LOCUS       NM_014417               1846 bp    mRNA    linear   PRI 06-APR-2024
DEFINITION  Homo sapiens BCL2 binding component 3 (BBC3), transcript variant 4,
            mRNA.
ACCESSION   NM_014417
VERSION     NM_014417.5
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 1846)
  AUTHORS   Hao,S., Tong,J., Jha,A., Risnik,D., Lizardo,D., Lu,X., Goel,A.,
            Opresko,P.L., Yu,J. and Zhang,L.
  TITLE     Synthetical lethality of Werner helicase and mismatch repair
            deficiency is mediated by p53 and PUMA in colon cancer
  JOURNAL   Proc Natl Acad Sci U S A 119 (51), e2211775119 (2022)
   PUBMED   36508676
  REMARK    GeneRIF: Synthetical lethality of Werner helicase and mismatch
            repair deficiency is mediated by p53 and PUMA in colon cancer.
REFERENCE   2  (bases 1 to 1846)
  AUTHORS   Chen,Y., Li,N., Yang,J., Li,K., Tang,M., Zhao,X., Guo,W., Tong,A.,
            Nie,C., Peng,Y. and Yuan,Z.
  TITLE     PUMA overexpression dissociates thioredoxin from ASK1 to activate
            the JNK/BCL-2/BCL-XL pathway augmenting apoptosis in ovarian cancer
  JOURNAL   Biochim Biophys Acta Mol Basis Dis 1868 (12), 166553 (2022)
   PUBMED   36122664
  REMARK    GeneRIF: PUMA overexpression dissociates thioredoxin from ASK1 to
            activate the JNK/BCL-2/BCL-XL pathway augmenting apoptosis in
            ovarian cancer.
REFERENCE   3  (bases 1 to 1846)
  AUTHORS   Neuberger,A., Menzer,C., Volk,N., Enk,A.H., Hadaschik,E.N. and
            Lonsdorf,A.S.
  TITLE     Expression of p53 up-regulated modulator of apoptosis (PUMA) in
            non-melanoma skin cancer of long-term immunosuppressed solid organ
            transplant recipients compared to immunocompetent patients
  JOURNAL   Eur J Dermatol 31 (5), 609-615 (2021)
   PUBMED   34903507
  REMARK    GeneRIF: Expression of p53 up-regulated modulator of apoptosis
            (PUMA) in non-melanoma skin cancer of long-term immunosuppressed
            solid organ transplant recipients compared to immunocompetent
            patients.
REFERENCE   4  (bases 1 to 1846)
  AUTHORS   Chipuk,J.E. and Green,D.R.
  TITLE     PUMA cooperates with direct activator proteins to promote
            mitochondrial outer membrane permeabilization and apoptosis
  JOURNAL   Cell Cycle 8 (17), 2692-2696 (2009)
   PUBMED   19652530
  REMARK    Review article
REFERENCE   5  (bases 1 to 1846)
  AUTHORS   Yu,J. and Zhang,L.
  TITLE     PUMA, a potent killer with or without p53
  JOURNAL   Oncogene 27 Suppl 1 (Suppl 1), S71-S83 (2008)
   PUBMED   19641508
  REMARK    GeneRIF: PUMA is a critical mediator of p53-dependent &
            -independent apoptosis induced by a wide variety of stimuli.It
            directly binds and antagonizes all known antiapoptotic Bcl-2 family
            members to induce mitochondrial dysfunction & caspase activation.
            Review.
            Review article
REFERENCE   6  (bases 1 to 1846)
  AUTHORS   Hoque,M.O., Begum,S., Sommer,M., Lee,T., Trink,B., Ratovitski,E.
            and Sidransky,D.
  TITLE     PUMA in head and neck cancer
  JOURNAL   Cancer Lett 199 (1), 75-81 (2003)
   PUBMED   12963126
  REMARK    GeneRIF: PUMA suppresses tumor cell growth in head/neck cancer, but
            it does not appear to be a direct target of inactivation in head
            and neck tumorigenesis.
REFERENCE   7  (bases 1 to 1846)
  AUTHORS   Yu,J., Wang,Z., Kinzler,K.W., Vogelstein,B. and Zhang,L.
