LOCUS       NM_005373               3633 bp    mRNA    linear   PRI 13-DEC-2024
DEFINITION  Homo sapiens MPL proto-oncogene, thrombopoietin receptor (MPL),
            mRNA.
ACCESSION   NM_005373
VERSION     NM_005373.3
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 3633)
  AUTHORS   Borsani,O., Pietra,D., Casetti,I.C., Vanni,D., Riccaboni,G.,
            Catricala,S., Grazia,B., Boveri,E., Arcaini,L. and Rumi,E.
  TITLE     Germline MPL mutations may be a rare cause of 'triple-negative'
            thrombocytosis
  JOURNAL   Exp Hematol 129, 104127 (2024)
   PUBMED   37939832
  REMARK    GeneRIF: Germline MPL mutations may be a rare cause of
            'triple-negative' thrombocytosis.
REFERENCE   2  (bases 1 to 3633)
  AUTHORS   Giraldo-Rincon,A.I., Naranjo Molina,S., Gomez-Lopera,N., Aguirre
            Acevedo,D., Ucroz Benavidez,A., Galvez Cardenas,K., Cuellar
            Ambrosi,F., Torres,J.D., Ospina,S., Palacio,K., Gaviria
            Jaramillo,L., Muneton,C.M. and Vasquez Palacio,G.
  TITLE     JAK2, CALR, and MPL Mutation Profiles in Colombian patients with
            BCR-ABL Negative Myeloproliferative Neoplasms
  JOURNAL   Colomb Med (Cali) 54 (3), e2035353 (2023)
   PUBMED   38111518
  REMARK    GeneRIF: JAK2, CALR, and MPL Mutation Profiles in Colombian
            patients with BCR-ABL Negative Myeloproliferative Neoplasms.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3633)
  AUTHORS   Hsiao,H.H., Yang,M.Y., Liu,Y.C., Lee,C.P., Yang,W.C., Liu,T.C.,
            Chang,C.S. and Lin,S.F.
  TITLE     The association of JAK2V617F mutation and leukocytosis with
            thrombotic events in essential thrombocythemia
  JOURNAL   Exp Hematol 35 (11), 1704-1707 (2007)
   PUBMED   17920754
REFERENCE   4  (bases 1 to 3633)
  AUTHORS   Norton,A., Fisher,C., Liu,H., Wen,Q., Mundschau,G., Fuster,J.L.,
            Hasle,H., Zeller,B., Webb,D.K., O'Marcaigh,A., Sorrell,A.,
            Hilden,J., Gamis,A., Crispino,J.D. and Vyas,P.
  TITLE     Analysis of JAK3, JAK2, and C-MPL mutations in transient
            myeloproliferative disorder and myeloid leukemia of Down syndrome
            blasts in children with Down syndrome
  JOURNAL   Blood 110 (3), 1077-1079 (2007)
   PUBMED   17644747
REFERENCE   5  (bases 1 to 3633)
  AUTHORS   Guglielmelli,P., Pancrazzi,A., Bergamaschi,G., Rosti,V.,
            Villani,L., Antonioli,E., Bosi,A., Barosi,G. and Vannucchi,A.M.
  CONSRTM   GIMEMA--Italian Registry of Myelofibrosis; MPD Research Consortium
  TITLE     Anaemia characterises patients with myelofibrosis harbouring Mpl
            mutation
  JOURNAL   Br J Haematol 137 (3), 244-247 (2007)
   PUBMED   17408465
  REMARK    GeneRIF: MPL mutation in myelofibrosis characterises patients with
            more severe anaemic phenotype
REFERENCE   6  (bases 1 to 3633)
  AUTHORS   Lasho,T.L., Pardanani,A., McClure,R.F., Mesa,R.A., Levine,R.L.,
            Gilliland,D.G. and Tefferi,A.
  TITLE     Concurrent MPL515 and JAK2V617F mutations in myelofibrosis:
            chronology of clonal emergence and changes in mutant allele burden
            over time
  JOURNAL   Br J Haematol 135 (5), 683-687 (2006)
   PUBMED   17107350
REFERENCE   7  (bases 1 to 3633)
  AUTHORS   Pardanani,A.D., Levine,R.L., Lasho,T., Pikman,Y., Mesa,R.A.,
            Wadleigh,M., Steensma,D.P., Elliott,M.A., Wolanskyj,A.P.,
            Hogan,W.J., McClure,R.F., Litzow,M.R., Gilliland,D.G. and
            Tefferi,A.
