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Protein

Hairy/enhancer-of-split related with YRPW motif protein 2

Gene

Hey2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcriptional repressor which functions as a downstream effector of Notch signaling in cardiovascular development. Specifically required for the Notch-induced endocardial epithelial to mesenchymal transition, which is itself criticial for cardiac valve and septum development. May be required in conjunction with HEY1 to specify arterial cell fate or identity. Promotes maintenance of neuronal precursor cells and glial versus neuronal fate specification. Binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Represses transcription by the cardiac transcriptional activators GATA4 and GATA6 and by the neuronal bHLH factors ASCL1/MASH1 and NEUROD4/MATH3.17 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding, Repressor
Biological processNotch signaling pathway, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Hairy/enhancer-of-split related with YRPW motif protein 2
Alternative name(s):
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:
mHRT2
Protein gridlock homolog
Gene namesi
Name:Hey2
Synonyms:Chf1, Herp, Herp1, Hesr2, Hrt2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1341884 Hey2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice display a spectrum of cardiac malformations including ventricular septal defects, tetralogy of Fallot and tricuspid atresia. The penetrance of the cardiac malformation phenotype varies according to the strain, suggesting the presence of modifier genes.7 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi33 – 37Missing : Abrogates interaction with GATA4 and repression of GATA4-mediated transcription. 1 Publication5
Mutagenesisi49 – 61RKKRR…EKRRR → LE: Abrogates DNA-binding and transcriptional repression. 1 PublicationAdd BLAST13

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002455161 – 339Hairy/enhancer-of-split related with YRPW motif protein 2Add BLAST339

Proteomic databases

PaxDbiQ9QUS4
PRIDEiQ9QUS4

PTM databases

PhosphoSitePlusiQ9QUS4

Expressioni

Tissue specificityi

Highly expressed in the aorta, lower expression detected in the heart, brain, kidney, lung, muscle, ovary and testis.4 Publications

Developmental stagei

Expressed in the developing somites and the ventricles of the heart. Expressed in the otic vesicles between E8.5 and E10.5. Expressed in the myocardium of the ventricles at E9.5 and in the atrioventricular cushions from E9.5 to E12.5. At E10.5, strongly expressed in the spinal nerves, the cranial ganglia and the telencephalon. At E11.5, expressed in the craniofacial region of the distal part of the maxillary arch, along the rostral mandibular arch and surrounding the lateral nasal processes. Expressed in the midbrain-hindbrain boundary and the posterior edge of the hand- and foot-paddle. Expressed in the mediodorsal region of the telencephalon and the ventricular zone of the ventral spinal cord at E12, then in the ventral region of the telencephalon and the cortical plate at E15. Expression in the heart is limited to the compact myocardial layer at E17.5. Also expressed in the developing retina up to P5, at which point expression decreases.10 Publications

Inductioni

By activation of the Notch signaling pathway.3 Publications

Gene expression databases

BgeeiENSMUSG00000019789 Expressed in 265 organ(s), highest expression level in cardiac ventricle
CleanExiMM_HEY2
ExpressionAtlasiQ9QUS4 baseline and differential
GenevisibleiQ9QUS4 MM

Interactioni

Subunit structurei

May self-associate (By similarity). Interacts with ARNT (By similarity). Interacts with GATA4, GATA6, HES1 and HEYL. Interacts with HDAC1, NCOR1 and SIN3A.By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200283, 1 interactor
IntActiQ9QUS4, 2 interactors
STRINGi10090.ENSMUSP00000019924

Structurei

3D structure databases

ProteinModelPortaliQ9QUS4
SMRiQ9QUS4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 103bHLHPROSITE-ProRule annotationAdd BLAST56
Domaini122 – 157OrangePROSITE-ProRule annotationAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni47 – 116Transcriptional repression and interaction with NCOR1 and SIN3A1 PublicationAdd BLAST70

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi329 – 332YQPW motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi175 – 191His-richAdd BLAST17
Compositional biasi262 – 304Ala-richAdd BLAST43

Sequence similaritiesi

Belongs to the HEY family.Curated

Phylogenomic databases

eggNOGiKOG4304 Eukaryota
ENOG4111F0X LUCA
GeneTreeiENSGT00700000104130
HOGENOMiHOG000286035
HOVERGENiHBG003275
InParanoidiQ9QUS4
KOiK09091
OMAiSTCASQR
OrthoDBiEOG091G0HNC
PhylomeDBiQ9QUS4
TreeFamiTF323617

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR003650 Orange_dom
PfamiView protein in Pfam
PF07527 Hairy_orange, 1 hit
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00511 ORANGE, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS51054 ORANGE, 1 hit

Sequencei

Sequence statusi: Complete.

