Macrophage-stimulating protein receptor

Details

Name
Macrophage-stimulating protein receptor
Synonyms
  • 2.7.10.1
  • CDw136
  • MSP receptor
  • p185-Ron
  • Protein-tyrosine kinase 8
  • PTK8
  • RON
Gene Name
MST1R
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051858|Macrophage-stimulating protein receptor
MELLPPLPQSFLLLLLLPAKPAAGEDWQCPRTPYAASRDFDVKYVVPSFSAGGLVQAMVT
YEGDRNESAVFVAIRNRLHVLGPDLKSVQSLATGPAGDPGCQTCAACGPGPHGPPGDTDT
KVLVLDPALPALVSCGSSLQGRCFLHDLEPQGTAVHLAAPACLFSAHHNRPDDCPDCVAS
PLGTRVTVVEQGQASYFYVASSLDAAVAASFSPRSVSIRRLKADASGFAPGFVALSVLPK
HLVSYSIEYVHSFHTGAFVYFLTVQPASVTDDPSALHTRLARLSATEPELGDYRELVLDC
RFAPKRRRRGAPEGGQPYPVLRVAHSAPVGAQLATELSIAEGQEVLFGVFVTGKDGGPGV
GPNSVVCAFPIDLLDTLIDEGVERCCESPVHPGLRRGLDFFQSPSFCPNPPGLEALSPNT
SCRHFPLLVSSSFSRVDLFNGLLGPVQVTALYVTRLDNVTVAHMGTMDGRILQVELVRSL
NYLLYVSNFSLGDSGQPVQRDVSRLGDHLLFASGDQVFQVPIQGPGCRHFLTCGRCLRAW
HFMGCGWCGNMCGQQKECPGSWQQDHCPPKLTEFHPHSGPLRGSTRLTLCGSNFYLHPSG
LVPEGTHQVTVGQSPCRPLPKDSSKLRPVPRKDFVEEFECELEPLGTQAVGPTNVSLTVT
NMPPGKHFRVDGTSVLRGFSFMEPVLIAVQPLFGPRAGGTCLTLEGQSLSVGTSRAVLVN
GTECLLARVSEGQLLCATPPGATVASVPLSLQVGGAQVPGSWTFQYREDPVVLSISPNCG
YINSHITICGQHLTSAWHLVLSFHDGLRAVESRCERQLPEQQLCRLPEYVVRDPQGWVAG
NLSARGDGAAGFTLPGFRFLPPPHPPSANLVPLKPEEHAIKFEYIGLGAVADCVGINVTV
GGESCQHEFRGDMVVCPLPPSLQLGQDGAPLQVCVDGECHILGRVVRPGPDGVPQSTLLG
ILLPLLLLVAALATALVFSYWWRRKQLVLPPNLNDLASLDQTAGATPLPILYSGSDYRSG
LALPAIDGLDSTTCVHGASFSDSEDESCVPLLRKESIQLRDLDSALLAEVKDVLIPHERV
VTHSDRVIGKGHFGVVYHGEYIDQAQNRIQCAIKSLSRITEMQQVEAFLREGLLMRGLNH
PNVLALIGIMLPPEGLPHVLLPYMCHGDLLQFIRSPQRNPTVKDLISFGLQVARGMEYLA
EQKFVHRDLAARNCMLDESFTVKVADFGLARDILDREYYSVQQHRHARLPVKWMALESLQ
TYRFTTKSDVWSFGVLLWELLTRGAPPYRHIDPFDLTHFLAQGRRLPQPEYCPDSLYQVM
QQCWEADPAVRPTFRVLVGEVEQIVSALLGDHYVQLPATYMNLGPSTSHEMNVRPEQPQF
SPMPGNVRRPRPLSEPPRPT
Number of residues
1400
Molecular Weight
152240.095
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / enzyme binding / macrophage colony-stimulating factor receptor activity
Processes
defense response / hepatocyte growth factor receptor signaling pathway / innate immune response / positive regulation of cell proliferation / positive regulation of MAP kinase activity / positive regulation of protein kinase B signaling / response to virus / signal transduction / single fertilization
Components
