UniProtKB - Q96HZ4 (HES6_HUMAN)
Protein
Transcription cofactor HES-6
Gene
HES6
Organism
Homo sapiens (Human)
Status
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
- DNA-binding transcription factor activity Source: ProtInc
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: Ensembl
- protein dimerization activity Source: InterPro
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II-specific DNA-binding transcription factor binding Source: ARUK-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription factor binding Source: UniProtKB
GO - Biological processi
- anterior/posterior pattern specification Source: GO_Central
- negative regulation of DNA-binding transcription factor activity Source: ARUK-UCL
- regulation of neurogenesis Source: GO_Central
- regulation of transcription, DNA-templated Source: ProtInc
- regulation of transcription by RNA polymerase II Source: GO_Central
Keywordsi
Molecular function | Developmental protein, Repressor |
Biological process | Differentiation, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q96HZ4 |
SIGNORi | Q96HZ4 |
Names & Taxonomyi
Protein namesi | Recommended name: Transcription cofactor HES-6Alternative name(s): C-HAIRY1 Class B basic helix-loop-helix protein 41 Short name: bHLHb41 Hairy and enhancer of split 6 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:18254, HES6 |
MIMi | 610331, gene |
neXtProti | NX_Q96HZ4 |
VEuPathDBi | HostDB:ENSG00000144485.10 |
Subcellular locationi
Nucleus
- Nucleus Curated
Nucleus
- nucleus Source: GO_Central
Other locations
- chromatin Source: NTNU_SB
- transcription regulator complex Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 55502 |
OpenTargetsi | ENSG00000144485 |
PharmGKBi | PA29253 |
Miscellaneous databases
Pharosi | Q96HZ4, Tbio |
Genetic variation databases
BioMutai | HES6 |
DMDMi | 50400609 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127214 | 1 – 224 | Transcription cofactor HES-6Add BLAST | 224 |
Proteomic databases
MassIVEi | Q96HZ4 |
PaxDbi | Q96HZ4 |
PeptideAtlasi | Q96HZ4 |
PRIDEi | Q96HZ4 |
ProteomicsDBi | 7344 76797 [Q96HZ4-1] 76798 [Q96HZ4-2] 76799 [Q96HZ4-3] |
PTM databases
iPTMneti | Q96HZ4 |
PhosphoSitePlusi | Q96HZ4 |
Expressioni
Gene expression databases
Bgeei | ENSG00000144485, Expressed in subventricular zone (inner) (primate) and 153 other tissues |
ExpressionAtlasi | Q96HZ4, baseline and differential |
Genevisiblei | Q96HZ4, HS |
Organism-specific databases
HPAi | ENSG00000144485, Tissue enhanced (brain) |
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 similarityBinary interactionsi
Hide detailsQ96HZ4
With | #Exp. | IntAct |
---|---|---|
C14orf119 [Q9NWQ9] | 3 | EBI-7469266,EBI-725606 |
KRTAP10-9 [P60411] | 3 | EBI-7469266,EBI-10172052 |
RAB2A [P61019] | 3 | EBI-7469266,EBI-752037 |
SMARCD1 [Q96GM5] | 3 | EBI-7469266,EBI-358489 |
GO - Molecular functioni
- protein dimerization activity Source: InterPro
- RNA polymerase II-specific DNA-binding transcription factor binding Source: ARUK-UCL
- transcription factor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 120682, 14 interactors |
ELMi | Q96HZ4 |
IntActi | Q96HZ4, 6 interactors |
MINTi | Q96HZ4 |
STRINGi | 9606.ENSP00000272937 |
Miscellaneous databases
RNActi | Q96HZ4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 25 – 77 | bHLHPROSITE-ProRule annotationAdd BLAST | 53 | |
Domaini | 96 – 129 | OrangePROSITE-ProRule annotationAdd BLAST | 34 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 221 – 224 | WRPW motif | 4 |
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).
