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Q99958

- FOXC2_HUMAN

UniProt

Q99958 - FOXC2_HUMAN

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Protein

Forkhead box protein C2

Gene

FOXC2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ99958.
CleanExiHS_FOXC2.
ExpressionAtlasiQ99958. baseline and differential.
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 – 8610Combined sources
Beta strandi89 – 935Combined sources
Helixi95 – 10511Combined sources
Helixi108 – 1114Combined sources
Helixi116 – 12611Combined sources
Beta strandi128 – 1325Combined sources
Beta strandi146 – 1483Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00760000118904.
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

        10         20         30         40         50
MQARYSVSDP NALGVVPYLS EQNYYRAAGS YGGMASPMGV YSGHPEQYSA
60 70 80 90 100
GMGRSYAPYH HHQPAAPKDL VKPPYSYIAL ITMAIQNAPE KKITLNGIYQ
110 120 130 140 150
FIMDRFPFYR ENKQGWQNSI RHNLSLNECF VKVPRDDKKP GKGSYWTLDP
160 170 180 190 200
DSYNMFENGS FLRRRRRFKK KDVSKEKEER AHLKEPPPAA SKGAPATPHL
210 220 230 240 250
ADAPKEAEKK VVIKSEAASP ALPVITKVET LSPESALQGS PRSAASTPAG
260 270 280 290 300
SPDGSLPEHH AAAPNGLPGF SVENIMTLRT SPPGGELSPG AGRAGLVVPP
310 320 330 340 350
LALPYAAAPP AAYGQPCAQG LEAGAAGGYQ CSMRAMSLYT GAERPAHMCV
360 370 380 390 400
PPALDEALSD HPSGPTSPLS ALNLAAGQEG ALAATGHHHQ HHGHHHPQAP
410 420 430 440 450
PPPPAPQPQP TPQPGAAAAQ AASWYLNHSG DLNHLPGHTF AAQQQTFPNV
460 470 480 490 500
REMFNSHRLG IENSTLGESQ VSGNASCQLP YRSTPPLYRH AAPYSYDCTK

Y
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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.
GeneTreei ENSGT00760000118904.
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

Bgeei Q99958.
CleanExi HS_FOXC2.
ExpressionAtlasi Q99958. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 143 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