ID   TPO_MOUSE               Reviewed;         356 AA.
AC   P40226;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   24-JAN-2024, entry version 156.
DE   RecName: Full=Thrombopoietin;
DE   AltName: Full=C-mpl ligand;
DE            Short=ML;
DE   AltName: Full=Megakaryocyte colony-stimulating factor;
DE   AltName: Full=Megakaryocyte growth and development factor;
DE            Short=MGDF;
DE   AltName: Full=Myeloproliferative leukemia virus oncogene ligand;
DE   Flags: Precursor;
GN   Name=Thpo;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Kidney;
RX   PubMed=8202158; DOI=10.1038/369565a0;
RA   Lok S., Kaushansky K., Holly R.D., Kuijper J.L., Lofton-Day C.E.,
RA   Oort P.J., Grant F.J., Heipel M.D., Burkhead S.K., Kramer J.M.,
RA   Bell L.A.N., Sprecher C.A., Blumberg H., Johnson R., Prunkard D.,
RA   Ching A.F.T., Mathewes S.L., Bailey M.C., Forstrom J.W., Buddle M.M.,
RA   Osborn S.G., Evans S.J., Sheppard P.O., Presnell S.R., O'Hara P.J.,
RA   Hagen F.S., Roth G.J., Foster D.C.;
RT   "Cloning and expression of murine thrombopoietin cDNA and stimulation of
RT   platelet production in vivo.";
RL   Nature 369:565-568(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=8020099; DOI=10.1016/0092-8674(94)90450-2;
RA   Bartley T.D., Bogenberger J., Hunt P., Li Y.-S., Lu H.S., Martin F.,
RA   Chang M.-S., Samal B.B., Nichol J.L., Swift S., Johnson M.J., Hsu R.-Y.,
RA   Parker V.P., Suggs S., Skrine J.D., Merewether L.A., Clogson C., Hsu E.,
RA   Hokom M.M., Hornkohl A., Choi E., Pangelinan M., Sun Y., Mar V., McNich J.,
RA   Simonet L., Jacobsen F., Xie C., Shutter J., Chute H., Basu R.,
RA   Selander L., Trollinger D., Sieu L., Padilla D., Trail G., Elliott G.,
RA   Izumi R., Covey T., Crouse J., Garcia A., Xu W., del Castillo J., Biron J.,
RA   Cole S., Hu M.C.-T., Pacifici R., Ponting I., Saris C., Wen D., Yung Y.P.,
RA   Lin H., Bosselman R.A.;
RT   "Identification and cloning of a megakaryocyte growth and development
RT   factor that is a ligand for the cytokine receptor Mpl.";
RL   Cell 77:1117-1124(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX   PubMed=7849319;
RA   Gurney A.L., Kuang W.-J., Xie M.-H., Malloy B.E., Eaton D.L.,
RA   de Sauvage F.J.;
RT   "Genomic structure, chromosomal localization, and conserved alternative
RT   splice forms of thrombopoietin.";
RL   Blood 85:981-988(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   INDUCTION.
RX   PubMed=22284746; DOI=10.1111/j.1538-7836.2012.04643.x;
RA   Tracey C.J., Pan X., Catterson J.H., Harmar A.J., Hussain M.M.,
RA   Hartley P.S.;
RT   "Diurnal expression of the thrombopoietin gene is regulated by CLOCK.";
RL   J. Thromb. Haemost. 10:662-669(2012).
CC   -!- FUNCTION: Lineage-specific cytokine affecting the proliferation and
CC       maturation of megakaryocytes from their committed progenitor cells. It
CC       acts at a late stage of megakaryocyte development. It may be the major
CC       physiological regulator of circulating platelets.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P40226-1; Sequence=Displayed;
CC       Name=2; Synonyms=TPO-2;
CC         IsoId=P40226-2; Sequence=VSP_001452;
CC   -!- TISSUE SPECIFICITY: Found mainly in the liver, kidney and skeletal
CC       muscle.
CC   -!- INDUCTION: Expression in the liver and bone marrow displays diurnal
CC       rhythmicity (a circadian rhythm that is synchronized with the day/night
CC       cycle). {ECO:0000269|PubMed:22284746}.
CC   -!- DOMAIN: Two-domain structure with an erythropoietin-like N-terminal and
CC       a Ser/Pro/Thr-rich C-terminal.
CC   -!- SIMILARITY: Belongs to the EPO/TPO family. {ECO:0000305}.
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DR   EMBL; L34169; AAA40436.1; -; mRNA.
DR   EMBL; BC003803; AAH03803.1; -; mRNA.
DR   CCDS; CCDS37292.1; -. [P40226-1]
DR   PIR; S45330; S45330.