cell surface / integral component of plasma membrane / plasma membrane / stress fiber / vacuole
General Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
958-978
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0051859|Macrophage-stimulating protein receptor (MST1R)
ATGGAGCTCCTCCCGCCGCTGCCTCAGTCCTTCCTGTTGCTGCTGCTGTTGCCTGCCAAG
CCCGCGGCGGGCGAGGACTGGCAGTGCCCGCGCACCCCCTACGCGGCCTCTCGCGACTTT
GACGTGAAGTACGTGGTGCCCAGCTTCTCCGCCGGAGGCCTGGTACAGGCCATGGTGACC
TACGAGGGCGACAGAAATGAGAGTGCTGTGTTTGTAGCCATACGCAATCGCCTGCATGTG
CTTGGGCCTGACCTGAAGTCTGTCCAGAGCCTGGCCACGGGCCCTGCTGGAGACCCTGGC
TGCCAGACGTGTGCAGCCTGTGGCCCAGGACCCCACGGCCCTCCCGGTGACACAGACACA
AAGGTGCTGGTGCTGGATCCCGCGCTGCCTGCGCTGGTCAGTTGTGGCTCCAGCCTGCAG
GGCCGCTGCTTCCTGCATGACCTAGAGCCCCAAGGGACAGCCGTGCATCTGGCAGCGCCA
GCCTGCCTCTTCTCAGCCCACCATAACCGGCCCGATGACTGCCCCGACTGTGTGGCCAGC
CCATTGGGCACCCGTGTAACTGTGGTTGAGCAAGGCCAGGCCTCCTATTTCTACGTGGCA
TCCTCACTGGACGCAGCCGTGGCTGCCAGCTTCAGCCCACGCTCAGTGTCTATCAGGCGT
CTCAAGGCTGACGCCTCGGGATTCGCACCGGGCTTTGTGGCGTTGTCAGTGCTGCCCAAG
CATCTTGTCTCCTACAGTATTGAATACGTGCACAGCTTCCACACGGGAGCCTTCGTATAC
TTCCTGACTGTACAGCCGGCCAGCGTGACAGATGATCCTAGTGCCCTGCACACACGCCTG
GCACGGCTTAGCGCCACTGAGCCAGAGTTGGGTGACTATCGGGAGCTGGTCCTCGACTGC
AGATTTGCTCCAAAACGCAGGCGCCGGGGGGCCCCAGAAGGCGGACAGCCCTACCCTGTG
CTGCGGGTGGCCCACTCCGCTCCAGTGGGTGCCCAACTTGCCACTGAGCTGAGCATCGCC
GAGGGCCAGGAAGTACTATTTGGGGTCTTTGTGACTGGCAAGGATGGTGGTCCTGGCGTG
GGCCCCAACTCTGTCGTCTGTGCCTTCCCCATTGACCTGCTGGACACACTAATTGATGAG
GGTGTGGAGCGCTGTTGTGAATCCCCAGTCCATCCAGGCCTCCGGCGAGGCCTCGACTTC
TTCCAGTCGCCCAGTTTTTGCCCCAACCCGCCTGGCCTGGAAGCCCTCAGCCCCAACACC
AGCTGCCGCCACTTCCCTCTGCTGGTCAGTAGCAGCTTCTCACGTGTGGACCTATTCAAT
GGGCTGTTGGGACCAGTACAGGTCACTGCATTGTATGTGACACGCCTTGACAACGTCACA
GTGGCACACATGGGCACAATGGATGGGCGTATCCTGCAGGTGGAGCTGGTCAGGTCACTA
AACTACTTGCTGTATGTGTCCAACTTCTCACTGGGTGACAGTGGGCAGCCCGTGCAGCGG
GATGTCAGTCGTCTTGGGGACCACCTACTCTTTGCCTCTGGGGACCAGGTTTTCCAGGTA
CCTATCCAAGGCCCTGGCTGCCGCCACTTCCTGACCTGTGGGCGTTGCCTAAGGGCATGG
CATTTCATGGGCTGTGGCTGGTGTGGGAACATGTGCGGCCAGCAGAAGGAGTGTCCTGGC
TCCTGGCAACAGGACCACTGCCCACCTAAGCTTACTGAGTTCCACCCCCACAGTGGACCT
CTAAGGGGCAGTACAAGGCTGACCCTGTGTGGCTCCAACTTCTACCTTCACCCTTCTGGT
CTGGTGCCTGAGGGAACCCATCAGGTCACTGTGGGCCAAAGTCCCTGCCGGCCACTGCCC
AAGGACAGCTCAAAACTCAGACCAGTGCCCCGGAAAGACTTTGTAGAGGAGTTTGAGTGT
GAACTGGAGCCCTTGGGCACCCAGGCAGTGGGGCCTACCAACGTCAGCCTCACCGTGACT
AACATGCCACCGGGCAAGCACTTCCGGGTAGACGGCACCTCCGTGCTGAGAGGCTTCTCT
TTCATGGAGCCAGTGCTGATAGCAGTGCAACCCCTCTTTGGCCCACGGGCAGGAGGCACC
TGTCTCACTCTTGAAGGCCAGAGTCTGTCTGTAGGCACCAGCCGGGCTGTGCTGGTCAAT
GGGACTGAGTGTCTGCTAGCACGGGTCAGTGAGGGGCAGCTTTTATGTGCCACACCCCCT
GGGGCCACGGTGGCCAGTGTCCCCCTTAGCCTGCAGGTGGGGGGTGCCCAGGTACCTGGT
TCCTGGACCTTCCAGTACAGAGAAGACCCTGTCGTGCTAAGCATCAGCCCCAACTGTGGC
TACATCAACTCCCACATCACCATCTGTGGCCAGCATCTAACTTCAGCATGGCACTTAGTG
CTGTCATTCCATGACGGGCTTAGGGCAGTGGAAAGCAGGTGTGAGAGGCAGCTTCCAGAG
CAGCAGCTGTGCCGCCTTCCTGAATATGTGGTCCGAGACCCCCAGGGATGGGTGGCAGGG
AATCTGAGTGCCCGAGGGGATGGAGCTGCTGGCTTTACACTGCCTGGCTTTCGCTTCCTA
CCCCCACCCCATCCACCCAGTGCCAACCTAGTTCCACTGAAGCCTGAGGAGCATGCCATT
AAGTTTGAGTATATTGGGCTGGGCGCTGTGGCTGACTGTGTGGGTATCAACGTGACCGTG
GGTGGTGAGAGCTGCCAGCACGAGTTCCGGGGGGACATGGTTGTCTGCCCCCTGCCCCCA
TCCCTGCAGCTTGGCCAGGATGGTGCCCCATTGCAGGTCTGCGTAGATGGTGAATGTCAT
ATCCTGGGTAGAGTGGTGCGGCCAGGGCCAGATGGGGTCCCACAGAGCACGCTCCTTGGT
ATCCTGCTGCCTTTGCTGCTGCTTGTGGCTGCACTGGCGACTGCACTGGTCTTCAGCTAC
TGGTGGCGGAGGAAGCAGCTAGTTCTTCCTCCCAACCTGAATGACCTGGCATCCCTGGAC
CAGACTGCTGGAGCCACACCCCTGCCTATTCTGTACTCGGGCTCTGACTACAGAAGTGGC
CTTGCACTCCCTGCCATTGATGGTCTGGATTCCACCACTTGTGTCCATGGAGCATCCTTC
TCCGATAGTGAAGATGAATCCTGTGTGCCACTGCTGCGGAAAGAGTCCATCCAGCTAAGG
GACCTGGACTCTGCGCTCTTGGCTGAGGTCAAGGATGTGCTGATTCCCCATGAGCGGGTG
GTCACCCACAGTGACCGAGTCATTGGCAAAGGCCACTTTGGAGTTGTCTACCACGGAGAA
TACATAGACCAGGCCCAGAATCGAATCCAATGTGCCATCAAGTCACTAAGTCGCATCACA
GAGATGCAGCAGGTGGAGGCCTTCCTGCGAGAGGGGCTGCTCATGCGTGGCCTGAACCAC
CCGAATGTGCTGGCTCTCATTGGTATCATGTTGCCACCTGAGGGCCTGCCCCATGTGCTG
CTGCCCTATATGTGCCACGGTGACCTGCTCCAGTTCATCCGCTCACCTCAGCGGAACCCC
ACCGTGAAGGACCTCATCAGCTTTGGCCTGCAGGTAGCCCGCGGCATGGAGTACCTGGCA
GAGCAGAAGTTTGTGCACAGGGACCTGGCTGCGCGGAACTGCATGCTGGACGAGTCATTC
ACAGTCAAGGTGGCTGACTTTGGTTTGGCCCGCGACATCCTGGACAGGGAGTACTATAGT
GTTCAACAGCATCGCCACGCTCGCCTACCTGTGAAGTGGATGGCGCTGGAGAGCCTGCAG
ACCTATAGATTTACCACCAAGTCTGATGTGTGGTCATTTGGTGTGCTGCTGTGGGAACTG
CTGACACGGGGTGCCCCACCATACCGCCACATTGACCCTTTTGACCTTACCCACTTCCTG
GCCCAGGGTCGGCGCCTGCCCCAGCCTGAGTATTGCCCTGATTCTCTGTACCAAGTGATG
CAGCAATGCTGGGAGGCAGACCCAGCAGTGCGACCCACCTTCAGAGTACTAGTGGGGGAG
GTGGAGCAGATAGTGTCTGCACTGCTTGGGGACCATTATGTGCAGCTGCCAGCAACCTAC
ATGAACTTGGGCCCCAGCACCTCGCATGAGATGAATGTGCGTCCAGAACAGCCGCAGTTC
TCACCCATGCCAGGGAATGTACGCCGGCCCCGGCCACTCTCAGAGCCTCCTCGGCCCACT
TGA
Chromosome Location
3
Locus
3p21.31
External Identifiers
ResourceLink
