Thrombopoietin receptor

Details

Name
Thrombopoietin receptor
Synonyms
  • Myeloproliferative leukemia protein
  • Proto-oncogene c-Mpl
  • TPO-R
  • TPOR
Gene Name
MPL
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006711|Thrombopoietin receptor
MPSWALFMVTSCLLLAPQNLAQVSSQDVSLLASDSEPLKCFSRTFEDLTCFWDEEEAAPS
GTYQLLYAYPREKPRACPLSSQSMPHFGTRYVCQFPDQEEVRLFFPLHLWVKNVFLNQTR
TQRVLFVDSVGLPAPPSIIKAMGGSQPGELQISWEEPAPEISDFLRYELRYGPRDPKNST
GPTVIQLIATETCCPALQRPHSASALDQSPCAQPTMPWQDGPKQTSPSREASALTAEGGS
CLISGLQPGNSYWLQLRSEPDGISLGGSWGSWSLPVTVDLPGDAVALGLQCFTLDLKNVT
CQWQQQDHASSQGFFYHSRARCCPRDRYPIWENCEEEEKTNPGLQTPQFSRCHFKSRNDS
IIHILVEVTTAPGTVHSYLGSPFWIHQAVRLPTPNLHWREISSGHLELEWQHPSSWAAQE
TCYQLRYTGEGHQDWKVLEPPLGARGGTLELRPRSRYRLQLRARLNGPTYQGPWSSWSDP
TRVETATETAWISLVTALHLVLGLSAVLGLLLLRWQFPAHYRRLRHALWPSLPDLHRVLG
QYLRDTAALSPPKATVSDTCEEVEPSLLEILPKSSERTPLPLCSSQAQMDYRRLQPSCLG
TMPLSVCPPMAESGSCCTTHIANHSYLPLSYWQQP
Number of residues
635
Molecular Weight
71244.08
Theoretical pI
6.46
GO Classification
Functions
thrombopoietin receptor activity / transmembrane signaling receptor activity
Processes
blood coagulation / cell proliferation / cell surface receptor signaling pathway / definitive hemopoiesis / homeostasis of number of cells / negative regulation of apoptotic process / platelet activation / platelet formation / positive regulation of gene expression / regulation of chemokine production / regulation of stem cell division / regulation of stem cell proliferation / thrombopoietin-mediated signaling pathway
Components
cell surface / Golgi apparatus / integral component of plasma membrane / plasma membrane
General Function
Transmembrane signaling receptor activity
Specific Function
Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.
Pfam Domain Function
Transmembrane Regions
492-513
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0012407|Thrombopoietin receptor (MPL)
ATGCCCTCCTGGGCCCTCTTCATGGTCACCTCCTGCCTCCTCCTGGCCCCTCAAAACCTG
GCCCAAGTCAGCAGCCAAGATGTCTCCTTGCTGGCATCAGACTCAGAGCCCCTGAAGTGT
TTCTCCCGAACATTTGAGGACCTCACTTGCTTCTGGGATGAGGAAGAGGCAGCGCCCAGT
GGGACATACCAGCTGCTGTATGCCTACCCGCGGGAGAAGCCCCGTGCTTGCCCCCTGAGT
TCCCAGAGCATGCCCCACTTTGGAACCCGATACGTGTGCCAGTTTCCAGACCAGGAGGAA
GTGCGTCTCTTCTTTCCGCTGCACCTCTGGGTGAAGAATGTGTTCCTAAACCAGACTCGG
ACTCAGCGAGTCCTCTTTGTGGACAGTGTAGGCCTGCCGGCTCCCCCCAGTATCATCAAG
GCCATGGGTGGGAGCCAGCCAGGGGAACTTCAGATCAGCTGGGAGGAGCCAGCTCCAGAA
ATCAGTGATTTCCTGAGGTACGAACTCCGCTATGGCCCCAGAGATCCCAAGAACTCCACT
GGTCCCACGGTCATACAGCTGATTGCCACAGAAACCTGCTGCCCTGCTCTGCAGAGGCCT
CACTCAGCCTCTGCTCTGGACCAGTCTCCATGTGCTCAGCCCACAATGCCCTGGCAAGAT
GGACCAAAGCAGACCTCCCCAAGTAGAGAAGCTTCAGCTCTGACAGCAGAGGGTGGAAGC
TGCCTCATCTCAGGACTCCAGCCTGGCAACTCCTACTGGCTGCAGCTGCGCAGCGAACCT
GATGGGATCTCCCTCGGTGGCTCCTGGGGATCCTGGTCCCTCCCTGTGACTGTGGACCTG
CCTGGAGATGCAGTGGCACTTGGACTGCAATGCTTTACCTTGGACCTGAAGAATGTTACC
TGTCAATGGCAGCAACAGGACCATGCTAGCTCCCAAGGCTTCTTCTACCACAGCAGGGCA
CGGTGCTGCCCCAGAGACAGGTACCCCATCTGGGAGAACTGCGAAGAGGAAGAGAAAACA
AATCCAGGACTACAGACCCCACAGTTCTCTCGCTGCCACTTCAAGTCACGAAATGACAGC
ATTATTCACATCCTTGTGGAGGTGACCACAGCCCCGGGTACTGTTCACAGCTACCTGGGC
TCCCCTTTCTGGATCCACCAGGCTGTGCGCCTCCCCACCCCAAACTTGCACTGGAGGGAG
ATCTCCAGTGGGCATCTGGAATTGGAGTGGCAGCACCCATCGTCCTGGGCAGCCCAAGAG
ACCTGTTATCAACTCCGATACACAGGAGAAGGCCATCAGGACTGGAAGGTGCTGGAGCCG
CCTCTCGGGGCCCGAGGAGGGACCCTGGAGCTGCGCCCGCGATCTCGCTACCGTTTACAG
CTGCGCGCCAGGCTCAACGGCCCCACCTACCAAGGTCCCTGGAGCTCGTGGTCGGACCCA
ACTAGGGTGGAGACCGCCACCGAGACCGCCTGGATCTCCTTGGTGACCGCTCTGCATCTA
GTGCTGGGCCTCAGCGCCGTCCTGGGCCTGCTGCTGCTGAGGTGGCAGTTTCCTGCACAC
TACAGGAGACTGAGGCATGCCCTGTGGCCCTCACTTCCAGACCTGCACCGGGTCCTAGGC
CAGTACCTTAGGGACACTGCAGCCCTGAGCCCGCCCAAGGCCACAGTCTCAGATACCTGT
GAAGAAGTGGAACCCAGCCTCCTTGAAATCCTCCCCAAGTCCTCAGAGAGGACTCCTTTG
CCCCTGTGTTCCTCCCAGGCCCAGATGGACTACCGAAGATTGCAGCCTTCTTGCCTGGGG
