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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)DescriptionActionsGraphical viewLength
DNA bindingi32 – 128Fork-headPROSITE-ProRule annotationAdd BLAST97

GO - Molecular functioni

  • androgen receptor binding Source: BHF-UCL
  • bHLH transcription factor binding Source: BHF-UCL
  • co-SMAD binding Source: BHF-UCL
  • enhancer binding Source: BHF-UCL
  • protein domain specific binding Source: UniProtKB
  • RNA polymerase II transcription cofactor activity Source: Ensembl
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: GO_Central
  • R-SMAD binding Source: BHF-UCL
  • sequence-specific DNA binding Source: UniProtKB
  • SMAD binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding Source: Ensembl
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: Ensembl
  • transcription factor activity, sequence-specific DNA binding Source: BHF-UCL
  • transcription regulatory region DNA binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160973-MONOMER.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
SignaLinkiO75593.
SIGNORiO75593.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:3814. FOXH1.

Subcellular locationi

GO - Cellular componenti

  • activin responsive factor complex Source: BHF-UCL
  • nuclear chromatin Source: BHF-UCL
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi83H → R: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi8928.
MalaCardsiFOXH1.
OpenTargetsiENSG00000160973.
Orphaneti93925. Alobar holoprosencephaly.
93924. Lobar holoprosencephaly.
280200. Microform holoprosencephaly.
93926. Midline interhemispheric variant of holoprosencephaly.
220386. Semilobar holoprosencephaly.
280195. Septopreoptic holoprosencephaly.
PharmGKBiPA28231.

Polymorphism and mutation databases

BioMutaiFOXH1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000918421 – 365Forkhead box protein H1Add BLAST365

Proteomic databases

PaxDbiO75593.
PeptideAtlasiO75593.
PRIDEiO75593.

PTM databases

iPTMnetiO75593.
PhosphoSitePlusiO75593.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiENSG00000160973.
CleanExiHS_FOXH1.
GenevisibleiO75593. HS.

Organism-specific databases

HPAiCAB034154.

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
SMAD2Q157963EBI-1759806,EBI-1040141
SMAD3P840225EBI-1759806,EBI-347161
TCF12Q990812EBI-1759806,EBI-722877
TCF3P159232EBI-1759806,EBI-769630

GO - Molecular functioni

  • androgen receptor binding Source: BHF-UCL
  • bHLH transcription factor binding Source: BHF-UCL
  • co-SMAD binding Source: BHF-UCL
  • protein domain specific binding Source: UniProtKB
  • R-SMAD binding Source: BHF-UCL
  • SMAD binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi114442. 40 interactors.
IntActiO75593. 47 interactors.
MINTiMINT-199205.
STRINGi9606.ENSP00000366534.

Structurei

3D structure databases

ProteinModelPortaliO75593.
SMRiO75593.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni273 – 354SMAD-interaction domain (SID)Add BLAST82

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi277 – 281Fast/FoxH1 motif 1 (FM1)5
Motifi287 – 293Fast/FoxH1 motif 2 (FM2)7
Motifi327 – 348SMAD interaction motif (SIM)Add BLAST22

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

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00800000124014.
HOGENOMiHOG000112630.
HOVERGENiHBG051647.
InParanoidiO75593.
KOiK09400.
OMAiVWVSHPR.
OrthoDBiEOG091G0X2S.
PhylomeDBiO75593.
TreeFamiTF350620.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_011381113S → T in colorectal cancer. 1 PublicationCorresponds to variant rs144830740dbSNPEnsembl.1
Natural variantiVAR_011382125T → S in colorectal cancer. 1 PublicationCorresponds to variant rs112028242dbSNPEnsembl.1

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.4. 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114442. 40 interactors.
IntActiO75593. 47 interactors.
MINTiMINT-199205.
STRINGi9606.ENSP00000366534.

PTM databases

iPTMnetiO75593.
PhosphoSitePlusiO75593.

Polymorphism and mutation databases

BioMutaiFOXH1.

Proteomic databases

PaxDbiO75593.
PeptideAtlasiO75593.
PRIDEiO75593.

Protocols and materials databases

DNASUi8928.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377317; ENSP00000366534; ENSG00000160973.
GeneIDi8928.
KEGGihsa:8928.
UCSCiuc003zdc.4. human.

Organism-specific databases

CTDi8928.
DisGeNETi8928.
GeneCardsiFOXH1.
GeneReviewsiFOXH1.
HGNCiHGNC:3814. FOXH1.
HPAiCAB034154.
MalaCardsiFOXH1.
MIMi603621. gene.
neXtProtiNX_O75593.
OpenTargetsiENSG00000160973.
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

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00800000124014.
HOGENOMiHOG000112630.
HOVERGENiHBG051647.
InParanoidiO75593.
KOiK09400.
OMAiVWVSHPR.
OrthoDBiEOG091G0X2S.
PhylomeDBiO75593.
TreeFamiTF350620.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000160973-MONOMER.
ReactomeiR-HSA-1181150. Signaling by NODAL.
R-HSA-1502540. Signaling by Activin.
SignaLinkiO75593.
SIGNORiO75593.

Miscellaneous databases

GeneWikiiFOXH1.
GenomeRNAii8928.
PROiO75593.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160973.
CleanExiHS_FOXH1.
GenevisibleiO75593. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 149 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

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 one 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.