Phylogenomic databases
eggNOGi | KOG4304, Eukaryota |
GeneTreei | ENSGT00940000161398 |
HOGENOMi | CLU_068550_0_0_1 |
InParanoidi | Q96HZ4 |
OMAi | SMPTMTY |
OrthoDBi | 1483774at2759 |
PhylomeDBi | Q96HZ4 |
TreeFami | TF351373 |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR003650, Orange_dom |
Pfami | View protein in Pfam PF07527, Hairy_orange, 1 hit PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS51054, ORANGE, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96HZ4-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB9A070 | B9A070_HUMAN | Transcription cofactor HES-6 | HES6 | 195 | Annotation score: | ||
B8ZZP9 | B8ZZP9_HUMAN | Transcription cofactor HES-6 | HES6 | 94 | Annotation score: | ||
C9JF41 | C9JF41_HUMAN | Transcription cofactor HES-6 | HES6 | 144 | Annotation score: | ||
H7C020 | H7C020_HUMAN | Transcription cofactor HES-6 | HES6 | 85 | Annotation score: | ||
H7C1R4 | H7C1R4_HUMAN | Transcription cofactor HES-6 | HES6 | 16 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 205 | P → R in BAA96082 (PubMed:10851137).Curated | 1 | |
Sequence conflicti | 210 – 211 | SL → AV in BAA96082 (PubMed:10851137).Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_019540 | 218 | R → Q. Corresponds to variant dbSNP:rs3739061Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_040128 | 57 – 58 | Missing in isoform 3. 1 Publication | 2 | |
Alternative sequenceiVSP_055615 | 71 – 112 | VRRVQ…HTFVS → SASSCRRKRASASLPATSSA CTRCTRSCPRARPSTLPSLP SS in isoform 4. CuratedAdd BLAST | 42 | |
Alternative sequenceiVSP_011152 | 84 – 224 | EREQL…VWRPW → GEWRRGGRGRRPRAPVTPAR RRTSLPAPLSCRRRGLPPEQ GAPPRLLGEPRPRGPGGLGH AVAAHRAGRGSLPPTLGPRA RAAAGGSERALRCRLHPVHA RGAHVRVHVPGHRRYRRCRA PEPSARVHAAA in isoform 2. 1 PublicationAdd BLAST | 141 | |
Alternative sequenceiVSP_055616 | 113 – 224 | Missing in isoform 4. CuratedAdd BLAST | 112 |
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 |
CCDSi | CCDS2527.1 [Q96HZ4-1] CCDS46556.1 [Q96HZ4-3] CCDS63180.1 [Q96HZ4-4] |
RefSeqi | NP_001136325.1, NM_001142853.2 [Q96HZ4-3] NP_001269363.1, NM_001282434.1 [Q96HZ4-4] NP_061115.2, NM_018645.5 [Q96HZ4-1] |
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.4, human [Q96HZ4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS2527.1 [Q96HZ4-1] CCDS46556.1 [Q96HZ4-3] CCDS63180.1 [Q96HZ4-4] |
RefSeqi | NP_001136325.1, NM_001142853.2 [Q96HZ4-3] NP_001269363.1, NM_001282434.1 [Q96HZ4-4] NP_061115.2, NM_018645.5 [Q96HZ4-1] |
3D structure databases
SMRi | Q96HZ4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120682, 14 interactors |
ELMi | Q96HZ4 |
IntActi | Q96HZ4, 6 interactors |
MINTi | Q96HZ4 |
STRINGi | 9606.ENSP00000272937 |
PTM databases
iPTMneti | Q96HZ4 |
PhosphoSitePlusi | Q96HZ4 |
Genetic variation databases
BioMutai | HES6 |
DMDMi | 50400609 |
Proteomic databases
MassIVEi | Q96HZ4 |
PaxDbi | Q96HZ4 |
PeptideAtlasi | Q96HZ4 |
PRIDEi | Q96HZ4 |
ProteomicsDBi | 7344 76797 [Q96HZ4-1] 76798 [Q96HZ4-2] 76799 [Q96HZ4-3] |
Protocols and materials databases
Antibodypediai | 20277, 285 antibodies |
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.4, human [Q96HZ4-1] |
Organism-specific databases
CTDi | 55502 |
DisGeNETi | 55502 |
GeneCardsi | HES6 |
HGNCi | HGNC:18254, HES6 |
HPAi | ENSG00000144485, Tissue enhanced (brain) |
MIMi | 610331, gene |
neXtProti | NX_Q96HZ4 |
OpenTargetsi | ENSG00000144485 |
PharmGKBi | PA29253 |
VEuPathDBi | HostDB:ENSG00000144485.10 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4304, Eukaryota |
GeneTreei | ENSGT00940000161398 |
HOGENOMi | CLU_068550_0_0_1 |
InParanoidi | Q96HZ4 |
OMAi | SMPTMTY |
OrthoDBi | 1483774at2759 |
PhylomeDBi | Q96HZ4 |
TreeFami | TF351373 |
Enzyme and pathway databases
PathwayCommonsi | Q96HZ4 |
SIGNORi | Q96HZ4 |
Miscellaneous databases
BioGRID-ORCSi | 55502, 10 hits in 1016 CRISPR screens |
ChiTaRSi | HES6, human |
GeneWikii | HES6 |
GenomeRNAii | 55502 |
Pharosi | Q96HZ4, Tbio |
PROi | PR:Q96HZ4 |
RNActi | Q96HZ4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000144485, Expressed in subventricular zone (inner) (primate) and 153 other tissues |
ExpressionAtlasi | Q96HZ4, baseline and differential |
Genevisiblei | Q96HZ4, HS |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR036638, HLH_DNA-bd_sf IPR003650, Orange_dom |
Pfami | View protein in Pfam PF07527, Hairy_orange, 1 hit PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit PS51054, ORANGE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HES6_HUMAN | |
Accessioni | Q96HZ4Primary (citable) accession number: Q96HZ4 Secondary accession number(s): A8KAP6 Q9P2S3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2004 |
Last sequence update: | December 1, 2001 | |
Last modified: | April 7, 2021 | |
This is version 161 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot