LOCUS       NM_007194               1844 bp    mRNA    linear   PRI 18-NOV-2024
DEFINITION  Homo sapiens checkpoint kinase 2 (CHEK2), transcript variant 1,
            mRNA.
ACCESSION   NM_007194
VERSION     NM_007194.4
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 1844)
  AUTHORS   Murray,C.E., Kornepati,A.V.R., Ontiveros,C., Liao,Y., de la Pena
            Avalos,B., Rogers,C.M., Liu,Z., Deng,Y., Bai,H., Kari,S.,
            Padron,A.S., Boyd,J.T., Reyes,R., Clark,C.A., Svatek,R.S., Li,R.,
            Hu,Y., Wang,M., Conejo-Garcia,J.R., Byers,L.A., Ramkumar,K.,
            Sood,A.K., Lee,J.M., Burd,C.E., Vadlamudi,R.K., Gupta,H.B.,
            Zhao,W., Dray,E., Sung,P. and Curiel,T.J.
  TITLE     Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response
            in cancer cells and mediate resistance to Chk1 inhibitors
  JOURNAL   Mol Cancer 23 (1), 242 (2024)
   PUBMED   39478560
  REMARK    GeneRIF: Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage
            response in cancer cells and mediate resistance to Chk1 inhibitors.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1844)
  AUTHORS   Kliche,J., Simonetti,L., Krystkowiak,I., Kuss,H., Diallo,M.,
            Rask,E., Nilsson,J., Davey,N.E. and Ivarsson,Y.
  TITLE     Proteome-scale characterisation of motif-based interactome rewiring
            by disease mutations
  JOURNAL   Mol Syst Biol 20 (9), 1025-1048 (2024)
   PUBMED   39009827
REFERENCE   3  (bases 1 to 1844)
  AUTHORS   Schreurs,M.A.C., Schmidt,M.K., Hollestelle,A., Schaapveld,M., van
            Asperen,C.J., Ausems,M.G.E.M., van de Beek,I., Broekema,M.F.,
            Margriet Collee,J., van der Hout,A.H., van Kaam,K.J.A.F.,
            Komdeur,F.L., Mensenkamp,A.R., Adank,M.A. and Hooning,M.J.
  CONSRTM   Hereditary Breast and Ovarian Cancer Research Group Netherlands
  TITLE     Cancer risks for other sites in addition to breast in CHEK2
            c.1100delC families
  JOURNAL   Genet Med 26 (9), 101171 (2024)
   PUBMED   38828701
  REMARK    GeneRIF: Cancer risks for other sites in addition to breast in
            CHEK2 c.1100delC families.
REFERENCE   4  (bases 1 to 1844)
  AUTHORS   McCarthy-Leo,C.E., Brush,G.S., Pique-Regi,R., Luca,F., Tainsky,M.A.
            and Finley,R.L. Jr.
  TITLE     Comprehensive analysis of the functional impact of single
            nucleotide variants of human CHEK2
  JOURNAL   PLoS Genet 20 (8), e1011375 (2024)
   PUBMED   39146382
  REMARK    GeneRIF: Comprehensive analysis of the functional impact of single
            nucleotide variants of human CHEK2.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 1844)
  AUTHORS   Hu,H.F., Han,L., Fu,J.Y., He,X., Tan,J.F., Chen,Q.P., Han,J.R. and
            He,Q.Y.
  TITLE     LINC00982-encoded protein PRDM16-DT regulates CHEK2 splicing to
            suppress colorectal cancer metastasis and chemoresistance
  JOURNAL   Theranostics 14 (8), 3317-3338 (2024)
   PUBMED   38855188
  REMARK    GeneRIF: LINC00982-encoded protein PRDM16-DT regulates CHEK2
            splicing to suppress colorectal cancer metastasis and
            chemoresistance.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 1844)
  AUTHORS   Martinho,R.G., Lindsay,H.D., Flaggs,G., DeMaggio,A.J.,
            Hoekstra,M.F., Carr,A.M. and Bentley,N.J.
  TITLE     Analysis of Rad3 and Chk1 protein kinases defines different
            checkpoint responses
  JOURNAL   EMBO J 17 (24), 7239-7249 (1998)
   PUBMED   9857181
REFERENCE   7  (bases 1 to 1844)
  AUTHORS   Matsuoka,S., Huang,M. and Elledge,S.J.
