LOCUS       NM_003620               4768 bp    mRNA    linear   PRI 12-NOV-2024
DEFINITION  Homo sapiens protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D),
            mRNA.
ACCESSION   NM_003620
VERSION     NM_003620.4
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 4768)
  AUTHORS   Stoyanov,M., Martinikova,A.S., Matejkova,K., Horackova,K.,
            Zemankova,P., Burdova,K., Zemanova,Z., Kleiblova,P., Kleibl,Z. and
            Macurek,L.
  TITLE     PPM1D activity promotes cellular transformation by preventing
            senescence and cell death
  JOURNAL   Oncogene 43 (42), 3081-3093 (2024)
   PUBMED   39237765
  REMARK    GeneRIF: PPM1D activity promotes cellular transformation by
            preventing senescence and cell death.
REFERENCE   2  (bases 1 to 4768)
  AUTHORS   Wang,Y., Cui,C., Zhao,W., Tian,X., Liu,P., Wei,L., Zhu,Z., Liu,M.,
            Fu,R. and Jia,L.
  TITLE     WIP1-mediated regulation of p38 MAPK signaling attenuates
            pyroptosis in sepsis-associated acute kidney injury
  JOURNAL   Immunobiology 229 (5), 152832 (2024)
   PUBMED   38943814
  REMARK    GeneRIF: WIP1-mediated regulation of p38 MAPK signaling attenuates
            pyroptosis in sepsis-associated acute kidney injury.
REFERENCE   3  (bases 1 to 4768)
  AUTHORS   Zhang,L., Hsu,J.I., Braekeleer,E.D., Chen,C.W., Patel,T.D.,
            Martell,A.G., Guzman,A.G., Wohlan,K., Waldvogel,S.M., Uryu,H.,
            Tovy,A., Callen,E., Murdaugh,R.L., Richard,R., Jansen,S.,
            Vissers,L., de Vries,B.B.A., Nussenzweig,A., Huang,S., Coarfa,C.,
            Anastas,J., Takahashi,K., Vassiliou,G. and Goodell,M.A.
  TITLE     SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells
  JOURNAL   Elife 12, 91611 (2024)
   PUBMED   38896450
  REMARK    GeneRIF: SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia
            cells.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4768)
  AUTHORS   Miller,P.G., Sperling,A.S., Mayerhofer,C., McConkey,M.E.,
            Ellegast,J.M., Da Silva,C., Cohen,D.N., Wang,C., Sharda,A., Yan,N.,
            Saha,S., Schluter,C., Schechter,I., Slabicki,M., Sandoval,B.,
            Kahn,J., Boettcher,S., Gibson,C.J., Scadden,D.T., Stegmaier,K.,
            Bhatt,S., Lindsley,R.C. and Ebert,B.L.
  TITLE     PPM1D modulates hematopoietic cell fitness and response to DNA
            damage and is a therapeutic target in myeloid malignancy
  JOURNAL   Blood 142 (24), 2079-2091 (2023)
   PUBMED   37595362
  REMARK    GeneRIF: PPM1D modulates hematopoietic cell fitness and response to
            DNA damage and is a therapeutic target in myeloid malignancy.
REFERENCE   5  (bases 1 to 4768)
  AUTHORS   Seipel,K., Frey,M., Nilius,H., Akhoundova,D., Banz,Y., Bacher,U.
            and Pabst,T.
  TITLE     Low-Frequency PPM1D Gene Mutations Affect Treatment Response to
            CD19-Targeted CAR T-Cell Therapy in Large B-Cell Lymphoma
  JOURNAL   Curr Oncol 30 (12), 10463-10476 (2023)
   PUBMED   38132396
  REMARK    GeneRIF: Low-Frequency PPM1D Gene Mutations Affect Treatment
            Response to CD19-Targeted CAR T-Cell Therapy in Large B-Cell
            Lymphoma.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 4768)
  AUTHORS   Ajuh,P., Kuster,B., Panov,K., Zomerdijk,J.C., Mann,M. and
            Lamond,A.I.
