HES4_HUMAN
ID HES4_HUMAN Reviewed; 221 AA.
AC Q9HCC6; Q5SVA5;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Transcription factor HES-4;
DE Short=hHES4;
DE AltName: Full=Class B basic helix-loop-helix protein 42;
DE Short=bHLHb42;
DE AltName: Full=Hairy and enhancer of split 4;
DE AltName: Full=bHLH factor Hes4;
GN Name=HES4; Synonyms=BHLHB42;
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].
RX PubMed=11260262; DOI=10.1046/j.1365-2443.2001.00409.x;
RA Bessho Y., Miyoshi G., Sakata R., Kageyama R.;
RT "Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the
RT presomitic mesoderm.";
RL Genes Cells 6:175-185(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Transcriptional repressor. Binds DNA on N-box motifs: 5'-
CC CACNAG-3' (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Transcription repression requires formation of a complex with
CC a corepressor protein of the Groucho/TLE family. {ECO:0000250}.
CC -!- INTERACTION:
CC Q9HCC6; Q01658: DR1; NbExp=3; IntAct=EBI-2680288, EBI-750300;
CC Q9HCC6; Q00403: GTF2B; NbExp=3; IntAct=EBI-2680288, EBI-389564;
CC Q9HCC6; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-2680288, EBI-1054873;
CC Q9HCC6; P42858: HTT; NbExp=12; IntAct=EBI-2680288, EBI-466029;
CC Q9HCC6; P37840: SNCA; NbExp=3; IntAct=EBI-2680288, EBI-985879;
CC Q9HCC6; Q13148: TARDBP; NbExp=6; IntAct=EBI-2680288, EBI-372899;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC ECO:0000255|PROSITE-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}.
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}.
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DR EMBL; AB048791; BAB13510.1; -; mRNA.
DR EMBL; AL645608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012351; AAH12351.1; -; mRNA.
DR CCDS; CCDS5.1; -.
DR RefSeq; NP_001135939.1; NM_001142467.1.
DR RefSeq; NP_066993.1; NM_021170.3.
DR AlphaFoldDB; Q9HCC6; -.
DR SMR; Q9HCC6; -.
DR BioGRID; 121772; 49.
DR IntAct; Q9HCC6; 18.
DR iPTMnet; Q9HCC6; -.
DR PhosphoSitePlus; Q9HCC6; -.
DR BioMuta; HES4; -.
DR UCD-2DPAGE; Q9HCC6; -.
DR EPD; Q9HCC6; -.
DR MassIVE; Q9HCC6; -.
DR PeptideAtlas; Q9HCC6; -.
DR PRIDE; Q9HCC6; -.
DR ProteomicsDB; 81667; -.
DR Antibodypedia; 12001; 101 antibodies from 26 providers.
DR DNASU; 57801; -.
DR Ensembl; ENST00000304952.11; ENSP00000304595.7; ENSG00000188290.11.
DR GeneID; 57801; -.
DR KEGG; hsa:57801; -.
DR MANE-Select; ENST00000304952.11; ENSP00000304595.7; NM_021170.4; NP_066993.1.
DR UCSC; uc001aci.3; human.
DR CTD; 57801; -.
DR DisGeNET; 57801; -.
DR GeneCards; HES4; -.
DR HGNC; HGNC:24149; HES4.
DR HPA; ENSG00000188290; Tissue enhanced (brain).
DR MIM; 608060; gene.
DR neXtProt; NX_Q9HCC6; -.
DR OpenTargets; ENSG00000188290; -.
DR PharmGKB; PA134975318; -.
DR VEuPathDB; HostDB:ENSG00000188290; -.
DR GeneTree; ENSGT00940000163056; -.
DR HOGENOM; CLU_068550_1_1_1; -.
DR InParanoid; Q9HCC6; -.
DR OrthoDB; 1427802at2759; -.
DR PhylomeDB; Q9HCC6; -.
DR PathwayCommons; Q9HCC6; -.
DR SignaLink; Q9HCC6; -.
DR BioGRID-ORCS; 57801; 8 hits in 1101 CRISPR screens.
DR GenomeRNAi; 57801; -.
DR Pharos; Q9HCC6; Tbio.
DR PRO; PR:Q9HCC6; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9HCC6; protein.
DR Bgee; ENSG00000188290; Expressed in ventricular zone and 155 other tissues.
DR ExpressionAtlas; Q9HCC6; baseline and differential.
DR Genevisible; Q9HCC6; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
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 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..221
FT /note="Transcription factor HES-4"
FT /id="PRO_0000127211"
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..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 216..219
FT /note="WRPW motif"
FT COMPBIAS 27..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 221 AA; 23523 MW; ADFAE485C36EEBC4 CRC64;
MAADTPGKPS ASPMAGAPAS ASRTPDKPRS AAEHRKSSKP VMEKRRRARI NESLAQLKTL
ILDALRKESS RHSKLEKADI LEMTVRHLRS LRRVQVTAAL SADPAVLGKY RAGFHECLAE
VNRFLAGCEG VPADVRSRLL GHLAACLRQL GPSRRPASLS PAAPAEAPAP EVYAGRPLLP
SLGGPFPLLA PPLLPGLTRA LPAAPRAGPQ GPGGPWRPWL R
