LOCUS       NM_000460               1918 bp    mRNA    linear   PRI 02-OCT-2024
DEFINITION  Homo sapiens thrombopoietin (THPO), transcript variant 1, mRNA.
ACCESSION   NM_000460
VERSION     NM_000460.4
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 1918)
  AUTHORS   Kimura,H., Onozawa,M., Hashiguchi,J., Hidaka,D., Kanaya,M.,
            Matsukawa,T., Okada,H., Kondo,T., Matsuno,Y. and Teshima,T.
  TITLE     Hereditary thrombocythemia due to splicing donor site mutation of
            THPO in a Japanese family
  JOURNAL   Ann Hematol 103 (1), 89-96 (2024)
   PUBMED   37962621
  REMARK    GeneRIF: Hereditary thrombocythemia due to splicing donor site
            mutation of THPO in a Japanese family.
REFERENCE   2  (bases 1 to 1918)
  AUTHORS   Dordelmann,C., Telgmann,R., Brand,E., Hagedorn,C., Schroer,B.,
            Hasenkamp,S., Baumgart,P., Kleine-Katthofer,P., Paul,M. and
            Brand-Herrmann,S.M.
  TITLE     Functional and structural profiling of the human thrombopoietin
            gene promoter
  JOURNAL   J Biol Chem 283 (36), 24382-24391 (2008)
   PUBMED   18617523
  REMARK    GeneRIF: THPO transcription is cell line-dependently initiated at
            two alternative promoters, which we newly designated P1a and P1
REFERENCE   3  (bases 1 to 1918)
  AUTHORS   Ghilardi,N., Wiestner,A. and Skoda,R.C.
  TITLE     Thrombopoietin production is inhibited by a translational mechanism
  JOURNAL   Blood 92 (11), 4023-4030 (1998)
   PUBMED   9834204
REFERENCE   4  (bases 1 to 1918)
  AUTHORS   Wiestner,A., Schlemper,R.J., van der Maas,A.P. and Skoda,R.C.
  TITLE     An activating splice donor mutation in the thrombopoietin gene
            causes hereditary thrombocythaemia
  JOURNAL   Nat Genet 18 (1), 49-52 (1998)
   PUBMED   9425899
REFERENCE   5  (bases 1 to 1918)
  AUTHORS   Kamura,T., Handa,H., Hamasaki,N. and Kitajima,S.
  TITLE     Characterization of the human thrombopoietin gene promoter. A
            possible role of an Ets transcription factor, E4TF1/GABP
  JOURNAL   J Biol Chem 272 (17), 11361-11368 (1997)
   PUBMED   9111044
REFERENCE   6  (bases 1 to 1918)
  AUTHORS   Gurney,A.L., Kuang,W.J., Xie,M.H., Malloy,B.E., Eaton,D.L. and de
            Sauvage,F.J.
  TITLE     Genomic structure, chromosomal localization, and conserved
            alternative splice forms of thrombopoietin
  JOURNAL   Blood 85 (4), 981-988 (1995)
   PUBMED   7849319
REFERENCE   7  (bases 1 to 1918)
  AUTHORS   Chang,M.S., McNinch,J., Basu,R., Shutter,J., Hsu,R.Y., Perkins,C.,
            Mar,V., Suggs,S., Welcher,A., Li,L. et al.
  TITLE     Cloning and characterization of the human megakaryocyte growth and
            development factor (MGDF) gene
  JOURNAL   J Biol Chem 270 (2), 511-514 (1995)
   PUBMED   7822271
REFERENCE   8  (bases 1 to 1918)
  AUTHORS   Foster,D.C., Sprecher,C.A., Grant,F.J., Kramer,J.M., Kuijper,J.L.,
            Holly,R.D., Whitmore,T.E., Heipel,M.D., Bell,L.A., Ching,A.F. et
            al.
  TITLE     Human thrombopoietin: gene structure, cDNA sequence, expression,
            and chromosomal localization
  JOURNAL   Proc Natl Acad Sci U S A 91 (26), 13023-13027 (1994)
   PUBMED   7809166
REFERENCE   9  (bases 1 to 1918)
  AUTHORS   Sohma,Y., Akahori,H., Seki,N., Hori,T., Ogami,K., Kato,T.,
            Shimada,Y., Kawamura,K. and Miyazaki,H.