  TITLE     Functional analysis of the human CDC5L complex and identification
            of its components by mass spectrometry
  JOURNAL   EMBO J 19 (23), 6569-6581 (2000)
   PUBMED   11101529
REFERENCE   7  (bases 1 to 4768)
  AUTHORS   Takekawa,M., Adachi,M., Nakahata,A., Nakayama,I., Itoh,F.,
            Tsukuda,H., Taya,Y. and Imai,K.
  TITLE     p53-inducible wip1 phosphatase mediates a negative feedback
            regulation of p38 MAPK-p53 signaling in response to UV radiation
  JOURNAL   EMBO J 19 (23), 6517-6526 (2000)
   PUBMED   11101524
REFERENCE   8  (bases 1 to 4768)
  AUTHORS   Fiscella,M., Zhang,H., Fan,S., Sakaguchi,K., Shen,S., Mercer,W.E.,
            Vande Woude,G.F., O'Connor,P.M. and Appella,E.
  TITLE     Wip1, a novel human protein phosphatase that is induced in response
            to ionizing radiation in a p53-dependent manner
  JOURNAL   Proc Natl Acad Sci U S A 94 (12), 6048-6053 (1997)
   PUBMED   9177166
REFERENCE   9  (bases 1 to 4768)
  AUTHORS   Adams,M.D., Kerlavage,A.R., Fleischmann,R.D., Fuldner,R.A.,
            Bult,C.J., Lee,N.H., Kirkness,E.F., Weinstock,K.G., Gocayne,J.D.,
            White,O. et al.
  TITLE     Initial assessment of human gene diversity and expression patterns
            based upon 83 million nucleotides of cDNA sequence
  JOURNAL   Nature 377 (6547 Suppl), 3-174 (1995)
   PUBMED   7566098
REFERENCE   10 (bases 1 to 4768)
  AUTHORS   Hirano,K., Ito,M. and Hartshorne,D.J.
  TITLE     Interaction of the ribosomal protein, L5, with protein phosphatase
            type 1
  JOURNAL   J Biol Chem 270 (34), 19786-19790 (1995)
   PUBMED   7649987
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC060877.1, U78305.1,
            AC110602.8 and BU616782.1.
            
            On Aug 31, 2019 this sequence version replaced NM_003620.3.
            
            Summary: The protein encoded by this gene is a member of the PP2C
            family of Ser/Thr protein phosphatases. PP2C family members are
            known to be negative regulators of cell stress response pathways.
            The expression of this gene is induced in a p53-dependent manner in
            response to various environmental stresses. While being induced by
            tumor suppressor protein TP53/p53, this phosphatase negatively
            regulates the activity of p38 MAP kinase, MAPK/p38, through which
            it reduces the phosphorylation of p53, and in turn suppresses
            p53-mediated transcription and apoptosis. This phosphatase thus
            mediates a feedback regulation of p38-p53 signaling that
            contributes to growth inhibition and the suppression of stress
            induced apoptosis. This gene is located in a chromosomal region
            known to be amplified in breast cancer. The amplification of this
            gene has been detected in both breast cancer cell line and primary
            breast tumors, which suggests a role of this gene in cancer
            development. [provided by RefSeq, Jul 2008].
