FOXH1_MOUSE
ID FOXH1_MOUSE Reviewed; 401 AA.
AC O88621; Q9QZL5; Q9R241;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Forkhead box protein H1;
DE AltName: Full=Forkhead activin signal transducer 1;
DE Short=Fast-1;
DE AltName: Full=Forkhead activin signal transducer 2;
DE Short=Fast-2;
GN Name=Foxh1; Synonyms=Fast1, Fast2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND FUNCTION.
RC TISSUE=Embryonic carcinoma;
RX PubMed=9702197; DOI=10.1016/s1097-2765(00)80119-7;
RA Labbe E., Silvestri C., Hoodless P.A., Wrana J.L., Attisano L.;
RT "Smad2 and Smad3 positively and negatively regulate TGF beta-dependent
RT transcription through the forkhead DNA-binding protein FAST2.";
RL Mol. Cell 2:109-120(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND FUNCTION.
RC TISSUE=Embryonic carcinoma;
RX PubMed=9858566; DOI=10.1128/mcb.19.1.424;
RA Liu B., Dou C.-L., Prabhu L., Lai E.;
RT "FAST-2 is a mammalian winged-helix protein which mediates transforming
RT growth factor beta signals.";
RL Mol. Cell. Biol. 19:424-430(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), FUNCTION, INTERACTION
RP WITH SMAD2 AND SMAD3, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=10349617; DOI=10.1016/s0925-4773(98)00160-9;
RA Weisberg E., Winnier G.E., Chen X., Farnsworth C.L., Hogan B.L.H.,
RA Whitman M.;
RT "A mouse homologue of FAST-1 transduces TGF beta superfamily signals and is
RT expressed during early embryogenesis.";
RL Mech. Dev. 79:17-27(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND FUNCTION.
RA Chen Y., Nagarajan R.P., Liu J., Vale W.;
RT "Mouse FAST-2 transduces the signals for TGF-beta and activin.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcriptional activator. Recognizes and binds to the DNA
CC sequence 5'-TGT[GT][GT]ATT-3'. Required for induction of the goosecoid
CC (GSC) promoter by TGF-beta or activin signaling. Forms a
CC transcriptionally active complex containing FOXH1/SMAD2/SMAD4 on a site
CC on the GSC promoter called TARE (TGF-beta/activin response element).
CC {ECO:0000269|PubMed:10349617, ECO:0000269|PubMed:9702197,
CC ECO:0000269|PubMed:9858566, ECO:0000269|Ref.4}.
CC -!- SUBUNIT: Interacts with the MH2 domains of SMAD2 and SMAD3.
CC {ECO:0000269|PubMed:10349617}.
CC -!- INTERACTION:
CC O88621; Q02591: Gsc; NbExp=2; IntAct=EBI-7457430, EBI-7457485;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O88621-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=O88621-2; Sequence=VSP_001542;
CC -!- DEVELOPMENTAL STAGE: Expressed predominantly throughout the epiblast
CC before gastrulation and declines as development progresses.
CC {ECO:0000269|PubMed:10349617}.
CC -!- DOMAIN: The FM region is required for binding SMAD2/SMAD4 complexes.
CC FM2 is more effective than FM1 and only interacts with phosphorylated
CC SMAD2 that is in an activated SMAD complex (By similarity).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform Short]: Fails to bind DNA and cannot confer
CC activin response element responsiveness. {ECO:0000305}.
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DR EMBL; AF069303; AAC79808.1; -; mRNA.
DR EMBL; AF079514; AAD12486.1; -; mRNA.
DR EMBL; AF177770; AAD55949.1; -; mRNA.
DR EMBL; AF110506; AAD14683.1; -; mRNA.
DR CCDS; CCDS27584.1; -. [O88621-1]
DR RefSeq; NP_032015.1; NM_007989.4. [O88621-1]
DR RefSeq; XP_006520499.1; XM_006520436.3. [O88621-2]
DR AlphaFoldDB; O88621; -.
DR SMR; O88621; -.
DR BioGRID; 199598; 7.
DR CORUM; O88621; -.
DR IntAct; O88621; 6.
DR MINT; O88621; -.
DR STRING; 10090.ENSMUSP00000036591; -.