  TITLE     Linkage of ATM to cell cycle regulation by the Chk2 protein kinase
  JOURNAL   Science 282 (5395), 1893-1897 (1998)
   PUBMED   9836640
REFERENCE   8  (bases 1 to 1844)
  AUTHORS   Lindsay,H.D., Griffiths,D.J., Edwards,R.J., Christensen,P.U.,
            Murray,J.M., Osman,F., Walworth,N. and Carr,A.M.
  TITLE     S-phase-specific activation of Cds1 kinase defines a subpathway of
            the checkpoint response in Schizosaccharomyces pombe
  JOURNAL   Genes Dev 12 (3), 382-395 (1998)
   PUBMED   9450932
REFERENCE   9  (bases 1 to 1844)
  AUTHORS   Lykidis,A., Jackson,P.D., Rock,C.O. and Jackowski,S.
  TITLE     The role of CDP-diacylglycerol synthetase and phosphatidylinositol
            synthase activity levels in the regulation of cellular
            phosphatidylinositol content
  JOURNAL   J Biol Chem 272 (52), 33402-33409 (1997)
   PUBMED   9407135
REFERENCE   10 (bases 1 to 1844)
  AUTHORS   Peng,C.Y., Graves,P.R., Thoma,R.S., Wu,Z., Shaw,A.S. and
            Piwnica-Worms,H.
  TITLE     Mitotic and G2 checkpoint control: regulation of 14-3-3 protein
            binding by phosphorylation of Cdc25C on serine-216
  JOURNAL   Science 277 (5331), 1501-1505 (1997)
   PUBMED   9278512
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BM838597.1, AF096279.1 and
            AW778747.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 13, 2018 this sequence version replaced NM_007194.3.
            
            Summary: In response to DNA damage and replication blocks, cell
            cycle progression is halted through the control of critical cell
            cycle regulators. The protein encoded by this gene is a cell cycle
            checkpoint regulator and putative tumor suppressor. It contains a
            forkhead-associated protein interaction domain essential for
            activation in response to DNA damage and is rapidly phosphorylated
            in response to replication blocks and DNA damage. When activated,
            the encoded protein is known to inhibit CDC25C phosphatase,
            preventing entry into mitosis, and has been shown to stabilize the
            tumor suppressor protein p53, leading to cell cycle arrest in G1.
            In addition, this protein interacts with and phosphorylates BRCA1,
            allowing BRCA1 to restore survival after DNA damage. Mutations in
            this gene have been linked with Li-Fraumeni syndrome, a highly
            penetrant familial cancer phenotype usually associated with
            inherited mutations in TP53. Also, mutations in this gene are
            thought to confer a predisposition to sarcomas, breast cancer, and
            brain tumors. This nuclear protein is a member of the CDS1
            subfamily of serine/threonine protein kinases. Several transcript
            variants encoding different isoforms have been found for this gene.
            [provided by RefSeq, Apr 2012].
            
            Transcript Variant: This variant (1) represents the predominant
            transcript and encodes isoform a.
            
            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 :: AK289360.1, AK290754.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000404276.6/ ENSP00000385747.1
            RefSeq Select criteria :: based on expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-58                BM838597.1         15-72
            59-1690             AF096279.1         1-1632
            1691-1844           AW778747.1         5-158               c
FEATURES             Location/Qualifiers
     source          1..1844
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q12.1"
     gene            1..1844
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /note="checkpoint kinase 2"
                     /db_xref="GeneID:11200"
                     /db_xref="HGNC:HGNC:16627"
                     /db_xref="MIM:604373"
     exon            1..52
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            53..377
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     CDS             59..1690
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /EC_number="2.7.11.1"
                     /note="isoform a is encoded by transcript variant 1;
                     checkpoint-like protein CHK2; serine/threonine-protein
                     kinase CHK2; CHK2 checkpoint homolog; cds1 homolog"
                     /codon_start=1
                     /product="serine/threonine-protein kinase Chk2 isoform a"
                     /protein_id="NP_009125.1"
