HES4B_XENLA
ID HES4B_XENLA Reviewed; 277 AA.
AC Q90VV1;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Transcription factor HES-4-B;
DE AltName: Full=Hairy and enhancer of split 4-B;
DE AltName: Full=Protein hairy-2;
DE Short=Xhairy2 {ECO:0000303|PubMed:17436284};
DE AltName: Full=Protein hairy-2a;
DE Short=Xhairy2b {ECO:0000303|PubMed:17724611};
GN Name=hes4-b;
GN Synonyms=hairy2 {ECO:0000303|PubMed:17436284},
GN hairy2b {ECO:0000303|PubMed:11703945};
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] {ECO:0000305, ECO:0000312|EMBL:AAK63842.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Tail bud {ECO:0000269|PubMed:11703945};
RX PubMed=11703945; DOI=10.1016/s1534-5807(01)00054-5;
RA Davis R.L., Turner D.L., Evans L.M., Kirschner M.W.;
RT "Molecular targets of vertebrate segmentation: two mechanisms control
RT segmental expression of Xenopus hairy2 during somite formation.";
RL Dev. Cell 1:553-565(2001).
RN [2] {ECO:0000312|EMBL:AAK39552.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ishibashi S., Katamura M., Hashimoto C., Cho K.W.Y.;
RT "Involvement of hairy-related gene in organizer patterning.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAK39552.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney {ECO:0000312|EMBL:AAH70547.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP INTERACTION WITH HEY1.
RX PubMed=14648848; DOI=10.1002/dvdy.10406;
RA Van Wayenbergh R., Taelman V., Pichon B., Fischer A., Kricha S.,
RA Gessler M., Christophe D., Bellefroid E.J.;
RT "Identification of BOIP, a novel cDNA highly expressed during
RT spermatogenesis that encodes a protein interacting with the orange domain
RT of the hairy-related transcription factor HRT1/Hey1 in Xenopus and mouse.";
RL Dev. Dyn. 228:716-725(2003).
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12774230; DOI=10.1007/s00427-003-0338-4;
RA Tsuji S., Cho K.W.Y., Hashimoto C.;
RT "Expression pattern of a basic helix-loop-helix transcription factor
RT Xhairy2b during Xenopus laevis development.";
RL Dev. Genes Evol. 213:407-411(2003).
RN [6] {ECO:0000305}
RP INTERACTION WITH HEY1, AND TISSUE SPECIFICITY.
RX PubMed=15531363; DOI=10.1016/j.ydbio.2004.08.019;
RA Taelman V., Van Wayenbergh R., Soelter M., Pichon B., Pieler T.,
RA Christophe D., Bellefroid E.J.;
RT "Sequences downstream of the bHLH domain of the Xenopus hairy-related
RT transcription factor-1 act as an extended dimerization domain that
RT contributes to the selection of the partners.";
RL Dev. Biol. 276:47-63(2004).
RN [7] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16059909; DOI=10.1002/dvdy.20523;
RA Yamaguti M., Cho K.W.Y., Hashimoto C.;
RT "Xenopus hairy2b specifies anterior prechordal mesoderm identity within
RT Spemann's organizer.";
RL Dev. Dyn. 234:102-113(2005).
RN [8] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16316406; DOI=10.1111/j.1440-169x.2005.00823.x;
RA Cui Y.;
RT "Hairy is a cell context signal controlling Notch activity.";
RL Dev. Growth Differ. 47:609-625(2005).
RN [9] {ECO:0000305}
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16818449; DOI=10.1242/dev.02458;
RA Taelman V., Van Campenhout C., Soelter M., Pieler T., Bellefroid E.J.;
RT "The Notch-effector HRT1 gene plays a role in glomerular development and
RT patterning of the Xenopus pronephros anlagen.";
RL Development 133:2961-2971(2006).
RN [10] {ECO:0000305}
RP FUNCTION, AND FUNCTION OF WRPW MOTIF.
RX PubMed=16586347; DOI=10.1387/ijdb.052106ym;
RA Murato Y., Yamaguti M., Katamura M., Cho K.W.Y., Hashimoto C.;
RT "Two modes of action by which Xenopus hairy2b establishes tissue
RT demarcation in the Spemann-Mangold organizer.";
RL Int. J. Dev. Biol. 50:463-471(2006).
RN [11] {ECO:0000305}
RP FUNCTION.
RX PubMed=17436284; DOI=10.1002/dvdy.21152;
RA Nagatomo K., Hashimoto C.;
RT "Xenopus hairy2 functions in neural crest formation by maintaining cells in
RT a mitotic and undifferentiated state.";
RL Dev. Dyn. 236:1475-1483(2007).
RN [12] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=17724611; DOI=10.1007/s00427-007-0176-x;
RA Murato Y., Nagatomo K., Yamaguti M., Hashimoto C.;
RT "Two alloalleles of Xenopus laevis hairy2 gene-evolution of duplicated gene
RT function from a developmental perspective.";
RL Dev. Genes Evol. 217:665-673(2007).