  TITLE     Molecular cloning and chromosomal localization of the human
            thrombopoietin gene
  JOURNAL   FEBS Lett 353 (1), 57-61 (1994)
   PUBMED   7926023
REFERENCE   10 (bases 1 to 1918)
  AUTHORS   Bartley,T.D., Bogenberger,J., Hunt,P., Li,Y.S., Lu,H.S., Martin,F.,
            Chang,M.S., Samal,B., Nichol,J.L., Swift,S. et al.
  TITLE     Identification and cloning of a megakaryocyte growth and
            development factor that is a ligand for the cytokine receptor Mpl
  JOURNAL   Cell 77 (7), 1117-1124 (1994)
   PUBMED   8020099
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC078797.20, L33410.1,
            BC143982.1, BC136338.1 and AA479058.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 9, 2018 this sequence version replaced NM_000460.3.
            
            Summary: Megakaryocytopoiesis is the cellular development process
            that leads to platelet production. The main functional protein
            encoded by this gene is a humoral growth factor that is necessary
            for megakaryocyte proliferation and maturation, as well as for
            thrombopoiesis. This protein is the ligand for MLP/C_MPL, the
            product of myeloproliferative leukemia virus oncogene. Mutations in
            this gene are the cause of thrombocythemia 1. Alternative promoter
            usage and differential splicing result in multiple transcript
            variants differing in the 5' UTR and/or coding region. Multiple AUG
            codons upstream of the main open reading frame (ORF) have been
            identified, and these upstream AUGs inhibit translation of the main
            ORF at different extent. [provided by RefSeq, Feb 2014].
            
            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 :: L33410.1, SRR5189664.158503.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1970526 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000647395.1/ ENSP00000494504.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            regulatory uORF        :: PMID: 9834204
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-63                AC078797.20        119510-119572       c
            64-142              L33410.1           1-79
            143-674             BC143982.1         76-607
            675-1455            BC136338.1         608-1388
            1456-1840           L33410.1           1393-1777
            1841-1918           AA479058.1         5-82                c
FEATURES             Location/Qualifiers
     source          1..1918
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="3q27.1"
     gene            1..1918
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /note="thrombopoietin"
                     /db_xref="GeneID:7066"
                     /db_xref="HGNC:HGNC:11795"
                     /db_xref="MIM:600044"
     exon            1..133
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /inference="alignment:Splign:2.1.0"
     regulatory      22..138
                     /regulatory_class="uORF"
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:9834204]"
                     /note="this uORF is predicted to encode a 38 aa peptide
                     (PMID:9834204)"
     regulatory      61..138
                     /regulatory_class="uORF"
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:9834204]"
                     /note="this uORF is predicted to encode a 25 aa peptide
                     (PMID:9834204)"
     exon            134..291
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /inference="alignment:Splign:2.1.0"
     regulatory      209..292
                     /regulatory_class="uORF"
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:9834204]"
                     /note="this uORF is predicted to encode a 27 aa peptide
                     (PMID:9834204)"
     CDS             279..1340
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; megakaryocyte stimulating factor; MPL ligand;
                     prepro-thrombopoietin; megakaryocyte colony-stimulating
                     factor; c-mpl ligand; myeloproliferative leukemia virus
                     oncogene ligand; megakaryocyte growth and development
                     factor; thrombopoietin nirs"
                     /codon_start=1
                     /product="thrombopoietin isoform 1 precursor"