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: AK312902.1, SRR11853562.15423.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000305921.8/ ENSP00000306682.2
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-42                BC060877.1         11-52
            43-2976             U78305.1           24-2957
            2977-4753           AC110602.8         94137-95913         c
            4754-4768           BU616782.1         13-27               c
FEATURES             Location/Qualifiers
     source          1..4768
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q23.2"
     gene            1..4768
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /note="protein phosphatase, Mg2+/Mn2+ dependent 1D"
                     /db_xref="GeneID:8493"
                     /db_xref="HGNC:HGNC:9277"
                     /db_xref="MIM:605100"
     exon            1..694
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /inference="alignment:Splign:2.1.0"
     CDS             223..2040
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /EC_number="3.1.3.16"
                     /note="wild-type p53-induced phosphatase 1; protein
                     phosphatase Wip1"
                     /codon_start=1
                     /product="protein phosphatase 1D"
                     /protein_id="NP_003611.1"
                     /db_xref="CCDS:CCDS11625.1"
                     /db_xref="GeneID:8493"
                     /db_xref="HGNC:HGNC:9277"
                     /db_xref="MIM:605100"
                     /translation="MAGLYSLGVSVFSDQGGRKYMEDVTQIVVEPEPTAEEKPSPRRS
                     LSQPLPPRPSPAALPGGEVSGKGPAVAAREARDPLPDAGASPAPSRCCRRRSSVAFFA
                     VCDGHGGREAAQFAREHLWGFIKKQKGFTSSEPAKVCAAIRKGFLACHLAMWKKLAEW
                     PKTMTGLPSTSGTTASVVIIRGMKMYVAHVGDSGVVLGIQDDPKDDFVRAVEVTQDHK
                     PELPKERERIEGLGGSVMNKSGVNRVVWKRPRLTHNGPVRRSTVIDQIPFLAVARALG
                     DLWSYDFFSGEFVVSPEPDTSVHTLDPQKHKYIILGSDGLWNMIPPQDAISMCQDQEE
                     KKYLMGEHGQSCAKMLVNRALGRWRQRMLRADNTSAIVICISPEVDNQGNFTNEDELY
                     LNLTDSPSYNSQETCVMTPSPCSTPPVKSLEEDPWPRVNSKDHIPALVRSNAFSENFL
                     EVSAEIARENVQGVVIPSKDPEPLEENCAKALTLRIHDSLNNSLPIGLVPTNSTNTVM
                     DQKNLKMSTPGQMKAQEIERTPPTNFKRTLEESNSGPLMKKHRRNGLSRSSGAQPASL
                     PTTSQRKNSVKLTMRRRLRGQKKIGNPLLHQHRKTVCVC"
     exon            695..923
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /inference="alignment:Splign:2.1.0"
     exon            924..1048
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1049..1239
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1240..1482
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1483..4768
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2405..2410
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /note="hexamer: ATTAAA"
     polyA_site      2426
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /note="major polyA site"
     regulatory      2943..2948
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /note="hexamer: AATAAA"
     polyA_site      2976
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /note="major polyA site"
