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O88621

- FOXH1_MOUSE

UniProt

O88621 - FOXH1_MOUSE

Protein

Forkhead box protein H1

Gene

Foxh1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
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    Functioni

    Transcriptional activator. Recognizes and binds to the DNA sequence 5'-TGT[GT][GT]ATT-3'. Required for induction of the goosecoid (GSC) promoter by TGF-beta or activin signaling. Forms a transcriptionally active complex containing FOXH1/SMAD2/SMAD4 on a site on the GSC promoter called TARE (TGF-beta/activin response element).4 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi64 – 163100Fork-headPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. protein binding Source: IntAct
    3. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: MGI
    4. RNA polymerase II transcription cofactor activity Source: BHF-UCL
    5. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    6. R-SMAD binding Source: BHF-UCL
    7. sequence-specific DNA binding Source: MGI
    8. sequence-specific DNA binding transcription factor activity Source: MGI
    9. SMAD binding Source: UniProtKB
    10. transcription regulatory region DNA binding Source: BHF-UCL

    GO - Biological processi

    1. anterior/posterior pattern specification Source: MGI
    2. aorta morphogenesis Source: BHF-UCL
    3. axial mesoderm development Source: MGI
    4. cardiac right ventricle morphogenesis Source: BHF-UCL
    5. determination of left/right symmetry Source: MGI
    6. embryonic heart tube anterior/posterior pattern specification Source: MGI
    7. heart looping Source: BHF-UCL
    8. negative regulation of androgen receptor activity Source: Ensembl
    9. negative regulation of androgen receptor signaling pathway Source: Ensembl
    10. negative regulation of intracellular estrogen receptor signaling pathway Source: Ensembl
    11. negative regulation of transcription from RNA polymerase II promoter Source: MGI
    12. outflow tract morphogenesis Source: BHF-UCL
    13. positive regulation of transcription, DNA-templated Source: UniProtKB
    14. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    15. regulation of transcription from RNA polymerase II promoter Source: MGI
    16. secondary heart field specification Source: BHF-UCL
    17. transcription from RNA polymerase II promoter Source: GOC
    18. transforming growth factor beta receptor signaling pathway Source: UniProtKB
    19. ventricular trabecula myocardium morphogenesis Source: BHF-UCL

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_216258. Signaling by Activin.
    REACT_220645. Signaling by NODAL.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Forkhead box protein H1
    Alternative name(s):
    Forkhead activin signal transducer 1
    Short name:
    Fast-1
    Forkhead activin signal transducer 2
    Short name:
    Fast-2
    Gene namesi
    Name:Foxh1
    Synonyms:Fast1, Fast2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 15

    Organism-specific databases

    MGIiMGI:1347465. Foxh1.

    Subcellular locationi

    GO - Cellular componenti

    1. activin responsive factor complex Source: UniProtKB
    2. nucleus Source: MGI
    3. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 401401Forkhead box protein H1PRO_0000091843Add
    BLAST

    Proteomic databases

    PRIDEiO88621.

    Expressioni

    Developmental stagei

    Expressed predominantly throughout the epiblast before gastrulation and declines as development progresses.1 Publication

    Gene expression databases

    ArrayExpressiO88621.
    BgeeiO88621.
    CleanExiMM_FOXH1.
    GenevestigatoriO88621.

    Interactioni

    Subunit structurei

    Interacts with the MH2 domains of SMAD2 and SMAD3.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GscQ025912EBI-7457430,EBI-7457485

    Protein-protein interaction databases

    BioGridi199598. 7 interactions.
    IntActiO88621. 1 interaction.
    MINTiMINT-4998752.

    Structurei

    3D structure databases

    ProteinModelPortaliO88621.
    SMRiO88621. Positions 64-142.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni307 – 39084SMAD-interaction domain (SID)Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi311 – 3155Fast/FoxH1 motif 1 (FM1)
    Motifi321 – 3277Fast/FoxH1 motif 2 (FM2)
    Motifi363 – 38422SMAD interaction motif (SIM)Add
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi187 – 1948Poly-Pro
    Compositional biasi243 – 2464Poly-Ser

    Domaini

    The FM region is required for binding SMAD2/SMAD4 complexes. FM2 is more effective than FM1 and only interacts with phosphorylated SMAD2 that is in an activated SMAD complex By similarity.By similarity

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG5025.
    HOGENOMiHOG000112630.
    HOVERGENiHBG051647.
    InParanoidiO88621.
    KOiK09400.
    OMAiNLSSNPC.
    OrthoDBiEOG76HQ1T.
    PhylomeDBiO88621.
    TreeFamiTF350620.

    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]
    PROSITEiPS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Long (identifier: O88621-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MASGWDLAST YTPTTPSPQL ALAPAQGYLP CMGPRDNSQL RPPEAESLSK    50
    TPKRRKKRYL RHDKPPYTYL AMIALVIQAA PFRRLKLAQI IRQVQAVFPF 100
    FRDDYEGWKD SIRHNLSSNR CFHKVPKDPA KPQAKGNFWA VDVSLIPAEA 150
    LRLQNTALCR RWQNRGTHRA FAKDLSPYVL HGQPYQPPSP PPPPREGFSI 200
    KSLLGDPGKE STWPQHPGLP GQSTAAQAGT LSKGEEGMGT GPSSSSETPL 250
    WPLCSLPGPT IIEGESSQGE VIRPSPVTPD QGSWPLHLLE DSADSRGVPR 300
    RGSRASLWGQ LPTSYLPIYT PNVVMPLATL PTTSCPQCPS SASPAYWSVG 350
    TESQGSQDLL CDLDSLFQGV PPNKSIYDVW VSHPRDLAAP APGWLLSWYS 400
    M 401
    Length:401
    Mass (Da):44,001
    Last modified:November 1, 1998 - v1
    Checksum:iFB11DC9779DF1454
    GO
    Isoform Short (identifier: O88621-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         89-92: Missing.

