LOCUS       NM_012259               2626 bp    mRNA    linear   PRI 20-FEB-2025
DEFINITION  Homo sapiens hes related family bHLH transcription factor with YRPW
            motif 2 (HEY2), mRNA.
ACCESSION   NM_012259
VERSION     NM_012259.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2626)
  AUTHORS   Qin,Y., Huttlin,E.L., Winsnes,C.F., Gosztyla,M.L., Wacheul,L.,
            Kelly,M.R., Blue,S.M., Zheng,F., Chen,M., Schaffer,L.V., Licon,K.,
            Backstrom,A., Vaites,L.P., Lee,J.J., Ouyang,W., Liu,S.N., Zhang,T.,
            Silva,E., Park,J., Pitea,A., Kreisberg,J.F., Gygi,S.P., Ma,J.,
            Harper,J.W., Yeo,G.W., Lafontaine,D.L.J., Lundberg,E. and Ideker,T.
  TITLE     A multi-scale map of cell structure fusing protein images and
            interactions
  JOURNAL   Nature 600 (7889), 536-542 (2021)
   PUBMED   34819669
REFERENCE   2  (bases 1 to 2626)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   3  (bases 1 to 2626)
  AUTHORS   van Walree,E.S., Dombrowsky,G., Jansen,I.E., Mirkov,M.U., Zwart,R.,
            Ilgun,A., Guo,D., Clur,S.B., Amin,A.S., Savage,J.E., van der
            Wal,A.C., Waisfisz,Q., Maugeri,A., Wilsdon,A., Bu'Lock,F.A.,
            Hurles,M.E., Dittrich,S., Berger,F., Audain Martinez,E.,
            Christoffels,V.M., Hitz,M.P., Milewicz,D.M., Posthuma,D.,
            Meijers-Heijboer,H., Postma,A.V. and Mathijssen,I.B.
  TITLE     Germline variants in HEY2 functional domains lead to congenital
            heart defects and thoracic aortic aneurysms
  JOURNAL   Genet Med 23 (1), 103-110 (2021)
   PUBMED   32820247
  REMARK    GeneRIF: Germline variants in HEY2 functional domains lead to
            congenital heart defects and thoracic aortic aneurysms.
            Erratum:[Genet Med. 2022 Apr;24(4):965. doi:
            10.1016/j.gim.2022.01.018.. PMID: 35394427]
REFERENCE   4  (bases 1 to 2626)
  AUTHORS   Fahim,Y., Yousefi,M., Izadpanah,M.H. and Forghanifard,M.M.
  TITLE     TWIST1 correlates with Notch signaling pathway to develop
            esophageal squamous cell carcinoma
  JOURNAL   Mol Cell Biochem 474 (1-2), 181-188 (2020)
   PUBMED   32712748
  REMARK    GeneRIF: TWIST1 correlates with Notch signaling pathway to develop
            esophageal squamous cell carcinoma.
REFERENCE   5  (bases 1 to 2626)
  AUTHORS   Yu,H., Hu,W., Song,X. and Zhao,Y.
  TITLE     Notch-HEY2 signaling pathway contributes to the differentiation of
            CD34+ hematopoietic-like stem cells from adult peripheral blood
            insulin-producing cells after the treatment with platelet-derived
            mitochondria
  JOURNAL   Mol Biol Rep 47 (10), 8347-8352 (2020)
   PUBMED   32997309
  REMARK    GeneRIF: Notch-HEY2 signaling pathway contributes to the
            differentiation of CD34(+) hematopoietic-like stem cells from adult
            peripheral blood insulin-producing cells after the treatment with
            platelet-derived mitochondria.
REFERENCE   6  (bases 1 to 2626)
  AUTHORS   Firulli,B.A., Hadzic,D.B., McDaid,J.R. and Firulli,A.B.
  TITLE     The basic helix-loop-helix transcription factors dHAND and eHAND
            exhibit dimerization characteristics that suggest complex
            regulation of function
  JOURNAL   J Biol Chem 275 (43), 33567-33573 (2000)
   PUBMED   10924525
REFERENCE   7  (bases 1 to 2626)
  AUTHORS   Steidl,C., Leimeister,C., Klamt,B., Maier,M., Nanda,I., Dixon,M.,
            Clarke,R., Schmid,M. and Gessler,M.
  TITLE     Characterization of the human and mouse HEY1, HEY2, and HEYL genes:
            cloning, mapping, and mutation screening of a new bHLH gene family
  JOURNAL   Genomics 66 (2), 195-203 (2000)
   PUBMED   10860664
REFERENCE   8  (bases 1 to 2626)
  AUTHORS   Zhong,T.P., Rosenberg,M., Mohideen,M.A., Weinstein,B. and
            Fishman,M.C.
