HES4A_XENLA
ID HES4A_XENLA Reviewed; 281 AA.
AC Q90Z12; Q6GR56; Q801T7; Q9YI65;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Transcription factor HES-4-A;
DE AltName: Full=Hairy and enhancer of split 4-A;
DE AltName: Full=Protein hairy-2;
DE Short=Xhairy2 {ECO:0000303|PubMed:17436284};
DE AltName: Full=Protein hairy-2a;
DE Short=Xhairy2a {ECO:0000303|PubMed:17724611};
GN Name=hes4-a;
GN Synonyms=hairy2 {ECO:0000312|EMBL:AAD43304.1},
GN hairy2a {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:AAK63841.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
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:0000305, ECO:0000312|EMBL:AAD43304.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Pourquie O., Mizuseki K., Kishi M., Sasai Y.;
RT "Xenopus hairy2, bHLH transcription factor.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAD43304.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH71075.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAD43304.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 69-281.
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH71075.1};
RA Mizuseki K., Kishi M., Matsui M., Nakanishi S., Sasai Y.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=9102304; DOI=10.1242/dev.124.6.1169;
RA Jen W.-C., Wettstein D., Turner D.L., Chitnis A., Kintner C.;
RT "The Notch ligand, X-Delta-2, mediates segmentation of the paraxial
RT mesoderm in Xenopus embryos.";
RL Development 124:1169-1178(1997).
RN [6] {ECO:0000305}
RP FUNCTION, DNA-BINDING, AND INTERACTION WITH HES6.
RX PubMed=10976052; DOI=10.1242/dev.127.19.4203;
RA Koyano-Nakagawa N., Kim J., Anderson D., Kintner C.;
RT "Hes6 acts in a positive feedback loop with the neurogenins to promote
RT neuronal differentiation.";
RL Development 127:4203-4216(2000).
RN [7] {ECO:0000305}
RP INDUCTION.
RX PubMed=12975341; DOI=10.1242/dev.00665;
RA Andreazzoli M., Gestri G., Cremisi F., Casarosa S., Dawid I.B.,
RA Barsacchi G.;
RT "Xrx1 controls proliferation and neurogenesis in Xenopus anterior neural
RT plate.";
RL Development 130:5143-5154(2003).
RN [8] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=14681193; DOI=10.1242/dev.00945;
RA Glavic A., Silva F., Aybar M.J., Bastidas F., Mayor R.;
RT "Interplay between Notch signaling and the homeoprotein Xiro1 is required
RT for neural crest induction in Xenopus embryos.";
RL Development 131:347-359(2004).
RN [9] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15689375; DOI=10.1242/dev.01659;
RA Lopez S.L., Rosato-Siri M.V., Franco P.G., Paganelli A.R., Carrasco A.E.;
RT "The Notch-target gene hairy2a impedes the involution of notochordal cells
RT by promoting floor plate fates in Xenopus embryos.";
RL Development 132:1035-1046(2005).
RN [10] {ECO:0000305}
RP INDUCTION.
RX PubMed=15843413; DOI=10.1242/dev.01814;
RA Gestri G., Carl M., Appolloni I., Wilson S.W., Barsacchi G.,
RA Andreazzoli M.;
RT "Six3 functions in anterior neural plate specification by promoting cell
RT proliferation and inhibiting Bmp4 expression.";
RL Development 132:2401-2413(2005).
RN [11] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=16077089; DOI=10.1242/dev.01937;
RA Lamar E., Kintner C.;
RT "The Notch targets Esr1 and Esr10 are differentially regulated in Xenopus
RT neural precursors.";
RL Development 132:3619-3630(2005).
RN [12] {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 [13] {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 [14] {ECO:0000305}
RP FUNCTION.
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 [15] {ECO:0000305}
RP FUNCTION.
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 [16] {ECO:0000305}
RP FUNCTION.
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'. Plays a role in the patterning of tissue boundaries.
CC Promotes floor plate development and prechordal plate development.
CC Required for lens development as early as the stage of lens field
CC formation, partly through regulation of gene expression of the cell
CC cycle inhibitor cdknx/p27(xic1). A role in neural crest development is
CC disputed. {ECO:0000269|PubMed:10976052, ECO:0000269|PubMed:14681193,
CC ECO:0000269|PubMed:15689375, ECO:0000269|PubMed:17436284,
CC ECO:0000269|PubMed:17724611, ECO:0000269|PubMed:18710660,
CC ECO:0000269|PubMed:18721802, ECO:0000269|PubMed:19253409}.
