HES2_HUMAN
ID HES2_HUMAN Reviewed; 173 AA.
AC Q9Y543; A2RTZ9; Q96EN4; Q9Y542;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Transcription factor HES-2;
DE AltName: Full=Class B basic helix-loop-helix protein 40;
DE Short=bHLHb40;
DE AltName: Full=Hairy and enhancer of split 2;
GN Name=HES2; Synonyms=BHLHB40;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Eye;
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).
RN [5]
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. {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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y543-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y543-2; Sequence=VSP_002104;
CC -!- TISSUE SPECIFICITY: Expressed in placenta, pancreatic cancer, colon
CC cancer with RER, cervical cancer, and in head and neck 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).
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; AK091122; BAG52286.1; -; mRNA.
DR EMBL; AL031848; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71533.1; -; Genomic_DNA.
DR EMBL; BC012091; AAH12091.1; -; mRNA.
DR EMBL; BC132698; AAI32699.1; -; mRNA.
DR EMBL; BC136963; AAI36964.1; -; mRNA.
DR EMBL; BC142687; AAI42688.1; -; mRNA.
DR CCDS; CCDS30574.1; -. [Q9Y543-1]
DR RefSeq; NP_061962.2; NM_019089.4. [Q9Y543-1]
DR AlphaFoldDB; Q9Y543; -.
DR SMR; Q9Y543; -.
DR BioGRID; 120083; 7.
DR ELM; Q9Y543; -.
DR STRING; 9606.ENSP00000367065; -.
DR PhosphoSitePlus; Q9Y543; -.
DR BioMuta; HES2; -.
DR DMDM; 12643954; -.
DR PaxDb; Q9Y543; -.
DR PeptideAtlas; Q9Y543; -.
DR PRIDE; Q9Y543; -.
DR ProteomicsDB; 86285; -. [Q9Y543-1]
DR ProteomicsDB; 86286; -. [Q9Y543-2]
DR Antibodypedia; 27325; 285 antibodies from 22 providers.
DR DNASU; 54626; -.
DR Ensembl; ENST00000377834.8; ENSP00000367065.4; ENSG00000069812.11. [Q9Y543-1]
DR Ensembl; ENST00000377836.8; ENSP00000367067.4; ENSG00000069812.11. [Q9Y543-2]
DR Ensembl; ENST00000377837.5; ENSP00000367068.1; ENSG00000069812.11. [Q9Y543-2]
DR GeneID; 54626; -.
DR KEGG; hsa:54626; -.
DR MANE-Select; ENST00000377834.8; ENSP00000367065.4; NM_019089.5; NP_061962.2.
DR UCSC; uc001amw.5; human. [Q9Y543-1]
DR CTD; 54626; -.
DR DisGeNET; 54626; -.
DR GeneCards; HES2; -.
DR HGNC; HGNC:16005; HES2.
DR HPA; ENSG00000069812; Tissue enhanced (esophagus, skin, vagina).
DR MIM; 609970; gene.
DR neXtProt; NX_Q9Y543; -.
DR OpenTargets; ENSG00000069812; -.
DR PharmGKB; PA134958805; -.
DR VEuPathDB; HostDB:ENSG00000069812; -.
DR eggNOG; KOG4304; Eukaryota.
DR GeneTree; ENSGT00940000161602; -.
DR HOGENOM; CLU_187816_0_0_1; -.
DR InParanoid; Q9Y543; -.
DR OMA; THCANEV; -.
DR OrthoDB; 1427802at2759; -.
DR PhylomeDB; Q9Y543; -.
DR TreeFam; TF351373; -.
DR PathwayCommons; Q9Y543; -.
DR SignaLink; Q9Y543; -.
DR BioGRID-ORCS; 54626; 9 hits in 1084 CRISPR screens.
DR ChiTaRS; HES2; human.
DR GenomeRNAi; 54626; -.
DR Pharos; Q9Y543; Tdark.
DR PRO; PR:Q9Y543; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y543; protein.
DR Bgee; ENSG00000069812; Expressed in esophagus mucosa and 101 other tissues.
DR ExpressionAtlas; Q9Y543; baseline and differential.
DR Genevisible; Q9Y543; 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:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
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: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 Alternative splicing; DNA-binding; Nucleus; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..173
FT /note="Transcription factor HES-2"
FT /id="PRO_0000127206"
FT DOMAIN 13..70
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 86..119
FT /note="Orange"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT REGION 128..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 170..173
FT /note="WRPW motif"
FT COMPBIAS 143..173
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 48..173
FT /note="NSNCSKLEKADVLEMTVRFLQELPASSWPTAAPLPCDSYREGYSACVARLAR
FT VLPACRVLEPAVSARLLEHLWRRAASATLDGGRAGDSSGPSAPAPAPASAPEPASAPVP
FT SPPSPPCGPGLWRPW -> DASGWHTWLPLHAQNCFLLYIQAPEQPPA (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_002104"
FT VARIANT 139
FT /note="P -> S (in dbSNP:rs2235687)"
FT /id="VAR_061256"
SQ SEQUENCE 173 AA; 18470 MW; B3751F4576E84F3D CRC64;
MGLPRRAGDA AELRKSLKPL LEKRRRARIN QSLSQLKGLI LPLLGRENSN CSKLEKADVL
EMTVRFLQEL PASSWPTAAP LPCDSYREGY SACVARLARV LPACRVLEPA VSARLLEHLW
RRAASATLDG GRAGDSSGPS APAPAPASAP EPASAPVPSP PSPPCGPGLW RPW