RN [13] {ECO:0000305}
RP FUNCTION, INTERACTION WITH ID3, INDUCTION, AND MUTAGENESIS OF
RP 43-GLU--ARG-47.
RX PubMed=18721802; DOI=10.1016/j.ydbio.2008.08.003;
RA Nichane M., de Croze N., Ren X., Souopgui J., Monsoro-Burq A.H.,
RA Bellefroid E.J.;
RT "Hairy2-Id3 interactions play an essential role in Xenopus neural crest
RT progenitor specification.";
RL Dev. Biol. 322:355-367(2008).
RN [14] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF 43-GLU--ARG-47.
RX PubMed=18710660; DOI=10.1016/j.ydbio.2008.07.026;
RA Nichane M., Ren X., Souopgui J., Bellefroid E.J.;
RT "Hairy2 functions through both DNA-binding and non DNA-binding mechanisms
RT at the neural plate border in Xenopus.";
RL Dev. Biol. 322:368-380(2008).
RN [15] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19253409; DOI=10.1002/dvdy.21883;
RA Murato Y., Hashimoto C.;
RT "Xhairy2 functions in Xenopus lens development by regulating p27(xic1)
RT expression.";
RL Dev. Dyn. 238:2179-2192(2009).
CC -!- FUNCTION: Transcriptional repressor. Binds DNA on N-box motifs: 5'-
CC CACNAG-3'. Promotes floor plate development and prechordal plate
CC development. Required for lens development as early as the stage of
CC lens field formation, partly through regulation of gene expression of
CC the cell cycle inhibitor cdknx/p27(xic1). Required for formation of the
CC neural crest downstream of multiple signaling pathways, and acts at the
CC neural plate border via both DNA-binding dependent and independent
CC mechanisms; acts in a DNA-binding dependent manner to repress pro-
CC apoptotic and neural crest differentiation genes, including id3,
CC delta1, and cdknx/p27(xic1), and thus promote the cell survival of
CC neural plate border cells and maintain them in an undifferentiated
CC state. Represses transcription of id3, at least in part through the
CC repression of bmp4. On the other hand, acts in a DNA-independent manner
CC separate from the transcriptional repressor function, to stimulate cell
CC proliferation and promote neural crest formation. Via this DNA-
CC independent route, acts in neurulae upstream of stat3 to transiently
CC up-regulate the notch ligand dll1/delta1, which in turn up-regulates
CC id3 expression. Then interacts directly with id3, which blocks the
CC transcriptional repressor function of hes4-B/hairy2b to allow the
CC progression of neural crest progenitors through specification and
CC differentiation. Also acts via repressor-dependent and repressor-
CC independent mechanisms in early gastrulae to establish the prospective
CC anterior prechordal mesoderm identity in the Spemann organizer; induces
CC specific genes independently from direct transcriptional regulation,
CC and represses the genes specific for neighboring tissues through direct
CC transcriptional repression. Modulates lateral inhibition during notch
CC signaling and regulates the cell context dependent effects of notch
CC (which can have inhibitory, permissive or enhancing roles in muscle or
CC neural differentiation). Inhibits myogenesis.
CC {ECO:0000250|UniProtKB:Q90Z12, ECO:0000269|PubMed:16059909,
CC ECO:0000269|PubMed:16316406, ECO:0000269|PubMed:16586347,
CC ECO:0000269|PubMed:17436284, ECO:0000269|PubMed:17724611,
CC ECO:0000269|PubMed:18710660, ECO:0000269|PubMed:18721802,
CC ECO:0000269|PubMed:19253409}.
CC -!- SUBUNIT: Transcription repression requires formation of a complex with
CC a corepressor protein of the Groucho/TLE family. Interacts with the
CC bHLH protein hes6; this interaction may inhibit the transcriptional
CC repressor activity (By similarity). Binds DNA in the form of a
CC heterodimer with the bHLH protein hey1/hrt1. Interacts (via Orange
CC domain) with id3 (via HLH domain). {ECO:0000250|UniProtKB:P14003,
CC ECO:0000250|UniProtKB:Q90Z12, ECO:0000269|PubMed:14648848,
CC ECO:0000269|PubMed:15531363, ECO:0000269|PubMed:18721802}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P14003,
CC ECO:0000255|PROSITE-ProRule:PRU00380, ECO:0000255|PROSITE-
CC ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Dynamically expressed in the borders of several
CC tissue territories. Expressed in the pre-placodal ectoderm (PPE) from
CC gastrula stage. During gastrulation, expressed in the deep layer of the
CC dorsal lip, the Spemann organizer and three distinct regions in the
CC prospective neuroectoderm: neural plate border, presumptive floor
CC plate/notoplate and anterior neural plate. At later stages, expression
CC is localized to the anterior of the prechordal plate, the presomitic
CC mesoderm, neural tube, neural crest derivatives and several tissues of
CC the central nervous system, with expression in the developing floor
CC plate continues to at least the tadpole stage. From the early tailbud
CC stage, expressed in the dorsoanterior region of the developing
CC pronephros. During early tailbud stages, broadly expressed within the
CC pronephric mesoderm. and in the sensorial layer of the ectoderm
CC covering the pronephros anlagen. During late tailbud to early tadpole
CC stages, expressed in the ventral region of the pronephros. Expression
CC remains in the proximal and distal tubules at late tadpole stages
CC (stage 35). {ECO:0000269|PubMed:11703945, ECO:0000269|PubMed:12774230,
CC ECO:0000269|PubMed:15531363, ECO:0000269|PubMed:16059909,
CC ECO:0000269|PubMed:16316406, ECO:0000269|PubMed:16818449,
CC ECO:0000269|PubMed:17724611, ECO:0000269|PubMed:18710660,
CC ECO:0000269|PubMed:19253409}.