ACCATGCCCCTGTCTGTGTGCCCACCCATGGCTGAGTCAGGGTCCTGCTGTACCACCCAC
ATTGCCAACCATTCCTACCTACCACTAAGCTATTGGCAGCAGCCTTGA
Chromosome Location
1
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP40238
UniProtKB Entry NameTPOR_HUMAN
GenBank Gene IDM90102
GenAtlas IDMPL
HGNC IDHGNC:7217
General References
  1. Vigon I, Mornon JP, Cocault L, Mitjavila MT, Tambourin P, Gisselbrecht S, Souyri M: Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5640-4. [PubMed:1608974]
  2. Mignotte V, Vigon I, Boucher de Crevecoeur E, Romeo PH, Lemarchandel V, Chretien S: Structure and transcription of the human c-mpl gene (MPL). Genomics. 1994 Mar 1;20(1):5-12. [PubMed:8020956]
  3. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414]
  4. Saur SJ, Sangkhae V, Geddis AE, Kaushansky K, Hitchcock IS: Ubiquitination and degradation of the thrombopoietin receptor c-Mpl. Blood. 2010 Feb 11;115(6):1254-63. doi: 10.1182/blood-2009-06-227033. Epub 2009 Oct 30. [PubMed:19880496]
  5. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed:10391209]
  6. Meunier C, Bordereaux D, Porteu F, Gisselbrecht S, Chretien S, Courtois G: Cloning and characterization of a family of proteins associated with Mpl. J Biol Chem. 2002 Mar 15;277(11):9139-47. Epub 2002 Jan 9. [PubMed:11784712]
  7. Ding J, Komatsu H, Wakita A, Kato-Uranishi M, Ito M, Satoh A, Tsuboi K, Nitta M, Miyazaki H, Iida S, Ueda R: Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood. 2004 Jun 1;103(11):4198-200. Epub 2004 Feb 5. [PubMed:14764528]
  8. Moliterno AR, Williams DM, Gutierrez-Alamillo LI, Salvatori R, Ingersoll RG, Spivak JL: Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11444-7. Epub 2004 Jul 21. [PubMed:15269348]
  9. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, Steensma DP, Elliott MA, Wolanskyj AP, Hogan WJ, McClure RF, Litzow MR, Gilliland DG, Tefferi A: MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006 Nov 15;108(10):3472-6. Epub 2006 Jul 25. [PubMed:16868251]
  10. Germeshausen M, Ballmaier M, Welte K: MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease. Hum Mutat. 2006 Mar;27(3):296. [PubMed:16470591]
  11. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, Cuker A, Wernig G, Moore S, Galinsky I, DeAngelo DJ, Clark JJ, Lee SJ, Golub TR, Wadleigh M, Gilliland DG, Levine RL: MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006 Jul;3(7):e270. [PubMed:16834459]
  12. Ding J, Komatsu H, Iida S, Yano H, Kusumoto S, Inagaki A, Mori F, Ri M, Ito A, Wakita A, Ishida T, Nitta M, Ueda R: The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity. Blood. 2009 Oct 8;114(15):3325-8. doi: 10.1182/blood-2008-04-149047. Epub 2009 May 29. [PubMed:19483125]
  13. Farruggia P, D'Angelo P, La Rosa M, Scibetta N, Santangelo G, Lo Bello A, Duner E, Randi ML, Putti MC, Santoro A: MPL W515L mutation in pediatric essential thrombocythemia. Pediatr Blood Cancer. 2013 Aug;60(8):E52-4. doi: 10.1002/pbc.24500. Epub 2013 Feb 25. [PubMed:23441089]
  14. Stockklausner C, Klotter AC, Dickemann N, Kuhlee IN, Duffert CM, Kerber C, Gehring NH, Kulozik AE: The thrombopoietin receptor P106L mutation functionally separates receptor signaling activity from thrombopoietin homeostasis. Blood. 2015 Feb 12;125(7):1159-69. doi: 10.1182/blood-2014-07-587170. Epub 2014 Dec 23. [PubMed:25538044]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05930SB-559448investigationalunknownDetails
DB06210EltrombopagapprovedunknownagonistDetails
DB06534ThrombopoietininvestigationalunknownDetails
DB05332RomiplostimapprovedyesagonistDetails
DB11995Avatrombopagapproved, investigationalyesagonistDetails
DB13125Lusutrombopagapproved, investigationalyesagonistDetails