Q9QUS4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKRPCEETTS ESDLDETIDV GSENNYPGHA TSSVMRSNSP TTTSQIMARK
60 70 80 90 100
KRRGIIEKRR RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL
110 120 130 140 150
KMLQATGGKG YFDAHALATD FMSIGFRECL TEVARYLSSV EGLDPSDPLR
160 170 180 190 200
VRLVSHLSTC ASQREAAVMT SSMAHHHHPL HPHHWAAAFH HLPTALLQPN
210 220 230 240 250
GLHTSESTPC RLSTSSEVPS AHGSALLTAT FAHADSALRM PSGGTVAPCV
260 270 280 290 300
PPLSTSLLSL SATVHAAAAA ATAAAHSFPL SFAGAFPMLP SNAAAAAAVA
310 320 330
AATAISPPLS VSAASSPQQT STGTNNKPYQ PWGTEVGAF
Length:339
Mass (Da):35,873
Last modified:May 1, 2000 - v1
Checksum:i105BEEA06DE50444
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti7E → K in BAC27428 (PubMed:16141072).Curated1
Sequence conflicti284G → E in BAE34310 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF172287 mRNA Translation: AAF14546.1
AJ271867 mRNA Translation: CAB71346.1
AF173902 mRNA Translation: AAF20174.1
AF232240 mRNA Translation: AAF37298.1
AB093589 mRNA Translation: BAC55066.1
AK031506 mRNA Translation: BAC27428.1
AK158000 mRNA Translation: BAE34310.1
BC103575 mRNA Translation: AAI03576.1
BC103576 mRNA Translation: AAI03577.1
CCDSiCCDS23766.1
RefSeqiNP_038932.1, NM_013904.1
UniGeneiMm.103573

Genome annotation databases

EnsembliENSMUST00000019924; ENSMUSP00000019924; ENSMUSG00000019789
GeneIDi15214
KEGGimmu:15214
UCSCiuc007etp.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF172287 mRNA Translation: AAF14546.1
AJ271867 mRNA Translation: CAB71346.1
AF173902 mRNA Translation: AAF20174.1
AF232240 mRNA Translation: AAF37298.1
AB093589 mRNA Translation: BAC55066.1
AK031506 mRNA Translation: BAC27428.1
AK158000 mRNA Translation: BAE34310.1
BC103575 mRNA Translation: AAI03576.1
BC103576 mRNA Translation: AAI03577.1
CCDSiCCDS23766.1
RefSeqiNP_038932.1, NM_013904.1
UniGeneiMm.103573

3D structure databases

ProteinModelPortaliQ9QUS4
SMRiQ9QUS4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200283, 1 interactor
IntActiQ9QUS4, 2 interactors
STRINGi10090.ENSMUSP00000019924

PTM databases

PhosphoSitePlusiQ9QUS4

Proteomic databases

PaxDbiQ9QUS4
PRIDEiQ9QUS4

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019924; ENSMUSP00000019924; ENSMUSG00000019789
GeneIDi15214
KEGGimmu:15214
UCSCiuc007etp.1 mouse

Organism-specific databases

CTDi23493
MGIiMGI:1341884 Hey2

Phylogenomic databases

eggNOGiKOG4304 Eukaryota
ENOG4111F0X LUCA
GeneTreeiENSGT00700000104130
HOGENOMiHOG000286035
HOVERGENiHBG003275
InParanoidiQ9QUS4
KOiK09091
OMAiSTCASQR
OrthoDBiEOG091G0HNC
PhylomeDBiQ9QUS4
TreeFamiTF323617

Miscellaneous databases

PROiPR:Q9QUS4
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000019789 Expressed in 265 organ(s), highest expression level in cardiac ventricle
CleanExiMM_HEY2
ExpressionAtlasiQ9QUS4 baseline and differential
GenevisibleiQ9QUS4 MM

Family and domain databases

CDDicd00083 HLH, 1 hit
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR003650 Orange_dom
PfamiView protein in Pfam
PF07527 Hairy_orange, 1 hit
PF00010 HLH, 1 hit
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00511 ORANGE, 1 hit
SUPFAMiSSF47459 SSF47459, 1 hit
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS51054 ORANGE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHEY2_MOUSE
AccessioniPrimary (citable) accession number: Q9QUS4
Secondary accession number(s): Q3TZ99, Q8CD44
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 142 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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