FOXH1_XENLA
ID FOXH1_XENLA Reviewed; 518 AA.
AC P70056; B1H1R2;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 19-JAN-2010, sequence version 3.
DT 25-MAY-2022, entry version 119.
DE RecName: Full=Forkhead box protein H1;
DE AltName: Full=Forkhead activin signal transducer 1;
DE Short=Fast-1;
DE Short=xFAST-1;
DE AltName: Full=XFoxH1a;
GN Name=foxh1; Synonyms=fast-1, fast1, foxh1a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION IN ARF1 COMPLEX,
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RC TISSUE=Oocyte;
RX PubMed=8878477; DOI=10.1038/383691a0;
RA Chen X., Rubock M.J., Whitman M.;
RT "A transcriptional partner for MAD proteins in TGF-beta signalling.";
RL Nature 383:691-696(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, INTERACTION WITH SMAD2, IDENTIFICATION IN ARF1 COMPLEX, AND
RP IDENTIFICATION OF SMAD INTERACTION DOMAIN.
RX PubMed=9288972; DOI=10.1038/38008;
RA Chen X., Weisberg E., Fridmacher V., Watanabe M., Naco G., Whitman M.;
RT "Smad4 and FAST-1 in the assembly of activin-responsive factor.";
RL Nature 389:85-89(1997).
RN [4]
RP FUNCTION, AND INTERACTION WITH SMAD2 AND SMAD3.
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 [5]
RP FUNCTION.
RX PubMed=10572039; DOI=10.1242/dev.126.24.5621;
RA Watanabe M., Whitman M.;
RT "FAST-1 is a key maternal effector of mesoderm inducers in the early
RT Xenopus embryo.";
RL Development 126:5621-5634(1999).
RN [6]
RP FUNCTION.
RX PubMed=10473623; DOI=10.1074/jbc.274.37.26584;
RA Yeo C.Y., Chen X., Whitman M.;
RT "The role of FAST-1 and Smads in transcriptional regulation by activin
RT during early Xenopus embryogenesis.";
RL J. Biol. Chem. 274:26584-26590(1999).
RN [7]
RP INTERACTION WITH SMAD2, AND IDENTIFICATION OF SMAD INTERACTION MOTIF.
RX PubMed=10691736;
RA Germain S., Howell M., Esslemont G.M., Hill C.S.;
RT "Homeodomain and winged-helix transcription factors recruit activated Smads
RT to distinct promoter elements via a common Smad interaction motif.";
RL Genes Dev. 14:435-451(2000).
RN [8]
RP FUNCTION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=12050132; DOI=10.1242/dev.129.12.2823;
RA Howell M., Inman G.J., Hill C.S.;
RT "A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3)
RT cooperates with XFast-1 in regulating gastrulation movements.";
RL Development 129:2823-2834(2002).
RN [9]
RP FUNCTION, AND INTERACTION WITH GTF2IRD1.
RX PubMed=11937490; DOI=10.1101/gad.963802;
RA Ring C., Ogata S., Meek L., Song J., Ohta T., Miyazono K., Cho K.W.;
RT "The role of a Williams-Beuren syndrome-associated helix-loop-helix domain-
RT containing transcription factor in activin/nodal signaling.";
RL Genes Dev. 16:820-835(2002).
RN [10]
RP SUBUNIT.
RX PubMed=12374795; DOI=10.1074/jbc.m208532200;
RA Inman G.J., Hill C.S.;
RT "Stoichiometry of active smad-transcription factor complexes on DNA.";
RL J. Biol. Chem. 277:51008-51016(2002).
RN [11]
RP INTERACTION WITH SMAD2, AND IDENTIFICATION OF FAST/FOXH1 MOTIF.
RX PubMed=14729957; DOI=10.1128/mcb.24.3.1106-1121.2004;
RA Randall R.A., Howell M., Page C.S., Daly A., Bates P.A., Hill C.S.;
RT "Recognition of phosphorylated-Smad2-containing complexes by a novel Smad
RT interaction motif.";
RL Mol. Cell. Biol. 24:1106-1121(2004).
RN [12]
RP REVIEW.
RX PubMed=15656969; DOI=10.1016/j.gene.2004.09.037;
RA Pohl B.S., Knoechel W.;
RT "Of fox and frogs: fox (fork head/winged helix) transcription factors in
RT Xenopus development.";
RL Gene 344:21-32(2005).
CC -!- FUNCTION: Transcriptional activator. Recognizes and binds to the DNA
CC sequence 5'-TGT[GT][GT]ATT-3'. Upon TGF-beta induction, forms a
CC transcriptionally active complex with smad2 and smad4 called activin-
CC responsive factor 1 (ARF1), which binds a site on the mix-B/mix.2
CC promoter called the activin response element (ARE). Binds to activated
CC smads and the ARE with much lower affinity than fast3. Necessary for
CC the first steps in mesoderm specification, directly inducing mesodermal
CC genes. Acts with fast3 to control the convergent extension movements of
CC gastrulation. Binds to the proximal element (PE) of the gsc gene and
CC cooperates with gtf2ird1/wbscr11 and SMAD proteins to regulate gsc
CC transcription. {ECO:0000269|PubMed:10349617,
CC ECO:0000269|PubMed:10473623, ECO:0000269|PubMed:10572039,
CC ECO:0000269|PubMed:11937490, ECO:0000269|PubMed:12050132,
CC ECO:0000269|PubMed:8878477, ECO:0000269|PubMed:9288972}.
