LOCUS       NM_000546               2512 bp    mRNA    linear   PRI 05-OCT-2024
DEFINITION  Homo sapiens tumor protein p53 (TP53), transcript variant 1, mRNA.
ACCESSION   NM_000546
VERSION     NM_000546.6
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 2512)
  AUTHORS   Mirgayazova,R., Khadiullina,R., Chasov,V., Mingaleeva,R.,
            Miftakhova,R., Rizvanov,A. and Bulatov,E.
  TITLE     Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option?
  JOURNAL   Genes (Basel) 11 (6), 704 (2020)
   PUBMED   32630614
  REMARK    GeneRIF: Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an
            Option?
            Review article
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2512)
  AUTHORS   Flynt,E., Bisht,K., Sridharan,V., Ortiz,M., Towfic,F. and
            Thakurta,A.
  TITLE     Prognosis, Biology, and Targeting of TP53 Dysregulation in Multiple
            Myeloma
  JOURNAL   Cells 9 (2), 287 (2020)
   PUBMED   31991614
  REMARK    Review article
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2512)
  AUTHORS   Barnoud,T., Parris,J.L.D. and Murphy,M.E.
  TITLE     Common genetic variants in the TP53 pathway and their impact on
            cancer
  JOURNAL   J Mol Cell Biol 11 (7), 578-585 (2019)
   PUBMED   31152665
  REMARK    GeneRIF: Common genetic variants in the TP53 pathway and their
            impact on cancer.
            Review article
REFERENCE   4  (bases 1 to 2512)
  AUTHORS   Hu,W., Chen,S., Thorne,R.F. and Wu,M.
  TITLE     TP53, TP53 Target Genes (DRAM, TIGAR), and Autophagy
  JOURNAL   Adv Exp Med Biol 1206, 127-149 (2019)
   PUBMED   31776983
  REMARK    Review article
REFERENCE   5  (bases 1 to 2512)
  AUTHORS   Baugh,E.H., Ke,H., Levine,A.J., Bonneau,R.A. and Chan,C.S.
  TITLE     Why are there hotspot mutations in the TP53 gene in human cancers?
  JOURNAL   Cell Death Differ 25 (1), 154-160 (2018)
   PUBMED   29099487
  REMARK    GeneRIF: TP53 missense mutant alleles that occur in human cancers
            are discussed in the context of high resolution models of these p53
            mutant protein structures to determine the structural features of
            mutations (review).
            Review article
REFERENCE   6  (bases 1 to 2512)
  AUTHORS   Aubrey,B.J., Strasser,A. and Kelly,G.L.
  TITLE     Tumor-Suppressor Functions of the TP53 Pathway
  JOURNAL   Cold Spring Harb Perspect Med 6 (5), a026062 (2016)
   PUBMED   27141080
  REMARK    Review article
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 2512)
  AUTHORS   Soussi,T. and Wiman,K.G.
  TITLE     TP53: an oncogene in disguise
  JOURNAL   Cell Death Differ 22 (8), 1239-1249 (2015)
   PUBMED   26024390
  REMARK    Review article
REFERENCE   8  (bases 1 to 2512)
  AUTHORS   Soussi,T.
  TITLE     The TP53 gene network in a postgenomic era
  JOURNAL   Hum Mutat 35 (6), 641-642 (2014)
   PUBMED   24753184
  REMARK    GeneRIF: Recommendations and guidelines for reporting and
            annotating TP53 variants are also provided, to help researchers
            generate standardized data that are easy to understand, analyze,
            and exchange across various cancer variant databases
            Review article
REFERENCE   9  (bases 1 to 2512)
  AUTHORS   Anczukow,O., Ware,M.D., Buisson,M., Zetoune,A.B.,
            Stoppa-Lyonnet,D., Sinilnikova,O.M. and Mazoyer,S.
  TITLE     Does the nonsense-mediated mRNA decay mechanism prevent the
            synthesis of truncated BRCA1, CHK2, and p53 proteins?
  JOURNAL   Hum Mutat 29 (1), 65-73 (2008)
   PUBMED   17694537
  REMARK    GeneRIF: the p53 protein encoded by the 770delT allele is as
            abundant as the wild-type protein, as removal of the C-terminal p53
            domain leads to a stabilized mutant protein, whose abundance is
            markedly increased when NMD is inhibited.
REFERENCE   10 (bases 1 to 2512)
  AUTHORS   Bourdon,J.C.
  TITLE     p53 Family isoforms
  JOURNAL   Curr Pharm Biotechnol 8 (6), 332-336 (2007)
   PUBMED   18289041
  REMARK    Review article
REFERENCE   11 (bases 1 to 2512)
  AUTHORS   Candeias,M.M., Powell,D.J., Roubalova,E., Apcher,S., Bourougaa,K.,
            Vojtesek,B., Bruzzoni-Giovanelli,H. and Fahraeus,R.
  TITLE     Expression of p53 and p53/47 are controlled by alternative
            mechanisms of messenger RNA translation initiation
  JOURNAL   Oncogene 25 (52), 6936-6947 (2006)
   PUBMED   16983332
  REMARK    GeneRIF: harbouring alternative translation initiation sites, the
            p53 mRNA gives rise to different levels of the p53 isoforms which
            help to orchestrate the cell biological outcome of p53 activation
REFERENCE   12 (bases 1 to 2512)
  AUTHORS   Murray-Zmijewski,F., Lane,D.P. and Bourdon,J.C.
  TITLE     p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell
            differentiation and response to stress
  JOURNAL   Cell Death Differ 13 (6), 962-972 (2006)
   PUBMED   16601753
  REMARK    Review article
REFERENCE   13 (bases 1 to 2512)
  AUTHORS   Bourdon,J.C., Fernandes,K., Murray-Zmijewski,F., Liu,G., Diot,A.,
            Xirodimas,D.P., Saville,M.K. and Lane,D.P.
  TITLE     p53 isoforms can regulate p53 transcriptional activity
  JOURNAL   Genes Dev 19 (18), 2122-2137 (2005)
   PUBMED   16131611
  REMARK    GeneRIF: p53 isoforms can regulate p53 transcriptional activity.
REFERENCE   14 (bases 1 to 2512)
  AUTHORS   Ghosh,A., Stewart,D. and Matlashewski,G.
  TITLE     Regulation of human p53 activity and cell localization by
            alternative splicing
  JOURNAL   Mol Cell Biol 24 (18), 7987-7997 (2004)
   PUBMED   15340061
  REMARK    GeneRIF: mechanism of p53 regulation originating through
            alternative splicing of the human p53 gene resulting in the
            expression of a novel p53 mRNA
REFERENCE   15 (bases 1 to 2512)
  AUTHORS   Flaman,J.M., Waridel,F., Estreicher,A., Vannier,A., Limacher,J.M.,
            Gilbert,D., Iggo,R. and Frebourg,T.
  TITLE     The human tumour suppressor gene p53 is alternatively spliced in
            normal cells
  JOURNAL   Oncogene 12 (4), 813-818 (1996)
   PUBMED   8632903
REFERENCE   16 (bases 1 to 2512)
  AUTHORS   Schneider,K., Zelley,K., Nichols,K.E., Schwartz Levine,A. and
            Garber,J.
  TITLE     Li-Fraumeni Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301488
REFERENCE   17 (bases 1 to 2512)
  AUTHORS   Turner,J.T., Brzezinski,J. and Dome,J.S.
  TITLE     Wilms Tumor Predisposition
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301471
REFERENCE   18 (bases 1 to 2512)
  AUTHORS   Lamb,P. and Crawford,L.
  TITLE     Characterization of the human p53 gene
  JOURNAL   Mol Cell Biol 6 (5), 1379-1385 (1986)
   PUBMED   2946935
REFERENCE   19 (bases 1 to 2512)
  AUTHORS   Isobe,M., Emanuel,B.S., Givol,D., Oren,M. and Croce,C.M.
  TITLE     Localization of gene for human p53 tumour antigen to band 17p13
  JOURNAL   Nature 320 (6057), 84-85 (1986)
   PUBMED   3456488
REFERENCE   20 (bases 1 to 2512)
  AUTHORS   Benchimol,S., Lamb,P., Crawford,L.V., Sheer,D., Shows,T.B.,
            Bruns,G.A. and Peacock,J.
  TITLE     Transformation associated p53 protein is encoded by a gene on human
            chromosome 17
  JOURNAL   Somat Cell Mol Genet 11 (5), 505-510 (1985)
   PUBMED   2994241
REFERENCE   21 (bases 1 to 2512)
  AUTHORS   Harlow,E., Williamson,N.M., Ralston,R., Helfman,D.M. and Adams,T.E.
  TITLE     Molecular cloning and in vitro expression of a cDNA clone for human
            cellular tumor antigen p53
  JOURNAL   Mol Cell Biol 5 (7), 1601-1610 (1985)
   PUBMED   3894933
REFERENCE   22 (bases 1 to 2512)
  AUTHORS   Zakut-Houri,R., Bienz-Tadmor,B., Givol,D. and Oren,M.
  TITLE     Human p53 cellular tumor antigen: cDNA sequence and expression in
            COS cells
  JOURNAL   EMBO J 4 (5), 1251-1255 (1985)
   PUBMED   4006916
REFERENCE   23 (bases 1 to 2512)
  AUTHORS   Matlashewski,G., Lamb,P., Pim,D., Peacock,J., Crawford,L. and
            Benchimol,S.
  TITLE     Isolation and characterization of a human p53 cDNA clone:
            expression of the human p53 gene
  JOURNAL   EMBO J 3 (13), 3257-3262 (1984)
   PUBMED   6396087
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA453049.1, X02469.1 and
            AK223026.1.
            
            On Feb 13, 2020 this sequence version replaced NM_000546.5.
            
            Summary: This gene encodes a tumor suppressor protein containing
            transcriptional activation, DNA binding, and oligomerization
            domains. The encoded protein responds to diverse cellular stresses
            to regulate expression of target genes, thereby inducing cell cycle
            arrest, apoptosis, senescence, DNA repair, or changes in
            metabolism. Mutations in this gene are associated with a variety of
            human cancers, including hereditary cancers such as Li-Fraumeni
            syndrome. Alternative splicing of this gene and the use of
            alternate promoters result in multiple transcript variants and
            isoforms. Additional isoforms have also been shown to result from
            the use of alternate translation initiation codons from identical
            transcript variants (PMIDs: 12032546, 20937277). [provided by
            RefSeq, Dec 2016].
            
            Transcript Variant: This variant (1) can initiate translation from
            two in-frame AUG start codons. The isoform represented in this
            variant (a, also known as p53alpha) results from translation
            initiation at the upstream start codon. Both variants 1 and 2
            encode isoform a, which is the longest isoform.
            
            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 :: BC003596.1, AF307851.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000269305.9/ ENSP00000269305.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-7                 DA453049.1         61-67
            8-1324              X02469.1           1-1317
            1325-2512           AK223026.1         478-1665
FEATURES             Location/Qualifiers
     source          1..2512
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17p13.1"
     gene            1..2512
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /note="tumor protein p53"
                     /db_xref="GeneID:7157"
                     /db_xref="HGNC:HGNC:11998"
                     /db_xref="MIM:191170"
     exon            1..114
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            115..216
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     CDS             143..1324
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /note="isoform a is encoded by transcript variant 1; tumor
                     protein 53; mutant tumor protein 53; cellular tumor
                     antigen p53; phosphoprotein p53; transformation-related
                     protein 53; antigen NY-CO-13; tumor supressor p53"
                     /codon_start=1
                     /product="cellular tumor antigen p53 isoform a"
                     /protein_id="NP_000537.3"
                     /db_xref="CCDS:CCDS11118.1"
                     /db_xref="GeneID:7157"
                     /db_xref="HGNC:HGNC:11998"
                     /db_xref="MIM:191170"
                     /translation="MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLM
                     LSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKT
                     YQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAM
                     AIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVV
                     PYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCA
                     CPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRG
                     RERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDS
                     D"
     exon            217..238
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            239..517
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            518..701
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            702..814
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            815..924
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            925..1061
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            1062..1135
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            1136..1242
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     exon            1243..2512
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2495..2500
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /note="hexamer: AATAAA"
     polyA_site      2512
                     /gene="TP53"
                     /gene_synonym="BCC7; BMFS5; LFS1; P53; TRP53"
                     /note="major polyA site"
ORIGIN      
        1 ctcaaaagtc tagagccacc gtccagggag caggtagctg ctgggctccg gggacacttt
       61 gcgttcgggc tgggagcgtg ctttccacga cggtgacacg cttccctgga ttggcagcca
      121 gactgccttc cgggtcactg ccatggagga gccgcagtca gatcctagcg tcgagccccc
      181 tctgagtcag gaaacatttt cagacctatg gaaactactt cctgaaaaca acgttctgtc
      241 ccccttgccg tcccaagcaa tggatgattt gatgctgtcc ccggacgata ttgaacaatg
      301 gttcactgaa gacccaggtc cagatgaagc tcccagaatg ccagaggctg ctccccccgt
      361 ggcccctgca ccagcagctc ctacaccggc ggcccctgca ccagccccct cctggcccct
      421 gtcatcttct gtcccttccc agaaaaccta ccagggcagc tacggtttcc gtctgggctt
      481 cttgcattct gggacagcca agtctgtgac ttgcacgtac tcccctgccc tcaacaagat
      541 gttttgccaa ctggccaaga cctgccctgt gcagctgtgg gttgattcca cacccccgcc
      601 cggcacccgc gtccgcgcca tggccatcta caagcagtca cagcacatga cggaggttgt
      661 gaggcgctgc ccccaccatg agcgctgctc agatagcgat ggtctggccc ctcctcagca
      721 tcttatccga gtggaaggaa atttgcgtgt ggagtatttg gatgacagaa acacttttcg
      781 acatagtgtg gtggtgccct atgagccgcc tgaggttggc tctgactgta ccaccatcca
      841 ctacaactac atgtgtaaca gttcctgcat gggcggcatg aaccggaggc ccatcctcac
      901 catcatcaca ctggaagact ccagtggtaa tctactggga cggaacagct ttgaggtgcg
      961 tgtttgtgcc tgtcctggga gagaccggcg cacagaggaa gagaatctcc gcaagaaagg
     1021 ggagcctcac cacgagctgc ccccagggag cactaagcga gcactgccca acaacaccag
     1081 ctcctctccc cagccaaaga agaaaccact ggatggagaa tatttcaccc ttcagatccg
     1141 tgggcgtgag cgcttcgaga tgttccgaga gctgaatgag gccttggaac tcaaggatgc
     1201 ccaggctggg aaggagccag gggggagcag ggctcactcc agccacctga agtccaaaaa
     1261 gggtcagtct acctcccgcc ataaaaaact catgttcaag acagaagggc ctgactcaga
     1321 ctgacattct ccacttcttg ttccccactg acagcctccc acccccatct ctccctcccc
     1381 tgccattttg ggttttgggt ctttgaaccc ttgcttgcaa taggtgtgcg tcagaagcac
     1441 ccaggacttc catttgcttt gtcccggggc tccactgaac aagttggcct gcactggtgt
     1501 tttgttgtgg ggaggaggat ggggagtagg acataccagc ttagatttta aggtttttac
     1561 tgtgagggat gtttgggaga tgtaagaaat gttcttgcag ttaagggtta gtttacaatc
     1621 agccacattc taggtagggg cccacttcac cgtactaacc agggaagctg tccctcactg
     1681 ttgaattttc tctaacttca aggcccatat ctgtgaaatg ctggcatttg cacctacctc
     1741 acagagtgca ttgtgagggt taatgaaata atgtacatct ggccttgaaa ccacctttta
     1801 ttacatgggg tctagaactt gacccccttg agggtgcttg ttccctctcc ctgttggtcg
     1861 gtgggttggt agtttctaca gttgggcagc tggttaggta gagggagttg tcaagtctct
     1921 gctggcccag ccaaaccctg tctgacaacc tcttggtgaa ccttagtacc taaaaggaaa
     1981 tctcacccca tcccacaccc tggaggattt catctcttgt atatgatgat ctggatccac
     2041 caagacttgt tttatgctca gggtcaattt cttttttctt tttttttttt ttttttcttt
     2101 ttctttgaga ctgggtctcg ctttgttgcc caggctggag tggagtggcg tgatcttggc
     2161 ttactgcagc ctttgcctcc ccggctcgag cagtcctgcc tcagcctccg gagtagctgg
     2221 gaccacaggt tcatgccacc atggccagcc aacttttgca tgttttgtag agatggggtc
     2281 tcacagtgtt gcccaggctg gtctcaaact cctgggctca ggcgatccac ctgtctcagc
     2341 ctcccagagt gctgggatta caattgtgag ccaccacgtc cagctggaag ggtcaacatc
     2401 ttttacattc tgcaagcaca tctgcatttt caccccaccc ttcccctcct tctccctttt
     2461 tatatcccat ttttatatcg atctcttatt ttacaataaa actttgctgc ca
//
