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Q96HZ4

- HES6_HUMAN

UniProt

Q96HZ4 - HES6_HUMAN

Protein

Transcription cofactor HES-6

Gene

HES6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 114 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Does not bind DNA itself but suppresses both HES1-mediated N box-dependent transcriptional repression and binding of HES1 to E box sequences. Also suppresses HES1-mediated inhibition of the heterodimer formed by ASCL1/MASH1 and TCF3/E47, allowing ASCL1 and TCF3 to up-regulate transcription in its presence. Promotes cell differentiation By similarity.By similarity

    GO - Molecular functioni

    1. DNA binding Source: InterPro
    2. sequence-specific DNA binding transcription factor activity Source: ProtInc
    3. transcription cofactor activity Source: UniProtKB
    4. transcription factor binding Source: UniProtKB

    GO - Biological processi

    1. cell differentiation Source: UniProtKB-KW
    2. nervous system development Source: Ensembl
    3. regulation of transcription, DNA-templated Source: ProtInc
    4. regulation of transcription from RNA polymerase II promoter Source: Ensembl
    5. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Developmental protein, Repressor

    Keywords - Biological processi

    Differentiation, Transcription, Transcription regulation

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcription cofactor HES-6
    Alternative name(s):
    C-HAIRY1
    Class B basic helix-loop-helix protein 41
    Short name:
    bHLHb41
    Hairy and enhancer of split 6
    Gene namesi
    Name:HES6Imported
    Synonyms:BHLHB41
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:18254. HES6.

    Subcellular locationi

    Nucleus Curated

    GO - Cellular componenti

    1. nucleus Source: UniProtKB-SubCell
    2. transcription factor complex Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29253.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 224224Transcription cofactor HES-6PRO_0000127214Add
    BLAST

    Proteomic databases

    PaxDbiQ96HZ4.
    PRIDEiQ96HZ4.

    PTM databases

    PhosphoSiteiQ96HZ4.

    Expressioni

    Gene expression databases

    ArrayExpressiQ96HZ4.
    BgeeiQ96HZ4.
    CleanExiHS_HES6.
    GenevestigatoriQ96HZ4.

    Organism-specific databases

    HPAiCAB034351.
    HPA038827.

    Interactioni

    Subunit structurei

    Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts with HES1 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi120682. 3 interactions.
    IntActiQ96HZ4. 1 interaction.
    MINTiMINT-8313354.
    STRINGi9606.ENSP00000272937.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96HZ4.
    SMRiQ96HZ4. Positions 26-81.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini25 – 7753bHLHPROSITE-ProRule annotationAdd
    BLAST
    Domaini96 – 12934OrangePROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi221 – 2244WRPW motif

    Domaini

    The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.By similarity
    Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).

    Sequence similaritiesi

    Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
    Contains 1 Orange domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG241578.
    HOGENOMiHOG000236346.
    HOVERGENiHBG107098.
    InParanoidiQ96HZ4.
    KOiK09087.
    OMAiREDEDGC.
    OrthoDBiEOG7GBFXZ.
    PhylomeDBiQ96HZ4.
    TreeFamiTF351373.

    Family and domain databases

    Gene3Di4.10.280.10. 1 hit.
    InterProiIPR011598. bHLH_dom.
    IPR003650. Orange.
    [Graphical view]
    PfamiPF07527. Hairy_orange. 1 hit.
    PF00010. HLH. 1 hit.
    [Graphical view]
    SMARTiSM00353. HLH. 1 hit.
    [Graphical view]
    SUPFAMiSSF47459. SSF47459. 1 hit.
    PROSITEiPS50888. BHLH. 1 hit.
    PS51054. ORANGE. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96HZ4-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAPPAAPGRD RVGREDEDGW ETRGDRKARK PLVEKKRRAR INESLQELRL    50
    LLAGAEVQAK LENAEVLELT VRRVQGVLRG RAREREQLQA EASERFAAGY 100
    IQCMHEVHTF VSTCQAIDAT VAAELLNHLL ESMPLREGSS FQDLLGDALA 150
    GPPRAPGRSG WPAGGAPGSP IPSPPGPGDD LCSDLEEAPE AELSQAPAEG 200
    PDLVPAALGS LTTAQIARSV WRPW 224
    Length:224
    Mass (Da):24,129
    Last modified:December 1, 2001 - v1
    Checksum:iE361BDDDCACBAD6F
    GO
    Isoform 2 (identifier: Q96HZ4-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         84-224: EREQLQAEAS...QIARSVWRPW → GEWRRGGRGR...EPSARVHAAA

    Note: No experimental confirmation available.