DR iPTMnet; O88621; -.
DR PhosphoSitePlus; O88621; -.
DR PaxDb; O88621; -.
DR PRIDE; O88621; -.
DR Antibodypedia; 28549; 260 antibodies from 33 providers.
DR DNASU; 14106; -.
DR Ensembl; ENSMUST00000037824; ENSMUSP00000036591; ENSMUSG00000033837. [O88621-1]
DR GeneID; 14106; -.
DR KEGG; mmu:14106; -.
DR UCSC; uc007wlm.2; mouse. [O88621-1]
DR CTD; 8928; -.
DR MGI; MGI:1347465; Foxh1.
DR VEuPathDB; HostDB:ENSMUSG00000033837; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000159537; -.
DR HOGENOM; CLU_039733_0_0_1; -.
DR InParanoid; O88621; -.
DR OMA; QCPPSNS; -.
DR PhylomeDB; O88621; -.
DR TreeFam; TF350620; -.
DR BioGRID-ORCS; 14106; 4 hits in 75 CRISPR screens.
DR PRO; PR:O88621; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O88621; protein.
DR Bgee; ENSMUSG00000033837; Expressed in epiblast (generic) and 58 other tissues.
DR ExpressionAtlas; O88621; baseline and differential.
DR Genevisible; O88621; MM.
DR GO; GO:0032444; C:activin responsive factor complex; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:MGI.
DR GO; GO:0070410; F:co-SMAD binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0050681; F:nuclear androgen receptor binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0070412; F:R-SMAD binding; IDA:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0046332; F:SMAD binding; IPI:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0035909; P:aorta morphogenesis; IMP:BHF-UCL.
DR GO; GO:0048318; P:axial mesoderm development; IMP:MGI.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISS:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI.
DR GO; GO:0035054; P:embryonic heart tube anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0001947; P:heart looping; IMP:BHF-UCL.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0003139; P:secondary heart field specification; IMP:BHF-UCL.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IMP:BHF-UCL.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; DNA-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..401
FT /note="Forkhead box protein H1"
FT /id="PRO_0000091843"
FT DNA_BIND 64..163
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 32..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..390
FT /note="SMAD-interaction domain (SID)"
FT MOTIF 311..315
FT /note="Fast/FoxH1 motif 1 (FM1)"
FT MOTIF 321..327
FT /note="Fast/FoxH1 motif 2 (FM2)"
FT MOTIF 363..384
FT /note="SMAD interaction motif (SIM)"
FT COMPBIAS 183..197
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 237..251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 89..92
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10349617"
FT /id="VSP_001542"
FT CONFLICT 167
FT /note="T -> A (in Ref. 3; AAD55949)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="P -> L (in Ref. 4; AAD14683)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="Q -> K (in Ref. 4; AAD14683)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="P -> L (in Ref. 4; AAD14683)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="S -> N (in Ref. 3; AAD55949)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="G -> R (in Ref. 3; AAD55949)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="L -> I (in Ref. 3; AAD55949)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="S -> C (in Ref. 3; AAD55949)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="S -> F (in Ref. 3; AAD55949)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="L -> F (in Ref. 3; AAD55949)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 401 AA; 44001 MW; FB11DC9779DF1454 CRC64;
MASGWDLAST YTPTTPSPQL ALAPAQGYLP CMGPRDNSQL RPPEAESLSK TPKRRKKRYL
RHDKPPYTYL AMIALVIQAA PFRRLKLAQI IRQVQAVFPF FRDDYEGWKD SIRHNLSSNR
CFHKVPKDPA KPQAKGNFWA VDVSLIPAEA LRLQNTALCR RWQNRGTHRA FAKDLSPYVL
HGQPYQPPSP PPPPREGFSI KSLLGDPGKE STWPQHPGLP GQSTAAQAGT LSKGEEGMGT
GPSSSSETPL WPLCSLPGPT IIEGESSQGE VIRPSPVTPD QGSWPLHLLE DSADSRGVPR
RGSRASLWGQ LPTSYLPIYT PNVVMPLATL PTTSCPQCPS SASPAYWSVG TESQGSQDLL
CDLDSLFQGV PPNKSIYDVW VSHPRDLAAP APGWLLSWYS M
