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 27-MAR-2024, entry version 219. 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 CAMT1 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 CAMT1 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: Amegakaryocytic thrombocytopenia, congenital, 1 (CAMT1) CC [MIM:604498]: An autosomal recessive form of congenital amegakaryocytic CC thrombocytopenia, an hematologic disorder characterized by severe CC reduction of megakaryocytes and platelets at birth, and evolving into CC generalized bone marrow aplasia during childhood. 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}. 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; 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 PDB; 8G04; EM; 3.40 A; B/C=26-635. DR PDBsum; 8G04; -. DR AlphaFoldDB; P40238; -. DR EMDB; EMD-29644; -. DR SMR; P40238; -. DR BioGRID; 110492; 45. 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 GlyCosmos; P40238; 4 sites, 1 glycan. 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; 9606-ENSP00000361548; -. DR PeptideAtlas; P40238; -. DR ProteomicsDB; 55354; -. [P40238-1] DR ProteomicsDB; 55355; -. [P40238-2] DR ABCD; P40238; 28 sequenced antibodies. DR Antibodypedia; 2379; 456 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 AGR; HGNC:7217; -. 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; IWEKCEE; -. DR OrthoDB; 5297263at2759; -. 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 1152 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 male germ line stem cell (sensu Vertebrata) in testis and 98 other cell types or tissues. DR ExpressionAtlas; P40238; baseline and differential. 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: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: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:1990959; P:eosinophil homeostasis; IEA:Ensembl. DR GO; GO:0016064; P:immunoglobulin mediated immune response; IBA:GO_Central. DR GO; GO:0035702; P:monocyte homeostasis; IEA:Ensembl. DR GO; GO:0001780; P:neutrophil homeostasis; IEA:Ensembl. 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; 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:SF42; CYTOKINE RECEPTOR COMMON SUBUNIT GAMMA ISOFORM X1-RELATED; 1. DR Pfam; PF09067; EpoR_lig-bind; 1. DR SMART; SM00060; FN3; 2. DR SUPFAM; SSF49265; Fibronectin type III; 3. DR PROSITE; PS50853; FN3; 2. DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1. DR Genevisible; P40238; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; Glycoprotein; Golgi apparatus; Isopeptide bond; Membrane; KW Receptor; Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix; 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 (risk factor for 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 CAMT1; dbSNP:rs763568293)" FT /evidence="ECO:0000269|PubMed:16470591" FT /id="VAR_073030" FT VARIANT 102 FT /note="R -> P (in CAMT1; 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 CAMT1; 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 CAMT1; dbSNP:rs764904424)" FT /evidence="ECO:0000269|PubMed:16470591" FT /id="VAR_073034" FT VARIANT 154 FT /note="W -> R (in CAMT1; 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 CAMT1)" FT /evidence="ECO:0000269|PubMed:16470591" FT /id="VAR_073036" FT VARIANT 275 FT /note="P -> T (in CAMT1; dbSNP:rs28928908)" FT /evidence="ECO:0000269|PubMed:16470591" FT /id="VAR_073037" FT VARIANT 435 FT /note="W -> C (in CAMT1; 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 FT cytokine-independent growth and thrombopoietin FT hypersensitivity; results in constitutive activation of FT JAK-STAT signaling 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 CAMT1; 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 //