    Show »
    Length:214
    Mass (Da):23,483
    Checksum:i0E0CA15863669591
    GO
    Isoform 3 (identifier: Q96HZ4-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         57-58: Missing.

    Show »
    Length:222
    Mass (Da):23,902
    Checksum:i4DA65A241AAFC073
    GO
    Isoform 4 (identifier: Q96HZ4-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         71-112: VRRVQGVLRG...CMHEVHTFVS → SASSCRRKRA...PSTLPSLPSS
         113-224: Missing.

    Note: No experimental confirmation available. Gene prediction based on EST data.

    Show »
    Length:112
    Mass (Da):12,240
    Checksum:i32921239A0C1F118
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti205 – 2051P → R in BAA96082. (PubMed:10851137)Curated
    Sequence conflicti210 – 2112SL → AV in BAA96082. (PubMed:10851137)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti218 – 2181R → Q.
    Corresponds to variant rs3739061 [ dbSNP | Ensembl ].
    VAR_019540

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei57 – 582Missing in isoform 3. 1 PublicationVSP_040128
    Alternative sequencei71 – 11242VRRVQ…HTFVS → SASSCRRKRASASLPATSSA CTRCTRSCPRARPSTLPSLP SS in isoform 4. CuratedVSP_055615Add
    BLAST
    Alternative sequencei84 – 224141EREQL…VWRPW → GEWRRGGRGRRPRAPVTPAR RRTSLPAPLSCRRRGLPPEQ GAPPRLLGEPRPRGPGGLGH AVAAHRAGRGSLPPTLGPRA RAAAGGSERALRCRLHPVHA RGAHVRVHVPGHRRYRRCRA PEPSARVHAAA in isoform 2. 1 PublicationVSP_011152Add
    BLAST
    Alternative sequencei113 – 224112Missing in isoform 4. CuratedVSP_055616Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB035179 mRNA. Translation: BAA96082.1.
    AF260237 mRNA. Translation: AAK51634.1.
    AK075040 mRNA. Translation: BAC11368.1.
    AK293111 mRNA. Translation: BAF85800.1.
    AC016757 Genomic DNA. Translation: AAY24337.1.
    CH471063 Genomic DNA. Translation: EAW71151.1.
    BC007939 mRNA. Translation: AAH07939.1.
    CCDSiCCDS2527.1. [Q96HZ4-1]
    CCDS46556.1. [Q96HZ4-3]
    RefSeqiNP_001136325.1. NM_001142853.2. [Q96HZ4-3]
    NP_001269363.1. NM_001282434.1.
    NP_061115.2. NM_018645.5. [Q96HZ4-1]
    UniGeneiHs.42949.

    Genome annotation databases

    EnsembliENST00000272937; ENSP00000272937; ENSG00000144485. [Q96HZ4-1]
    ENST00000409002; ENSP00000387155; ENSG00000144485. [Q96HZ4-3]
    ENST00000409160; ENSP00000387215; ENSG00000144485. [Q96HZ4-2]
    ENST00000409574; ENSP00000387008; ENSG00000144485. [Q96HZ4-4]
    GeneIDi55502.
    KEGGihsa:55502.
    UCSCiuc002vxz.3. human. [Q96HZ4-1]
    uc002vya.3. human. [Q96HZ4-3]
    uc002vyb.2. human. [Q96HZ4-2]

    Polymorphism databases

    DMDMi50400609.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB035179 mRNA. Translation: BAA96082.1 .
    AF260237 mRNA. Translation: AAK51634.1 .
    AK075040 mRNA. Translation: BAC11368.1 .
    AK293111 mRNA. Translation: BAF85800.1 .
    AC016757 Genomic DNA. Translation: AAY24337.1 .
    CH471063 Genomic DNA. Translation: EAW71151.1 .
    BC007939 mRNA. Translation: AAH07939.1 .
    CCDSi CCDS2527.1. [Q96HZ4-1 ]
    CCDS46556.1. [Q96HZ4-3 ]
    RefSeqi NP_001136325.1. NM_001142853.2. [Q96HZ4-3 ]
    NP_001269363.1. NM_001282434.1.
    NP_061115.2. NM_018645.5. [Q96HZ4-1 ]
    UniGenei Hs.42949.

    3D structure databases

    ProteinModelPortali Q96HZ4.
    SMRi Q96HZ4. Positions 26-81.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120682. 3 interactions.
    IntActi Q96HZ4. 1 interaction.
    MINTi MINT-8313354.
    STRINGi 9606.ENSP00000272937.

    PTM databases

    PhosphoSitei Q96HZ4.

    Polymorphism databases

    DMDMi 50400609.

    Proteomic databases

    PaxDbi Q96HZ4.
    PRIDEi Q96HZ4.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000272937 ; ENSP00000272937 ; ENSG00000144485 . [Q96HZ4-1 ]
    ENST00000409002 ; ENSP00000387155 ; ENSG00000144485 . [Q96HZ4-3 ]
    ENST00000409160 ; ENSP00000387215 ; ENSG00000144485 . [Q96HZ4-2 ]
    ENST00000409574 ; ENSP00000387008 ; ENSG00000144485 . [Q96HZ4-4 ]
    GeneIDi 55502.
    KEGGi hsa:55502.
    UCSCi uc002vxz.3. human. [Q96HZ4-1 ]
    uc002vya.3. human. [Q96HZ4-3 ]
    uc002vyb.2. human. [Q96HZ4-2 ]

    Organism-specific databases

    CTDi 55502.
    GeneCardsi GC02M239187.
    HGNCi HGNC:18254. HES6.
    HPAi CAB034351.
    HPA038827.
    MIMi 610331. gene.
    neXtProti NX_Q96HZ4.
    PharmGKBi PA29253.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG241578.
    HOGENOMi HOG000236346.
    HOVERGENi HBG107098.
    InParanoidi Q96HZ4.
    KOi K09087.
    OMAi REDEDGC.
    OrthoDBi EOG7GBFXZ.
    PhylomeDBi Q96HZ4.
    TreeFami TF351373.

    Miscellaneous databases

    ChiTaRSi HES6. human.
    GeneWikii HES6.
    GenomeRNAii 55502.
    NextBioi 59883.
    PROi Q96HZ4.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96HZ4.
    Bgeei Q96HZ4.
    CleanExi HS_HES6.
    Genevestigatori Q96HZ4.

    Family and domain databases

    Gene3Di 4.10.280.10. 1 hit.
    InterProi IPR011598. bHLH_dom.
    IPR003650. Orange.
    [Graphical view ]
    Pfami PF07527. Hairy_orange. 1 hit.
    PF00010. HLH. 1 hit.
    [Graphical view ]
    SMARTi SM00353. HLH. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47459. SSF47459. 1 hit.
    PROSITEi PS50888. BHLH. 1 hit.
    PS51054. ORANGE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation."
      Bae S.-K., Bessho Y., Hojo M., Kageyama R.
      Development 127:2933-2943(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
    2. "Expression of mouse HES-6, a new member of the Hairy/Enhancer of split family of bHLH transcription factors."
      Vasiliauskas D., Stern C.D.
      Mech. Dev. 98:133-137(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Ovary.
    4. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: MuscleImported.

    Entry informationi

    Entry nameiHES6_HUMAN
    AccessioniPrimary (citable) accession number: Q96HZ4
    Secondary accession number(s): A8KAP6
    , B8ZZA9, Q53SN9, Q8N2J2, Q96T93, Q9P2S3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 114 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3