  TITLE     gridlock, an HLH gene required for assembly of the aorta in
            zebrafish
  JOURNAL   Science 287 (5459), 1820-1824 (2000)
   PUBMED   10710309
REFERENCE   9  (bases 1 to 2626)
  AUTHORS   Chin,M.T., Maemura,K., Fukumoto,S., Jain,M.K., Layne,M.D.,
            Watanabe,M., Hsieh,C.M. and Lee,M.E.
  TITLE     Cardiovascular basic helix loop helix factor 1, a novel
            transcriptional repressor expressed preferentially in the
            developing and adult cardiovascular system
  JOURNAL   J Biol Chem 275 (9), 6381-6387 (2000)
   PUBMED   10692439
REFERENCE   10 (bases 1 to 2626)
  AUTHORS   Leimeister,C., Externbrink,A., Klamt,B. and Gessler,M.
  TITLE     Hey genes: a novel subfamily of hairy- and Enhancer of split
            related genes specifically expressed during mouse embryogenesis
  JOURNAL   Mech Dev 85 (1-2), 173-177 (1999)
   PUBMED   10415358
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI549391.1, BC007707.2 and
            AJ249545.1.
            
            On Nov 22, 2018 this sequence version replaced NM_012259.2.
            
            Summary: This gene encodes a member of the hairy and enhancer of
            split-related (HESR) family of basic helix-loop-helix (bHLH)-type
            transcription factors. The encoded protein forms homo- or
            hetero-dimers that localize to the nucleus and interact with a
            histone deacetylase complex to repress transcription. Expression of
            this gene is induced by the Notch signal transduction pathway. Two
            similar and redundant genes in mouse are required for embryonic
            cardiovascular development, and are also implicated in neurogenesis
            and somitogenesis. Alternatively spliced transcript variants have
            been found, but their biological validity has not been determined.
            [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660807.90043.1,
                                           SRR1660809.152616.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1966682, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000368364.4/ ENSP00000357348.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-56                BI549391.1         56-111
            57-1295             BC007707.2         1-1239
            1296-2626           AJ249545.1         1201-2531
FEATURES             Location/Qualifiers
     source          1..2626
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6q22.31"
     gene            1..2626
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /note="hes related family bHLH transcription factor with
                     YRPW motif 2"
                     /db_xref="GeneID:23493"
                     /db_xref="HGNC:HGNC:4881"
                     /db_xref="MIM:604674"
     exon            1..228
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /inference="alignment:Splign:2.1.0"
     CDS             146..1159
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /note="HES-related repressor protein 1; cardiovascular
                     basic helix-loop-helix factor 1; hairy-related
                     transcription factor 2; HRT-2; hCHF1; hHRT2; HESR-2;
                     protein gridlock homolog; HES-related repressor protein 2;
                     cardiovascular helix-loop-helix factor 1; class B basic
                     helix-loop-helix protein 32; hairy and enhancer of
                     split-related protein 2; hairy/enhancer-of-split related
                     with YRPW motif 2"
                     /codon_start=1
                     /product="hairy/enhancer-of-split related with YRPW motif
                     protein 2"
                     /protein_id="NP_036391.1"
                     /db_xref="CCDS:CCDS5131.1"
                     /db_xref="GeneID:23493"
                     /db_xref="HGNC:HGNC:4881"
                     /db_xref="MIM:604674"
                     /translation="MKRPCEETTSESDMDETIDVGSENNYSGQSTSSVIRLNSPTTTS
                     QIMARKKRRGIIEKRRRDRINNSLSELRRLVPTAFEKQGSAKLEKAEILQMTVDHLKM
                     LQATGGKGYFDAHALAMDFMSIGFRECLTEVARYLSSVEGLDSSDPLRVRLVSHLSTC
                     ATQREAAAMTSSMAHHHHPLHPHHWAAAFHHLPAALLQPNGLHASESTPCRLSTTSEV
                     PPAHGSALLTATFAHADSALRMPSTGSVAPCVPPLSTSLLSLSATVHAAAAAATAAAH
