ID TPOR_MOUSE Reviewed; 625 AA. AC Q08351; A6H8H6; Q8BRX0; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 184. DE RecName: Full=Thrombopoietin receptor; DE Short=TPO-R; DE AltName: Full=Myeloproliferative leukemia protein; DE AltName: Full=Proto-oncogene c-Mpl; DE AltName: CD_antigen=CD110; DE Flags: Precursor; GN Name=Mpl; Synonyms=Tpor; 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 [GENOMIC DNA / MRNA]. RX PubMed=8334987; DOI=10.1002/j.1460-2075.1993.tb05925.x; RA Skoda R.C., Seldin D.C., Chiang M.K., Peichel C.L., Vogt T.F., Leder P.; RT "Murine c-mpl: a member of the hematopoietic growth factor receptor RT superfamily that transduces a proliferative signal."; RL EMBO J. 12:2645-2653(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=ICFW; TISSUE=Fetal liver; RX PubMed=8397366; RA Vigon I., Florindo C., Fichelson S., Guenet J.-L., Mattei M.-G., Souyri M., RA Cosman D., Gisselbrecht S.; RT "Characterization of the murine Mpl proto-oncogene, a member of the RT hematopoietic cytokine receptor family: molecular cloning, chromosomal RT location and evidence for a function in cell growth."; RL Oncogene 8:2607-2615(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Aorta, and Vein; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [6] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=15210714; DOI=10.1074/jbc.m401386200; RA Coers J., Ranft C., Skoda R.C.; RT "A truncated isoform of c-Mpl with an essential C-terminal peptide targets RT the full-length receptor for degradation."; RL J. Biol. Chem. 279:36397-36404(2004). RN [7] 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). RN [8] RP ALTERNATIVE SPLICING. RX PubMed=25468569; DOI=10.1182/blood-2014-08-593392; RA Xiao N., Laha S., Das S.P., Morlock K., Jesneck J.L., Raffel G.D.; RT "Ott1 (Rbm15) regulates thrombopoietin response in hematopoietic stem cells RT through alternative splicing of c-Mpl."; RL Blood 125:941-948(2015). CC -!- FUNCTION: Receptor for thrombopoietin that acts as a primary regulator CC of megakaryopoiesis and platelet production. May represent a regulatory CC molecule specific for TPO-R-dependent immune responses. CC {ECO:0000269|PubMed:15210714}. CC -!- FUNCTION: [Isoform Mpl-tr]: Acts as an inhibitor of thrombopoietin CC signaling by promoting protein down-regulation of full-length isoform CC Mpl-fl. {ECO:0000269|PubMed:15210714}. CC -!- SUBUNIT: Homodimer. Interacts with ATXN2L. CC {ECO:0000250|UniProtKB:P40238}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein {ECO:0000250|UniProtKB:P40238}. Golgi apparatus CC {ECO:0000250|UniProtKB:P40238}. Cell surface CC {ECO:0000250|UniProtKB:P40238}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Mpl-fl {ECO:0000303|PubMed:15210714}; Synonyms=Mpl-full-length CC {ECO:0000303|PubMed:15210714}; CC IsoId=Q08351-1; Sequence=Displayed; CC Name=Mpl-tr {ECO:0000303|PubMed:15210714}; Synonyms=Mpl-truncated CC {ECO:0000303|PubMed:15210714}; CC IsoId=Q08351-2; Sequence=VSP_059621, VSP_059622; CC -!- INDUCTION: Expression in the bone marrow displays diurnal rhythmicity CC (a circadian rhythm that is synchronized with the day/night cycle). CC {ECO:0000269|PubMed:22284746}. CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein CC folding and thereby efficient intracellular transport and cell-surface CC receptor binding. CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or CC activation. CC -!