     regulatory      4747..4752
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /note="hexamer: AATAAA"
     polyA_site      4768
                     /gene="PPM1D"
                     /gene_synonym="IDDGIP; JDVS; PP2C-DELTA; WIP1"
                     /note="major polyA site"
ORIGIN      
        1 agtgcgcagg cgcaactgcc tggctctgct cgctccggcg ctccggccca gctctcgcgg
       61 acaagtccag acatcgcgcg cccccccttc tccgggtccg ccccctcccc cttctcggcg
      121 tcgtcgaaga taaacaatag ttggccggcg agcgcctagt gtgtctcccg ccgccggatt
      181 cggcgggctg cgtgggaccg gcgggatccc ggccagccgg ccatggcggg gctgtactcg
      241 ctgggagtga gcgtcttctc cgaccagggc gggaggaagt acatggagga cgttactcaa
      301 atcgttgtgg agcccgaacc gacggctgaa gaaaagccct cgccgcggcg gtcgctgtct
      361 cagccgttgc ctccgcggcc gtcgccggcc gcccttcccg gcggcgaagt ctcggggaaa
      421 ggcccagcgg tggcagcccg agaggctcgc gaccctctcc cggacgccgg ggcctcgccg
      481 gcacctagcc gctgctgccg ccgccgttcc tccgtggcct ttttcgccgt gtgcgacggg
      541 cacggcgggc gggaggcggc acagtttgcc cgggagcact tgtggggttt catcaagaag
      601 cagaagggtt tcacctcgtc cgagccggct aaggtttgcg ctgccatccg caaaggcttt
      661 ctcgcttgtc accttgccat gtggaagaaa ctggcggaat ggccaaagac tatgacgggt
      721 cttcctagca catcagggac aactgccagt gtggtcatca ttcggggcat gaagatgtat
      781 gtagctcacg taggtgactc aggggtggtt cttggaattc aggatgaccc gaaggatgac
      841 tttgtcagag ctgtggaggt gacacaggac cataagccag aacttcccaa ggaaagagaa
      901 cgaatcgaag gacttggtgg gagtgtaatg aacaagtctg gggtgaatcg tgtagtttgg
      961 aaacgacctc gactcactca caatggacct gttagaagga gcacagttat tgaccagatt
     1021 ccttttctgg cagtagcaag agcacttggt gatttgtgga gctatgattt cttcagtggt
     1081 gaatttgtgg tgtcacctga accagacaca agtgtccaca ctcttgaccc tcagaagcac
     1141 aagtatatta tattggggag tgatggactt tggaatatga ttccaccaca agatgccatc
     1201 tcaatgtgcc aggaccaaga ggagaaaaaa tacctgatgg gtgagcatgg acaatcttgt
     1261 gccaaaatgc ttgtgaatcg agcattgggc cgctggaggc agcgtatgct ccgagcagat
     1321 aacactagtg ccatagtaat ctgcatctct ccagaagtgg acaatcaggg aaactttacc
     1381 aatgaagatg agttatacct gaacctgact gacagccctt cctataatag tcaagaaacc
     1441 tgtgtgatga ctccttcccc atgttctaca ccaccagtca agtcactgga ggaggatcca
     1501 tggccaaggg tgaattctaa ggaccatata cctgccctgg ttcgtagcaa tgccttctca
     1561 gagaattttt tagaggtttc agctgagata gctcgagaga atgtccaagg tgtagtcata
     1621 ccctcaaaag atccagaacc acttgaagaa aattgcgcta aagccctgac tttaaggata
     1681 catgattctt tgaataatag ccttccaatt ggccttgtgc ctactaattc aacaaacact
     1741 gtcatggacc aaaaaaattt gaagatgtca actcctggcc aaatgaaagc ccaagaaatt
     1801 gaaagaaccc ctccaacaaa ctttaaaagg acattagaag agtccaattc tggccccctg
     1861 atgaagaagc atagacgaaa tggcttaagt cgaagtagtg gtgctcagcc tgcaagtctc
     1921 cccacaacct cacagcgaaa gaactctgtt aaactcacca tgcgacgcag acttaggggc
     1981 cagaagaaaa ttggaaatcc tttacttcat caacacagga aaactgtttg tgtttgctga
     2041 aatgcatctg ggaaatgagg tttttccaaa cttaggatat aagagggctt tttaaatttg
     2101 gtgccgatgt tgaacttttt ttaaggggag aaaattaaaa gaaatataca gtttgacttt
     2161 ttggaattca gcagttttat cctggccttg tacttgcttg tattgtaaat gtggattttg
     2221 tagatgttag ggtataagtt gctgtaaaat ttgtgtaaat ttgtatccac acaaattcag