  TITLE     MPL515 mutations in myeloproliferative and other myeloid disorders:
            a study of 1182 patients
  JOURNAL   Blood 108 (10), 3472-3476 (2006)
   PUBMED   16868251
  REMARK    GeneRIF: MPLW515L or MPLW515K mutations are present in patients
            with MMM or ET at a frequency of approximately 5% and 1%,
            respectively, but are not observed in patients with polycythemia
            vera (PV) or other myeloid disorders
            GeneRIF: Observational study of genotype prevalence. (HuGE
            Navigator)
REFERENCE   8  (bases 1 to 3633)
  AUTHORS   Pikman,Y., Lee,B.H., Mercher,T., McDowell,E., Ebert,B.L., Gozo,M.,
            Cuker,A., Wernig,G., Moore,S., Galinsky,I., DeAngelo,D.J.,
            Clark,J.J., Lee,S.J., Golub,T.R., Wadleigh,M., Gilliland,D.G. and
            Levine,R.L.
  TITLE     MPLW515L is a novel somatic activating mutation in myelofibrosis
            with myeloid metaplasia
  JOURNAL   PLoS Med 3 (7), e270 (2006)
   PUBMED   16834459
  REMARK    GeneRIF: Activation of JAK-STAT signaling via a somatic activating
            mutation in the transmembrane domain of MPL (MPLW515L) is an
            important pathogenetic event in patients with JAK2V617F-negative
            MF.
REFERENCE   9  (bases 1 to 3633)
  AUTHORS   Vigon,I., Mornon,J.P., Cocault,L., Mitjavila,M.T., Tambourin,P.,
            Gisselbrecht,S. and Souyri,M.
  TITLE     Molecular cloning and characterization of MPL, the human homolog of
            the v-mpl oncogene: identification of a member of the hematopoietic
            growth factor receptor superfamily
  JOURNAL   Proc Natl Acad Sci U S A 89 (12), 5640-5644 (1992)
   PUBMED   1608974
REFERENCE   10 (bases 1 to 3633)
  AUTHORS   Souyri,M., Vigon,I., Penciolelli,J.F., Heard,J.M., Tambourin,P. and
            Wendling,F.
  TITLE     A putative truncated cytokine receptor gene transduced by the
            myeloproliferative leukemia virus immortalizes hematopoietic
            progenitors
  JOURNAL   Cell 63 (6), 1137-1147 (1990)
   PUBMED   2175677
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL139289.6 and M90102.1.
            
            On Aug 31, 2019 this sequence version replaced NM_005373.2.
            
            Summary: In 1990 an oncogene, v-mpl, was identified from the murine
            myeloproliferative leukemia virus that was capable of immortalizing
            bone marrow hematopoietic cells from different lineages. In 1992
            the human homologue, named, c-mpl, was cloned. Sequence data
            revealed that c-mpl encoded a protein that was homologous with
            members of the hematopoietic receptor superfamily. Presence of
            anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte
            colony formation. The ligand for c-mpl, thrombopoietin, was cloned
            in 1994. Thrombopoietin was shown to be the major regulator of
            megakaryocytopoiesis and platelet formation. The protein encoded by
            the c-mpl gene, CD110, is a 635 amino acid transmembrane domain,
            with two extracellular cytokine receptor domains and two
            intracellular cytokine receptor box motifs . TPO-R deficient mice
            were severely thrombocytopenic, emphasizing the important role of
            CD110 and thrombopoietin in megakaryocyte and platelet formation.