                     /db_xref="CCDS:CCDS13843.1"
                     /db_xref="GeneID:11200"
                     /db_xref="HGNC:HGNC:16627"
                     /db_xref="MIM:604373"
                     /translation="MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTS
                     TMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDG
                     FANLECVNDNYWFGRDKSCEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYI
                     EDHSGNGTFVNTELVGKGKRRPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRD
                     EYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEI
                     LKKLNHPCIIKIKNFFDAEDYYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLA
                     VQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYLA
                     PEVLVSVGTAGYNRAVDCWSLGVILFICLSGYPPFSEHRTQVSLKDQITSGKYNFIPE
                     VWAEVSEKALDLVKKLLVVDPKARFTTEEALRHPWLQDEDMKRKFQDLLSEENESTAL
                     PQVLAQPSTSRKRPREGEAEGAETTKRPAVCAAVL"
     exon            378..502
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            503..650
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            651..741
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            742..850
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            851..904
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            905..966
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            967..1066
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            1067..1153
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            1154..1317
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            1318..1433
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            1434..1519
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            1520..1600
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
     exon            1601..1844
                     /gene="CHEK2"
                     /gene_synonym="CDS1; CHK2; hCds1; HuCds1; LFS2; PP1425;
                     RAD53; TPDS4"
                     /inference="alignment:Splign:2.1.0"
ORIGIN      
        1 actctgctgg ctgaggctgc ggagagtgtg cggctccagg tgggctcacg cggtcgtgat
       61 gtctcgggag tcggatgttg aggctcagca gtctcatggc agcagtgcct gttcacagcc
      121 ccatggcagc gttacccagt cccaaggctc ctcctcacag tcccagggca tatccagctc
      181 ctctaccagc acgatgccaa actccagcca gtcctctcac tccagctctg ggacactgag
      241 ctccttagag acagtgtcca ctcaggaact ctattctatt cctgaggacc aagaacctga
      301 ggaccaagaa cctgaggagc ctacccctgc cccctgggct cgattatggg cccttcagga
      361 tggatttgcc aatcttgaat gtgtgaatga caactactgg tttgggaggg acaaaagctg
      421 tgaatattgc tttgatgaac cactgctgaa aagaacagat aaataccgaa catacagcaa
      481 gaaacacttt cggattttca gggaagtggg tcctaaaaac tcttacattg catacataga
      541 agatcacagt ggcaatggaa cctttgtaaa tacagagctt gtagggaaag gaaaacgccg
      601 tcctttgaat aacaattctg aaattgcact gtcactaagc agaaataaag tttttgtctt
      661 ttttgatctg actgtagatg atcagtcagt ttatcctaag gcattaagag atgaatacat
      721 catgtcaaaa actcttggaa gtggtgcctg tggagaggta aagctggctt tcgagaggaa
      781 aacatgtaag aaagtagcca taaagatcat cagcaaaagg aagtttgcta ttggttcagc
      841 aagagaggca gacccagctc tcaatgttga aacagaaata gaaattttga aaaagctaaa
      901 tcatccttgc atcatcaaga ttaaaaactt ttttgatgca gaagattatt atattgtttt
      961 ggaattgatg gaagggggag agctgtttga caaagtggtg gggaataaac gcctgaaaga
     1021 agctacctgc aagctctatt tttaccagat gctcttggct gtgcagtacc ttcatgaaaa
     1081 cggtattata caccgtgact taaagccaga gaatgtttta ctgtcatctc aagaagagga
     1141 ctgtcttata aagattactg attttgggca ctccaagatt ttgggagaga cctctctcat
     1201 gagaacctta tgtggaaccc ccacctactt ggcgcctgaa gttcttgttt ctgttgggac
     1261 tgctgggtat aaccgtgctg tggactgctg gagtttagga gttattcttt ttatctgcct
     1321 tagtgggtat ccacctttct ctgagcatag gactcaagtg tcactgaagg atcagatcac
     1381 cagtggaaaa tacaacttca ttcctgaagt ctgggcagaa gtctcagaga aagctctgga
     1441 ccttgtcaag aagttgttgg tagtggatcc aaaggcacgt tttacgacag aagaagcctt
     1501 aagacacccg tggcttcagg atgaagacat gaagagaaag tttcaagatc ttctgtctga
     1561 ggaaaatgaa tccacagctc taccccaggt tctagcccag ccttctacta gtcgaaagcg
     1621 gccccgtgaa ggggaagccg agggtgccga gaccacaaag cgcccagctg tgtgtgctgc
     1681 tgtgttgtga actccgtggt ttgaacacga aagaaatgta ccttctttca ctctgtcatc
     1741 tttcttttct ttgagtctgt ttttttatag tttgtatttt aattatggga ataattgctt
     1801 tttcacagtc actgatgtac aattaaaaac ctgatggaac ctgg
//