UniProtKB IDQ04912
UniProtKB Entry NameRON_HUMAN
HGNC IDHGNC:7381
General References
  1. Ronsin C, Muscatelli F, Mattei MG, Breathnach R: A novel putative receptor protein tyrosine kinase of the met family. Oncogene. 1993 May;8(5):1195-202. [Article]
  2. Collesi C, Santoro MM, Gaudino G, Comoglio PM: A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. Mol Cell Biol. 1996 Oct;16(10):5518-26. [Article]
  3. Jin P, Zhang J, Sumariwalla PF, Ni I, Jorgensen B, Crawford D, Phillips S, Feldmann M, Shepard HM, Paleolog EM: Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res Ther. 2008;10(4):R73. doi: 10.1186/ar2447. Epub 2008 Jul 1. [Article]
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  5. Ponzetto C, Bardelli A, Maina F, Longati P, Panayotou G, Dhand R, Waterfield MD, Comoglio PM: A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor. Mol Cell Biol. 1993 Aug;13(8):4600-8. [Article]
  6. Gaudino G, Follenzi A, Naldini L, Collesi C, Santoro M, Gallo KA, Godowski PJ, Comoglio PM: RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J. 1994 Aug 1;13(15):3524-32. [Article]
  7. Wang MH, Ronsin C, Gesnel MC, Coupey L, Skeel A, Leonard EJ, Breathnach R: Identification of the ron gene product as the receptor for the human macrophage stimulating protein. Science. 1994 Oct 7;266(5182):117-9. [Article]
  8. Nanney LB, Skeel A, Luan J, Polis S, Richmond A, Wang MH, Leonard EJ: Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury. J Invest Dermatol. 1998 Oct;111(4):573-81. doi: 10.1046/j.1523-1747.1998.00332.x. [Article]
  9. Danilkovitch A, Skeel A, Leonard EJ: Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism. Exp Cell Res. 1999 May 1;248(2):575-82. doi: 10.1006/excr.1999.4429. [Article]
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  11. Wang MH, Zhou YQ, Chen YQ: Macrophage-stimulating protein and RON receptor tyrosine kinase: potential regulators of macrophage inflammatory activities. Scand J Immunol. 2002 Dec;56(6):545-53. [Article]
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  20. Chao KL, Tsai IW, Chen C, Herzberg O: Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase. PLoS One. 2012;7(7):e41912. doi: 10.1371/journal.pone.0041912. Epub 2012 Jul 25. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails