HES4_XENTR
ID HES4_XENTR Reviewed; 281 AA.
AC Q6PBD4;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Transcription factor HES-4 {ECO:0000250|UniProtKB:Q9HCC6};
DE AltName: Full=Hairy and enhancer of split 4;
DE AltName: Full=Protein hairy-2;
GN Name=hes4; Synonyms=hairy2 {ECO:0000250|UniProtKB:Q90VV1};
GN ORFNames=TNeu056p12.2;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1] {ECO:0000312|EMBL:AAZ04408.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Qin S., Dors M., Johnson E., Bloom S., Hood L., Rowen L.;
RT "Sequence of Xenopus tropicalis development genes.";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:AAZ04408.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula {ECO:0000312|EMBL:CAJ82465.1};
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAZ04408.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula {ECO:0000312|EMBL:CAJ82465.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
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. Also acts via repressor-dependent and repressor-independent
CC mechanisms in early gastrulae to establish the prospective anterior
CC prechordal mesoderm identity in the Spemann organizer; induces specific
CC genes independently from direct transcriptional regulation, and
CC 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q90VV1}.
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. Binds DNA in the form of a heterodimer with the
CC bHLH protein hey1/hrt1. Interacts (via Orange domain) with id3 (via HLH
CC domain) (By similarity). {ECO:0000250|UniProtKB:P14003,
CC ECO:0000250|UniProtKB:Q90VV1, ECO:0000250|UniProtKB:Q90Z12}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P14003,
CC ECO:0000255|PROSITE-ProRule:PRU00380, ECO:0000255|PROSITE-
CC ProRule:PRU00981}.
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. The WPRW motif is also required for the inductive
CC function, independent of transcription regulation activity (By
CC similarity). {ECO:0000250|UniProtKB:P14003,
CC ECO:0000250|UniProtKB:Q90VV1}.
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DR EMBL; AC151819; AAZ04408.1; -; Genomic_DNA.
DR EMBL; CR760275; CAJ82465.1; -; mRNA.
DR EMBL; BC059761; AAH59761.1; -; mRNA.
DR RefSeq; NP_988870.1; NM_203539.1.
DR AlphaFoldDB; Q6PBD4; -.
DR SMR; Q6PBD4; -.
DR STRING; 8364.ENSXETP00000055937; -.
DR PaxDb; Q6PBD4; -.
DR DNASU; 394465; -.
DR GeneID; 394465; -.
DR KEGG; xtr:394465; -.
DR CTD; 57801; -.
DR Xenbase; XB-GENE-487830; hes4.
DR eggNOG; KOG4304; Eukaryota.
DR HOGENOM; CLU_068550_1_0_1; -.
DR InParanoid; Q6PBD4; -.
DR OrthoDB; 1427802at2759; -.
DR PhylomeDB; Q6PBD4; -.
DR Proteomes; UP000008143; Chromosome 7.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000001769; Expressed in neurula embryo and 28 other tissues.
DR ExpressionAtlas; Q6PBD4; baseline.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0033504; P:floor plate development; ISS:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:0048642; P:negative regulation of skeletal muscle tissue development; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0021501; P:prechordal plate formation; ISS:UniProtKB.
DR GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Developmental protein; Differentiation; DNA-binding; Myogenesis;
KW Neurogenesis; Notch signaling pathway; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..281
FT /note="Transcription factor HES-4"
FT /id="PRO_0000371247"
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"
SQ SEQUENCE 281 AA; 30170 MW; 7C0F2E271F9A8ADF CRC64;
MPADSMEKPT ASPIAGAPAS SAQTPDKPKS ASEHRKSSKP IMEKRRRARI NESLGQLKTL
ILDALKKDSS RHSKLEKADI LEMTVKHLRN LQRVQMTAAL TADPSVLGKY RAGFNECMNE
VTRFLSTCEG VNTEVRTRLL GHLSSCLGQI VAMNYQQPPS SQQPLHVQLP SSTPAPVPMP
CKVNPAEAIS PKVFQGGFQL VPATDGQFAF LIPNPAYTTS PGPVIPLYAN TNVTSPGGPQ
SQSPVQGLTT FGHKMPHMAQ AVSPLGGSTG ADSAESVWRP W
