TPOR_HUMAN
ID TPOR_HUMAN Reviewed; 635 AA.
AC P40238; Q5JUZ0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 210.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=1608974; DOI=10.1073/pnas.89.12.5640;
RA Vigon I., Mornon J.-P., Cocault L., Mitjavila M.-T., Tambourin P.,
RA Gisselbrecht S., Souyri M.;
RT "Molecular cloning and characterization of MPL, the human homolog of the v-
RT mpl oncogene: identification of a member of the hematopoietic growth factor
RT receptor superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5640-5644(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2).
RX PubMed=8020956; DOI=10.1006/geno.1994.1120;
RA Mignotte V., Vigon I., Boucher de Crevecoeur E., Romeo P.-H.,
RA Lemarchandel V., Chretien S.;
RT "Structure and transcription of the human c-mpl gene (MPL).";
RL Genomics 20:5-12(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP UBIQUITINATION AT LYS-553 AND LYS573.
RX PubMed=19880496; DOI=10.1182/blood-2009-06-227033;
RA Saur S.J., Sangkhae V., Geddis A.E., Kaushansky K., Hitchcock I.S.;
RT "Ubiquitination and degradation of the thrombopoietin receptor c-Mpl.";
RL Blood 115:1254-1263(2010).
RN [6]
RP VARIANTS VAL-58 AND LYS-168.
RX PubMed=10391209; DOI=10.1038/10290;
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RT "Characterization of single-nucleotide polymorphisms in coding regions of
RT human genes.";
RL Nat. Genet. 22:231-238(1999).
RN [7]
RP ERRATUM OF PUBMED:10391209.
RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA Lander E.S.;
RL Nat. Genet. 23:373-373(1999).
RN [8]
RP INTERACTION WITH ATXN2L.
RX PubMed=11784712; DOI=10.1074/jbc.m105970200;
RA Meunier C.F., Bordereaux D., Porteu F., Gisselbrecht S., Chretien S.,
RA Courtois G.;
RT "Cloning and characterization of a family of proteins associated with
RT Mpl.";
RL J. Biol. Chem. 277:9139-9147(2002).
RN [9]
RP VARIANT THCYT2 ASN-505.
RX PubMed=14764528; DOI=10.1182/blood-2003-10-3471;
RA Ding J., Komatsu H., Wakita A., Kato-Uranishi M., Ito M., Satoh A.,
RA Tsuboi K., Nitta M., Miyazaki H., Iida S., Ueda R.;
RT "Familial essential thrombocythemia associated with a dominant-positive
RT activating mutation of the c-MPL gene, which encodes for the receptor for
RT thrombopoietin.";
RL Blood 103:4198-4200(2004).
RN [10]
RP VARIANT ASN-39, AND CHARACTERIZATION OF VARIANT ASN-39.
RX PubMed=15269348; DOI=10.1073/pnas.0404241101;
RA Moliterno A.R., Williams D.M., Gutierrez-Alamillo L.I., Salvatori R.,
RA Ingersoll R.G., Spivak J.L.;
RT "Mpl Baltimore: a thrombopoietin receptor polymorphism associated with
RT thrombocytosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:11444-11447(2004).
RN [11]
RP VARIANT MMM LYS-515.
RX PubMed=16868251; DOI=10.1182/blood-2006-04-018879;
RA Pardanani A.D., Levine R.L., Lasho T., Pikman Y., Mesa R.A., Wadleigh M.,
RA Steensma D.P., Elliott M.A., Wolanskyj A.P., Hogan W.J., McClure R.F.,
RA Litzow M.R., Gilliland D.G., Tefferi A.;
RT "MPL515 mutations in myeloproliferative and other myeloid disorders: a
RT study of 1182 patients.";
RL Blood 108:3472-3476(2006).
RN [12]
RP VARIANTS CAMT CYS-102; PRO-102; SER-104; LEU-136; ARG-154; LEU-257;
RP THR-275; CYS-435 AND TRP-594.
RX PubMed=16470591; DOI=10.1002/humu.9415;
RA Germeshausen M., Ballmaier M., Welte K.;
RT "MPL mutations in 23 patients suffering from congenital amegakaryocytic
RT thrombocytopenia: the type of mutation predicts the course of the
RT disease.";
RL Hum. Mutat. 27:296-296(2006).
RN [13]
RP VARIANT MMM LEU-515, AND CHARACTERIZATION OF VARIANT MMM LEU-515.
RX PubMed=16834459; DOI=10.1371/journal.pmed.0030270;
RA Pikman Y., Lee B.H., Mercher T., McDowell E., Ebert B.L., Gozo M.,
RA Cuker A., Wernig G., Moore S., Galinsky I., DeAngelo D.J., Clark J.J.,
RA Lee S.J., Golub T.R., Wadleigh M., Gilliland D.G., Levine R.L.;
RT "MPLW515L is a novel somatic activating mutation in myelofibrosis with
RT myeloid metaplasia.";
RL PLoS Med. 3:E270-E270(2006).
RN [14]
RP CHARACTERIZATION OF VARIANT THCYT2 ASN-505.
RX PubMed=19483125; DOI=10.1182/blood-2008-04-149047;
RA Ding J., Komatsu H., Iida S., Yano H., Kusumoto S., Inagaki A., Mori F.,
RA Ri M., Ito A., Wakita A., Ishida T., Nitta M., Ueda R.;
RT "The Asn505 mutation of the c-MPL gene, which causes familial essential
RT thrombocythemia, induces autonomous homodimerization of the c-Mpl protein
RT due to strong amino acid polarity.";
RL Blood 114:3325-3328(2009).
RN [15]
RP VARIANT THCYT2 LEU-515.
RX PubMed=23441089; DOI=10.1002/pbc.24500;
RA Farruggia P., D'Angelo P., La Rosa M., Scibetta N., Santangelo G.,
RA Lo Bello A., Duner E., Randi M.L., Putti M.C., Santoro A.;
RT "MPL W515L mutation in pediatric essential thrombocythemia.";
RL Pediatr. Blood Cancer 60:E52-E54(2013).
RN [16]
RP VARIANT THCYT2 LEU-106, CHARACTERIZATION OF VARIANT THCYT2 LEU-106,
RP CHARACTERIZATION OF VARIANTS CAMT PRO-102 AND SER-104, GLYCOSYLATION,
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=25538044; DOI=10.1182/blood-2014-07-587170;
RA Stockklausner C., Klotter A.C., Dickemann N., Kuhlee I.N., Duffert C.M.,
RA Kerber C., Gehring N.H., Kulozik A.E.;
RT "The thrombopoietin receptor P106L mutation functionally separates receptor
RT signaling activity from thrombopoietin homeostasis.";
RL Blood 125:1159-1169(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:0000250|UniProtKB:Q08351}.
CC -!- SUBUNIT: Homodimer (PubMed:25538044). Interacts with ATXN2L.
CC {ECO:0000269|PubMed:11784712, ECO:0000303|PubMed:25538044}.
CC -!- INTERACTION:
CC P40238; O60674: JAK2; NbExp=6; IntAct=EBI-6511486, EBI-518647;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25538044};
CC Single-pass type I membrane protein. Golgi apparatus
CC {ECO:0000269|PubMed:25538044}. Cell surface
CC {ECO:0000269|PubMed:25538044}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=C-mpl-P;
CC IsoId=P40238-1; Sequence=Displayed;
CC Name=2; Synonyms=C-mpl-K;
CC IsoId=P40238-2; Sequence=VSP_001734, VSP_001735;
CC -!- TISSUE SPECIFICITY: Expressed at a low level in a large number of cells
CC of hematopoietic origin. Isoform 1 and isoform 2 are always found to be
CC coexpressed.
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-553 and Lys-573 targets MPL for degradation
CC by both the lysosomal and proteasomal pathways. The E3 ubiquitin-
CC protein ligase CBL significantly contributes to this ubiquitination.
CC {ECO:0000269|PubMed:19880496}.
CC -!- DISEASE: Congenital amegakaryocytic thrombocytopenia (CAMT)
CC [MIM:604498]: Disease characterized by isolated thrombocytopenia and
CC megakaryocytopenia with no physical anomalies.
CC {ECO:0000269|PubMed:16470591, ECO:0000269|PubMed:25538044}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Thrombocythemia 2 (THCYT2) [MIM:601977]: A myeloproliferative
CC disorder characterized by excessive platelet production, resulting in
CC increased numbers of circulating platelets. It can be associated with
CC spontaneous hemorrhages and thrombotic episodes.
CC {ECO:0000269|PubMed:14764528, ECO:0000269|PubMed:19483125,
CC ECO:0000269|PubMed:23441089, ECO:0000269|PubMed:25538044}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myelofibrosis with myeloid metaplasia (MMM) [MIM:254450]: A
CC chronic myeloproliferative disorder characterized by replacement of the
CC bone marrow by fibrous tissue, extramedullary hematopoiesis, anemia,
CC leukoerythroblastosis and hepatosplenomegaly.
CC {ECO:0000269|PubMed:16834459, ECO:0000269|PubMed:16868251}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-8 is the initiator.
CC {ECO:0000305}.
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DR EMBL; M90102; AAA69971.1; -; mRNA.
DR EMBL; M90103; AAA69972.1; -; mRNA.
DR EMBL; U68162; AAB08424.1; -; Genomic_DNA.
DR EMBL; U68159; AAB08424.1; JOINED; Genomic_DNA.
DR EMBL; U68160; AAB08424.1; JOINED; Genomic_DNA.
DR EMBL; U68161; AAB08424.1; JOINED; Genomic_DNA.
DR EMBL; U68162; AAB08425.1; -; Genomic_DNA.
DR EMBL; U68159; AAB08425.1; JOINED; Genomic_DNA.
DR EMBL; U68160; AAB08425.1; JOINED; Genomic_DNA.
DR EMBL; U68161; AAB08425.1; JOINED; Genomic_DNA.
DR EMBL; AL139289; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07103.1; -; Genomic_DNA.
DR CCDS; CCDS483.1; -. [P40238-1]
DR PIR; A45266; A45266.
DR PIR; B45266; B45266.
DR RefSeq; NP_005364.1; NM_005373.2. [P40238-1]
DR AlphaFoldDB; P40238; -.
DR BioGRID; 110492; 44.
DR DIP; DIP-5730N; -.
DR ELM; P40238; -.
DR IntAct; P40238; 2.
DR STRING; 9606.ENSP00000361548; -.
DR BindingDB; P40238; -.
DR ChEMBL; CHEMBL1864; -.
DR DrugBank; DB11995; Avatrombopag.
DR DrugBank; DB06210; Eltrombopag.
DR DrugBank; DB13125; Lusutrombopag.
DR DrugBank; DB05332; Romiplostim.
DR DrugBank; DB05930; SB-559448.
DR DrugBank; DB06534; Thrombopoietin.
DR DrugCentral; P40238; -.
DR GuidetoPHARMACOLOGY; 1722; -.
DR GlyConnect; 1803; 1 N-Linked glycan (1 site).
DR GlyGen; P40238; 4 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P40238; -.
DR PhosphoSitePlus; P40238; -.
DR BioMuta; MPL; -.
DR DMDM; 730980; -.
DR MassIVE; P40238; -.
DR PaxDb; P40238; -.
DR PeptideAtlas; P40238; -.
DR PRIDE; P40238; -.
DR ProteomicsDB; 55354; -. [P40238-1]
DR ProteomicsDB; 55355; -. [P40238-2]
DR ABCD; P40238; 28 sequenced antibodies.
DR Antibodypedia; 2379; 324 antibodies from 31 providers.
DR DNASU; 4352; -.
DR Ensembl; ENST00000372470.9; ENSP00000361548.3; ENSG00000117400.18. [P40238-1]
DR GeneID; 4352; -.
DR KEGG; hsa:4352; -.
DR MANE-Select; ENST00000372470.9; ENSP00000361548.3; NM_005373.3; NP_005364.1.
DR UCSC; uc001ciw.4; human. [P40238-1]
DR CTD; 4352; -.
DR DisGeNET; 4352; -.
DR GeneCards; MPL; -.
DR HGNC; HGNC:7217; MPL.
DR HPA; ENSG00000117400; Low tissue specificity.
DR MalaCards; MPL; -.
DR MIM; 159530; gene.
DR MIM; 254450; phenotype.
DR MIM; 601977; phenotype.
DR MIM; 604498; phenotype.
DR neXtProt; NX_P40238; -.
DR OpenTargets; ENSG00000117400; -.
DR Orphanet; 3319; Congenital amegakaryocytic thrombocytopenia.
DR Orphanet; 3318; Essential thrombocythemia.
DR Orphanet; 71493; Familial thrombocytosis.
DR Orphanet; 397692; Hereditary isolated aplastic anemia.
DR Orphanet; 729; Polycythemia vera.
DR Orphanet; 824; Primary myelofibrosis.