                     /protein_id="NP_000451.1"
                     /db_xref="CCDS:CCDS3265.1"
                     /db_xref="GeneID:7066"
                     /db_xref="HGNC:HGNC:11795"
                     /db_xref="MIM:600044"
                     /translation="MELTELLLVVMLLLTARLTLSSPAPPACDLRVLSKLLRDSHVLH
                     SRLSQCPEVHPLPTPVLLPAVDFSLGEWKTQMEETKAQDILGAVTLLLEGVMAARGQL
                     GPTCLSSLLGQLSGQVRLLLGALQSLLGTQLPPQGRTTAHKDPNAIFLSFQHLLRGKV
                     RFLMLVGGSTLCVRRAPPTTAVPSRTSLVLTLNELPNRTSGLLETNFTASARTTGSGL
                     LKWQQGFRAKIPGLLNQTSRSLDQIPGYLNRIHELLNGTRGLFPGPSRRTLGAPDISS
                     GTSDTGSLPPNLQPGYSPSPTHPPTGQYTLFPLPPTLPTPVVQLHPLLPDPSAPTPTP
                     TSPLLNTSYTHSQNLSQEG"
     exon            292..419
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /inference="alignment:Splign:2.1.0"
     exon            420..506
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /inference="alignment:Splign:2.1.0"
     exon            507..674
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /inference="alignment:Splign:2.1.0"
     exon            675..1918
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1507..1512
                     /regulatory_class="polyA_signal_sequence"
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /note="hexamer: TATAAA"
     polyA_site      1525
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /note="major polyA site"
     polyA_site      1563
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
     polyA_site      1600
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
     regulatory      1882..1887
                     /regulatory_class="polyA_signal_sequence"
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
                     /note="hexamer: AATAAA"
     polyA_site      1918
                     /gene="THPO"
                     /gene_synonym="CAMT2; MGDF; MKCSF; ML; MPLLG; THC9;
                     THCYT1; TPO"
ORIGIN      
        1 agaagtggcc caggcaggcg tatgacctgc tgctgtggag gggctgtgcc ccaccgccac
       61 atgtcttcct acccatctgc tccccagagg gctgcctgct gtgcacttgg gtcctggagc
      121 ccttctccac ccggatagat tcttcaccct tggcccgcct ttgccccacc ctactctgcc
      181 cagaagtgca agagcctaag ccgcctccat ggccccagga aggattcagg ggagaggccc
      241 caaacaggga gccacgccag ccagacaccc cggccagaat ggagctgact gaattgctcc
      301 tcgtggtcat gcttctccta actgcaaggc taacgctgtc cagcccggct cctcctgctt
      361 gtgacctccg agtcctcagt aaactgcttc gtgactccca tgtccttcac agcagactga
      421 gccagtgccc agaggttcac cctttgccta cacctgtcct gctgcctgct gtggacttta
      481 gcttgggaga atggaaaacc cagatggagg agaccaaggc acaggacatt ctgggagcag
      541 tgacccttct gctggaggga gtgatggcag cacggggaca actgggaccc acttgcctct
      601 catccctcct ggggcagctt tctggacagg tccgtctcct ccttggggcc ctgcagagcc
      661 tccttggaac ccagcttcct ccacagggca ggaccacagc tcacaaggat cccaatgcca
      721 tcttcctgag cttccaacac ctgctccgag gaaaggtgcg tttcctgatg cttgtaggag
      781 ggtccaccct ctgcgtcagg cgggccccac ccaccacagc tgtccccagc agaacctctc
      841 tagtcctcac actgaacgag ctcccaaaca ggacttctgg attgttggag acaaacttca
      901 ctgcctcagc cagaactact ggctctgggc ttctgaagtg gcagcaggga ttcagagcca
      961 agattcctgg tctgctgaac caaacctcca ggtccctgga ccaaatcccc ggatacctga
     1021 acaggataca cgaactcttg aatggaactc gtggactctt tcctggaccc tcacgcagga
     1081 ccctaggagc cccggacatt tcctcaggaa catcagacac aggctccctg ccacccaacc
     1141 tccagcctgg atattctcct tccccaaccc atcctcctac tggacagtat acgctcttcc
     1201 ctcttccacc caccttgccc acccctgtgg tccagctcca ccccctgctt cctgaccctt
     1261 ctgctccaac gcccacccct accagccctc ttctaaacac atcctacacc cactcccaga
     1321 atctgtctca ggaagggtaa ggttctcaga cactgccgac atcagcattg tctcgtgtac
     1381 agctcccttc cctgcagggc gcccctggga gacaactgga caagatttcc tactttctcc
     1441 tgaaacccaa agccctggta aaagggatac acaggactga aaagggaatc atttttcact
     1501 gtacattata aaccttcaga agctattttt ttaagctatc agcaatactc atcagagcag
     1561 ctagctcttt ggtctatttt ctgcagaaat ttgcaactca ctgattctct acatgctctt
     1621 tttctgtgat aactctgcaa aggcctgggc tggcctggca gttgaacaga gggagagact
     1681 aaccttgagt cagaaaacag agaaagggta atttcctttg cttcaaattc aaggccttcc
     1741 aacgccccca tcccctttac tatcattctc agtgggactc tgatcccata ttcttaacag
     1801 atctttactc ttgagaaatg aataagcttt ctctcagaaa tgctgtccct atacactaga
     1861 caaaactgag cctgtataag gaataaatgg gagcgccgaa aagctcccta aaaagcaa
//