DR   RefSeq; NP_001166976.1; NM_001173505.1. [P40226-1]
DR   RefSeq; NP_001276823.1; NM_001289894.1. [P40226-2]
DR   RefSeq; NP_033405.1; NM_009379.3. [P40226-1]
DR   AlphaFoldDB; P40226; -.
DR   SMR; P40226; -.
DR   STRING; 10090.ENSMUSP00000111097; -.
DR   GlyCosmos; P40226; 7 sites, No reported glycans.
DR   GlyGen; P40226; 7 sites.
DR   PhosphoSitePlus; P40226; -.
DR   PaxDb; 10090-ENSMUSP00000111097; -.
DR   Antibodypedia; 19145; 682 antibodies from 36 providers.
DR   DNASU; 21832; -.
DR   Ensembl; ENSMUST00000076422.13; ENSMUSP00000075756.6; ENSMUSG00000022847.16. [P40226-1]
DR   Ensembl; ENSMUST00000115437.4; ENSMUSP00000111097.3; ENSMUSG00000022847.16. [P40226-1]
DR   GeneID; 21832; -.
DR   KEGG; mmu:21832; -.
DR   UCSC; uc007yra.2; mouse. [P40226-1]
DR   UCSC; uc033gyk.1; mouse. [P40226-2]
DR   AGR; MGI:101875; -.
DR   CTD; 7066; -.
DR   MGI; MGI:101875; Thpo.
DR   VEuPathDB; HostDB:ENSMUSG00000022847; -.
DR   eggNOG; ENOG502S9T0; Eukaryota.
DR   GeneTree; ENSGT00390000006294; -.
DR   HOGENOM; CLU_039844_0_0_1; -.
DR   InParanoid; P40226; -.
DR   OrthoDB; 5347971at2759; -.
DR   PhylomeDB; P40226; -.
DR   TreeFam; TF338084; -.
DR   BioGRID-ORCS; 21832; 1 hit in 78 CRISPR screens.
DR   ChiTaRS; Thpo; mouse.
DR   PRO; PR:P40226; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; P40226; Protein.
DR   Bgee; ENSMUSG00000022847; Expressed in kidney vasculature and 73 other cell types or tissues.
DR   ExpressionAtlas; P40226; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0008283; P:cell population proliferation; IEA:InterPro.
DR   GO; GO:0035855; P:megakaryocyte development; ISO:MGI.
DR   GO; GO:0030219; P:megakaryocyte differentiation; ISO:MGI.
DR   GO; GO:0030099; P:myeloid cell differentiation; IDA:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR   GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; ISO:MGI.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR   GO; GO:0045654; P:positive regulation of megakaryocyte differentiation; IDA:UniProtKB.
DR   GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0097696; P:receptor signaling pathway via STAT; ISO:MGI.
DR   GO; GO:0038163; P:thrombopoietin-mediated signaling pathway; IDA:UniProtKB.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR019767; EPO/TPO_CS.
DR   InterPro; IPR001323; EPO_TPO.
DR   InterPro; IPR003978; Thrombopoietin.
DR   PANTHER; PTHR10560; THROMBOPOIETIN; 1.
DR   PANTHER; PTHR10560:SF0; THROMBOPOIETIN; 1.
DR   Pfam; PF00758; EPO_TPO; 1.
DR   PRINTS; PR01485; THROMBOPTN.
DR   SUPFAM; SSF47266; 4-helical cytokines; 1.
DR   PROSITE; PS00817; EPO_TPO; 1.
DR   Genevisible; P40226; MM.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Cytokine; Disulfide bond; Glycoprotein; Hormone;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..356
FT                   /note="Thrombopoietin"
FT                   /id="PRO_0000008412"
FT   REGION          291..356
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        299..328
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        206
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        249
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        256
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        28..172
FT                   /evidence="ECO:0000255"
FT   DISULFID        50..106
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         133..136
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7849319"
FT                   /id="VSP_001452"
SQ   SEQUENCE   356 AA;  37836 MW;  D346DBAE8392053C CRC64;
     MELTDLLLAA MLLAVARLTL SSPVAPACDP RLLNKLLRDS HLLHSRLSQC PDVDPLSIPV
     LLPAVDFSLG EWKTQTEQSK AQDILGAVSL LLEGVMAARG QLEPSCLSSL LGQLSGQVRL
     LLGALQGLLG TQLPLQGRTT AHKDPNALFL SLQQLLRGKV RFLLLVEGPT LCVRRTLPTT
     AVPSSTSQLL TLNKFPNRTS GLLETNFSVT ARTAGPGLLS RLQGFRVKIT PGQLNQTSRS
     PVQISGYLNR THGPVNGTHG LFAGTSLQTL EASDISPGAF NKGSLAFNLQ GGLPPSPSLA
     PDGHTPFPPS PALPTTHGSP PQLHPLFPDP STTMPNSTAP HPVTMYPHPR NLSQET
//