Q96HZ4 (HES6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	HES6
Synonyms:	BHLHB41

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	224 AA.
Sequence status	Complete.
Protein existence	Evidence 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 basic helix-loop-helix (bHLH) domain. Contains 1 Orange domain.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Developmental protein Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	transcription factor complex Inferred from sequence or structural similarity Ref.1. Source: UniProtKB
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Traceable author statement. Source: ProtInc transcription cofactor activity Inferred from sequence or structural similarity Ref.1. Source: UniProtKB transcription factor binding Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 224	224	Transcription cofactor HES-6		PRO_0000127214
Regions
	Domain	39 – 78	40	Helix-loop-helix motif
	Domain	96 – 129	34	Orange
	DNA binding	26 – 38	13	Basic motif
	Motif	221 – 224	4	WRPW motif
Natural variations
	Alternative sequence	57 – 58	2	Missing in isoform 3.		VSP_040128
	Alternative sequence	84 – 224	141	EREQL…VWRPW → GEWRRGGRGRRPRAPVTPAR RRTSLPAPLSCRRRGLPPEQ GAPPRLLGEPRPRGPGGLGH AVAAHRAGRGSLPPTLGPRA RAAAGGSERALRCRLHPVHA RGAHVRVHVPGHRRYRRCRA PEPSARVHAAA in isoform 2.		VSP_011152
	Natural variant	218	1	R → Q. Corresponds to variant rs3739061 [ dbSNP | Ensembl ].		VAR_019540
Experimental info
	Sequence conflict	205	1	P → R in BAA96082. Ref.1
	Sequence conflict	210 – 211	2	SL → AV in BAA96082. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: E361BDDDCACBAD6F	FASTA	224	24,129
	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
	Isoform 2 [UniParc]. Checksum: 0E0CA15863669591	FASTA	214	23,483
	10 20 30 40 50 60 MAPPAAPGRD RVGREDEDGW ETRGDRKARK PLVEKKRRAR INESLQELRL LLAGAEVQAK 70 80 90 100 110 120 LENAEVLELT VRRVQGVLRG RARGEWRRGG RGRRPRAPVT PARRRTSLPA PLSCRRRGLP 130 140 150 160 170 180 PEQGAPPRLL GEPRPRGPGG LGHAVAAHRA GRGSLPPTLG PRARAAAGGS ERALRCRLHP 190 200 210 VHARGAHVRV HVPGHRRYRR CRAPEPSARV HAAA
	Isoform 3 [UniParc]. Checksum: 4DA65A241AAFC073	FASTA	222	23,902
	10 20 30 40 50 60 MAPPAAPGRD RVGREDEDGW ETRGDRKARK PLVEKKRRAR INESLQELRL LLAGAEAKLE 70 80 90 100 110 120 NAEVLELTVR RVQGVLRGRA REREQLQAEA SERFAAGYIQ CMHEVHTFVS TCQAIDATVA 130 140 150 160 170 180 AELLNHLLES MPLREGSSFQ DLLGDALAGP PRAPGRSGWP AGGAPGSPIP SPPGPGDDLC 190 200 210 220 SDLEEAPEAE LSQAPAEGPD LVPAALGSLT TAQIARSVWR PW

References

	« Hide 'large scale' referencesShow '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: 10851137] [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: 11044617] [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: 14702039] [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: 15815621] [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. , 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: 15489334] [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.
IPI	IPI00452727. IPI00452728. IPI00915924.
RefSeq	NP_001136325.1. NM_001142853.1. NP_061115.2. NM_018645.4.
UniGene	Hs.42949.
3D structure databases
ProteinModelPortal	Q96HZ4.
SMR	Q96HZ4. Positions 22-83, 89-135.
ModBase	Search...
Protein-protein interaction databases
STRING	Q96HZ4.
PTM databases
PhosphoSite	Q96HZ4.
Polymorphism databases
DMDM	50400609.
Proteomic databases
PRIDE	Q96HZ4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000272937; ENSP00000272937; ENSG00000144485.
GeneID	55502.
KEGG	hsa:55502.
UCSC	uc002vxz.1. human.
Organism-specific databases
CTD	55502.
GeneCards	GC02M239163.
H-InvDB	HIX0002966.
HGNC	HGNC:18254. HES6.
HPA	CAB034351.
MIM	610331. gene.
neXtProt	NX_Q96HZ4.
PharmGKB	PA29253.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG21204.
GeneTree	ENSGT00550000074362.
HOGENOM	HBG716105.
HOVERGEN	HBG107098.
InParanoid	Q96HZ4.
OMA	EDEDRWE.
OrthoDB	EOG4G7C0H.
PhylomeDB	Q96HZ4.
Gene expression databases
ArrayExpress	Q96HZ4.
Bgee	Q96HZ4.
CleanEx	HS_HES6.
Genevestigator	Q96HZ4.
GermOnline	ENSG00000144485. Homo sapiens.
Family and domain databases
InterPro	IPR011598. HLH_DNA-bd. IPR003650. Orange. [Graphical view]
Gene3D	G3DSA:4.10.280.10. HLH_DNA_bd. 1 hit.
KO	K09087.
Pfam	PF07527. Hairy_orange. 1 hit. PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. HLH. 1 hit. PS51054. ORANGE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	59883.
SOURCE	Search...

Entry information

Entry name

HES6_HUMAN

Accession

Primary (citable) accession number: Q96HZ4
Secondary accession number(s): A8KAP6 , Q53SN9, Q8N2J2, Q96T93, Q9P2S3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.