOXC2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Transcriptional activator. Might be involved in the formation of special mesenchymal tissues.1 Publication

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi71 – 16292Fork-headPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. chromatin DNA binding Source: UniProtKB
    2. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    3. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
    4. sequence-specific DNA binding Source: UniProtKB
    5. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    6. transcription regulatory region DNA binding Source: BHF-UCL

    GO - Biological processi

    1. artery morphogenesis Source: Ensembl
    2. blood vessel remodeling Source: Ensembl
    3. camera-type eye development Source: Ensembl
    4. cardiac muscle cell proliferation Source: Ensembl
    5. collagen fibril organization Source: Ensembl
    6. embryonic heart tube development Source: Ensembl
    7. embryonic viscerocranium morphogenesis Source: Ensembl
    8. glomerular endothelium development Source: Ensembl
    9. glomerular mesangial cell development Source: Ensembl
    10. glomerular visceral epithelial cell differentiation Source: Ensembl
    11. heart development Source: DFLAT
    12. insulin receptor signaling pathway Source: UniProtKB
    13. lymphangiogenesis Source: UniProtKB
    14. mesoderm development Source: UniProtKB
    15. metanephros development Source: Ensembl
    16. negative regulation of apoptotic process involved in outflow tract morphogenesis Source: Ensembl
    17. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    18. neural crest cell development Source: Ensembl
    19. Notch signaling pathway Source: Ensembl
    20. ossification Source: Ensembl
    21. paraxial mesodermal cell fate commitment Source: Ensembl
    22. patterning of blood vessels Source: Ensembl
    23. positive regulation of cell adhesion mediated by integrin Source: BHF-UCL
    24. positive regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
    25. positive regulation of endothelial cell migration Source: BHF-UCL
    26. positive regulation of transcription, DNA-templated Source: UniProtKB
    27. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    28. positive regulation of vascular wound healing Source: BHF-UCL
    29. regulation of blood vessel size Source: Ensembl
    30. regulation of organ growth Source: Ensembl
    31. response to hormone Source: UniProtKB
    32. somitogenesis Source: Ensembl
    33. ureteric bud development Source: Ensembl
    34. vascular endothelial growth factor receptor signaling pathway Source: Ensembl
    35. ventricular cardiac muscle tissue morphogenesis Source: Ensembl

    Keywords - Molecular functioni

    Activator, Developmental protein

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    SignaLinkiQ99958.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:FOXC2
    Synonyms:FKHL14, MFH1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:3801. FOXC2.

    Subcellular locationi

    Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti125 – 1251S → L in LYD. 1 Publication
    VAR_018418

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi153200. phenotype.
    153300. phenotype.
    153400. phenotype.
    602402. gene+phenotype.
    Orphaneti33001. Lymphedema - distichiasis.
    PharmGKBiPA28218.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 501501Forkhead box protein C2PRO_0000091808Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei215 – 2151Phosphoserine1 Publication
    Modified residuei219 – 2191Phosphoserine3 Publications
    Modified residuei232 – 2321Phosphoserine3 Publications
    Modified residuei235 – 2351Phosphoserine1 Publication
    Modified residuei240 – 2401Phosphoserine6 Publications
    Modified residuei247 – 2471Phosphothreonine1 Publication
    Modified residuei251 – 2511Phosphoserine1 Publication
    Modified residuei281 – 2811Phosphoserine1 Publication
    Modified residuei288 – 2881Phosphoserine2 Publications
    Modified residuei367 – 3671Phosphoserine1 Publication

    Post-translational modificationi

    Phosphorylation regulates FOXC2 transcriptional activity by promoting its recruitment to chromatin.7 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ99958.
    PaxDbiQ99958.
    PRIDEiQ99958.

    PTM databases

    PhosphoSiteiQ99958.

    Expressioni

    Gene expression databases

    ArrayExpressiQ99958.
    BgeeiQ99958.
    CleanExiHS_FOXC2.
    GenevestigatoriQ99958.

    Interactioni

    Protein-protein interaction databases

    BioGridi108592. 2 interactions.
    IntActiQ99958. 2 interactions.
    STRINGi9606.ENSP00000326371.

    Structurei

    Secondary structure

    1
    501
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi77 – 8610
    Beta strandi89 – 935
    Helixi95 – 10511
    Helixi108 – 1114
    Helixi116 – 12611
    Beta strandi128 – 1325
    Beta strandi146 – 1483

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1D5VNMR-A70-162[»]
    ProteinModelPortaliQ99958.
    SMRiQ99958. Positions 70-162.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ99958.