            Upon binding of thrombopoietin CD110 is dimerized and the JAK
            family of non-receptor tyrosine kinases, as well as the STAT
            family, the MAPK family, the adaptor protein Shc and the receptors
            themselves become tyrosine phosphorylated. [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 :: M90102.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000372470.9/ ENSP00000361548.3
            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
            1-31                AL139289.6         18748-18778
            32-1939             M90102.1           1-1908
            1940-3631           AL139289.6         33703-35394
            3632-3633           AL139289.6         35395-35396
FEATURES             Location/Qualifiers
     source          1..3633
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p34.2"
     gene            1..3633
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /note="MPL proto-oncogene, thrombopoietin receptor"
                     /db_xref="GeneID:4352"
                     /db_xref="HGNC:HGNC:7217"
                     /db_xref="MIM:159530"
     exon            1..110
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     CDS             32..1939
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /note="thrombopoietin receptor; TPO-R; myeloproliferative
                     leukemia protein; proto-oncogene c-Mpl; myeloproliferative
                     leukemia virus oncogene"
                     /codon_start=1
                     /product="thrombopoietin receptor precursor"
                     /protein_id="NP_005364.1"
                     /db_xref="CCDS:CCDS483.1"
                     /db_xref="GeneID:4352"
                     /db_xref="HGNC:HGNC:7217"
                     /db_xref="MIM:159530"
                     /translation="MPSWALFMVTSCLLLAPQNLAQVSSQDVSLLASDSEPLKCFSRT
                     FEDLTCFWDEEEAAPSGTYQLLYAYPREKPRACPLSSQSMPHFGTRYVCQFPDQEEVR
                     LFFPLHLWVKNVFLNQTRTQRVLFVDSVGLPAPPSIIKAMGGSQPGELQISWEEPAPE
                     ISDFLRYELRYGPRDPKNSTGPTVIQLIATETCCPALQRPHSASALDQSPCAQPTMPW
                     QDGPKQTSPSREASALTAEGGSCLISGLQPGNSYWLQLRSEPDGISLGGSWGSWSLPV
                     TVDLPGDAVALGLQCFTLDLKNVTCQWQQQDHASSQGFFYHSRARCCPRDRYPIWENC
                     EEEEKTNPGLQTPQFSRCHFKSRNDSIIHILVEVTTAPGTVHSYLGSPFWIHQAVRLP
                     TPNLHWREISSGHLELEWQHPSSWAAQETCYQLRYTGEGHQDWKVLEPPLGARGGTLE
                     LRPRSRYRLQLRARLNGPTYQGPWSSWSDPTRVETATETAWISLVTALHLVLGLSAVL
                     GLLLLRWQFPAHYRRLRHALWPSLPDLHRVLGQYLRDTAALSPPKATVSDTCEEVEPS
                     LLEILPKSSERTPLPLCSSQAQMDYRRLQPSCLGTMPLSVCPPMAESGSCCTTHIANH
                     SYLPLSYWQQP"
     exon            111..243
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            244..422
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            423..721
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            722..884
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            885..1011
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1012..1196
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1197..1339
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1340..1499
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1500..1596
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1597..1684
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     exon            1685..3633
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3608..3613
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /note="hexamer: AATAAA"
     polyA_site      3633
                     /gene="MPL"
                     /gene_synonym="C-MPL; CD110; MPLV; THCYT2; THPOR; TPOR"
                     /note="major polyA site"
ORIGIN      
        1 gggctaaggc aggcacacag tggcggagaa gatgccctcc tgggccctct tcatggtcac
       61 ctcctgcctc ctcctggccc ctcaaaacct ggcccaagtc agcagccaag atgtctcctt
      121 gctggcatca gactcagagc ccctgaagtg tttctcccga acatttgagg acctcacttg
      181 cttctgggat gaggaagagg cagcgcccag tgggacatac cagctgctgt atgcctaccc
      241 gcgggagaag ccccgtgctt gccccctgag ttcccagagc atgccccact ttggaacccg
