Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Transcription cofactor HES-6

Gene

HES6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiQ96HZ4.
CleanExiHS_HES6.
ExpressionAtlasiQ96HZ4. baseline and differential.
GenevestigatoriQ96HZ4.

Organism-specific databases

HPAiCAB034351.
HPA061763.

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.
GeneTreeiENSGT00700000104168.
HOGENOMiHOG000236346.
HOVERGENiHBG107098.
InParanoidiQ96HZ4.
KOiK09087.
OMAiEDEDRWE.
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. AlignAdd to basket

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

        10         20         30         40         50
MAPPAAPGRD RVGREDEDGW ETRGDRKARK PLVEKKRRAR INESLQELRL
60 70 80 90 100
LLAGAEVQAK LENAEVLELT VRRVQGVLRG RAREREQLQA EASERFAAGY
110 120 130 140 150
IQCMHEVHTF VSTCQAIDAT VAAELLNHLL ESMPLREGSS FQDLLGDALA
160 170 180 190 200
GPPRAPGRSG WPAGGAPGSP IPSPPGPGDD LCSDLEEAPE AELSQAPAEG
210 220
PDLVPAALGS LTTAQIARSV WRPW
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:
EMBLi
GenBanki
DDBJi
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]
CCDS63180.1. [Q96HZ4-4]
RefSeqiNP_001136325.1. NM_001142853.2. [Q96HZ4-3]
NP_001269363.1. NM_001282434.1. [Q96HZ4-4]
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:
EMBLi
GenBanki
DDBJi
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]
CCDS63180.1. [Q96HZ4-4]
RefSeqiNP_001136325.1. NM_001142853.2. [Q96HZ4-3]
NP_001269363.1. NM_001282434.1. [Q96HZ4-4]
NP_061115.2. NM_018645.5. [Q96HZ4-1]
UniGeneiHs.42949.

3D structure databases

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiQ96HZ4.

Polymorphism databases

DMDMi50400609.

Proteomic databases

PaxDbiQ96HZ4.
PRIDEiQ96HZ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi55502.
GeneCardsiGC02M239205.
HGNCiHGNC:18254. HES6.
HPAiCAB034351.
HPA061763.
MIMi610331. gene.
neXtProtiNX_Q96HZ4.
PharmGKBiPA29253.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG241578.
GeneTreeiENSGT00700000104168.
HOGENOMiHOG000236346.
HOVERGENiHBG107098.
InParanoidiQ96HZ4.
KOiK09087.
OMAiEDEDRWE.
OrthoDBiEOG7GBFXZ.
PhylomeDBiQ96HZ4.
TreeFamiTF351373.

Miscellaneous databases

ChiTaRSiHES6. human.
GeneWikiiHES6.
GenomeRNAii55502.
NextBioi35481750.
PROiQ96HZ4.
SOURCEiSearch...

Gene expression databases

BgeeiQ96HZ4.
CleanExiHS_HES6.
ExpressionAtlasiQ96HZ4. baseline and differential.
GenevestigatoriQ96HZ4.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: March 4, 2015
This is version 117 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.