DR PharmGKB; PA30923; -.
DR VEuPathDB; HostDB:ENSG00000117400; -.
DR eggNOG; ENOG502RYN1; Eukaryota.
DR GeneTree; ENSGT00940000161225; -.
DR HOGENOM; CLU_029931_1_0_1; -.
DR InParanoid; P40238; -.
DR OMA; LPFGTRY; -.
DR OrthoDB; 100680at2759; -.
DR PhylomeDB; P40238; -.
DR TreeFam; TF336573; -.
DR PathwayCommons; P40238; -.
DR Reactome; R-HSA-76009; Platelet Aggregation (Plug Formation).
DR SignaLink; P40238; -.
DR SIGNOR; P40238; -.
DR BioGRID-ORCS; 4352; 15 hits in 1068 CRISPR screens.
DR ChiTaRS; MPL; human.
DR GeneWiki; Thrombopoietin_receptor; -.
DR GenomeRNAi; 4352; -.
DR Pharos; P40238; Tclin.
DR PRO; PR:P40238; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P40238; protein.
DR Bgee; ENSG00000117400; Expressed in mononuclear cell and 98 other tissues.
DR ExpressionAtlas; P40238; baseline and differential.
DR Genevisible; P40238; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0038164; F:thrombopoietin receptor activity; IMP:UniProtKB.
DR GO; GO:1990960; P:basophil homeostasis; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:1990959; P:eosinophil homeostasis; IEA:Ensembl.
DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central.
DR GO; GO:0035702; P:monocyte homeostasis; IEA:Ensembl.
DR GO; GO:0001780; P:neutrophil homeostasis; IEA:Ensembl.
DR GO; GO:0070527; P:platelet aggregation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IEA:Ensembl.
DR GO; GO:1905221; P:positive regulation of platelet formation; IEA:Ensembl.
DR GO; GO:0038163; P:thrombopoietin-mediated signaling pathway; IBA:GO_Central.
DR CDD; cd00063; FN3; 2.
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 Pfam; PF00041; fn3; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF49265; SSF49265; 3.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disease variant; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Isopeptide bond; Membrane; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..635
FT /note="Thrombopoietin receptor"
FT /id="PRO_0000010987"
FT TOPO_DOM 26..491
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 492..513
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 514..635
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 172..281
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 392..486
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 205..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 474..478
FT /note="WSXWS motif"
FT MOTIF 528..536
FT /note="Box 1 motif"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..50
FT /evidence="ECO:0000250"
FT DISULFID 77..93
FT /evidence="ECO:0000250"
FT DISULFID 291..301
FT /evidence="ECO:0000250"
FT DISULFID 323..334
FT /evidence="ECO:0000250"
FT CROSSLNK 553
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19880496"
FT CROSSLNK 573
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT VAR_SEQ 523..579
FT /note="RLRHALWPSLPDLHRVLGQYLRDTAALSPPKATVSDTCEEVEPSLLEILPKS
FT SERTP -> YRPRQAGDWRWTRWSRTCKQAFLVRSVTPDLRPPPVRTYGFALPARHLWD
FT SPRLLTL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1608974"
FT /id="VSP_001734"
FT VAR_SEQ 580..635
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1608974"
FT /id="VSP_001735"
FT VARIANT 39
FT /note="K -> N (associated with thrombocytosis; results in
FT altered MPL expression; dbSNP:rs17292650)"
FT /evidence="ECO:0000269|PubMed:15269348"
FT /id="VAR_049173"
FT VARIANT 58