CC -!- DEVELOPMENTAL STAGE: Expressed zygotically. Shows higher zygotic
CC expression than hes4-A/hairy2a. {ECO:0000269|PubMed:12774230,
CC ECO:0000269|PubMed:17724611}.
CC -!- INDUCTION: By Notch-signaling. Acts in a complex regulatory loop with
CC other transcription factors and neural crest inducing signals at the
CC neural plate border. {ECO:0000269|PubMed:16059909,
CC ECO:0000269|PubMed:16316406, ECO:0000269|PubMed:16818449,
CC ECO:0000269|PubMed:18721802}.
CC -!- DOMAIN: Has a particular type of basic domain (presence of a helix-
CC interrupting proline) that binds to the N-box (CACNAG), rather than the
CC canonical E-box (CANNTG). {ECO:0000250|UniProtKB:P14003}.
CC -!- DOMAIN: The C-terminal WRPW motif is a transcriptional repression
CC domain necessary for the interaction with Groucho/TLE family members,
CC transcriptional corepressors recruited to specific target DNA by Hairy-
CC related proteins (By similarity). The WPRW motif is also required for
CC the inductive function, independent of a transcription regulation
CC activity. {ECO:0000250|UniProtKB:P14003, ECO:0000269|PubMed:16586347}.
CC -!- CAUTION: PubMed:17724611 reports that the probe used in PubMed:12774230
CC cross-hybridizes with hes4-A/hairy2a, so the maternal expression
CC reported in PubMed:12774230 is in fact due to hes4-A/hairy2a and not
CC hes4-B/hairy2b. {ECO:0000305}.
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DR EMBL; AF383160; AAK63842.1; -; mRNA.
DR EMBL; BC070547; AAH70547.1; -; mRNA.
DR EMBL; AF356000; AAK39552.1; -; mRNA.
DR RefSeq; NP_001082161.1; NM_001088692.1.
DR AlphaFoldDB; Q90VV1; -.
DR SMR; Q90VV1; -.
DR ELM; Q90VV1; -.
DR DNASU; 398258; -.
DR GeneID; 398258; -.
DR KEGG; xla:398258; -.
DR CTD; 398258; -.
DR Xenbase; XB-GENE-865740; hes4.L.
DR OMA; PCKLNPA; -.
DR OrthoDB; 1427802at2759; -.
DR Proteomes; UP000186698; Chromosome 7L.
DR Bgee; 398258; Expressed in heart and 19 other tissues.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IPI:UniProtKB.
DR GO; GO:0033504; P:floor plate development; IMP:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IMP:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0048642; P:negative regulation of skeletal muscle tissue development; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; IMP:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0021501; P:prechordal plate formation; IMP:UniProtKB.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR003650; Orange_dom.
DR Pfam; PF07527; Hairy_orange; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00511; ORANGE; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS51054; ORANGE; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Myogenesis;
KW Neurogenesis; Notch signaling pathway; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..277
FT /note="Transcription factor HES-4-B"
FT /id="PRO_0000371246"
FT DOMAIN 34..91
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 110..143
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 258..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 274..277
FT /note="WRPW motif"
FT /evidence="ECO:0000255"
FT COMPBIAS 28..44
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 43..47
FT /note="EKRRR->RELEE: Disrupts DNA-binding. Unable to
FT repress id3 transcription. Disrupts the ability to promote
FT cell survival and up-regulate neural border genes. Does not
FT disrupt the ability to promote cell proliferation and
FT neural crest cell formation."
FT /evidence="ECO:0000269|PubMed:18710660,
FT ECO:0000269|PubMed:18721802"
SQ SEQUENCE 277 AA; 29825 MW; F46C357B23484040 CRC64;
MPADSMEKPT ASPIAGAPAN SAQTPDKPKS ASEHRKSSKP IMEKRRRARI NESLGQLKTL
ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRVQMTAAL TADPSVLGKY RAGFNECMNE
VTRFLSTCEG VNTEVRTRLL GHLSSCLGQI VAMNYQQPPS SQQPVHVQLP SSTPVPMPCK
VNPAEAISPK VFQGGFQLVP ATDGQFAFLI PNPAYTSSPG PVIPLYANAT SPGGPPSQSP
VQGLTSFAHK MPHMAQAVSP LGGSTRADSA ESVWRPW
