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Protein

Forkhead box protein H1

Gene

FOXH1

Organism
Homo sapiens (Human)
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).1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi32 – 12897Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. androgen receptor binding Source: BHF-UCL
  2. bHLH transcription factor binding Source: BHF-UCL
  3. co-SMAD binding Source: BHF-UCL
  4. enhancer binding Source: BHF-UCL
  5. protein domain specific binding Source: UniProtKB
  6. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  7. RNA polymerase II transcription cofactor activity Source: Ensembl
  8. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  9. R-SMAD binding Source: BHF-UCL
  10. sequence-specific DNA binding Source: UniProtKB
  11. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: GO_Central
  12. sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  13. SMAD binding Source: BHF-UCL
  14. transcription regulatory region DNA binding Source: BHF-UCL

GO - Biological processi

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

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_111057. Signaling by NODAL.
REACT_150238. Signaling by Activin.
SignaLinkiO75593.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:FOXH1
Synonyms:FAST1, FAST2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:3814. FOXH1.

Subcellular locationi

GO - Cellular componenti

  1. activin responsive factor complex Source: BHF-UCL
  2. nuclear chromatin Source: BHF-UCL
  3. nucleoplasm Source: Reactome
  4. nucleus Source: UniProtKB
  5. transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi83 – 831H → R: Loss of activity. 1 Publication

Organism-specific databases

Orphaneti93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBiPA28231.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 365365Forkhead box protein H1PRO_0000091842Add
BLAST

Proteomic databases

PaxDbiO75593.
PRIDEiO75593.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiO75593.
CleanExiHS_FOXH1.
GenevestigatoriO75593.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP102753EBI-1759806,EBI-608057
NCK1P163332EBI-1759806,EBI-389883
TCF12Q990812EBI-1759806,EBI-722877
TCF3P159232EBI-1759806,EBI-769630

Protein-protein interaction databases

BioGridi114442. 9 interactions.
IntActiO75593. 8 interactions.
MINTiMINT-199205.
STRINGi9606.ENSP00000366534.

Structurei

3D structure databases

ProteinModelPortaliO75593.
SMRiO75593. Positions 33-111.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni273 – 35482SMAD-interaction domain (SID)Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi277 – 2815Fast/FoxH1 motif 1 (FM1)
Motifi287 – 2937Fast/FoxH1 motif 2 (FM2)
Motifi327 – 34822SMAD interaction motif (SIM)Add
BLAST

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.
GeneTreeiENSGT00780000121868.
HOGENOMiHOG000112630.
HOVERGENiHBG051647.
InParanoidiO75593.
KOiK09400.
OMAiSERPLWP.
OrthoDBiEOG76HQ1T.
PhylomeDBiO75593.
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]

Sequencei

Sequence statusi: Complete.

O75593-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPCSGSRLG PPEAESPSQP PKRRKKRYLR HDKPPYTYLA MIALVIQAAP
60 70 80 90 100
SRRLKLAQII RQVQAVFPFF REDYEGWKDS IRHNLSSNRC FRKVPKDPAK
110 120 130 140 150
PQAKGNFWAV DVSLIPAEAL RLQNTALCRR WQNGGARGAF AKDLGPYVLH
160 170 180 190 200
GRPYRPPSPP PPPSEGFSIK SLLGGSGEGA PWPGLAPQSS PVPAGTGNSG
210 220 230 240 250
EEAVPTPPLP SSERPLWPLC PLPGPTRVEG ETVQGGAIGP STLSPEPRAW
260 270 280 290 300
PLHLLQGTAV PGGRSSGGHR ASLWGQLPTS YLPIYTPNVV MPLAPPPTSC
310 320 330 340 350
PQCPSTSPAY WGVAPETRGP PGLLCDLDAL FQGVPPNKSI YDVWVSHPRD
360
LAAPGPGWLL SWCSL
Length:365
Mass (Da):39,257
Last modified:November 1, 1998 - v1
Checksum:i27A13F39C089F722
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti113 – 1131S → T in colorectal cancer. 1 Publication
Corresponds to variant rs144830740 [ dbSNP | Ensembl ].
VAR_011381
Natural varianti125 – 1251T → S in colorectal cancer. 1 Publication
Corresponds to variant rs112028242 [ dbSNP | Ensembl ].
VAR_011382

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076292 mRNA. Translation: AAC34303.1.
CH471162 Genomic DNA. Translation: EAW82083.1.
CH471162 Genomic DNA. Translation: EAW82084.1.
CCDSiCCDS6428.1.
RefSeqiNP_003914.1. NM_003923.2.
UniGeneiHs.708365.

Genome annotation databases

EnsembliENST00000377317; ENSP00000366534; ENSG00000160973.
GeneIDi8928.
KEGGihsa:8928.
UCSCiuc003zdc.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF076292 mRNA. Translation: AAC34303.1.
CH471162 Genomic DNA. Translation: EAW82083.1.
CH471162 Genomic DNA. Translation: EAW82084.1.
CCDSiCCDS6428.1.
RefSeqiNP_003914.1. NM_003923.2.
UniGeneiHs.708365.

3D structure databases

ProteinModelPortaliO75593.
SMRiO75593. Positions 33-111.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114442. 9 interactions.
IntActiO75593. 8 interactions.
MINTiMINT-199205.
STRINGi9606.ENSP00000366534.

Proteomic databases

PaxDbiO75593.
PRIDEiO75593.

Protocols and materials databases

DNASUi8928.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377317; ENSP00000366534; ENSG00000160973.
GeneIDi8928.
KEGGihsa:8928.
UCSCiuc003zdc.3. human.

Organism-specific databases

CTDi8928.
GeneCardsiGC08M145698.
GeneReviewsiFOXH1.
HGNCiHGNC:3814. FOXH1.
MIMi603621. gene.
neXtProtiNX_O75593.
Orphaneti93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBiPA28231.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00780000121868.
HOGENOMiHOG000112630.
HOVERGENiHBG051647.
InParanoidiO75593.
KOiK09400.
OMAiSERPLWP.
OrthoDBiEOG76HQ1T.
PhylomeDBiO75593.
TreeFamiTF350620.

Enzyme and pathway databases

ReactomeiREACT_111057. Signaling by NODAL.
REACT_150238. Signaling by Activin.
SignaLinkiO75593.

Miscellaneous databases

GeneWikiiFOXH1.
GenomeRNAii8928.
NextBioi33570.
PROiO75593.
SOURCEiSearch...

Gene expression databases

BgeeiO75593.
CleanExiHS_FOXH1.
GenevestigatoriO75593.

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

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Entry informationi

Entry nameiFOXH1_HUMAN
AccessioniPrimary (citable) accession number: O75593
Secondary accession number(s): D3DWM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1998
Last modified: March 4, 2015
This is version 131 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: 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. 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.