TPO_MOUSE
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 03-AUG-2022, entry version 149.
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 GlyGen; P40226; 7 sites.
DR PhosphoSitePlus; P40226; -.
DR PaxDb; P40226; -.
DR PRIDE; P40226; -.
DR Antibodypedia; 19145; 615 antibodies from 36 providers.
DR DNASU; 21832; -.
DR Ensembl; ENSMUST00000076422; ENSMUSP00000075756; ENSMUSG00000022847. [P40226-1]
DR Ensembl; ENSMUST00000115437; ENSMUSP00000111097; ENSMUSG00000022847. [P40226-1]
DR GeneID; 21832; -.
DR KEGG; mmu:21832; -.
DR UCSC; uc007yra.2; mouse. [P40226-1]
DR UCSC; uc033gyk.1; mouse. [P40226-2]
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; 906192at2759; -.
DR PhylomeDB; P40226; -.
DR TreeFam; TF338084; -.
DR BioGRID-ORCS; 21832; 1 hit in 73 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 71 other tissues.
DR ExpressionAtlas; P40226; baseline and differential.
DR Genevisible; P40226; MM.
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 protein kinase B signaling; 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; PTHR10560; 1.
DR Pfam; PF00758; EPO_TPO; 1.
DR PRINTS; PR01485; THROMBOPTN.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00817; EPO_TPO; 1.
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
