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Protein

Forkhead box protein H1

Gene

Foxh1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. androgen receptor binding Source: MGI
  2. bHLH transcription factor binding Source: MGI
  3. co-SMAD binding Source: MGI
  4. DNA binding Source: MGI
  5. protein domain specific binding Source: MGI
  6. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: MGI
  7. RNA polymerase II transcription cofactor activity Source: BHF-UCL
  8. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
  9. R-SMAD binding Source: BHF-UCL
  10. sequence-specific DNA binding Source: MGI
  11. sequence-specific DNA binding transcription factor activity Source: MGI
  12. SMAD binding Source: UniProtKB
  13. 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: MGI
  9. negative regulation of androgen receptor signaling pathway Source: MGI
  10. negative regulation of intracellular estrogen receptor signaling pathway Source: MGI
  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
Complete GO annotation...

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. nuclear chromatin Source: MGI
  3. nucleus Source: MGI
  4. transcription factor complex Source: MGI
Complete GO annotation...

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

BgeeiO88621.
CleanExiMM_FOXH1.
ExpressionAtlasiO88621. baseline and differential.
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.
OMAiSERPLWP.
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. AlignAdd to basket

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

        10         20         30         40         50
MASGWDLAST YTPTTPSPQL ALAPAQGYLP CMGPRDNSQL RPPEAESLSK
60 70 80 90 100
TPKRRKKRYL RHDKPPYTYL AMIALVIQAA PFRRLKLAQI IRQVQAVFPF
110 120 130 140 150
FRDDYEGWKD SIRHNLSSNR CFHKVPKDPA KPQAKGNFWA VDVSLIPAEA
160 170 180 190 200
LRLQNTALCR RWQNRGTHRA FAKDLSPYVL HGQPYQPPSP PPPPREGFSI
210 220 230 240 250
KSLLGDPGKE STWPQHPGLP GQSTAAQAGT LSKGEEGMGT GPSSSSETPL
260 270 280 290 300
WPLCSLPGPT IIEGESSQGE VIRPSPVTPD QGSWPLHLLE DSADSRGVPR
310 320 330 340 350
RGSRASLWGQ LPTSYLPIYT PNVVMPLATL PTTSCPQCPS SASPAYWSVG
360 370 380 390 400
TESQGSQDLL CDLDSLFQGV PPNKSIYDVW VSHPRDLAAP APGWLLSWYS

M
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 (Ref. 4) Curated
Sequence conflicti215 – 2151Q → K in AAD14683 (Ref. 4) Curated
Sequence conflicti220 – 2201P → L in AAD14683 (Ref. 4) Curated
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

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

Proteomic databases

PRIDEiO88621.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi8928.
MGIiMGI:1347465. Foxh1.

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

NextBioi285148.
PROiO88621.
SOURCEiSearch...

Gene expression databases

BgeeiO88621.
CleanExiMM_FOXH1.
ExpressionAtlasiO88621. baseline and differential.
GenevestigatoriO88621.

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]
ProtoNetiSearch...

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: February 4, 2015
This is version 124 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.