                     SFPLSFAGAFPMLPPNAAAAVAAATAISPPLSVSATSSPQQTSSGTNNKPYRPWGTEV
                     GAF"
     exon            229..307
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /inference="alignment:Splign:2.1.0"
     exon            308..391
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /inference="alignment:Splign:2.1.0"
     exon            392..473
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /inference="alignment:Splign:2.1.0"
     exon            474..2626
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1273..1278
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /note="hexamer: AATAAA"
     polyA_site      1295
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /note="major polyA site"
     regulatory      2603..2608
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
                     /note="hexamer: ATTAAA"
     polyA_site      2626
                     /gene="HEY2"
                     /gene_synonym="bHLHb32; CHF1; GRIDLOCK; GRL; HERP1; HESR2;
                     HRT2"
ORIGIN      
        1 gaaagagccg ctaggagcag accgcgccgc cgccggagcc gcgcctgccc aggcccgggg
       61 agggaggagg cgggcgtcag ggtgctgcgc cccgctcggc gtccgagctt ccggccgggc
      121 tgtgccccgc gcggtcttcg ccgggatgaa gcgcccctgc gaggagacga cctccgagag
      181 cgacatggac gagaccatcg acgtggggag cgagaacaat tactcggggc aaagtactag
      241 ctctgtgatt agattgaatt ctccaacaac aacatctcag attatggcaa gaaagaaaag
      301 gagagggatt atagagaaaa ggcgtcggga tcggataaat aacagtttat ctgagttgag
      361 aagacttgtg ccaactgctt ttgaaaaaca aggatctgca aagttagaaa aagctgaaat
      421 attgcaaatg acagtggatc atttgaagat gcttcaggca acagggggta aaggctactt
      481 tgacgcacac gctcttgcca tggacttcat gagcatagga ttccgagagt gcctaacaga
      541 agttgcgcgg tacctgagct ccgtggaagg cctggactcc tcggatccgc tgcgggtgcg
      601 gcttgtgtct catctcagca cttgcgccac ccagcgggag gcggcggcca tgacatcctc
      661 catggcccac caccatcatc cgctccaccc gcatcactgg gccgccgcct tccaccacct
      721 gcccgcagcc ctgctccagc ccaacggcct ccatgcctca gagtcaaccc cttgtcgcct
      781 ctccacaact tcagaagtgc ctcctgccca cggctctgct ctcctcacgg ccacgtttgc
      841 ccatgcggat tcagccctcc gaatgccatc cacgggcagc gtcgccccct gcgtgccacc
      901 tctctccacc tctctcttgt ccctctctgc caccgtccac gccgcagccg cagcagccac
      961 cgcggctgca cacagcttcc ctctgtcctt cgcgggggca ttccccatgc ttcccccaaa
     1021 cgcagcagca gcagtggccg cggccacagc catcagcccg cccttgtcag tatcagccac
     1081 gtccagtcct cagcagacca gcagtggaac aaacaataaa ccttaccgac cctgggggac
     1141 agaagttgga gctttttaaa tttttcttga acttcttgca atagtaactg aatgtcctcc
     1201 atttcagagt cagcttaaaa cctctgcacc ctgaaggtag ccatacagat gccgacagat
     1261 ccacaaagga acaataaagc tatttgagac acaaacctca cgagtggaaa tgtggtattc
     1321 tctttttttt ctctcccttt tttgtttggt tcaaggcagc tcggtaactg acatcagcaa
     1381 cttttgaaaa cttcacactt gttaccattt agaagtttcc tggaaaatat atggaccgta
     1441 ccatccagca gtgcatcagt atgtctgaat tggggaagta aaatgccctg actgaattct
     1501 cttgagacta gatgggacat acatatatag agagagagtg agagagtcgt gtttcgtaag
     1561 tgcctgagct taggaagttt tcttctggat atataacatt gcacaaggga agacgagtgt
     1621 ggaggatagg ttaagaaagg aaagggacag aagtcttgca ataggctgca gacattttaa
     1681 taccatgcca gagaagagta ttctgctgaa accaacaggt tttactggtc aaaatgactg
     1741 ctgaaaataa ttttcaagtt gaaagatcta gttttatctt agtttgcctt ctttgtacag
     1801 acatgccaag aggtgacatt tagcagtgca ttggtataag caattatttc atcagttctc
     1861 agattaacaa gcatttctgc tctgcctgca ggcccccagg cacttttttt tttggatggc
     1921 tcaaaatatg gtgctgcttt atataaacct tacatttata tagtgcacct atgagcagtt
     1981 gcctaccatg tgtccaccag aggctattta attcatgcca acttgaaaac tctccagttt
     2041 gtaggagttt ggtttaattt attcagtttc attaggacta tttttatata tttatcctct
     2101 tcattttctc ctaatgatgc aacatctatt cttgtcaccc tttgggagaa gttacatttc
     2161 tggaggtgat gaagcaagga gggagcacta ggaagagaaa agctacaatt tttaaagctc
     2221 tttgtcaagt tagtgattgc atttgatccc aaaacaagat gaatgtatgc aatgggatgt
     2281 acataagtta tttttgccca tgcctaaact agtgctatgt aatggggttg tggttttgtt
     2341 tttttcgatt tcgtttaatg acaaaataat ctcttaatat gctgaaatca agcacgtgag
     2401 agtttttgtt taaaagataa gagacacagc atgtattatg cacttcattt ctctactgtg
     2461 tggagaaagc aataaacatt atgagaatgt taaacgttat gcaaaattat acttttaaat
     2521 atttgttttg aaattactgt acctagtctt ttttgcatta ctttgtaacc tttttctatg
     2581 caagagtctt tacataccac taattaaatg aagtcctttt tgacta
//
