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Protein

Forkhead box protein H1

Gene

foxh1

Organism
Xenopus laevis (African clawed frog)
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'. Upon TGF-beta induction, forms a transcriptionally active complex with smad2 and smad4 called activin-responsive factor 1 (ARF1), which binds a site on the mix-B/mix.2 promoter called the activin response element (ARE). Binds to activated smads and the ARE with much lower affinity than fast3. Necessary for the first steps in mesoderm specification, directly inducing mesodermal genes. Acts with fast3 to control the convergent extension movements of gastrulation. Binds to the proximal element (PE) of the gsc gene and cooperates with gtf2ird1/wbscr11 and SMAD proteins to regulate gsc transcription.7 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi117 – 213Fork-headPROSITE-ProRule annotationAdd BLAST97

GO - Molecular functioni

  • sequence-specific DNA binding Source: UniProtKB
  • SMAD binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: InterPro
  • transcription factor binding Source: UniProtKB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • activin receptor signaling pathway Source: UniProtKB
  • gastrulation with mouth forming second Source: UniProtKB
  • mesodermal cell fate specification Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • transforming growth factor beta receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Gastrulation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein H1
Alternative name(s):
Forkhead activin signal transducer 1
Short name:
Fast-1
Short name:
xFAST-1
XFoxH1a
Gene namesi
Name:foxh1
Synonyms:fast-1, fast1, foxh1a
OrganismiXenopus laevis (African clawed frog)
Taxonomic identifieri8355 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

Organism-specific databases

XenbaseiXB-GENE-1194377. foxh1.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  • activin responsive factor complex Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000918451 – 518Forkhead box protein H1Add BLAST518

Expressioni

Tissue specificityi

Highly expressed in the animal cap (prospective ectoderm) and prospective mesoderm of stage 10.25 embryos.1 Publication

Developmental stagei

Expressed both maternally and zygotically. Present in oocytes and in early embryos until shortly after gastrulation, after which levels decline and remain low through tadpole development.1 Publication

Interactioni

Subunit structurei

ARF1 contains 2 smad2s, 1 smad4 and 1 foxh1/fast-1 protein. Interaction with smad4 is most likely indirect through interaction with the MH2 domain of smad2. Binds to the MH2 domain of smad3, which can incorporate into the ARF1 complex. The ARF1 and ARF2 complexes are activated by distinct TGF-beta family members; formation of ARF1 is promoted by activin. Interacts (via Fork-head domain) with gtf2ird1/wbscr11 (via repeats 4-5).8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SMAD2Q157964EBI-9969973,EBI-1040141From a different organism.
SMAD4Q134852EBI-9969973,EBI-347263From a different organism.

GO - Molecular functioni

  • SMAD binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

IntActiP70056. 2 interactors.

Structurei

3D structure databases

ProteinModelPortaliP70056.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni380 – 506SMAD-interaction domain (SID)Add BLAST127

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi405 – 409Fast/FoxH1 motif 1 (FM1)5
Motifi415 – 421Fast/FoxH1 motif 2 (FM2)7
Motifi470 – 491SMAD interaction motif (SIM)Add BLAST22

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi336 – 343Poly-Ser8

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.

Sequence similaritiesi

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

Phylogenomic databases

HOVERGENiHBG051646.
KOiK09400.

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.

P70056-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRDPSSLYSG FPAGSQYESV EPPSLALLSS IDQEQLPVAT GQSYNHSVQH
60 70 80 90 100
WPQPWPPLSL YREGGTWSPD RGSMYGLSPG THEGSCTHTH EGPKDSMAGD
110 120 130 140 150
QTRSRKSKKK NYHRYNKPPY SYLAMIALVI QNSPEKRLKL SQILKEVSTL
160 170 180 190 200
FPFFNGDYMG WKDSIRHNLS SSDCFKKILK DPGKPQAKGN FWTVDVSRIP
210 220 230 240 250
LDAMKLQNTA LTRGGSDYFV QDLAPYILHN YKYEHNAGAY GHQMPPSHAR
260 270 280 290 300
SLSLAEDSQQ TNTGGKLNTS FMIDSLLHDL QEVDLPDASR NLENQRISPA
310 320 330 340 350
VAMNNMWSSA PLLYTHSKPT RNARSPGLST IHSTYSSSSS SISTISPVGF
360 370 380 390 400
QKEQEKSGRQ TQRVGHPIKR SREDDDCSTT SSDPDTGNYS PIEPPKKMPL
410 420 430 440 450
LSLDLPTSYT KSVAPNVVAP PSVLPFFHFP RFTYYNYGPS PYMTPPYWGF
460 470 480 490 500
PHPTNSGGDS PRGPQSPLDL DNMLRAMPPN KSVFDVLTSH PGDLVHPSFL
510
SQCLGSSGSP YPSRQGLM
Length:518
Mass (Da):57,445
Last modified:January 19, 2010 - v3
Checksum:i1BEC587943F92D1F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti50H → P in AAC60219 (PubMed:8878477).Curated1
Sequence conflicti101Q → H in AAC60219 (PubMed:8878477).Curated1
Sequence conflicti116N → Y in AAC60219 (PubMed:8878477).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70980 mRNA. Translation: AAC60219.1.
BC160705 mRNA. Translation: AAI60705.1.
RefSeqiNP_001081820.1. NM_001088351.1.
UniGeneiXl.381.

Genome annotation databases

GeneIDi398070.
KEGGixla:398070.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U70980 mRNA. Translation: AAC60219.1.
BC160705 mRNA. Translation: AAI60705.1.
RefSeqiNP_001081820.1. NM_001088351.1.
UniGeneiXl.381.

3D structure databases

ProteinModelPortaliP70056.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP70056. 2 interactors.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi398070.
KEGGixla:398070.

Organism-specific databases

CTDi8928.
XenbaseiXB-GENE-1194377. foxh1.

Phylogenomic databases

HOVERGENiHBG051646.
KOiK09400.

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_XENLA
AccessioniPrimary (citable) accession number: P70056
Secondary accession number(s): B1H1R2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 14, 2001
Last sequence update: January 19, 2010
Last modified: March 16, 2016
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. 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.