      301 atacgtgtgc cagtttccag accaggagga agtgcgtctc ttctttccgc tgcacctctg
      361 ggtgaagaat gtgttcctaa accagactcg gactcagcga gtcctctttg tggacagtgt
      421 aggcctgccg gctcccccca gtatcatcaa ggccatgggt gggagccagc caggggaact
      481 tcagatcagc tgggaggagc cagctccaga aatcagtgat ttcctgaggt acgaactccg
      541 ctatggcccc agagatccca agaactccac tggtcccacg gtcatacagc tgattgccac
      601 agaaacctgc tgccctgctc tgcagaggcc tcactcagcc tctgctctgg accagtctcc
      661 atgtgctcag cccacaatgc cctggcaaga tggaccaaag cagacctccc caagtagaga
      721 agcttcagct ctgacagcag agggtggaag ctgcctcatc tcaggactcc agcctggcaa
      781 ctcctactgg ctgcagctgc gcagcgaacc tgatgggatc tccctcggtg gctcctgggg
      841 atcctggtcc ctccctgtga ctgtggacct gcctggagat gcagtggcac ttggactgca
      901 atgctttacc ttggacctga agaatgttac ctgtcaatgg cagcaacagg accatgctag
      961 ctcccaaggc ttcttctacc acagcagggc acggtgctgc cccagagaca ggtaccccat
     1021 ctgggagaac tgcgaagagg aagagaaaac aaatccagga ctacagaccc cacagttctc
     1081 tcgctgccac ttcaagtcac gaaatgacag cattattcac atccttgtgg aggtgaccac
     1141 agccccgggt actgttcaca gctacctggg ctcccctttc tggatccacc aggctgtgcg
     1201 cctccccacc ccaaacttgc actggaggga gatctccagt gggcatctgg aattggagtg
     1261 gcagcaccca tcgtcctggg cagcccaaga gacctgttat caactccgat acacaggaga
     1321 aggccatcag gactggaagg tgctggagcc gcctctcggg gcccgaggag ggaccctgga
     1381 gctgcgcccg cgatctcgct accgtttaca gctgcgcgcc aggctcaacg gccccaccta
     1441 ccaaggtccc tggagctcgt ggtcggaccc aactagggtg gagaccgcca ccgagaccgc
     1501 ctggatctcc ttggtgaccg ctctgcatct agtgctgggc ctcagcgccg tcctgggcct
     1561 gctgctgctg aggtggcagt ttcctgcaca ctacaggaga ctgaggcatg ccctgtggcc
     1621 ctcacttcca gacctgcacc gggtcctagg ccagtacctt agggacactg cagccctgag
     1681 cccgcccaag gccacagtct cagatacctg tgaagaagtg gaacccagcc tccttgaaat
     1741 cctccccaag tcctcagaga ggactccttt gcccctgtgt tcctcccagg cccagatgga
     1801 ctaccgaaga ttgcagcctt cttgcctggg gaccatgccc ctgtctgtgt gcccacccat
     1861 ggctgagtca gggtcctgct gtaccaccca cattgccaac cattcctacc taccactaag
     1921 ctattggcag cagccttgag gacaggctcc tcactcccag ttccctggac agagctaaac
     1981 tctcgagact tctctgtgaa cttccctacc ctacccccac aacacaagca ccccagacct
     2041 cacctccatc cccctctgtc tgccctcaca attaggcttc attgcactga tcttactcta
     2101 ctgctgctga cataaaacca ggaccctttc tccacaggca ggctcatttc actaagctcc
     2161 tcctttactt tctctctcct ctttgatgtc aaacgccttg aaaacaagcc tccacttccc
     2221 cacacttccc atttactctt gagactactt caattagttc ccctactaca ctttgctagt
     2281 gaaactgccc aggcaaagtg cacctcaaat cttctaattc caagatccaa taggatctcg
     2341 ttaatcatca gttcctttga tctcgctgta agatttgtca aggctgacta ctcacttctc
     2401 ctttaaattc tttcctacct tggtcctgcc tctttgagta tattagtagg ttttttttat
     2461 ttgtttgaga cagggtctca ctctgtcacc caggctgcag tgcaatggcg cgatctcagc
     2521 tcactgcaac ctccacctcc gggttcaagc gattcttgtg cctcggcctc cctagtagct
     2581 gggattacag gcgcacacca ccacacacag ctaatttttt tttttttttt tttttttttt
     2641 ttttagacgg agccttgctc tgttgccaga ctggagtgca gtggcacgat ctcggctcac
     2701 tgcaacctct gcctcccggg ttcaagccat tctgcctcag cctcccaagt agctgggagt
     2761 acaggcgtct gccaccatgc ctaatttttt tctattttta ggagagaccg gttttcacca
     2821 cgttggccag gatggtctcg atatcctgat ctcgtgatcc gcctgcctct gcctcccaaa
     2881 gtgctgggat tacaggtgtg acccactgcg cacagcccca gctaattttc atatttttag
     2941 tagagacagg gttttgccat gttgcccagg ctggtcttga actcctaacc tcgggtgatc
     3001 cacccacctt ggcctcccaa agtgttagga ttacaggcat gagccactgc gcccggctga
     3061 gtgtactagt agttaagaga ataaactaga tctagaatca gagctggatt caattcctgt
     3121 ccttcacatt tactagctgt gcaaccttgg gcacataact taatgtcttt gagccttagt
     3181 tttttcatct gtaaaacagg gataataaca gcaccccata gagttgtgac gaggattgag
     3241 ataatctaag taaagcacag tccctaggac atagtaaatg attcatatat ccgaactact
     3301 gttataatta ttccttctta ctctcctctt ctagcatttc ttccaattat tacagtcctt
     3361 caagattcca tttcttaaca gtctccaatc ccatctattc tctgccttta ctatatgttg
     3421 accattccaa agttcttatc tctagctcag acatctacta cagcactgtg atgctttatg
     3481 caactaactg tttacatatc tgtcccctgc tactagattg tgagctcctt gagggaaagg
     3541 aacatgattt atttgtcctt ttcccccagc acctagagta gtgcttggtg catgatagta
     3601 ggccttcaat aaattttttc taaatgaatg aaa
//