FT /note="A -> V (in dbSNP:rs6087)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_011988"
FT VARIANT 102
FT /note="R -> C (in CAMT; dbSNP:rs763568293)"
FT /evidence="ECO:0000269|PubMed:16470591"
FT /id="VAR_073030"
FT VARIANT 102
FT /note="R -> P (in CAMT; loss of function; loss of membrane
FT localization, impaired glycosylation; dbSNP:rs28928907)"
FT /evidence="ECO:0000269|PubMed:16470591,
FT ECO:0000269|PubMed:25538044"
FT /id="VAR_073031"
FT VARIANT 104
FT /note="F -> S (in CAMT; loss of function;
FT dbSNP:rs1196161699)"
FT /evidence="ECO:0000269|PubMed:16470591,
FT ECO:0000269|PubMed:25538044"
FT /id="VAR_073032"
FT VARIANT 106
FT /note="P -> L (in THCYT2; gain of function; loss of
FT membrane localization, impaired glycosylation;
FT dbSNP:rs750046020)"
FT /evidence="ECO:0000269|PubMed:25538044"
FT /id="VAR_073033"
FT VARIANT 114
FT /note="V -> M (in dbSNP:rs12731981)"
FT /id="VAR_049174"
FT VARIANT 136
FT /note="P -> L (in CAMT; dbSNP:rs764904424)"
FT /evidence="ECO:0000269|PubMed:16470591"
FT /id="VAR_073034"
FT VARIANT 154
FT /note="W -> R (in CAMT; dbSNP:rs758428763)"
FT /evidence="ECO:0000269|PubMed:16470591"
FT /id="VAR_073035"
FT VARIANT 168
FT /note="E -> K (in dbSNP:rs6088)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_011989"
FT VARIANT 257
FT /note="R -> L (in CAMT)"
FT /evidence="ECO:0000269|PubMed:16470591"
FT /id="VAR_073036"
FT VARIANT 275
FT /note="P -> T (in CAMT; dbSNP:rs28928908)"
FT /evidence="ECO:0000269|PubMed:16470591"
FT /id="VAR_073037"
FT VARIANT 435
FT /note="W -> C (in CAMT; dbSNP:rs1006158872)"
FT /evidence="ECO:0000269|PubMed:16470591"
FT /id="VAR_073038"
FT VARIANT 505
FT /note="S -> N (in THCYT2; activating mutation; induces MPL
FT autonomous dimerization and signal activation in the
FT absence of the ligand; dbSNP:rs121913614)"
FT /evidence="ECO:0000269|PubMed:14764528,
FT ECO:0000269|PubMed:19483125"
FT /id="VAR_067559"
FT VARIANT 515
FT /note="W -> K (in MMM; somatic mutation; requires 2
FT nucleotide substitutions; dbSNP:rs121913616)"
FT /evidence="ECO:0000269|PubMed:16868251"
FT /id="VAR_067560"
FT VARIANT 515
FT /note="W -> L (in THCYT2 and MMM; somatic mutation in
FT myelofibrosis with myeloid metaplasia; results in cytokine-
FT independent growth and thrombopoietin hypersensitivity;
FT results in constitutive activation of JAK-STAT signaling
FT pathway; dbSNP:rs121913615)"
FT /evidence="ECO:0000269|PubMed:16834459,
FT ECO:0000269|PubMed:23441089"
FT /id="VAR_067561"
FT VARIANT 594
FT /note="L -> W (in CAMT; dbSNP:rs1448812001)"
FT /evidence="ECO:0000269|PubMed:16470591"
FT /id="VAR_073039"
SQ SEQUENCE 635 AA; 71245 MW; D25D8D8959359DDC CRC64;
MPSWALFMVT SCLLLAPQNL AQVSSQDVSL LASDSEPLKC FSRTFEDLTC FWDEEEAAPS
GTYQLLYAYP REKPRACPLS SQSMPHFGTR YVCQFPDQEE VRLFFPLHLW VKNVFLNQTR
TQRVLFVDSV GLPAPPSIIK AMGGSQPGEL QISWEEPAPE ISDFLRYELR YGPRDPKNST
GPTVIQLIAT ETCCPALQRP HSASALDQSP CAQPTMPWQD GPKQTSPSRE ASALTAEGGS
CLISGLQPGN SYWLQLRSEP DGISLGGSWG SWSLPVTVDL PGDAVALGLQ CFTLDLKNVT
CQWQQQDHAS SQGFFYHSRA RCCPRDRYPI WENCEEEEKT NPGLQTPQFS RCHFKSRNDS
IIHILVEVTT APGTVHSYLG SPFWIHQAVR LPTPNLHWRE ISSGHLELEW QHPSSWAAQE
TCYQLRYTGE GHQDWKVLEP PLGARGGTLE LRPRSRYRLQ LRARLNGPTY QGPWSSWSDP
TRVETATETA WISLVTALHL VLGLSAVLGL LLLRWQFPAH YRRLRHALWP SLPDLHRVLG
QYLRDTAALS PPKATVSDTC EEVEPSLLEI LPKSSERTPL PLCSSQAQMD YRRLQPSCLG
TMPLSVCPPM AESGSCCTTH IANHSYLPLS YWQQP