  TITLE     PUMA mediates the apoptotic response to p53 in colorectal cancer
            cells
  JOURNAL   Proc Natl Acad Sci U S A 100 (4), 1931-1936 (2003)
   PUBMED   12574499
  REMARK    GeneRIF: role in mediating the apoptotic response to p53 in
            colorectal cancer cells
REFERENCE   8  (bases 1 to 1846)
  AUTHORS   Han,J., Flemington,C., Houghton,A.B., Gu,Z., Zambetti,G.P.,
            Lutz,R.J., Zhu,L. and Chittenden,T.
  TITLE     Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by
            diverse cell death and survival signals
  JOURNAL   Proc Natl Acad Sci U S A 98 (20), 11318-11323 (2001)
   PUBMED   11572983
REFERENCE   9  (bases 1 to 1846)
  AUTHORS   Nakano,K. and Vousden,K.H.
  TITLE     PUMA, a novel proapoptotic gene, is induced by p53
  JOURNAL   Mol Cell 7 (3), 683-694 (2001)
   PUBMED   11463392
REFERENCE   10 (bases 1 to 1846)
  AUTHORS   Yu,J., Zhang,L., Hwang,P.M., Kinzler,K.W. and Vogelstein,B.
  TITLE     PUMA induces the rapid apoptosis of colorectal cancer cells
  JOURNAL   Mol Cell 7 (3), 673-682 (2001)
   PUBMED   11463391
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC008532.7.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_014417.4.
            
            Summary: This gene encodes a member of the BCL-2 family of
            proteins. This family member belongs to the BH3-only pro-apoptotic
            subclass. The protein cooperates with direct activator proteins to
            induce mitochondrial outer membrane permeabilization and apoptosis.
            It can bind to anti-apoptotic Bcl-2 family members to induce
            mitochondrial dysfunction and caspase activation. Because of its
            pro-apoptotic role, this gene is a potential drug target for cancer
            therapy and for tissue injury. Alternative splicing results in
            multiple transcript variants. [provided by RefSeq, Dec 2011].
            
            Transcript Variant: This variant (4) has alternate exon structure
            at its 5' end and it thus differs in the 5' UTR and 5' coding
            region, compared to variant 2. The encoded isoform (4, also known
            as PUMA-alpha) has a distinct N-terminus and is longer than isoform
            2. Isoform 4 also includes the C-terminal BH3 domain and can
            localize to the mitochondria.
            
            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 :: ERR279869.944.1, DRR138517.347682.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN02400288, SAMN02400289
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: PMID: 11463392
            MANE Ensembl match                 :: ENST00000439096.3/
                                                  ENSP00000395862.2
            RefSeq Select criteria             :: based on manual assertion,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-271               AC008532.7         84699-84969         c
            272-560             AC008532.7         81928-82216         c
            561-751             AC008532.7         80334-80524         c
            752-1846            AC008532.7         74594-75688         c
FEATURES             Location/Qualifiers
     source          1..1846
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19q13.32"
     gene            1..1846
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /note="BCL2 binding component 3"
                     /db_xref="GeneID:27113"
                     /db_xref="HGNC:HGNC:17868"
                     /db_xref="MIM:605854"
     exon            1..271
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /inference="alignment:Splign:2.1.0"
     exon            272..560
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /inference="alignment:Splign:2.1.0"
