FOXH1_HUMAN
ID FOXH1_HUMAN Reviewed; 365 AA.
AC O75593; D3DWM4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Forkhead box protein H1;
DE AltName: Full=Forkhead activin signal transducer 1;
DE Short=Fast-1;
DE Short=hFAST-1;
DE AltName: Full=Forkhead activin signal transducer 2;
DE Short=Fast-2;
GN Name=FOXH1; Synonyms=FAST1, FAST2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DNA-BINDING, INTERACTION WITH SMAD2,
RP TISSUE SPECIFICITY, MUTAGENESIS OF HIS-83, AND VARIANTS THR-113 AND
RP SER-125.
RC TISSUE=Colon adenocarcinoma;
RX PubMed=9702198; DOI=10.1016/s1097-2765(00)80120-3;
RA Zhou S., Zawel L., Lengauer C., Kinzler K.W., Vogelstein B.;
RT "Characterization of human FAST-1, a TGF beta and activin signal
RT transducer.";
RL Mol. Cell 2:121-127(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) 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:9702198}.
CC -!- SUBUNIT: Interacts with the MH2 domains of SMAD2 and SMAD3.
CC {ECO:0000269|PubMed:9702198}.
CC -!- INTERACTION:
CC O75593; P19801: AOC1; NbExp=3; IntAct=EBI-1759806, EBI-12826295;
CC O75593; P10275: AR; NbExp=3; IntAct=EBI-1759806, EBI-608057;
CC O75593; Q03989: ARID5A; NbExp=4; IntAct=EBI-1759806, EBI-948603;
CC O75593; Q9Y6H3: ATP23; NbExp=3; IntAct=EBI-1759806, EBI-12811889;
CC O75593; P0C7T5: ATXN1L; NbExp=6; IntAct=EBI-1759806, EBI-8624731;
CC O75593; Q8N1L9: BATF2; NbExp=3; IntAct=EBI-1759806, EBI-742695;
CC O75593; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-1759806, EBI-12809220;
CC O75593; Q9H5F2: C11orf1; NbExp=3; IntAct=EBI-1759806, EBI-718615;
CC O75593; Q5BKX5-3: C19orf54; NbExp=3; IntAct=EBI-1759806, EBI-11976299;
CC O75593; P40199: CEACAM6; NbExp=3; IntAct=EBI-1759806, EBI-4314501;
CC O75593; O43186: CRX; NbExp=3; IntAct=EBI-1759806, EBI-748171;
CC O75593; P05813: CRYBA1; NbExp=3; IntAct=EBI-1759806, EBI-7043337;
CC O75593; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1759806, EBI-3867333;
CC O75593; Q15038: DAZAP2; NbExp=5; IntAct=EBI-1759806, EBI-724310;
CC O75593; A1KXE4-2: FAM168B; NbExp=3; IntAct=EBI-1759806, EBI-12193763;
CC O75593; Q86UY5: FAM83A; NbExp=3; IntAct=EBI-1759806, EBI-1384254;
CC O75593; O60548: FOXD2; NbExp=3; IntAct=EBI-1759806, EBI-17282008;
CC O75593; Q9BSH5: HDHD3; NbExp=3; IntAct=EBI-1759806, EBI-745201;
CC O75593; Q9Y5J3: HEY1; NbExp=3; IntAct=EBI-1759806, EBI-7231130;
CC O75593; Q14774: HLX; NbExp=3; IntAct=EBI-1759806, EBI-6678255;
CC O75593; P49639: HOXA1; NbExp=3; IntAct=EBI-1759806, EBI-740785;
CC O75593; Q9ULV5-2: HSF4; NbExp=3; IntAct=EBI-1759806, EBI-12056251;
CC O75593; Q53HC5: KLHL26; NbExp=3; IntAct=EBI-1759806, EBI-724915;
CC O75593; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-1759806, EBI-1052037;
CC O75593; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-1759806, EBI-10241252;
CC O75593; Q3LHN2: KRTAP19-2; NbExp=3; IntAct=EBI-1759806, EBI-12196745;
CC O75593; Q3LI70: KRTAP19-6; NbExp=3; IntAct=EBI-1759806, EBI-12805508;
CC O75593; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-1759806, EBI-10241353;
CC O75593; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-1759806, EBI-9996449;
CC O75593; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-1759806, EBI-3957694;
CC O75593; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-1759806, EBI-18394498;
