TPOR_MOUSE
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 03-AUG-2022, entry version 175.
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}.
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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 BioGRID; 201478; 2.
DR IntAct; Q08351; 1.
DR STRING; 10090.ENSMUSP00000099732; -.
DR ChEMBL; CHEMBL1075309; -.
DR GlyGen; Q08351; 1 site.
DR iPTMnet; Q08351; -.
DR PhosphoSitePlus; Q08351; -.
DR MaxQB; Q08351; -.
DR PaxDb; Q08351; -.
DR PRIDE; Q08351; -.
DR ProteomicsDB; 259503; -. [Q08351-1]
DR ABCD; Q08351; 3 sequenced antibodies.
DR Antibodypedia; 2379; 324 antibodies from 31 providers.
DR DNASU; 17480; -.
DR Ensembl; ENSMUST00000102671; ENSMUSP00000099732; ENSMUSG00000006389. [Q08351-1]
DR GeneID; 17480; -.
DR KEGG; mmu:17480; -.
DR UCSC; uc008uke.3; mouse. [Q08351-1]
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; LPFGTRY; -.
DR OrthoDB; 253180at2759; -.
DR TreeFam; TF336573; -.
DR BioGRID-ORCS; 17480; 2 hits in 75 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 39 other tissues.
DR ExpressionAtlas; Q08351; baseline and differential.
DR Genevisible; Q08351; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
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:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0038164; F:thrombopoietin receptor activity; ISS:UniProtKB.
DR GO; GO:1990960; P:basophil homeostasis; ISO:MGI.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0060216; P:definitive hemopoiesis; IMP:MGI.
DR GO; GO:1990959; P:eosinophil homeostasis; ISO:MGI.
DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central.
DR GO; GO:0048872; P:homeostasis of number of cells; IMP:MGI.
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:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
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; -; 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 Pfam; PF09067; EpoR_lig-bind; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF49265; SSF49265; 3.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
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
