ID HES5_HUMAN Reviewed; 166 AA. AC Q5TA89; B9DI85; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 24-JAN-2024, entry version 144. DE RecName: Full=Transcription factor HES-5; DE AltName: Full=Class B basic helix-loop-helix protein 38; DE Short=bHLHb38; DE AltName: Full=Hairy and enhancer of split 5; GN Name=HES5; Synonyms=BHLHB38; 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]. RA Wistow G.; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. 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 GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP IDENTIFICATION, AND TISSUE SPECIFICITY. RX PubMed=15254753; RA Katoh M., Katoh M.; RT "Identification and characterization of human HES2, HES3, and HES5 genes in RT silico."; RL Int. J. Oncol. 25:529-534(2004). CC -!- FUNCTION: Transcriptional repressor of genes that require a bHLH CC protein for their transcription. Plays an important role as CC neurogenesis negative regulator (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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380, CC ECO:0000255|PROSITE-ProRule:PRU00981}. CC -!- TISSUE SPECIFICITY: Expressed in fetal heart and brain tumors. CC {ECO:0000269|PubMed:15254753}. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; DQ272660; ABB83829.1; -; mRNA. DR EMBL; AL139246; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471183; EAW56096.1; -; Genomic_DNA. DR CCDS; CCDS41233.1; -. DR RefSeq; NP_001010926.1; NM_001010926.3. DR AlphaFoldDB; Q5TA89; -. DR SMR; Q5TA89; -. DR BioGRID; 132759; 4. DR STRING; 9606.ENSP00000367714; -. DR iPTMnet; Q5TA89; -. DR PhosphoSitePlus; Q5TA89; -. DR BioMuta; HES5; -. DR DMDM; 74745795; -. DR MassIVE; Q5TA89; -. DR PaxDb; 9606-ENSP00000367714; -. DR PeptideAtlas; Q5TA89; -. DR ProteomicsDB; 64837; -. DR Antibodypedia; 26785; 264 antibodies from 35 providers. DR DNASU; 388585; -. DR Ensembl; ENST00000378453.4; ENSP00000367714.3; ENSG00000197921.6. DR Ensembl; ENST00000612705.2; ENSP00000482150.1; ENSG00000273529.2. DR GeneID; 388585; -. DR KEGG; hsa:388585; -. DR MANE-Select; ENST00000378453.4; ENSP00000367714.3; NM_001010926.4; NP_001010926.1. DR UCSC; uc001ajn.3; human. DR AGR; HGNC:19764; -. DR CTD; 388585; -. DR DisGeNET; 388585; -. DR GeneCards; HES5; -. DR HGNC; HGNC:19764; HES5. DR HPA; ENSG00000197921; Tissue enhanced (brain, skin). DR MIM; 607348; gene. DR neXtProt; NX_Q5TA89; -. DR OpenTargets; ENSG00000197921; -. DR PharmGKB; PA134967985; -. DR VEuPathDB; HostDB:ENSG00000197921; -. DR eggNOG; ENOG502S6S1; Eukaryota. DR GeneTree; ENSGT00940000162836; -. DR HOGENOM; CLU_068550_3_1_1; -. DR InParanoid; Q5TA89; -. DR OMA; EVQTQAH; -. DR OrthoDB; 2961710at2759; -. DR PhylomeDB; Q5TA89; -. DR TreeFam; TF351373; -. DR PathwayCommons; Q5TA89; -. DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription. DR Reactome; R-HSA-2197563; NOTCH2 intracellular domain regulates transcription. DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants. DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription. DR Reactome; R-HSA-9013695; NOTCH4 Intracellular Domain Regulates Transcription. DR SignaLink; Q5TA89; -. DR SIGNOR; Q5TA89; -. DR BioGRID-ORCS; 388585; 13 hits in 1165 CRISPR screens. DR GeneWiki; HES5; -. DR GenomeRNAi; 388585; -. DR Pharos; Q5TA89; Tbio. DR PRO; PR:Q5TA89; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q5TA89; Protein. DR Bgee; ENSG00000197921; Expressed in primordial germ cell in gonad and 78 other cell types or tissues. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB. 