ID   HES6_MOUSE              Reviewed;         224 AA.
AC   Q9JHE6; Q3U2D7;
DT   19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 150.
DE   RecName: Full=Transcription cofactor HES-6;
DE   AltName: Full=Hairy and enhancer of split 6;
GN   Name=Hes6 {ECO:0000312|EMBL:BAA96081.1};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:BAA96081.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH HES1, AND
RP   DEVELOPMENTAL STAGE.
RC   TISSUE=Embryo {ECO:0000269|PubMed:10851137};
RX   PubMed=10851137; DOI=10.1242/dev.127.13.2933;
RA   Bae S.-K., Bessho Y., Hojo M., Kageyama R.;
RT   "The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal
RT   differentiation.";
RL   Development 127:2933-2943(2000).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:AAF63757.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=10906477; DOI=10.1016/s0925-4773(00)00348-8;
RA   Pissarra L., Henrique D., Duarte A.;
RT   "Expression of hes6, a new member of the Hairy/Enhancer-of-split family, in
RT   mouse development.";
RL   Mech. Dev. 95:275-278(2000).
RN   [3] {ECO:0000305, ECO:0000312|EMBL:AAK51633.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J {ECO:0000312|EMBL:AAK51633.1};
RX   PubMed=11044617; DOI=10.1016/s0925-4773(00)00443-3;
RA   Vasiliauskas D., Stern C.D.;
RT   "Expression of mouse HES-6, a new member of the Hairy/Enhancer of split
RT   family of bHLH transcription factors.";
RL   Mech. Dev. 98:133-137(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Embryo;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5] {ECO:0000305, ECO:0000312|EMBL:AAH12897.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II {ECO:0000312|EMBL:AAH12897.1}; TISSUE=Mammary tumor;
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: Does not bind DNA itself but suppresses both HES1-mediated N
CC       box-dependent transcriptional repression and binding of HES1 to E box
CC       sequences. Also suppresses HES1-mediated inhibition of the heterodimer
CC       formed by ASCL1/MASH1 and TCF3/E47, allowing ASCL1 and TCF3 to up-
CC       regulate transcription in its presence. Promotes cell differentiation.
CC       {ECO:0000269|PubMed:10851137}.
CC   -!- SUBUNIT: Transcription repression requires formation of a complex with
CC       a corepressor protein of the Groucho/TLE family (By similarity).
CC       Interacts with HES1. {ECO:0000250, ECO:0000269|PubMed:10851137}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in both undifferentiated and
CC       differentiated cells. High levels of expression are observed in several
CC       embryonic tissues including the nervous system, muscle and thymus. In
CC       the nervous system, initially expressed in the closing neural tube,
CC       then in the spinal cord, cranial and dorsal root ganglia, and brain
CC       neuroepithelium. Also expressed in epithelial cells of the embryonic
CC       respiratory, urinary and digestive systems. In the limb buds, expressed
CC       in skeletal muscle and presumptive tendons.
CC       {ECO:0000269|PubMed:10906477, ECO:0000269|PubMed:11044617}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in both embryo and adult. Expression in
CC       the embryo is detected from 8.5 dpc. In the retina, expressed at high
CC       levels at postnatal 0 dpc. Expression in brain and retina decreases
CC       postnatally but still detectable in adult.
CC       {ECO:0000269|PubMed:10851137}.
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   -!- 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).
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DR   EMBL; AB035178; BAA96081.1; -; mRNA.
DR   EMBL; AF247040; AAF63757.1; -; mRNA.
DR   EMBL; AF260236; AAK51633.1; -; mRNA.
DR   EMBL; AK013443; BAB28856.1; -; mRNA.
DR   EMBL; AK076135; BAC36210.1; -; mRNA.
DR   EMBL; AK155340; BAE33204.1; -; mRNA.
DR   EMBL; BC012897; AAH12897.1; -; mRNA.
DR   CCDS; CCDS15163.1; -.
DR   RefSeq; NP_062352.1; NM_019479.3.
DR   AlphaFoldDB; Q9JHE6; -.
DR   SMR; Q9JHE6; -.
DR   BioGRID; 207731; 6.
DR   IntAct; Q9JHE6; 4.
DR   STRING; 10090.ENSMUSP00000084062; -.
DR   PhosphoSitePlus; Q9JHE6; -.
DR   PaxDb; 10090-ENSMUSP00000084062; -.
DR   ProteomicsDB; 269659; -.
DR   Antibodypedia; 20277; 340 antibodies from 31 providers.
DR   DNASU; 55927; -.
DR   Ensembl; ENSMUST00000086851.2; ENSMUSP00000084062.2; ENSMUSG00000067071.9.
DR   GeneID; 55927; -.
DR   KEGG; mmu:55927; -.
DR   UCSC; uc007cau.1; mouse.
DR   AGR; MGI:1859852; -.
DR   CTD; 55502; -.
DR   MGI; MGI:1859852; Hes6.
DR   VEuPathDB; HostDB:ENSMUSG00000067071; -.
DR   eggNOG; KOG4304; Eukaryota.
DR   GeneTree; ENSGT00940000161398; -.
DR   HOGENOM; CLU_068550_0_0_1; -.
DR   InParanoid; Q9JHE6; -.
DR   OMA; EDESCYG; -.
DR   OrthoDB; 3679915at2759; -.
DR   PhylomeDB; Q9JHE6; -.
DR   TreeFam; TF351373; -.
DR   BioGRID-ORCS; 55927; 4 hits in 82 CRISPR screens.
DR   ChiTaRS; Hes6; mouse.
DR   PRO; PR:Q9JHE6; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q9JHE6; Protein.
DR   Bgee; ENSMUSG00000067071; Expressed in floor plate of midbrain and 323 other cell types or tissues.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IDA:MGI.
DR   GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:ARUK-UCL.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR   GO; GO:0007399; P:nervous system development; IMP:MGI.
DR   GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR   Gene3D; 6.10.250.980; -; 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:SF11; TRANSCRIPTION COFACTOR HES-6; 1.
DR   Pfam; PF07527; Hairy_orange; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SUPFAM; SSF47459; HLH, helix-loop-helix DNA-binding domain; 1.
DR   SUPFAM; SSF158457; Orange domain-like; 1.
DR   PROSITE; PS50888; BHLH; 1.
DR   PROSITE; PS51054; ORANGE; 1.
DR   Genevisible; Q9JHE6; MM.
PE   1: Evidence at protein level;
KW   Developmental protein; Differentiation; Nucleus; Reference proteome;
KW   Repressor; Transcription; Transcription regulation.
FT   CHAIN           1..224
FT                   /note="Transcription cofactor HES-6"
FT                   /id="PRO_0000127215"
FT   DOMAIN          25..77
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   DOMAIN          96..129
FT                   /note="Orange"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          146..209
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           221..224
FT                   /note="WRPW motif"
FT   COMPBIAS        10..29
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   224 AA;  24454 MW;  F5160A69D913DBE2 CRC64;
     MAPSQAPSRD RAGQEDEDRW EARGDRKARK PLVEKKRRAR INESLQELRL LLAGTEVQAK
     LENAEVLELT VRRVQGALRG RAREREQLQA EASERFAAGY IQCMHEVHTF VSTCQAIDAT
     VSAELLNHLL ESMPLREGSS FQDLLGDSLA GLPGGSGRSS WPPGGSPESP LSSPPGPGDD
     LCSDLEEIPE AELNRVPAEG PDLVSTSLGS LTAARRAQSV WRPW
//