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi163 – 1675Poly-Arg
    Compositional biasi387 – 39610His-rich
    Compositional biasi397 – 41418Pro-richAdd
    BLAST

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG5025.
    HOGENOMiHOG000007939.
    HOVERGENiHBG051640.
    InParanoidiQ99958.
    KOiK09396.
    OMAiLNHLPGH.
    OrthoDBiEOG7C8GHD.
    PhylomeDBiQ99958.
    TreeFamiTF316127.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF00250. Fork_head. 1 hit.
    [Graphical view]
    PRINTSiPR00053. FORKHEAD.
    SMARTiSM00339. FH. 1 hit.
    [Graphical view]
    PROSITEiPS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q99958-1 [UniParc]FASTAAdd to Basket

    « Hide

    MQARYSVSDP NALGVVPYLS EQNYYRAAGS YGGMASPMGV YSGHPEQYSA    50
    GMGRSYAPYH HHQPAAPKDL VKPPYSYIAL ITMAIQNAPE KKITLNGIYQ 100
    FIMDRFPFYR ENKQGWQNSI RHNLSLNECF VKVPRDDKKP GKGSYWTLDP 150
    DSYNMFENGS FLRRRRRFKK KDVSKEKEER AHLKEPPPAA SKGAPATPHL 200
    ADAPKEAEKK VVIKSEAASP ALPVITKVET LSPESALQGS PRSAASTPAG 250
    SPDGSLPEHH AAAPNGLPGF SVENIMTLRT SPPGGELSPG AGRAGLVVPP 300
    LALPYAAAPP AAYGQPCAQG LEAGAAGGYQ CSMRAMSLYT GAERPAHMCV 350
    PPALDEALSD HPSGPTSPLS ALNLAAGQEG ALAATGHHHQ HHGHHHPQAP 400
    PPPPAPQPQP TPQPGAAAAQ AASWYLNHSG DLNHLPGHTF AAQQQTFPNV 450
    REMFNSHRLG IENSTLGESQ VSGNASCQLP YRSTPPLYRH AAPYSYDCTK 500
    Y 501
    Length:501
    Mass (Da):53,719
    Last modified:May 1, 1997 - v1
    Checksum:iF66513878EDC3A87
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti125 – 1251S → L in LYD. 1 Publication
    VAR_018418
    Natural varianti191 – 1911S → F.1 Publication
    Corresponds to variant rs78018668 [ dbSNP | Ensembl ].
    VAR_060950

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y08223 Genomic DNA. Translation: CAA69400.1.
    GQ282998 Genomic DNA. Translation: ACS83751.1.
    BC113437 mRNA. Translation: AAI13438.1.
    BC113439 mRNA. Translation: AAI13440.1.
    CCDSiCCDS10958.1.
    RefSeqiNP_005242.1. NM_005251.2.
    UniGeneiHs.436448.

    Genome annotation databases

    EnsembliENST00000320354; ENSP00000326371; ENSG00000176692.
    GeneIDi2303.
    KEGGihsa:2303.
    UCSCiuc002fjq.3. human.

    Polymorphism databases

    DMDMi3024149.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y08223 Genomic DNA. Translation: CAA69400.1 .
    GQ282998 Genomic DNA. Translation: ACS83751.1 .
    BC113437 mRNA. Translation: AAI13438.1 .
    BC113439 mRNA. Translation: AAI13440.1 .
    CCDSi CCDS10958.1.
    RefSeqi NP_005242.1. NM_005251.2.
    UniGenei Hs.436448.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1D5V NMR - A 70-162 [» ]
    ProteinModelPortali Q99958.
    SMRi Q99958. Positions 70-162.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108592. 2 interactions.
    IntActi Q99958. 2 interactions.
    STRINGi 9606.ENSP00000326371.

    PTM databases

    PhosphoSitei Q99958.

    Polymorphism databases

    DMDMi 3024149.

    Proteomic databases

    MaxQBi Q99958.
    PaxDbi Q99958.
    PRIDEi Q99958.

    Protocols and materials databases

    DNASUi 2303.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000320354 ; ENSP00000326371 ; ENSG00000176692 .
    GeneIDi 2303.
    KEGGi hsa:2303.
    UCSCi uc002fjq.3. human.

    Organism-specific databases

    CTDi 2303.
    GeneCardsi GC16P086600.
    GeneReviewsi FOXC2.
    HGNCi HGNC:3801. FOXC2.
    MIMi 153200. phenotype.
    153300. phenotype.
    153400. phenotype.
    602402. gene+phenotype.
    neXtProti NX_Q99958.
    Orphaneti 33001. Lymphedema - distichiasis.
    PharmGKBi PA28218.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5025.
    HOGENOMi HOG000007939.
    HOVERGENi HBG051640.
    InParanoidi Q99958.
    KOi K09396.
    OMAi LNHLPGH.
    OrthoDBi EOG7C8GHD.
    PhylomeDBi Q99958.
    TreeFami TF316127.

    Enzyme and pathway databases

    SignaLinki Q99958.

    Miscellaneous databases

    EvolutionaryTracei Q99958.
    GeneWikii FOXC2.
    GenomeRNAii 2303.
    NextBioi 9351.
    PROi Q99958.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q99958.
    Bgeei Q99958.
    CleanExi HS_FOXC2.
    Genevestigatori Q99958.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF00250. Fork_head. 1 hit.
    [Graphical view ]
    PRINTSi PR00053. FORKHEAD.
    SMARTi SM00339. FH. 1 hit.
    [Graphical view ]
    PROSITEi PS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-219; SER-232; SER-240 AND SER-288, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    10. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. "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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. "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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-219; SER-232; SER-240; THR-247; SER-251; SER-281; SER-288 AND SER-367, IDENTIFICATION BY MASS SPECTROMETRY.
    14. "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.
    15. "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.

    Entry informationi

    Entry nameiFOXC2_HUMAN
    AccessioniPrimary (citable) accession number: Q99958
    Secondary accession number(s): C6KMR9, Q14DA6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 141 of the entry and version 1 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3