CC -!- SUBUNIT: Transcription repression requires formation of a complex with
CC a corepressor protein of the Groucho/TLE family. Binds DNA in the form
CC of a heterodimer with the bHLH protein hey1/hrt1. Interacts (via Orange
CC domain) with id3 (via HLH domain) (By similarity). Interacts with the
CC bHLH protein hes6; this interaction may inhibit the transcriptional
CC repressor activity. {ECO:0000250|UniProtKB:P14003,
CC ECO:0000250|UniProtKB:Q90VV1, ECO:0000269|PubMed:10976052}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P14003,
CC ECO:0000255|PROSITE-ProRule:PRU00380, ECO:0000255|PROSITE-
CC ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: Shows a complex and dynamic expression pattern in
CC developing embryos. In neurulae, expressed in the presumptive floor
CC plate, the anterior part of the prechordal plate and in the anterior
CC neural border. In tailbud embryos, expressed in various neuroectoderm
CC derivatives and in the mesoderm, where expression is limited to the
CC presomitic mesoderm (PSM) and pronephros. In the PSM, expressed in an
CC anterior stripe prior to the formation of each somite. Expression in
CC the presumptive neural crest is disputed. {ECO:0000269|PubMed:11703945,
CC ECO:0000269|PubMed:14681193, ECO:0000269|PubMed:15689375,
CC ECO:0000269|PubMed:16077089, ECO:0000269|PubMed:17724611,
CC ECO:0000269|PubMed:9102304}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Shows
CC lower zygotic expression than hes4-B/hairy2b.
CC {ECO:0000269|PubMed:17724611}.
CC -!- INDUCTION: By Notch-signaling. Acts in a complex regulatory loop with
CC other bHLH proteins. {ECO:0000269|PubMed:11703945,
CC ECO:0000269|PubMed:12975341, ECO:0000269|PubMed:14681193,
CC ECO:0000269|PubMed:15689375, ECO:0000269|PubMed:15843413}.
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. {ECO:0000250|UniProtKB:P14003}.
CC -!- CAUTION: Multiple papers report expression in the developing neural
CC crest and a role in neural crest formation. However, PubMed:17724611
CC reports differences between the duplicated hes4 gene products and shows
CC that hes4-B/hairy2b but not hes4-A/hairy2a has a role in neural crest
CC formation, and that hes4-B/hairy2b but not hes4-A/hairy2a is expressed
CC in the presumptive neural crest. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD01745.1; Type=Miscellaneous discrepancy; Note=Probable intron retention at N-terminus and possible frameshift and contaminating sequence at C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF383159; AAK63841.1; -; mRNA.
DR EMBL; AF139914; AAD43304.1; -; mRNA.
DR EMBL; BC071075; AAH71075.1; -; mRNA.
DR EMBL; AF022798; AAD01745.1; ALT_SEQ; mRNA.
DR RefSeq; NP_001082574.1; NM_001089105.1.
DR AlphaFoldDB; Q90Z12; -.
DR SMR; Q90Z12; -.
DR ELM; Q90Z12; -.
DR DNASU; 398579; -.
DR GeneID; 398579; -.
DR KEGG; xla:398579; -.
DR CTD; 398579; -.
DR Xenbase; XB-GENE-6256031; hes4.S.
DR OrthoDB; 1427802at2759; -.
DR Proteomes; UP000186698; Chromosome 7S.
DR Bgee; 398579; Expressed in heart and 19 other tissues.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IMP: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:0043066; P:negative regulation of apoptotic process; 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: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; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..281
FT /note="Transcription factor HES-4-A"
FT /id="PRO_0000371245"
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 262..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 278..281
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 CONFLICT 20
FT /note="N -> S (in Ref. 3; AAH71075)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="M -> T (in Ref. 1; AAK63841)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="N -> S (in Ref. 1; AAK63841)"
FT /evidence="ECO:0000305"
FT CONFLICT 230..231
FT /note="Missing (in Ref. 2; AAD43304)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 281 AA; 30216 MW; 7EC0CDF0DD31F8D1 CRC64;
MPADTMEKPT ASPIAGAPAN SAQTPDKPKS ASEHRKSSKP IMEKRRRARI NESLGQLKTL
ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRVQMTAAL TSDPSVLGKY RAGFNECTNE
VTRFLSTCEG VNTEVRTRLL GHLSSCLGQI VAMNYQQPPS SQQPLHVQLP SSTPAPMPIS
CKVNPAEAIS PKVFQGGFQL VPATDGQFAF LIPNPAYTSS PGPVIPLYAN ANVTSPGGRQ
SQSPVQGLTT FGHKMPHMAQ AVSPLGGSTG ADSAESVWRP W