     CDS             287..868
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /note="isoform 4 is encoded by transcript variant 4; p53
                     up-regulated modulator of apoptosis; p53-upregulated
                     modulator of apoptosis"
                     /codon_start=1
                     /product="bcl-2-binding component 3 isoform 4"
                     /protein_id="NP_055232.1"
                     /db_xref="CCDS:CCDS12697.1"
                     /db_xref="GeneID:27113"
                     /db_xref="HGNC:HGNC:17868"
                     /db_xref="MIM:605854"
                     /translation="MARARQEGSSPEPVEGLARDGPRPFPLGRLVPSAVSCGLCEPGL
                     AAAPAAPTLLPAAYLCAPTAPPAVTAALGGSRWPGGPRSRPRGPRPDGPQPSLSLAEQ
                     HLESPVPSAPGALAGGPTQAAPGVRGEEEQWAREIGAQLRRMADDLNAQYERRRQEEQ
                     QRHRPSPWRVLYNLIMGLLPLPRGHRAPEMEPN"
     exon            561..751
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /inference="alignment:Splign:2.1.0"
     exon            752..1846
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1824..1829
                     /regulatory_class="polyA_signal_sequence"
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /note="hexamer: AATAAA"
     polyA_site      1846
                     /gene="BBC3"
                     /gene_synonym="JFY-1; JFY1; PUMA"
                     /note="major polyA site"
ORIGIN      
        1 gagacgcggc gcgagccaca tgcgagcggg cgcctggcgg cggcggcggc ggcaccagcg
       61 atcccagcag cggccacgac gcggacgcgc ctgcggcccg gggagcagca gcagccacag
      121 ccacagcagc cgccactgca gttagagcgg cagcagcagc gacagccaca gcagcagccg
      181 ccgcggagag cggcgctcgg cgggcgcgcc ctcctgaagg aagccgcccg ccccccaccg
      241 ccgccccctc cggcgtgttc atgcccccgg ggccccaggg agcgccatgg cccgcgcacg
      301 ccaggagggc agctccccgg agcccgtaga gggcctggcc cgcgacggcc cgcgcccctt
      361 cccgctcggc cgcctggtgc cctcggcagt gtcctgcggc ctctgcgagc ccggcctggc
      421 tgccgccccc gccgccccca ccctgctgcc cgctgcctac ctctgcgccc ccaccgcccc
      481 acccgccgtc accgccgccc tggggggttc ccgctggcct gggggtcccc gcagccggcc
      541 ccgaggcccg cgcccggacg gtcctcagcc ctcgctctcg ctggcggagc agcacctgga
      601 gtcgcccgtg cccagcgccc cgggggctct ggcgggcggt cccacccagg cggccccggg
      661 agtccgcggg gaggaggaac agtgggcccg ggagatcggg gcccagctgc ggcggatggc
      721 ggacgacctc aacgcacagt acgagcggcg gagacaagag gagcagcagc ggcaccgccc
      781 ctcaccctgg agggtcctgt acaatctcat catgggactc ctgcccttac ccaggggcca
      841 cagagccccc gagatggagc ccaattaggt gcctgcaccc gcccggtgga cgtcagggac
      901 tcggggggca ggcccctccc acctcctgac accctggcca gcgcggggga ctttctctgc
      961 accatgtagc atactggact cccagccctg cctgtcccgg gggcgggccg gggcagccac
     1021 tccagcccca gcccagcctg gggtgcactg acggagatgc ggactcctgg gtccctggcc
     1081 aagaagccag gagagggacg gctgatggac tcagcatcgg aaggtggcgg tgaccgaggg
     1141 ggtggggact gagccgcccg cctctgccgc ccaccaccat ctcaggaaag gctgttgtgc
     1201 tggtgcccgt tccagctgca ggggtgacac tgggaggggg gggctctcct ctcggtgctc
     1261 cttcactctg ggcctggcct caggcccctg gtgcttcccc ccctcctcct gggagggggc
     1321 ccgtgaagag caaatgagcc aaacgtgacc actagcctcc tggagccaga gagtggggct
     1381 cgtttgccgg ttgctccagc ccggcgccca gccatcttcc ctgagccagc cggcgggtgg
     1441 tgggcatgcc tgcctcacct tcatcagggg gtggccagga ggggcccaga ctgtgaatcc
     1501 tgtgctctgc ccgtgaccgc cccccgcccc atcaatccca ttgcataggt ttagagagag
     1561 cacgtgtgac cactggcatt catttggggg gtgggagatt ttggctgaag ccgccccagc
     1621 cttagtcccc agggccaagc gctgggggga agacggggag tcagggaggg ggggaaatct
     1681 cggaagaggg aggagtctgg gagtggggag ggatggccca gcctgtaaga tactgtatat
     1741 gcgctgctgt agataccgga atgaattttc tgtacatgtt tggttaattt tttttgtaca
     1801 tgatttttgt atgtttcctt ttcaataaaa tcagattgga acagtg
//