CC -!- SUBUNIT: ARF1 contains 2 smad2s, 1 smad4 and 1 foxh1/fast-1 protein.
CC Interaction with smad4 is most likely indirect through interaction with
CC the MH2 domain of smad2. Binds to the MH2 domain of smad3, which can
CC incorporate into the ARF1 complex. The ARF1 and ARF2 complexes are
CC activated by distinct TGF-beta family members; formation of ARF1 is
CC promoted by activin. Interacts (via Fork-head domain) with
CC gtf2ird1/wbscr11 (via repeats 4-5). {ECO:0000269|PubMed:10349617,
CC ECO:0000269|PubMed:10691736, ECO:0000269|PubMed:11937490,
CC ECO:0000269|PubMed:12050132, ECO:0000269|PubMed:12374795,
CC ECO:0000269|PubMed:14729957, ECO:0000269|PubMed:8878477,
CC ECO:0000269|PubMed:9288972}.
CC -!- INTERACTION:
CC P70056; Q15796: SMAD2; Xeno; NbExp=4; IntAct=EBI-9969973, EBI-1040141;
CC P70056; Q13485: SMAD4; Xeno; NbExp=2; IntAct=EBI-9969973, EBI-347263;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089,
CC ECO:0000269|PubMed:8878477}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the animal cap (prospective
CC ectoderm) and prospective mesoderm of stage 10.25 embryos.
CC {ECO:0000269|PubMed:12050132}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Present
CC in oocytes and in early embryos until shortly after gastrulation, after
CC which levels decline and remain low through tadpole development.
CC {ECO:0000269|PubMed:8878477}.
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.
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DR EMBL; U70980; AAC60219.1; -; mRNA.
DR EMBL; BC160705; AAI60705.1; -; mRNA.
DR RefSeq; NP_001081820.1; NM_001088351.1.
DR AlphaFoldDB; P70056; -.
DR SMR; P70056; -.
DR IntAct; P70056; 2.
DR GeneID; 398070; -.
DR KEGG; xla:398070; -.
DR CTD; 398070; -.
DR Xenbase; XB-GENE-1194377; foxh1.L.
DR Proteomes; UP000186698; Chromosome 6L.
DR GO; GO:0032444; C:activin responsive factor complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0032924; P:activin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISS:UniProtKB.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IMP:UniProtKB.
DR GO; GO:0007501; P:mesodermal cell fate specification; IMP:UniProtKB.
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:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
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; Developmental protein; DNA-binding; Gastrulation; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..518
FT /note="Forkhead box protein H1"
FT /id="PRO_0000091845"
FT DNA_BIND 117..213
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 72..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..506
FT /note="SMAD-interaction domain (SID)"
FT MOTIF 405..409
FT /note="Fast/FoxH1 motif 1 (FM1)"
FT MOTIF 415..421
FT /note="Fast/FoxH1 motif 2 (FM2)"
FT MOTIF 470..491
FT /note="SMAD interaction motif (SIM)"
FT COMPBIAS 87..105
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 356..379
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 50
FT /note="H -> P (in Ref. 1; AAC60219)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="Q -> H (in Ref. 1; AAC60219)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="N -> Y (in Ref. 1; AAC60219)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 518 AA; 57445 MW; 1BEC587943F92D1F CRC64;
MRDPSSLYSG FPAGSQYESV EPPSLALLSS IDQEQLPVAT GQSYNHSVQH WPQPWPPLSL
YREGGTWSPD RGSMYGLSPG THEGSCTHTH EGPKDSMAGD QTRSRKSKKK NYHRYNKPPY
SYLAMIALVI QNSPEKRLKL SQILKEVSTL FPFFNGDYMG WKDSIRHNLS SSDCFKKILK
DPGKPQAKGN FWTVDVSRIP LDAMKLQNTA LTRGGSDYFV QDLAPYILHN YKYEHNAGAY
GHQMPPSHAR SLSLAEDSQQ TNTGGKLNTS FMIDSLLHDL QEVDLPDASR NLENQRISPA
VAMNNMWSSA PLLYTHSKPT RNARSPGLST IHSTYSSSSS SISTISPVGF QKEQEKSGRQ
TQRVGHPIKR SREDDDCSTT SSDPDTGNYS PIEPPKKMPL LSLDLPTSYT KSVAPNVVAP
PSVLPFFHFP RFTYYNYGPS PYMTPPYWGF PHPTNSGGDS PRGPQSPLDL DNMLRAMPPN
KSVFDVLTSH PGDLVHPSFL SQCLGSSGSP YPSRQGLM
