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Q9UBP5 (HEY2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. 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·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hairy/enhancer-of-split related with YRPW motif protein 2
Alternative name(s):
Cardiovascular helix-loop-helix factor 1
Short name=hCHF1
Class B basic helix-loop-helix protein 32
Short name=bHLHb32
HES-related repressor protein 2
Hairy and enhancer of split-related protein 2
Short name=HESR-2
Hairy-related transcription factor 2
Short name=HRT-2
Short name=hHRT2
Protein gridlock homolog
Gene names
Name:HEY2
Synonyms:BHLHB32, CHF1, GRL, HERP, HERP1, HRT2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length337 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Downstream effector of Notch signaling which may be required for cardiovascular development. Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6. Ref.3 Ref.4 Ref.10 Ref.11

Subunit structure

May self-associate By similarity. Interacts with GATA4, HES1 and HEYL By similarity. Interacts with HDAC1, NCOR1 and SIN3A By similarity. Interacts with ARNT and GATA6. Ref.3 Ref.11

Subcellular location

Nucleus By similarity.

Sequence similarities

Belongs to the HEY family.

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

Contains 1 Orange domain.

Ontologies

Keywords
   Biological processNotch signaling pathway
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   LigandDNA-binding
   Molecular functionDevelopmental protein
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch signaling involved in heart development

Inferred by curator PubMed 12372254. Source: BHF-UCL

Notch signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

anterior/posterior axis specification

Inferred from electronic annotation. Source: Ensembl

arterial endothelial cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

ascending aorta morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

atrial septum morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

atrioventricular valve development

Inferred from electronic annotation. Source: Ensembl

cardiac epithelial to mesenchymal transition

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac left ventricle morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac muscle hypertrophy in response to stress

Inferred from electronic annotation. Source: Ensembl

cardiac right ventricle morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac septum morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

cardiac vascular smooth muscle cell development

Inferred from electronic annotation. Source: Ensembl

cardiac ventricle morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cell fate commitment

Inferred from electronic annotation. Source: Ensembl

cochlea development

Inferred from electronic annotation. Source: Ensembl

coronary vasculature morphogenesis

Inferred from electronic annotation. Source: Ensembl

dorsal aorta morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

endocardial cushion to mesenchymal transition involved in heart valve formation

Inferred from electronic annotation. Source: Ensembl

heart trabecula formation

Inferred from electronic annotation. Source: Ensembl

labyrinthine layer blood vessel development

Inferred from sequence or structural similarity. Source: BHF-UCL

mesenchymal cell development

Inferred from sequence or structural similarity. Source: BHF-UCL

muscular septum morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of Notch signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of cardiac muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of cardiac vascular smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription by transcription factor localization

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 21290414. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of transcription initiation from RNA polymerase II promoter

Inferred from direct assay Ref.3. Source: BHF-UCL

negative regulation of transcription regulatory region DNA binding

Inferred from direct assay Ref.3. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from direct assay Ref.10. Source: UniProtKB

outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cardiac muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of heart rate

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

protein-DNA complex assembly

Inferred from electronic annotation. Source: Ensembl

pulmonary artery morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

pulmonary valve morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of auditory receptor cell differentiation

Inferred from electronic annotation. Source: Ensembl

regulation of vasculogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

smooth muscle cell differentiation

Non-traceable author statement Ref.3. Source: BHF-UCL

transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: GOC

tricuspid valve formation

Inferred from electronic annotation. Source: Ensembl

tricuspid valve morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

umbilical cord morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

vascular smooth muscle cell development

Inferred from expression pattern PubMed 15821257. Source: UniProtKB

vasculogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

ventricular cardiac muscle cell development

Inferred from sequence or structural similarity. Source: UniProtKB

ventricular septum morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

ventricular trabecula myocardium morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

transcriptional repressor complex

Inferred from direct assay PubMed 11486045. Source: BHF-UCL

   Molecular_functionRNA polymerase II activating transcription factor binding

Inferred from physical interaction Ref.11. Source: BHF-UCL

RNA polymerase II core promoter sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

histone deacetylase binding

Inferred from physical interaction PubMed 12535671. Source: BHF-UCL

microsatellite binding

Inferred from direct assay PubMed 21290414. Source: UniProtKB

protein binding transcription factor activity

Inferred from direct assay PubMed 21290414. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 11486045. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.10. Source: UniProtKB

transcription factor binding

Non-traceable author statement PubMed 17611704. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 337337Hairy/enhancer-of-split related with YRPW motif protein 2
PRO_0000245515

Regions

Domain48 – 10356bHLH
Domain122 – 15736Orange
Region47 – 11670Transcriptional repression and interaction with NCOR1 and SIN3A By similarity
Motif327 – 3304YRPW motif
Compositional bias175 – 19117His-rich
Compositional bias262 – 30241Ala-rich

Natural variations

Natural variant961T → A in a patient with atrioventricular septal defects. Ref.12
VAR_026974
Natural variant981D → A in a patient with atrioventricular septal defects. Ref.12
VAR_026975
Natural variant1001L → S in a patient with atrioventricular septal defects. Ref.12
VAR_026976
Natural variant1401V → M.
Corresponds to variant rs3734638 [ dbSNP | Ensembl ].
VAR_026977

Experimental info

Mutagenesis541G → P: Impairs transcriptional repression. Ref.11

Sequences

Sequence LengthMass (Da)Tools
Q9UBP5 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 71B7B1AA69BA88D2