- PTM: Ubiquitination at Lys-544 and Lys-564 targets MPL for degradation CC by both the lysosomal and proteasomal pathways. The E3 ubiquitin- CC protein ligase CBL significantly contributes to this ubiquitination (By CC similarity). {ECO:0000250}. CC -!- MISCELLANEOUS: [Isoform Mpl-tr]: Rbm15 regulates the production of CC isoform Mpl-tr. {ECO:0000269|PubMed:25468569}. CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1 CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z22649; CAA80365.1; -; mRNA. DR EMBL; Z22657; CAA80372.1; -; Genomic_DNA. DR EMBL; X73677; CAA52031.1; -; mRNA. DR EMBL; AK041166; BAC30846.1; -; mRNA. DR EMBL; AL627212; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC146613; AAI46614.1; -; mRNA. DR CCDS; CCDS18552.1; -. [Q08351-1] DR PIR; S35317; S35317. DR PIR; S37622; S37622. DR RefSeq; NP_001116421.1; NM_001122949.2. DR RefSeq; NP_001272425.1; NM_001285496.1. DR RefSeq; NP_001272426.1; NM_001285497.1. DR RefSeq; NP_034953.2; NM_010823.3. [Q08351-1] DR AlphaFoldDB; Q08351; -. DR SMR; Q08351; -. DR BioGRID; 201478; 2. DR IntAct; Q08351; 1. DR STRING; 10090.ENSMUSP00000006556; -. DR ChEMBL; CHEMBL1075309; -. DR GlyCosmos; Q08351; 1 site, No reported glycans. DR GlyGen; Q08351; 1 site. DR iPTMnet; Q08351; -. DR PhosphoSitePlus; Q08351; -. DR MaxQB; Q08351; -. DR PaxDb; 10090-ENSMUSP00000099732; -. DR ProteomicsDB; 259503; -. [Q08351-1] DR ABCD; Q08351; 3 sequenced antibodies. DR Antibodypedia; 2379; 456 antibodies from 31 providers. DR DNASU; 17480; -. DR Ensembl; ENSMUST00000102671.10; ENSMUSP00000099732.4; ENSMUSG00000006389.14. [Q08351-1] DR GeneID; 17480; -. DR KEGG; mmu:17480; -. DR UCSC; uc008uke.3; mouse. [Q08351-1] DR AGR; MGI:97076; -. DR CTD; 4352; -. DR MGI; MGI:97076; Mpl. DR VEuPathDB; HostDB:ENSMUSG00000006389; -. DR eggNOG; ENOG502RYN1; Eukaryota. DR GeneTree; ENSGT00940000161225; -. DR HOGENOM; CLU_029931_1_0_1; -. DR InParanoid; Q08351; -. DR OMA; IWEKCEE; -. DR OrthoDB; 5297263at2759; -. DR TreeFam; TF336573; -. DR BioGRID-ORCS; 17480; 2 hits in 80 CRISPR screens. DR ChiTaRS; Mpl; mouse. DR PRO; PR:Q08351; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; Q08351; Protein. DR Bgee; ENSMUSG00000006389; Expressed in blood and 41 other cell types or tissues. DR ExpressionAtlas; Q08351; baseline and differential. DR GO; GO:0009986; C:cell surface; ISS:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0031965; C:nuclear membrane; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0038164; F:thrombopoietin receptor activity; ISS:UniProtKB. DR GO; GO:1990960; P:basophil homeostasis; ISO:MGI. DR GO; GO:0060216; P:definitive hemopoiesis; IMP:MGI. DR GO; GO:1990959; P:eosinophil homeostasis; ISO:MGI. DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IBA:GO_Central. DR GO; GO:0035702; P:monocyte homeostasis; ISO:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI. DR GO; GO:0001780; P:neutrophil homeostasis; ISO:MGI. DR GO; GO:0030220; P:platelet formation; IGI:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:MGI. DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; ISO:MGI. DR GO; GO:1905221; P:positive regulation of platelet formation; ISO:MGI. DR GO; GO:0032642; P:regulation of chemokine production; IMP:MGI. DR GO; GO:2000035; P:regulation of stem cell division; IMP:MGI. DR GO; GO:0072091; P:regulation of stem cell proliferation; IMP:MGI. DR GO; GO:0038163; P:thrombopoietin-mediated signaling pathway; IDA:UniProtKB. DR CDD; cd00063; FN3; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 4. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR015152; Growth/epo_recpt_lig-bind. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003528; Long_hematopoietin_rcpt_CS. DR PANTHER; PTHR23037; CYTOKINE RECEPTOR; 1. DR PANTHER; PTHR23037:SF31; THROMBOPOIETIN RECEPTOR; 1. DR Pfam; PF09067; EpoR_lig-bind; 1. DR SMART; SM00060; FN3; 2. DR SUPFAM; SSF49265; Fibronectin type III; 3. DR PROSITE; PS50853; FN3; 1. DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1. DR Genevisible; Q08351; MM. PE 2: Evidence at transcript level; KW Alternative splicing; Cell membrane; Glycoprotein; Golgi apparatus; KW Isopeptide bond; Membrane; Receptor; Reference proteome; Repeat; Signal; KW Transmembrane; Transmembrane helix; Ubl conjugation. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..625 FT /note="Thrombopoietin receptor" FT /id="PRO_0000010988" FT TOPO_DOM 26..482 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 483..504 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 505..625 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 178..270 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 383..479 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT MOTIF 465..469 FT /note="WSXWS motif" FT MOTIF 519..527 FT /note="Box 1 motif" FT CARBOHYD 117 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CROSSLNK 544 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P40238" FT CROSSLNK 564 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P40238" FT VAR_SEQ 428..457 FT /note="VLEPSLGARGGTLELRPRARYSLQLRARLN -> ETEACFVALASRPTPGPR FT PVPQRHCSPKSF (in isoform Mpl-tr)" FT /id="VSP_059621" FT VAR_SEQ 458..625 FT /note="Missing (in isoform Mpl-tr)" FT /id="VSP_059622" FT CONFLICT 1..7 FT /note="Missing (in Ref. 2; CAA52031)" FT /evidence="ECO:0000305" FT CONFLICT 99 FT /note="D -> V (in Ref. 2; CAA52031)" FT /evidence="ECO:0000305" FT CONFLICT 222 FT /note="P -> PVRTSPAGE (in Ref. 2; CAA52031)" FT /evidence="ECO:0000305" FT CONFLICT 241 FT /note="G -> S (in Ref. 1; CAA80365, 2; CAA52031 and 5; FT AAI46614)" FT /evidence="ECO:0000305" SQ SEQUENCE 625 AA; 69788 MW; 87836E6EA4688ED7 CRC64; MPSWALFMVT SCLLLALPNQ AQVTSQDVFL LALGTEPLNC FSQTFEDLTC FWDEEEAAPS GTYQLLYAYR GEKPRACPLY SQSVPTFGTR YVCQFPAQDE VRLFFPLHLW VKNVSLNQTL IQRVLFVDSV GLPAPPRVIK ARGGSQPGEL QIHWEAPAPE ISDFLRHELR YGPTDSSNAT APSVIQLLST ETCCPTLWMP NPVPVLDQPP CVHPTASQPH GPAPFLTVKG GSCLVSGLQA GKSYWLQLRS QPDGVSLRGS WGPWSFPVTV DLPGDAVTIG LQCFTLDLKM VTCQWQQQDR TSSQGFFRHS RTRCCPTDRD PTWEKCEEEE PRPGSQPALV SRCHFKSRND SVIHILVEVT TAQGAVHSYL GSPFWIHQAV LLPTPSLHWR EVSSGRLELE WQHQSSWAAQ ETCYQLRYTG EGREDWKVLE PSLGARGGTL ELRPRARYSL QLRARLNGPT YQGPWSAWSP PARVSTGSET AWITLVTALL LVLSLSALLG LLLLKWQFPA HYRRLRHALW PSLPDLHRVL GQYLRDTAAL SPSKATVTDS CEEVEPSLLE ILPKSSESTP LPLCPSQPQM DYRGLQPCLR TMPLSVCPPM AETGSCCTTH IANHSYLPLS YWQQP //