    Note: Fails to bind DNA and cannot confer activin response element responsiveness.

    Show »
    Length:397
    Mass (Da):43,490
    Checksum:i3FBEF9C838B20567
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti167 – 1671T → A in AAD55949. (PubMed:10349617)Curated
    Sequence conflicti207 – 2071P → L in AAD14683. 1 PublicationCurated
    Sequence conflicti215 – 2151Q → K in AAD14683. 1 PublicationCurated
    Sequence conflicti220 – 2201P → L in AAD14683. 1 PublicationCurated
    Sequence conflicti223 – 2231S → N in AAD55949. (PubMed:10349617)Curated
    Sequence conflicti237 – 2371G → R in AAD55949. (PubMed:10349617)Curated
    Sequence conflicti330 – 3301L → I in AAD55949. (PubMed:10349617)Curated
    Sequence conflicti334 – 3341S → C in AAD55949. (PubMed:10349617)Curated
    Sequence conflicti340 – 3401S → F in AAD55949. (PubMed:10349617)Curated
    Sequence conflicti366 – 3661L → F in AAD55949. (PubMed:10349617)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei89 – 924Missing in isoform Short. 1 PublicationVSP_001542

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF069303 mRNA. Translation: AAC79808.1.
    AF079514 mRNA. Translation: AAD12486.1.
    AF177770 mRNA. Translation: AAD55949.1.
    AF110506 mRNA. Translation: AAD14683.1.
    CCDSiCCDS27584.1. [O88621-1]
    RefSeqiNP_032015.1. NM_007989.4. [O88621-1]
    XP_006520499.1. XM_006520436.1. [O88621-2]
    UniGeneiMm.42011.

    Genome annotation databases

    EnsembliENSMUST00000037824; ENSMUSP00000036591; ENSMUSG00000033837. [O88621-1]
    GeneIDi14106.
    KEGGimmu:14106.
    UCSCiuc007wlm.1. mouse. [O88621-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF069303 mRNA. Translation: AAC79808.1 .
    AF079514 mRNA. Translation: AAD12486.1 .
    AF177770 mRNA. Translation: AAD55949.1 .
    AF110506 mRNA. Translation: AAD14683.1 .
    CCDSi CCDS27584.1. [O88621-1 ]
    RefSeqi NP_032015.1. NM_007989.4. [O88621-1 ]
    XP_006520499.1. XM_006520436.1. [O88621-2 ]
    UniGenei Mm.42011.

    3D structure databases

    ProteinModelPortali O88621.
    SMRi O88621. Positions 64-142.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 199598. 7 interactions.
    IntActi O88621. 1 interaction.
    MINTi MINT-4998752.

    Proteomic databases

    PRIDEi O88621.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000037824 ; ENSMUSP00000036591 ; ENSMUSG00000033837 . [O88621-1 ]
    GeneIDi 14106.
    KEGGi mmu:14106.
    UCSCi uc007wlm.1. mouse. [O88621-1 ]

    Organism-specific databases

    CTDi 8928.
    MGIi MGI:1347465. Foxh1.

    Phylogenomic databases

    eggNOGi COG5025.
    HOGENOMi HOG000112630.
    HOVERGENi HBG051647.
    InParanoidi O88621.
    KOi K09400.
    OMAi NLSSNPC.
    OrthoDBi EOG76HQ1T.
    PhylomeDBi O88621.
    TreeFami TF350620.

    Enzyme and pathway databases

    Reactomei REACT_216258. Signaling by Activin.
    REACT_220645. Signaling by NODAL.

    Miscellaneous databases

    NextBioi 285148.
    PROi O88621.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O88621.
    Bgeei O88621.
    CleanExi MM_FOXH1.
    Genevestigatori O88621.

    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 PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Smad2 and Smad3 positively and negatively regulate TGF beta-dependent transcription through the forkhead DNA-binding protein FAST2."
      Labbe E., Silvestri C., Hoodless P.A., Wrana J.L., Attisano L.
      Mol. Cell 2:109-120(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), FUNCTION.
      Tissue: Embryonic carcinoma.
    2. "FAST-2 is a mammalian winged-helix protein which mediates transforming growth factor beta signals."
      Liu B., Dou C.-L., Prabhu L., Lai E.
      Mol. Cell. Biol. 19:424-430(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), FUNCTION.
      Tissue: Embryonic carcinoma.
    3. "A mouse homologue of FAST-1 transduces TGF beta superfamily signals and is expressed during early embryogenesis."
      Weisberg E., Winnier G.E., Chen X., Farnsworth C.L., Hogan B.L.H., Whitman M.
      Mech. Dev. 79:17-27(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), FUNCTION, INTERACTION WITH SMAD2 AND SMAD3, DEVELOPMENTAL STAGE.
      Tissue: Embryo.
    4. "Mouse FAST-2 transduces the signals for TGF-beta and activin."
      Chen Y., Nagarajan R.P., Liu J., Vale W.
      Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), FUNCTION.

    Entry informationi

    Entry nameiFOXH1_MOUSE
    AccessioniPrimary (citable) accession number: O88621
    Secondary accession number(s): Q9QZL5, Q9R241
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 14, 2001
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 121 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3