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O75593 (FOXH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein H1
Alternative name(s):
Forkhead activin signal transducer 1
Short name=Fast-1
Short name=hFAST-1
Forkhead activin signal transducer 2
Short name=Fast-2
Gene names
Name:FOXH1
Synonyms:FAST1, FAST2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length365 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.1

Subunit structure

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

Subcellular location

Nucleus.

Tissue specificity

Ubiquitous. Ref.1

Domain

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.

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   LigandDNA-binding
   Molecular functionActivator
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaorta morphogenesis

Inferred from electronic annotation. Source: Ensembl

axial mesoderm development

Inferred from Biological aspect of Ancestor. Source: RefGenome

blood vessel development

Inferred from Biological aspect of Ancestor. Source: RefGenome

cardiac right ventricle morphogenesis

Inferred from electronic annotation. Source: Ensembl

cell migration involved in gastrulation

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic heart tube anterior/posterior pattern specification

Inferred from Biological aspect of Ancestor. Source: RefGenome

floor plate formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

heart looping

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of androgen receptor activity

Inferred from direct assay PubMed 16120611. Source: BHF-UCL

negative regulation of androgen receptor signaling pathway

Inferred from direct assay PubMed 16120611. Source: BHF-UCL

negative regulation of intracellular estrogen receptor signaling pathway

Inferred from direct assay PubMed 16120611. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry

Non-traceable author statement PubMed 17507406. Source: BHF-UCL

outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.1. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.1. Source: UniProtKB

secondary heart field specification

Inferred from electronic annotation. Source: Ensembl

specification of organ position

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: GOC

transforming growth factor beta receptor signaling pathway

Traceable author statement Ref.1. Source: UniProtKB

ventricular trabecula myocardium morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentactivin responsive factor complex

Inferred from direct assay PubMed 9389648. Source: BHF-UCL

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred by curator Ref.1. Source: UniProtKB

transcription factor complex

Inferred from direct assay PubMed 17438144. Source: BHF-UCL

   Molecular_functionDNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

R-SMAD binding

Inferred from mutant phenotype PubMed 16120611. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription cofactor activity

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

androgen receptor binding

Inferred from physical interaction PubMed 16120611. Source: BHF-UCL

co-SMAD binding

Inferred from mutant phenotype PubMed 16120611. Source: BHF-UCL

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein domain specific binding

Inferred from physical interaction Ref.1. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay Ref.1. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Non-traceable author statement PubMed 17507406. Source: BHF-UCL

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription regulatory region DNA binding

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NCK1P163332EBI-1759806,EBI-389883

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 365365Forkhead box protein H1
PRO_0000091842

Regions

DNA binding32 – 12897Fork-head Ref.1
Region273 – 35482SMAD-interaction domain (SID)
Motif277 – 2815Fast/FoxH1 motif 1 (FM1)
Motif287 – 2937Fast/FoxH1 motif 2 (FM2)
Motif327 – 34822SMAD interaction motif (SIM)

Natural variations

Natural variant1131S → T in colorectal cancer. Ref.1
Corresponds to variant rs144830740 [ dbSNP | Ensembl ].
VAR_011381
Natural variant1251T → S in colorectal cancer. Ref.1
Corresponds to variant rs112028242 [ dbSNP | Ensembl ].
VAR_011382

Experimental info

Mutagenesis831H → R: Loss of activity. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O75593 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 27A13F39C089F722

FASTA36539,257
        10         20         30         40         50         60 
MGPCSGSRLG PPEAESPSQP PKRRKKRYLR HDKPPYTYLA MIALVIQAAP SRRLKLAQII 

        70         80         90        100        110        120 
RQVQAVFPFF REDYEGWKDS IRHNLSSNRC FRKVPKDPAK PQAKGNFWAV DVSLIPAEAL 

       130        140        150        160        170        180 
RLQNTALCRR WQNGGARGAF AKDLGPYVLH GRPYRPPSPP PPPSEGFSIK SLLGGSGEGA 

       190        200        210        220        230        240 
PWPGLAPQSS PVPAGTGNSG EEAVPTPPLP SSERPLWPLC PLPGPTRVEG ETVQGGAIGP 

       250        260        270        280        290        300 
STLSPEPRAW PLHLLQGTAV PGGRSSGGHR ASLWGQLPTS YLPIYTPNVV MPLAPPPTSC 

       310        320        330        340        350        360 
PQCPSTSPAY WGVAPETRGP PGLLCDLDAL FQGVPPNKSI YDVWVSHPRD LAAPGPGWLL 


SWCSL 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of human FAST-1, a TGF beta and activin signal transducer."
Zhou S., Zawel L., Lengauer C., Kinzler K.W., Vogelstein B.
Mol. Cell 2:121-127(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DNA-BINDING, INTERACTION WITH SMAD2, TISSUE SPECIFICITY, MUTAGENESIS OF HIS-83, VARIANTS COLORECTAL CANCER THR-113 AND COLORECTAL CANCER SER-125.
Tissue: Colon adenocarcinoma.
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF076292 mRNA. Translation: AAC34303.1.
CH471162 Genomic DNA. Translation: EAW82083.1.
CH471162 Genomic DNA. Translation: EAW82084.1.
RefSeqNP_003914.1. NM_003923.2.
UniGeneHs.708365.

3D structure databases

ProteinModelPortalO75593.
SMRO75593. Positions 33-111.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114442. 10 interactions.
IntActO75593. 3 interactions.
MINTMINT-199205.
STRING9606.ENSP00000366534.

Proteomic databases

PaxDbO75593.
PRIDEO75593.

Protocols and materials databases

DNASU8928.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377317; ENSP00000366534; ENSG00000160973.
GeneID8928.
KEGGhsa:8928.
UCSCuc003zdc.3. human.

Organism-specific databases

CTD8928.
GeneCardsGC08M145698.
HGNCHGNC:3814. FOXH1.
MIM603621. gene.
neXtProtNX_O75593.
Orphanet93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBPA28231.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000112630.
HOVERGENHBG051647.
InParanoidO75593.
KOK09400.
OMANLSSNPC.
OrthoDBEOG76HQ1T.
PhylomeDBO75593.
TreeFamTF350620.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
SignaLinkO75593.

Gene expression databases

BgeeO75593.
CleanExHS_FOXH1.
GenevestigatorO75593.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFOXH1.
GenomeRNAi8928.
NextBio33570.
PROO75593.
SOURCESearch...

Entry information

Entry nameFOXH1_HUMAN
AccessionPrimary (citable) accession number: O75593
Secondary accession number(s): D3DWM4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM