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Q96HZ4 (HES6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:HES6
Synonyms:BHLHB41
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length224 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. UniProtKB Q9JHE6

Subunit structure

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

Subcellular location

Nucleus Probable.

Domain

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. UniProtKB Q26263

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 similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Contains 1 Orange domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96HZ4-1)

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.
Isoform 2 (identifier: Q96HZ4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     84-224: EREQLQAEAS...QIARSVWRPW → GEWRRGGRGR...EPSARVHAAA
Note: No experimental confirmation available.
Isoform 3 (identifier: Q96HZ4-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 224224Transcription cofactor HES-6
PRO_0000127214

Regions

Domain25 – 7753bHLH
Domain96 – 12934Orange
Motif221 – 2244WRPW motif

Natural variations

Alternative sequence57 – 582Missing in isoform 3.
VSP_040128
Alternative sequence84 – 224141EREQL…VWRPW → GEWRRGGRGRRPRAPVTPAR RRTSLPAPLSCRRRGLPPEQ GAPPRLLGEPRPRGPGGLGH AVAAHRAGRGSLPPTLGPRA RAAAGGSERALRCRLHPVHA RGAHVRVHVPGHRRYRRCRA PEPSARVHAAA in isoform 2.
VSP_011152
Natural variant2181R → Q.
Corresponds to variant rs3739061 [ dbSNP | Ensembl ].
VAR_019540

Experimental info

Sequence conflict2051P → R in BAA96082. Ref.1
Sequence conflict210 – 2112SL → AV in BAA96082. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: E361BDDDCACBAD6F

FASTA22424,129
        10         20         30         40         50         60 
MAPPAAPGRD RVGREDEDGW ETRGDRKARK PLVEKKRRAR INESLQELRL LLAGAEVQAK 

        70         80         90        100        110        120 
LENAEVLELT VRRVQGVLRG RAREREQLQA EASERFAAGY IQCMHEVHTF VSTCQAIDAT 

       130        140        150        160        170        180 
VAAELLNHLL ESMPLREGSS FQDLLGDALA GPPRAPGRSG WPAGGAPGSP IPSPPGPGDD 

       190        200        210        220 
LCSDLEEAPE AELSQAPAEG PDLVPAALGS LTTAQIARSV WRPW 

« Hide

Isoform 2 [UniParc].

Checksum: 0E0CA15863669591
Show »

FASTA21423,483
Isoform 3 [UniParc].

Checksum: 4DA65A241AAFC073
Show »

FASTA22223,902

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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: Muscle.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS2527.1. [Q96HZ4-1]
CCDS46556.1. [Q96HZ4-3]
RefSeqNP_001136325.1. NM_001142853.2. [Q96HZ4-3]
NP_001269363.1. NM_001282434.1.
NP_061115.2. NM_018645.5. [Q96HZ4-1]
UniGeneHs.42949.

3D structure databases

ProteinModelPortalQ96HZ4.
SMRQ96HZ4. Positions 26-81.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120682. 3 interactions.
IntActQ96HZ4. 1 interaction.
MINTMINT-8313354.
STRING9606.ENSP00000272937.

PTM databases

PhosphoSiteQ96HZ4.

Polymorphism databases

DMDM50400609.

Proteomic databases

PaxDbQ96HZ4.
PRIDEQ96HZ4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000272937; ENSP00000272937; ENSG00000144485. [Q96HZ4-1]
ENST00000409002; ENSP00000387155; ENSG00000144485. [Q96HZ4-3]
ENST00000409160; ENSP00000387215; ENSG00000144485. [Q96HZ4-2]
GeneID55502.
KEGGhsa:55502.
UCSCuc002vxz.3. human. [Q96HZ4-1]
uc002vya.3. human. [Q96HZ4-3]
uc002vyb.2. human. [Q96HZ4-2]

Organism-specific databases

CTD55502.
GeneCardsGC02M239187.
HGNCHGNC:18254. HES6.
HPACAB034351.
HPA038827.
MIM610331. gene.
neXtProtNX_Q96HZ4.
PharmGKBPA29253.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241578.
HOGENOMHOG000236346.
HOVERGENHBG107098.
InParanoidQ96HZ4.
KOK09087.
OMAREDEDGC.
OrthoDBEOG7GBFXZ.
PhylomeDBQ96HZ4.
TreeFamTF351373.

Gene expression databases

ArrayExpressQ96HZ4.
BgeeQ96HZ4.
CleanExHS_HES6.
GenevestigatorQ96HZ4.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR003650. Orange.
[Graphical view]
PfamPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHES6. human.
GeneWikiHES6.
GenomeRNAi55502.
NextBio59883.
PROQ96HZ4.
SOURCESearch...

Entry information

Entry nameHES6_HUMAN
AccessionPrimary (citable) accession number: Q96HZ4
Secondary accession number(s): A8KAP6 expand/collapse secondary AC list , Q53SN9, Q8N2J2, Q96T93, Q9P2S3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM