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HEY2_DANRE
ID   HEY2_DANRE              Reviewed;         324 AA.
AC   Q9I9L0; Q24JW1;
DT   11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2007, sequence version 2.
DT   03-AUG-2022, entry version 126.
DE   RecName: Full=Hairy/enhancer-of-split related with YRPW motif protein 2;
DE   AltName: Full=Protein gridlock;
GN   Name=hey2; Synonyms=grl; ORFNames=zgc:136746;
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=10710309; DOI=10.1126/science.287.5459.1820;
RA   Zhong T.P., Rosenberg M., Mohideen M.-A.P.K., Weinstein B., Fishman M.C.;
RT   "Gridlock, an HLH gene required for assembly of the aorta in zebrafish.";
RL   Science 287:1820-1824(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=11700560; DOI=10.1038/35102599;
RA   Zhong T.P., Childs S., Leu J.P., Fishman M.C.;
RT   "Gridlock signalling pathway fashions the first embryonic artery.";
RL   Nature 414:216-220(2001).
RN   [4]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=14593478; DOI=10.1007/s00427-003-0360-6;
RA   Winkler C., Elmasri H., Klamt B., Volff J.-N., Gessler M.;
RT   "Characterization of hey bHLH genes in teleost fish.";
RL   Dev. Genes Evol. 213:541-553(2003).
CC   -!- FUNCTION: Transcriptional repressor (By similarity). Downstream
CC       effector of Notch signaling which regulates cell fate choice in
CC       angioblasts. Represses the venous cell fate, thereby promoting the
CC       arterial cell fate and aorta formation. {ECO:0000250,
CC       ECO:0000269|PubMed:10710309, ECO:0000269|PubMed:11700560}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00380,
CC       ECO:0000255|PROSITE-ProRule:PRU00981}.
CC   -!- DEVELOPMENTAL STAGE: Expressed from the first somite stage. Expressed
CC       in lateral plate mesoderm before vessel formation, and thereafter in
CC       the aorta but not in the vein. At the 6-somite stage expression is seen
CC       in the lateral mesoderm of the head and trunk. While expression in the
CC       trunk lateral mesoderm is initially uniform, at the 16-somite stage,
CC       expression is restricted to angioblast precursors that have not yet
CC       migrated dorsally. At the 16-somite stage expression is also seen in
CC       the telencephalon, dorsal midbrain, neural crest and in the dorsal
CC       aorta and its vascular progenitors. {ECO:0000269|PubMed:10710309,
CC       ECO:0000269|PubMed:14593478}.
CC   -!- INDUCTION: By activation of the Notch signaling pathway.
CC       {ECO:0000269|PubMed:11700560}.
CC   -!- SIMILARITY: Belongs to the HEY family. {ECO:0000305}.
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DR   EMBL; AF237948; AAF44780.1; -; mRNA.
DR   EMBL; BC114263; AAI14264.1; -; mRNA.
DR   RefSeq; NP_571697.2; NM_131622.2.
DR   AlphaFoldDB; Q9I9L0; -.
DR   SMR; Q9I9L0; -.
DR   DIP; DIP-46472N; -.
DR   ELM; Q9I9L0; -.
DR   IntAct; Q9I9L0; 1.
DR   STRING; 7955.ENSDARP00000002357; -.
DR   PaxDb; Q9I9L0; -.
DR   Ensembl; ENSDART00000023531; ENSDARP00000002357; ENSDARG00000013441.
DR   GeneID; 58146; -.
DR   KEGG; dre:58146; -.
DR   CTD; 23493; -.
DR   ZFIN; ZDB-GENE-000526-1; hey2.
DR   eggNOG; KOG4304; Eukaryota.
DR   GeneTree; ENSGT00940000160636; -.
DR   HOGENOM; CLU_048294_1_0_1; -.
DR   InParanoid; Q9I9L0; -.
DR   OMA; HWTAAFH; -.
DR   OrthoDB; 1201152at2759; -.
DR   PhylomeDB; Q9I9L0; -.
DR   TreeFam; TF323617; -.
DR   PRO; PR:Q9I9L0; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 20.
DR   Bgee; ENSDARG00000013441; Expressed in artery and 67 other tissues.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR   GO; GO:0060840; P:artery development; IMP:ZFIN.
DR   GO; GO:0048844; P:artery morphogenesis; IMP:ZFIN.
DR   GO; GO:0001568; P:blood vessel development; IMP:ZFIN.
DR   GO; GO:0048514; P:blood vessel morphogenesis; IMP:ZFIN.
DR   GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:ZFIN.
DR   GO; GO:0072359; P:circulatory system development; IBA:GO_Central.
DR   GO; GO:0035912; P:dorsal aorta morphogenesis; IMP:ZFIN.
DR   GO; GO:0007507; P:heart development; IMP:ZFIN.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IGI:ZFIN.
DR   GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR   GO; GO:0060853; P:Notch signaling pathway involved in arterial endothelial cell fate commitment; IMP:ZFIN.
DR   GO; GO:0050767; P:regulation of neurogenesis; IBA:GO_Central.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0001570; P:vasculogenesis; IMP:ZFIN.
DR   Gene3D; 4.10.280.10; -; 1.
DR   InterPro; IPR011598; bHLH_dom.
DR   InterPro; IPR036638; HLH_DNA-bd_sf.
DR   InterPro; IPR003650; Orange_dom.
DR   Pfam; PF07527; Hairy_orange; 1.
DR   Pfam; PF00010; HLH; 1.
DR   SMART; SM00353; HLH; 1.
DR   SMART; SM00511; ORANGE; 1.
DR   SUPFAM; SSF47459; SSF47459; 1.
DR   PROSITE; PS50888; BHLH; 1.
DR   PROSITE; PS51054; ORANGE; 1.
PE   2: Evidence at transcript level;
KW   Developmental protein; DNA-binding; Notch signaling pathway; Nucleus;
KW   Reference proteome; Repressor; Transcription; Transcription regulation.
FT   CHAIN           1..324
FT                   /note="Hairy/enhancer-of-split related with YRPW motif
FT                   protein 2"
FT                   /id="PRO_0000245517"
FT   DOMAIN          48..103
FT                   /note="bHLH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT   DOMAIN          122..157
FT                   /note="Orange"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00380"
FT   REGION          1..34
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          294..324
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           314..317
FT                   /note="YRPW motif"
FT   COMPBIAS        19..34
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        294..314
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        23
FT                   /note="E -> Q (in Ref. 1; AAF44780)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        310
FT                   /note="S -> N (in Ref. 1; AAF44780)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   324 AA;  34329 MW;  CEA9DAC5F6C98700 CRC64;
     MKRPCEDSTS DSDMDETIDV GSENNYSGQS NGSFIRCGSP TTTSQVMARK KRRGIIEKRR
     RDRINNSLSE LRRLVPTAFE KQGSAKLEKA EILQMTVDHL KMLQATGGKG YFDAHSLAMD
     FLSIGFRECL TEVARYLSSV EGLDSSDPLR VRLVSHLSSC ASQREAAAMT TSIAHHQQAL
     HPHHWAAALH PIPAAFLQQS GLPSSESSSG RLSEAPQRGA ALFSHSDSAL RAPSTGSVAP
     CVPPLSTSLL SLSATVHAAA AAAAAQTFPL SFPAGFPLFS PSVTASSVAS STVSSSVSTS
     TTSQQSSGSS SKPYRPWGTE VGAF
 
 
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