     2281 tctctgaata cacagtattc agagtctctg atacacagta attgtgacaa tagggctaaa
     2341 tgtttaaaga aatcaaaaga atctattaga ttttagaaaa acatttaaac tttttaaaat
     2401 acttattaaa aaatttgtat aagccacttg tcttgaaaac tgtgcaactt tttaaagtaa
     2461 attattaagc agactggaaa agtgatgtat tttcatagtg acctgtgttt cacttaatgt
     2521 ttcttagagc caagtgtctt ttaaacatta ttttttattt ctgatttcat aattcagaac
     2581 taaatttttc atagaagtgt tgagccatgc tacagttagt cttgtcccaa ttaaaatact
     2641 atgcagtatc tcttacatca gtagcatttt tctaaaacct tagtcatcag atatgcttac
     2701 taaatcttca gcatagaagg aagtgtgttt gcctaaaaca atctaaaaca attcccttct
     2761 ttttcatccc agaccaatgg cattattagg tcttaaagta gttactccct tctcgtgttt
     2821 gcttaaaata tgtgaagttt tccttgctat ttcaataaca gatggtgctg ctaattccca
     2881 acatttctta aattatttta tatcatacag ttttcattga ttatatgggt atatattcat
     2941 ctaataaatc agtgaactgt tcctcatgtt gctgaatttg tagttgttgg tttattttaa
     3001 tggtatgtac aagttgagta tcccttatcc aaaatgcttg ggaccagaag tgtttcagat
     3061 tttttaaaat tttggaatat ttgctttata ctgagctttt gagtgttccc aatctgaaat
     3121 tcaaaatgct ctaatgagca tttcctttga gcatcatgcc tgctctgaaa aagtttctga
     3181 ttctggagca ttttggattt tggattttca gattagggat gcttaacctg gattaacatt
     3241 ctgttgtgcc atgatcatgc tttacagtga gtgtatttta tttatttatt attttgtttg
     3301 tttgtttgag atggagtctc actctgtcat ccaggctaga gtgcagtggc gtgatctcgg
     3361 ctgactgcaa cctctgcctc ccgggttcaa gtgattctcc tgcctcaatc tctctcccca
     3421 gaagctggga ttacaggtgt gtgccaccac acccggctaa tttttttttt tttttttgag
     3481 atggagtcta gctctgtcat ccaggctgga gtgcagtggt gtgatctcgg ctccctgcaa
     3541 cctctgcctt ctgggttcct gcgattctcc tgcctcagcc tcctgagtag ctgagattac
     3601 aggcacgcgc cactgtgccc agccaatttt tgtattttta gtagagatgg ggtttcacat
     3661 gtcagtcatg ctggtcttga tctcctgacc tcgtgatcca cccgcctcga cctcccaaag
     3721 tactgggatt acaggcgtga gccaccgcat ccggcctgag ttttatgctt tcaatgtatt
     3781 tcttacattt cagttcaagt gattttcatg tctcagcctc ctgagtagct ggaactacag
     3841 gtgcgtgcca ccatgcctgg ctaagttttg tatttttagt agagatgggt tttcatcatg
     3901 ttggccaaga tggtcttgat ctcttgacct catgatccac cagcctaggc ctcccaaagt
     3961 gctgggatta caggtgtgag ccaccgtgcc cagccaacta tgccattatt taaccatgtc
     4021 cacacattct ggttattttc aatattttgc agaagataat tcttgatcgg tgtgtcttat
     4081 gccacaagga ttaaaatatg tattcattgc tacaaaacaa tatctcgaaa tttagcagtt
     4141 taaaacaaca aatattatct ccagtttctg agcctcagaa atctgagagt ggtttagctg
     4201 ggtgatagtc tcgtggtttt ggtcaagcta ccaaccaggg ctacaatctt tcgaaggtgt
     4261 cattggggct agaagatctg cttcccgcaa gactcacagc tgttggcagg agacctcagt
     4321 ttgttgccac atgttcccct ccagagggcc tctcacaaca tggcagttat ttgtccccag
     4381 agcaagcaac accggagggc aaggaagaag ccatgatgtt ttttgtaacc tagcctctga
     4441 aagtgtcata ccaattctgt attttgttgg tcacacagac caagtcaact acaacgtggg
     4501 agactcctac acaaggcatg aattctagga ggtgggcatt tttaagtgtc atctggaagg
     4561 aggctgtcac aacctggaag ttaaaagcat tgatattctg aaatacagcg tgtataacat
     4621 tgttttagta gggtgtgcaa tagttatgtt ttggtaatag cattaatgaa caatgttatt
     4681 ttcatcttcc agacatctgg aagattgctc tagtggagta aaacatctta atgtattttg
     4741 tccctaaata aactatctca ctaacaaa
//