CC O75593; Q14847-2: LASP1; NbExp=3; IntAct=EBI-1759806, EBI-9088686;
CC O75593; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-1759806, EBI-716006;
CC O75593; P35548: MSX2; NbExp=3; IntAct=EBI-1759806, EBI-6447480;
CC O75593; P16333: NCK1; NbExp=2; IntAct=EBI-1759806, EBI-389883;
CC O75593; A8MTQ0: NOTO; NbExp=3; IntAct=EBI-1759806, EBI-17490746;
CC O75593; Q8TDS5: OXER1; NbExp=3; IntAct=EBI-1759806, EBI-12813389;
CC O75593; O15496: PLA2G10; NbExp=3; IntAct=EBI-1759806, EBI-726466;
CC O75593; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-1759806, EBI-10171633;
CC O75593; O75864: PPP1R37; NbExp=3; IntAct=EBI-1759806, EBI-5235692;
CC O75593; P86480: PRR20D; NbExp=3; IntAct=EBI-1759806, EBI-12754095;
CC O75593; Q8TBY0: RBM46; NbExp=3; IntAct=EBI-1759806, EBI-12068216;
CC O75593; Q6ZRY4: RBPMS2; NbExp=3; IntAct=EBI-1759806, EBI-11987469;
CC O75593; Q9UGK8: SERGEF; NbExp=3; IntAct=EBI-1759806, EBI-465368;
CC O75593; Q15796: SMAD2; NbExp=4; IntAct=EBI-1759806, EBI-1040141;
CC O75593; P84022: SMAD3; NbExp=4; IntAct=EBI-1759806, EBI-347161;
CC O75593; O95416: SOX14; NbExp=3; IntAct=EBI-1759806, EBI-9087806;
CC O75593; Q99081: TCF12; NbExp=2; IntAct=EBI-1759806, EBI-722877;
CC O75593; P15923: TCF3; NbExp=2; IntAct=EBI-1759806, EBI-769630;
CC O75593; Q96M29: TEKT5; NbExp=3; IntAct=EBI-1759806, EBI-10239812;
CC O75593; Q92734: TFG; NbExp=3; IntAct=EBI-1759806, EBI-357061;
CC O75593; O43711: TLX3; NbExp=3; IntAct=EBI-1759806, EBI-3939165;
CC O75593; Q86WV8: TSC1; NbExp=5; IntAct=EBI-1759806, EBI-12806590;
CC O75593; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-1759806, EBI-2514383;
CC O75593; Q6NVU6: UFSP1; NbExp=3; IntAct=EBI-1759806, EBI-12068150;
CC O75593; Q96K80: ZC3H10; NbExp=3; IntAct=EBI-1759806, EBI-742550;
CC O75593; Q15915: ZIC1; NbExp=3; IntAct=EBI-1759806, EBI-11963196;
CC O75593; Q96F45: ZNF503; NbExp=3; IntAct=EBI-1759806, EBI-8832437;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9702198}.
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}.
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DR EMBL; AF076292; AAC34303.1; -; mRNA.
DR EMBL; CH471162; EAW82083.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82084.1; -; Genomic_DNA.
DR CCDS; CCDS6428.1; -.
DR RefSeq; NP_003914.1; NM_003923.2.
DR PDB; 5XOC; X-ray; 2.40 A; B=322-345.
DR PDBsum; 5XOC; -.
DR AlphaFoldDB; O75593; -.
DR SMR; O75593; -.
DR BioGRID; 114442; 101.
DR CORUM; O75593; -.
DR IntAct; O75593; 90.
DR MINT; O75593; -.
DR STRING; 9606.ENSP00000366534; -.
DR iPTMnet; O75593; -.
DR PhosphoSitePlus; O75593; -.
DR BioMuta; FOXH1; -.
DR EPD; O75593; -.
DR MassIVE; O75593; -.
DR PaxDb; O75593; -.
DR PeptideAtlas; O75593; -.
DR PRIDE; O75593; -.
DR ProteomicsDB; 50103; -.
DR Antibodypedia; 28549; 260 antibodies from 33 providers.
DR DNASU; 8928; -.
DR Ensembl; ENST00000377317.5; ENSP00000366534.4; ENSG00000160973.8.
DR GeneID; 8928; -.
DR KEGG; hsa:8928; -.
DR MANE-Select; ENST00000377317.5; ENSP00000366534.4; NM_003923.3; NP_003914.1.
DR UCSC; uc003zdc.4; human.
DR CTD; 8928; -.
DR DisGeNET; 8928; -.
DR GeneCards; FOXH1; -.
DR GeneReviews; FOXH1; -.
DR HGNC; HGNC:3814; FOXH1.
DR HPA; ENSG00000160973; Tissue enhanced (retina, skin).
DR MalaCards; FOXH1; -.
DR MIM; 603621; gene.
DR neXtProt; NX_O75593; -.
DR OpenTargets; ENSG00000160973; -.
DR Orphanet; 93925; Alobar holoprosencephaly.
DR Orphanet; 93924; Lobar holoprosencephaly.
DR Orphanet; 280200; Microform holoprosencephaly.
DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly.
DR Orphanet; 220386; Semilobar holoprosencephaly.
DR Orphanet; 280195; Septopreoptic holoprosencephaly.
DR PharmGKB; PA28231; -.
DR VEuPathDB; HostDB:ENSG00000160973; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000159537; -.
DR HOGENOM; CLU_039733_0_0_1; -.
DR InParanoid; O75593; -.
DR OMA; QCPPSNS; -.
DR OrthoDB; 1270467at2759; -.
DR PhylomeDB; O75593; -.
DR TreeFam; TF350620; -.
DR PathwayCommons; O75593; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1502540; Signaling by Activin.
DR SignaLink; O75593; -.
DR SIGNOR; O75593; -.
DR BioGRID-ORCS; 8928; 13 hits in 1099 CRISPR screens.
DR ChiTaRS; FOXH1; human.
DR GeneWiki; FOXH1; -.
DR GenomeRNAi; 8928; -.
DR Pharos; O75593; Tbio.
DR PRO; PR:O75593; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O75593; protein.
DR Bgee; ENSG00000160973; Expressed in mucosa of transverse colon and 103 other tissues.
DR Genevisible; O75593; HS.
DR GO; GO:0032444; C:activin responsive factor complex; IDA:BHF-UCL.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IC:ARUK-UCL.
DR GO; GO:0070410; F:co-SMAD binding; IMP:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IPI:BHF-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0070412; F:R-SMAD binding; IMP:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IPI:BHF-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:BHF-UCL.
DR GO; GO:0035909; P:aorta morphogenesis; IEA:Ensembl.
DR GO; GO:0048318; P:axial mesoderm development; IEA:Ensembl.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; IEA:Ensembl.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:UniProtKB.
DR GO; GO:0035054; P:embryonic heart tube anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:1900164; P:nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; NAS:BHF-UCL.
DR GO; GO:0003151; P:outflow tract morphogenesis; IEA:Ensembl.
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:0003139; P:secondary heart field specification; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IEA:Ensembl.
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 3D-structure; Activator; DNA-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..365
FT /note="Forkhead box protein H1"
FT /id="PRO_0000091842"
FT DNA_BIND 32..128
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..354
FT /note="SMAD-interaction domain (SID)"
FT MOTIF 277..281
FT /note="Fast/FoxH1 motif 1 (FM1)"
FT MOTIF 287..293
FT /note="Fast/FoxH1 motif 2 (FM2)"
FT MOTIF 327..348
FT /note="SMAD interaction motif (SIM)"
FT COMPBIAS 152..166
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 113
FT /note="S -> T (in dbSNP:rs144830740)"
FT /evidence="ECO:0000269|PubMed:9702198"
FT /id="VAR_011381"
FT VARIANT 125
FT /note="T -> S (in dbSNP:rs112028242)"
FT /evidence="ECO:0000269|PubMed:9702198"
FT /id="VAR_011382"
FT MUTAGEN 83
FT /note="H->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:9702198"
FT HELIX 327..330
FT /evidence="ECO:0007829|PDB:5XOC"
FT STRAND 331..333
FT /evidence="ECO:0007829|PDB:5XOC"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:5XOC"
FT HELIX 340..343
FT /evidence="ECO:0007829|PDB:5XOC"
SQ SEQUENCE 365 AA; 39257 MW; 27A13F39C089F722 CRC64;
MGPCSGSRLG PPEAESPSQP PKRRKKRYLR HDKPPYTYLA MIALVIQAAP SRRLKLAQII
RQVQAVFPFF REDYEGWKDS IRHNLSSNRC FRKVPKDPAK PQAKGNFWAV DVSLIPAEAL
RLQNTALCRR WQNGGARGAF AKDLGPYVLH GRPYRPPSPP PPPSEGFSIK SLLGGSGEGA
PWPGLAPQSS PVPAGTGNSG EEAVPTPPLP SSERPLWPLC PLPGPTRVEG ETVQGGAIGP
STLSPEPRAW PLHLLQGTAV PGGRSSGGHR ASLWGQLPTS YLPIYTPNVV MPLAPPPTSC
PQCPSTSPAY WGVAPETRGP PGLLCDLDAL FQGVPPNKSI YDVWVSHPRD LAAPGPGWLL
SWCSL