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:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central. DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB. DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl. DR GO; GO:0007420; P:brain development; ISS:UniProtKB. DR GO; GO:0043010; P:camera-type eye development; ISS:UniProtKB. DR GO; GO:0051216; P:cartilage development; IDA:UniProtKB. DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB. DR GO; GO:0048469; P:cell maturation; ISS:UniProtKB. DR GO; GO:0022010; P:central nervous system myelination; ISS:UniProtKB. DR GO; GO:0072049; P:comma-shaped body morphogenesis; IEA:Ensembl. DR GO; GO:0090162; P:establishment of epithelial cell polarity; IEA:Ensembl. DR GO; GO:0021861; P:forebrain radial glial cell differentiation; IEA:Ensembl. DR GO; GO:0021781; P:glial cell fate commitment; ISS:UniProtKB. DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl. DR GO; GO:0060122; P:inner ear receptor cell stereocilium organization; IEA:Ensembl. DR GO; GO:0072282; P:metanephric nephron tubule morphogenesis; IEA:Ensembl. DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; ISS:UniProtKB. DR GO; GO:2000978; P:negative regulation of forebrain neuron differentiation; IEA:Ensembl. DR GO; GO:0045608; P:negative regulation of inner ear auditory receptor cell differentiation; IEA:Ensembl. DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB. DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISS:UniProtKB. DR GO; GO:2000974; P:negative regulation of pro-B cell differentiation; ISS:UniProtKB. DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0021915; P:neural tube development; ISS:UniProtKB. DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEP:UniProtKB. DR GO; GO:0007219; P:Notch signaling pathway; IMP:UniProtKB. DR GO; GO:0014003; P:oligodendrocyte development; ISS:UniProtKB. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IGI:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB. DR GO; GO:0045595; P:regulation of cell differentiation; ISS:UniProtKB. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0031641; P:regulation of myelination; ISS:UniProtKB. DR GO; GO:0050767; P:regulation of neurogenesis; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0072050; P:S-shaped body morphogenesis; IEA:Ensembl. DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB. DR GO; GO:0072086; P:specification of loop of Henle identity; IEA:Ensembl. DR GO; GO:0021537; P:telencephalon development; ISS:UniProtKB. DR CDD; cd11461; bHLH-O_HES5; 1. DR Gene3D; 4.10.280.10; Helix-loop-helix DNA-binding domain; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR036638; HLH_DNA-bd_sf. DR InterPro; IPR003650; Orange_dom. DR PANTHER; PTHR10985; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTOR, HES-RELATED; 1. DR PANTHER; PTHR10985:SF104; TRANSCRIPTION FACTOR HES-5; 1. DR Pfam; PF07527; Hairy_orange; 1. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SMART; SM00511; ORANGE; 1. DR SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1. DR PROSITE; PS50888; BHLH; 1. DR PROSITE; PS51054; ORANGE; 1. DR Genevisible; Q5TA89; HS. PE 2: Evidence at transcript level; KW Developmental protein; Differentiation; DNA-binding; Neurogenesis; Nucleus; KW Reference proteome; Repressor; Transcription; Transcription regulation. FT CHAIN 1..166 FT /note="Transcription factor HES-5" FT /id="PRO_0000269175" FT DOMAIN 16..72 FT /note="bHLH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981" FT DOMAIN 88..119 FT /note="Orange" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380" FT REGION 125..144 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 163..166 FT /note="WRPW motif" FT COMPBIAS 126..140 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" SQ SEQUENCE 166 AA; 18226 MW; 6B0ECF2482EBE43B CRC64; MAPSTVAVEL LSPKEKNRLR KPVVEKMRRD RINSSIEQLK LLLEQEFARH QPNSKLEKAD ILEMAVSYLK HSKAFVAAAG PKSLHQDYSE GYSWCLQEAV QFLTLHAASD TQMKLLYHFQ RPPAAPAAPA KEPKAPGAAP PPALSAKATA AAAAAHQPAC GLWRPW //