FASTA33735,808
        10         20         30         40         50         60 
MKRPCEETTS ESDMDETIDV GSENNYSGQS TSSVIRLNSP TTTSQIMARK KRRGIIEKRR 

        70         80         90        100        110        120 
RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL KMLQATGGKG YFDAHALAMD 

       130        140        150        160        170        180 
FMSIGFRECL TEVARYLSSV EGLDSSDPLR VRLVSHLSTC ATQREAAAMT SSMAHHHHPL 

       190        200        210        220        230        240 
HPHHWAAAFH HLPAALLQPN GLHASESTPC RLSTTSEVPP AHGSALLTAT FAHADSALRM 

       250        260        270        280        290        300 
PSTGSVAPCV PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP PNAAAAVAAA 

       310        320        330 
TAISPPLSVS ATSSPQQTSS GTNNKPYRPW GTEVGAF 

« Hide

References

« Hide 'large scale' references
[1]"Hey genes: a novel subfamily of hairy- and enhancer of split related genes specifically expressed during mouse embryogenesis."
Leimeister C., Externbrinck A., Klamt B., Gessler M.
Mech. Dev. 85:173-177(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Gridlock, an HLH gene required for assembly of the aorta in zebrafish."
Zhong T.P., Rosenberg M., Mohideen M.-A.P.K., Weinstein B., Fishman M.C.
Science 287:1820-1824(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[3]"Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system."
Chin M.T., Maemura K., Fukumoto S., Jain M.K., Layne M.D., Watanabe M., Hsieh C.-M., Lee M.-E.
J. Biol. Chem. 275:6381-6387(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ARNT.
Tissue: Heart.
[4]"Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling."
Nakagawa O., McFadden D.G., Nakagawa M., Yanagisawa H., Hu T., Srivastava D., Olson E.N.
Proc. Natl. Acad. Sci. U.S.A. 97:13655-13660(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DNA-BINDING.
[5]"HERP, a new primary target of Notch regulated by ligand binding."
Iso T., Sartorelli V., Chung G., Shichinohe T., Kedes L., Hamamori Y.
Mol. Cell. Biol. 21:6071-6079(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[6]"Homo sapiens testis cDNA clone, basic-helix-loop-helix protein (Hey2)."
Tanaka K., Miyata J., Ikeda J.
Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Testis.
[7]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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].
Tissue: Lung.
[10]"Hairy-related transcription factors inhibit GATA-dependent cardiac gene expression through a signal-responsive mechanism."
Kathiriya I.S., King I.N., Murakami M., Nakagawa M., Astle J.M., Gardner K.A., Gerard R.D., Olson E.N., Srivastava D., Nakagawa O.
J. Biol. Chem. 279:54937-54943(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"CHF1/Hey2 suppresses SM-MHC promoter activity through an interaction with GATA-6."
Shirvani S., Xiang F., Koibuchi N., Chin M.T.
Biochem. Biophys. Res. Commun. 339:151-156(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GATA6, MUTAGENESIS OF GLY-54.
[12]"HEY2 mutations in malformed hearts."
Reamon-Buettner S.M., Borlak J.
Hum. Mutat. 27:118-118(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-96; ALA-98 AND SER-100.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ249545 mRNA. Translation: CAB56839.1.
AF237949 mRNA. Translation: AAF44781.1.
AF173901 mRNA. Translation: AAF20173.1.
AF311884 mRNA. Translation: AAG31157.1.
AF232238 mRNA. Translation: AAF37296.1.
AB044755 mRNA. Translation: BAA96781.1.
BT020067 mRNA. Translation: AAV38870.1.
BT020068 mRNA. Translation: AAV38871.1.
AL078594 Genomic DNA. Translation: CAB87581.1.
BC007707 mRNA. Translation: AAH07707.1.
RefSeqNP_036391.1. NM_012259.2.
UniGeneHs.144287.

3D structure databases

ProteinModelPortalQ9UBP5.
SMRQ9UBP5. Positions 56-107, 110-164.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117045. 14 interactions.
IntActQ9UBP5. 5 interactions.
MINTMINT-1469894.
STRING9606.ENSP00000357348.

PTM databases

PhosphoSiteQ9UBP5.

Polymorphism databases

DMDM74762767.

Proteomic databases

PaxDbQ9UBP5.
PRIDEQ9UBP5.

Protocols and materials databases

DNASU23493.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368364; ENSP00000357348; ENSG00000135547.
GeneID23493.
KEGGhsa:23493.
UCSCuc003qad.3. human.

Organism-specific databases

CTD23493.
GeneCardsGC06P126068.
HGNCHGNC:4881. HEY2.
HPAHPA030205.
MIM604674. gene.
neXtProtNX_Q9UBP5.
PharmGKBPA29259.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324798.
HOGENOMHOG000286035.
HOVERGENHBG003275.
InParanoidQ9UBP5.
KOK09091.
OMATCASQRE.
PhylomeDBQ9UBP5.
TreeFamTF323617.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpressQ9UBP5.
BgeeQ9UBP5.
CleanExHS_HEY2.
GenevestigatorQ9UBP5.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
IPR003650. Orange.
IPR018352. Orange_subgr.
[Graphical view]
PfamPF07527. Hairy_orange. 1 hit.
PF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
SM00511. ORANGE. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
PS51054. ORANGE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHEY2.
GenomeRNAi23493.
NextBio45859.
PROQ9UBP5.
SOURCESearch...

Entry information

Entry nameHEY2_HUMAN
AccessionPrimary (citable) accession number: Q9UBP5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 114 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 6

Human chromosome 6: entries, gene names and cross-references to MIM