ID RON_HUMAN Reviewed; 1400 AA. AC Q04912; B5A944; B5A945; B5A946; B5A947; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 20-APR-2010, sequence version 2. DT 03-APR-2013, entry version 143. DE RecName: Full=Macrophage-stimulating protein receptor; DE Short=MSP receptor; DE EC=2.7.10.1; DE AltName: Full=CDw136; DE AltName: Full=Protein-tyrosine kinase 8; DE AltName: Full=p185-Ron; DE AltName: CD_antigen=CD136; DE Contains: DE RecName: Full=Macrophage-stimulating protein receptor alpha chain; DE Contains: DE RecName: Full=Macrophage-stimulating protein receptor beta chain; DE Flags: Precursor; GN Name=MST1R; Synonyms=PTK8, RON; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM RON), AND VARIANTS GLN-322; RP ARG-523 AND GLY-1195. RC TISSUE=Keratinocyte; RX PubMed=8386824; RA Ronsin C., Muscatelli F., Mattei M.-G., Breathnach R.; RT "A novel putative receptor protein tyrosine kinase of the met RT family."; RL Oncogene 8:1195-1202(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING. RX PubMed=8816464; RA Collesi C., Santoro M.M., Gaudino G., Comoglio P.M.; RT "A splicing variant of the RON transcript induces constitutive RT tyrosine kinase activity and an invasive phenotype."; RL Mol. Cell. Biol. 16:5518-5526(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS RON-1; RON-2; RON-3 AND RON-4). RX PubMed=18593464; DOI=10.1186/ar2447; RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.; RT "Novel splice variants derived from the receptor tyrosine kinase RT superfamily are potential therapeutics for rheumatoid arthritis."; RL Arthritis Res. Ther. 10:R73-R73(2008). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [5] RP INTERACTION WITH PIK3R1. RX PubMed=7687741; RA Ponzetto C., Bardelli A., Maina F., Longati P., Panayotou G., RA Dhand R., Waterfield M.D., Comoglio P.M.; RT "A novel recognition motif for phosphatidylinositol 3-kinase binding RT mediates its association with the hepatocyte growth factor/scatter RT factor receptor."; RL Mol. Cell. Biol. 13:4600-4608(1993). RN [6] RP TISSUE SPECIFICITY. RX PubMed=8062829; RA Gaudino G., Follenzi A., Naldini L., Collesi C., Santoro M., RA Gallo K.A., Godowski P.J., Comoglio P.M.; RT "RON is a heterodimeric tyrosine kinase receptor activated by the HGF RT homologue MSP."; RL EMBO J. 13:3524-3532(1994). RN [7] RP FUNCTION. RX PubMed=7939629; DOI=10.1126/science.7939629; RA Wang M.-H., Ronsin C., Gesnel M.-C., Coupey L., Skeel A., RA Leonard E.J., Breatnach R.; RT "Identification of the ron gene product as the receptor for the human RT macrophage stimulating protein."; RL Science 266:117-119(1994). RN [8] RP FUNCTION IN WOUND HEALING RESPONSE. RX PubMed=9764835; DOI=10.1046/j.1523-1747.1998.00332.x; RA Nanney L.B., Skeel A., Luan J., Polis S., Richmond A., Wang M.H., RA Leonard E.J.; RT "Proteolytic cleavage and activation of pro-macrophage-stimulating RT protein and upregulation of its receptor in tissue injury."; RL J. Invest. Dermatol. 111:573-581(1998). RN [9] RP INTERACTION WITH ITGB1. RX PubMed=10222149; DOI=10.1006/excr.1999.4429; RA Danilkovitch A., Skeel A., Leonard E.J.; RT "Macrophage stimulating protein-induced epithelial cell adhesion is RT mediated by a PI3-K-dependent, but FAK-independent mechanism."; RL Exp. Cell Res. 248:575-582(1999). RN [10] RP INTERACTION WITH MST1. RX PubMed=10514476; DOI=10.1074/jbc.274.42.29937; RA Danilkovitch A., Miller M., Leonard E.J.; RT "Interaction of macrophage-stimulating protein with its receptor. RT Residues critical for beta chain binding and evidence for independent RT alpha chain binding."; RL J. Biol. Chem. 274:29937-29943(1999). RN [11] RP REVIEW ON FUNCTION. RX PubMed=12472665; DOI=10.1046/j.1365-3083.2002.01177.x; RA Wang M.H., Zhou Y.Q., Chen Y.Q.; RT "Macrophage-stimulating protein and RON receptor tyrosine kinase: RT potential regulators of macrophage inflammatory activities."; RL Scand. J. Immunol. 56:545-553(2002). RN [12] RP UBIQUITINATION. RX PubMed=12802274; DOI=10.1038/sj.onc.1206585; RA Penengo L., Rubin C., Yarden Y., Gaudino G.; RT "c-Cbl is a critical modulator of the Ron tyrosine kinase receptor."; RL Oncogene 22:3669-3679(2003). RN [13] RP INTERACTION WITH HYAL2. RX PubMed=12676986; DOI=10.1073/pnas.0837136100; RA Danilkovitch-Miagkova A., Duh F.-M., Kuzmin I., Angeloni D., RA Liu S.-L., Miller A.D., Lerman M.I.; RT "Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and RT mediates transformation of epithelial cells by jaagsiekte sheep RT retrovirus."; RL Proc. Natl. Acad. Sci. U.S.A. 100:4580-4585(2003). RN [14] RP INTERACTION WITH PLXNB1. RX PubMed=15184888; DOI=10.1038/sj.onc.1207650; RA Conrotto P., Corso S., Gamberini S., Comoglio P.M., Giordano S.; RT "Interplay between scatter factor receptors and B plexins controls RT invasive growth."; RL Oncogene 23:5131-5137(2004). RN [15] RP AUTOPHOSPHORYLATION, AND ENZYME REGULATION. RX PubMed=15632155; DOI=10.1074/jbc.M412623200; RA Yokoyama N., Ischenko I., Hayman M.J., Miller W.T.; RT "The C terminus of RON tyrosine kinase plays an autoinhibitory role."; RL J. Biol. Chem. 280:8893-8900(2005). RN [16] RP FUNCTION. RX PubMed=18836480; DOI=10.1038/onc.2008.383; RA Feres K.J., Ischenko I., Hayman M.J.; RT "The RON receptor tyrosine kinase promotes MSP-independent cell RT spreading and survival in breast epithelial cells."; RL Oncogene 28:279-288(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP INTERACTION WITH GAB1 AND GRB2. RX PubMed=21784853; DOI=10.1074/jbc.M111.239384; RA Chaudhuri A., Xie M.H., Yang B., Mahapatra K., Liu J., Marsters S., RA Bodepudi S., Ashkenazi A.; RT "Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal RT transduction by the related receptor tyrosine kinases RON and MET."; RL J. Biol. Chem. 286:32762-32774(2011). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 1060-1357 IN COMPLEX WITH RP AMP-PNP AND MAGNESIUM, ACTIVE SITE, AND PHOSPHORYLATION AT TYR-1238. RX PubMed=20726546; DOI=10.1021/bi100409w; RA Wang J., Steinbacher S., Augustin M., Schreiner P., Epstein D., RA Mulvihill M.J., Crew A.P.; RT "The crystal structure of a constitutively active mutant RON kinase RT suggests an intramolecular autophosphorylation hypothesis."; RL Biochemistry 49:7972-7974(2010). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 42-568, GLYCOSYLATION AT RP ASN-488, AND DISULFIDE BONDS. RX PubMed=22848655; DOI=10.1371/journal.pone.0041912; RA Chao K.L., Tsai I.W., Chen C., Herzberg O.; RT "Crystal structure of the Sema-PSI extracellular domain of human RON RT receptor tyrosine kinase."; RL PLoS ONE 7:E41912-E41912(2012). RN [21] RP VARIANTS [LARGE SCALE ANALYSIS] SER-75; THR-95; CYS-185; GLN-322; RP ASP-356; LEU-434; ASP-465; CYS-504; ARG-523; PRO-613; MET-900; RP GLY-1304; GLY-1335 AND CYS-1360. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Receptor tyrosine kinase that transduces signals from CC the extracellular matrix into the cytoplasm by binding to MST1 CC ligand. Regulates many physiological processes including cell CC survival, migration and differentiation. Ligand binding at the CC cell surface induces autophosphorylation of RON on its CC intracellular domain that provides docking sites for downstream CC signaling molecules. Following activation by ligand, interacts CC with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. CC Recruitment of these downstream effectors by RON leads to the CC activation of several signaling cascades including the RAS-ERK, CC PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound CC healing response by promoting epithelial cell migration, CC proliferation as well as survival at the wound site. Plays also a CC role in the innate immune response by regulating the migration and CC phagocytic activity of macrophages. Alternatively, RON can also CC promote signals such as cell migration and proliferation in CC response to growth factors other than MST1 ligand. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- ENZYME REGULATION: In its inactive state, the C-terminal tail CC interacts with the catalytic domain and inhibits the kinase CC activity. Upon ligand binding, the C-terminal tail is displaced CC and becomes phosphorylated, thus increasing the kinase activity. CC -!- SUBUNIT: Heterodimer of an alpha chain and a beta chain which are CC disulfide linked. Binds PLXNB1. Associates with and is negatively CC regulated by HYAL2. Interacts when phosphorylated with downstream CC effectors including PIK3R1, PCLG1, GRB2 and GAB1. Interacts with CC integrin beta1/ITGB1 in a ligand-independent fashion. CC -!- INTERACTION: CC O43157:PLXNB1; NbExp=3; IntAct=EBI-2637518, EBI-1111488; CC O15031:PLXNB2; NbExp=2; IntAct=EBI-2637518, EBI-722004; CC Q9ULL4:PLXNB3; NbExp=2; IntAct=EBI-2637518, EBI-311073; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=RON; CC IsoId=Q04912-1; Sequence=Displayed; CC Name=Delta-RON; CC IsoId=Q04912-2; Sequence=VSP_005007; CC Note=Lacks part of the extracellular domain, oligomerizes and is CC constitutively activated; CC Name=RON-1; CC IsoId=Q04912-3; Sequence=VSP_038920, VSP_038921; CC Name=RON-2; CC IsoId=Q04912-4; Sequence=VSP_038919, VSP_038922, VSP_038923; CC Name=RON-3; CC IsoId=Q04912-5; Sequence=VSP_038924, VSP_038925; CC Name=RON-4; CC IsoId=Q04912-6; Sequence=VSP_038922, VSP_038923; CC -!- TISSUE SPECIFICITY: Expressed in colon, skin, lung and bone CC marrow. CC -!- PTM: Proteolytic processing yields the two subunits. CC -!- PTM: Autophosphorylated in response to ligand binding on Tyr-1238 CC and Tyr-1239 in the kinase domain leading to further CC phosphorylation of Tyr-1353 and Tyr-1360 in the C-terminal CC multifunctional docking site. CC -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor CC stability and activity through proteasomal degradation. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CC -!- SIMILARITY: Contains 3 IPT/TIG domains. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 Sema domain. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/RONID287.html"; 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; X70040; CAA49634.1; -; mRNA. DR EMBL; EU826582; ACF47618.1; -; mRNA. DR EMBL; EU826583; ACF47619.1; -; mRNA. DR EMBL; EU826584; ACF47620.1; -; mRNA. DR EMBL; EU826585; ACF47621.1; -; mRNA. DR EMBL; AC105935; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR IPI; IPI00030273; -. DR IPI; IPI00219706; -. DR IPI; IPI00910383; -. DR IPI; IPI00926020; -. DR IPI; IPI00956299; -. DR IPI; IPI00956695; -. DR PIR; I38185; I38185. DR RefSeq; NP_001231866.1; NM_001244937.1. DR RefSeq; NP_002438.2; NM_002447.2. DR UniGene; Hs.517973; -. DR PDB; 3PLS; X-ray; 2.24 A; A=1060-1357. DR PDB; 4FWW; X-ray; 1.85 A; A=42-568. DR PDBsum; 3PLS; -. DR PDBsum; 4FWW; -. DR ProteinModelPortal; Q04912; -. DR SMR; Q04912; 42-865, 1060-1357. DR DIP; DIP-6029N; -. DR IntAct; Q04912; 5. DR MINT; MINT-6539690; -. DR STRING; 9606.ENSP00000296474; -. DR PhosphoSite; Q04912; -. DR DMDM; 294862462; -. DR PaxDb; Q04912; -. DR PRIDE; Q04912; -. DR DNASU; 4486; -. DR Ensembl; ENST00000296474; ENSP00000296474; ENSG00000164078. DR Ensembl; ENST00000344206; ENSP00000341325; ENSG00000164078. DR GeneID; 4486; -. DR KEGG; hsa:4486; -. DR UCSC; uc003cxy.4; human. DR UCSC; uc011bdc.2; human. DR UCSC; uc011bdd.2; human. DR UCSC; uc011bde.1; human. DR UCSC; uc011bdf.1; human. DR UCSC; uc011bdg.2; human. DR CTD; 4486; -. DR GeneCards; GC03M049924; -. DR HGNC; HGNC:7381; MST1R. DR HPA; CAB008972; -. DR HPA; HPA007657; -. DR HPA; HPA008180; -. DR MIM; 600168; gene. DR neXtProt; NX_Q04912; -. DR PharmGKB; PA31186; -. DR eggNOG; COG0515; -. DR HOGENOM; HOG000220900; -. DR HOVERGEN; HBG104342; -. DR InParanoid; Q04912; -. DR KO; K05100; -. DR OMA; EQKFVHR; -. DR OrthoDB; EOG4M65GR; -. DR PhylomeDB; Q04912; -. DR BRENDA; 2.7.10.1; 2681. DR Pathway_Interaction_DB; a6b1_a6b4_integrin_pathway; a6b1 and a6b4 Integrin signaling. DR Pathway_Interaction_DB; amb2_neutrophils_pathway; amb2 Integrin signaling. DR BindingDB; Q04912; -. DR ChEMBL; CHEMBL2689; -. DR ChiTaRS; MST1R; human. DR GenomeRNAi; 4486; -. DR NextBio; 17355; -. DR Bgee; Q04912; -. DR CleanEx; HS_MST1R; -. DR Genevestigator; Q04912; -. DR GermOnline; ENSG00000164078; Homo sapiens. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0001725; C:stress fiber; IEA:Compara. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005011; F:macrophage colony-stimulating factor receptor activity; TAS:ProtInc. DR GO; GO:0006928; P:cellular component movement; TAS:ProtInc. DR GO; GO:0006952; P:defense response; TAS:ProtInc. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0007275; P:multicellular organismal development; IEA:InterPro. DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IDA:UniProtKB. DR GO; GO:0009615; P:response to virus; IDA:UniProtKB. DR GO; GO:0007338; P:single fertilization; TAS:ProtInc. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro. DR Gene3D; 2.130.10.10; -; 1. DR Gene3D; 2.60.40.10; -; 4. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR002909; IPT_TIG_rcpt. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR003659; Plexin-like. DR InterPro; IPR016201; Plexin-like_fold. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001627; Semaphorin/CD100_Ag. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016244; Tyr_kinase_HGF/MSP_rcpt. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom. DR Pfam; PF07714; Pkinase_Tyr; 1. DR Pfam; PF01403; Sema; 1. DR Pfam; PF01833; TIG; 2. DR PIRSF; PIRSF000617; TyrPK_HGF-R; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00429; IPT; 3. DR SMART; SM00423; PSI; 1. DR SMART; SM00630; Sema; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF81296; Ig_E-set; 3. DR SUPFAM; SSF56112; Kinase_like; 1. DR SUPFAM; SSF103575; Plexin-like_fold; 1. DR SUPFAM; SSF101912; Sema; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS51004; SEMA; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; KW Cleavage on pair of basic residues; Complete proteome; Disulfide bond; KW Glycoprotein; Immunity; Innate immunity; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Polymorphism; Receptor; KW Reference proteome; Repeat; Signal; Transferase; Transmembrane; KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1 24 Potential. FT CHAIN 25 1400 Macrophage-stimulating protein receptor. FT /FTId=PRO_0000024452. FT CHAIN 25 304 Macrophage-stimulating protein receptor FT alpha chain (Potential). FT /FTId=PRO_0000024453. FT CHAIN 310 1400 Macrophage-stimulating protein receptor FT beta chain (Potential). FT /FTId=PRO_0000024454. FT TOPO_DOM 25 957 Extracellular (Potential). FT TRANSMEM 958 978 Helical; (Potential). FT TOPO_DOM 979 1400 Cytoplasmic (Potential). FT DOMAIN 31 522 Sema. FT DOMAIN 569 671 IPT/TIG 1. FT DOMAIN 684 767 IPT/TIG 2. FT DOMAIN 770 860 IPT/TIG 3. FT DOMAIN 1082 1345 Protein kinase. FT NP_BIND 1088 1096 ATP. FT NP_BIND 1161 1164 ATP. FT COMPBIAS 306 309 Poly-Arg. FT COMPBIAS 962 968 Poly-Leu. FT ACT_SITE 1208 1208 Proton acceptor (Probable). FT BINDING 1114 1114 ATP. FT BINDING 1212 1212 ATP. FT MOD_RES 1238 1238 Phosphotyrosine; by autocatalysis FT (Probable). FT MOD_RES 1239 1239 Phosphotyrosine; by autocatalysis FT (Probable). FT MOD_RES 1353 1353 Phosphotyrosine; by autocatalysis. FT MOD_RES 1360 1360 Phosphotyrosine; by autocatalysis. FT CARBOHYD 66 66 N-linked (GlcNAc...) (Potential). FT CARBOHYD 419 419 N-linked (GlcNAc...) (Potential). FT CARBOHYD 458 458 N-linked (GlcNAc...) (Potential). FT CARBOHYD 488 488 N-linked (GlcNAc...). FT CARBOHYD 654 654 N-linked (GlcNAc...) (Potential). FT CARBOHYD 720 720 N-linked (GlcNAc...) (Potential). FT CARBOHYD 841 841 N-linked (GlcNAc...) (Potential). FT CARBOHYD 897 897 N-linked (GlcNAc...) (Potential). FT DISULFID 101 104 FT DISULFID 107 162 FT DISULFID 135 143 FT DISULFID 174 177 FT DISULFID 300 367 FT DISULFID 385 407 FT DISULFID 386 422 FT DISULFID 527 545 FT DISULFID 533 567 FT DISULFID 536 552 FT DISULFID 548 558 FT VAR_SEQ 411 516 Missing (in isoform RON-2). FT /FTId=VSP_038919. FT VAR_SEQ 475 495 ELVRSLNYLLYVSNFSLGDSG -> GPHPHSPLALGPCLHP FT HFAHI (in isoform RON-1). FT /FTId=VSP_038920. FT VAR_SEQ 496 1400 Missing (in isoform RON-1). FT /FTId=VSP_038921. FT VAR_SEQ 628 647 PVPRKDFVEEFECELEPLGT -> YNLVPPLPFPEGGNQAA FT PSP (in isoform RON-2 and isoform RON-4). FT /FTId=VSP_038922. FT VAR_SEQ 648 1400 Missing (in isoform RON-2 and isoform FT RON-4). FT /FTId=VSP_038923. FT VAR_SEQ 884 932 Missing (in isoform Delta-RON). FT /FTId=VSP_005007. FT VAR_SEQ 884 907 YIGLGAVADCVGINVTVGGESCQH -> VSVRDRGRDSWGS FT ESRGQPTGWSS (in isoform RON-3). FT /FTId=VSP_038924. FT VAR_SEQ 908 1400 Missing (in isoform RON-3). FT /FTId=VSP_038925. FT VARIANT 75 75 R -> S (in dbSNP:rs35887539). FT /FTId=VAR_041768. FT VARIANT 95 95 P -> T (in dbSNP:rs55908300). FT /FTId=VAR_041769. FT VARIANT 185 185 R -> C (in dbSNP:rs55633379). FT /FTId=VAR_041770. FT VARIANT 322 322 R -> Q (in dbSNP:rs2230593). FT /FTId=VAR_006350. FT VARIANT 356 356 G -> D (in dbSNP:rs35924402). FT /FTId=VAR_041771. FT VARIANT 434 434 S -> L (in dbSNP:rs2230591). FT /FTId=VAR_029238. FT VARIANT 440 440 N -> S (in dbSNP:rs2230592). FT /FTId=VAR_029239. FT VARIANT 465 465 G -> D (in dbSNP:rs34564898). FT /FTId=VAR_041772. FT VARIANT 504 504 R -> C (in dbSNP:rs34350470). FT /FTId=VAR_041773. FT VARIANT 523 523 Q -> R (in dbSNP:rs2230590). FT /FTId=VAR_041774. FT VARIANT 613 613 Q -> P (in dbSNP:rs35986685). FT /FTId=VAR_041775. FT VARIANT 900 900 V -> M (in dbSNP:rs56091918). FT /FTId=VAR_041776. FT VARIANT 1195 1195 S -> G (in dbSNP:rs7433231). FT /FTId=VAR_061749. FT VARIANT 1304 1304 R -> G. FT /FTId=VAR_041777. FT VARIANT 1335 1335 R -> G (in dbSNP:rs1062633). FT /FTId=VAR_024577. FT VARIANT 1360 1360 Y -> C (in dbSNP:rs56330223). FT /FTId=VAR_041778. FT CONFLICT 209 209 A -> G (in Ref. 1; CAA49634). FT CONFLICT 813 813 R -> RQ (in Ref. 3; ACF47620). FT STRAND 43 45 FT STRAND 48 50 FT STRAND 55 62 FT STRAND 68 74 FT STRAND 77 81 FT STRAND 87 92 FT HELIX 102 105 FT STRAND 108 110 FT STRAND 120 126 FT TURN 127 130 FT STRAND 131 138 FT HELIX 139 141 FT STRAND 143 151 FT STRAND 154 157 FT STRAND 184 191 FT STRAND 194 201 FT HELIX 205 208 FT STRAND 209 211 FT STRAND 215 221 FT STRAND 233 235 FT HELIX 239 242 FT STRAND 248 255 FT STRAND 258 268 FT STRAND 275 288 FT STRAND 294 302 FT STRAND 316 318 FT STRAND 320 328 FT HELIX 331 337 FT STRAND 344 351 FT STRAND 365 370 FT HELIX 371 386 FT STRAND 387 389 FT TURN 399 401 FT HELIX 422 424 FT STRAND 433 436 FT TURN 438 445 FT STRAND 448 456 FT STRAND 459 466 FT STRAND 469 475 FT STRAND 485 491 FT STRAND 503 505 FT STRAND 508 513 FT STRAND 516 521 FT HELIX 527 529 FT HELIX 533 538 FT HELIX 541 543 FT STRAND 549 553 FT HELIX 555 557 FT TURN 559 561 FT HELIX 1064 1069 FT HELIX 1071 1073 FT HELIX 1077 1079 FT STRAND 1080 1091 FT STRAND 1094 1102 FT STRAND 1104 1106 FT STRAND 1108 1116 FT HELIX 1122 1136 FT STRAND 1148 1150 FT STRAND 1153 1155 FT STRAND 1158 1161 FT HELIX 1169 1174 FT HELIX 1182 1201 FT HELIX 1211 1213 FT STRAND 1214 1216 FT STRAND 1222 1224 FT TURN 1232 1235 FT HELIX 1236 1239 FT HELIX 1250 1253 FT HELIX 1256 1259 FT HELIX 1266 1282 FT TURN 1287 1290 FT HELIX 1293 1295 FT HELIX 1296 1301 FT HELIX 1314 1323 FT HELIX 1328 1330 FT HELIX 1334 1347 SQ SEQUENCE 1400 AA; 152271 MW; EB5CA79ABC69A882 CRC64; MELLPPLPQS FLLLLLLPAK PAAGEDWQCP RTPYAASRDF DVKYVVPSFS AGGLVQAMVT YEGDRNESAV FVAIRNRLHV LGPDLKSVQS LATGPAGDPG CQTCAACGPG PHGPPGDTDT KVLVLDPALP ALVSCGSSLQ GRCFLHDLEP QGTAVHLAAP ACLFSAHHNR PDDCPDCVAS PLGTRVTVVE QGQASYFYVA SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC RFAPKRRRRG APEGGQPYPV LRVAHSAPVG AQLATELSIA EGQEVLFGVF VTGKDGGPGV GPNSVVCAFP IDLLDTLIDE GVERCCESPV HPGLRRGLDF FQSPSFCPNP PGLEALSPNT SCRHFPLLVS SSFSRVDLFN GLLGPVQVTA LYVTRLDNVT VAHMGTMDGR ILQVELVRSL NYLLYVSNFS LGDSGQPVQR DVSRLGDHLL FASGDQVFQV PIQGPGCRHF LTCGRCLRAW HFMGCGWCGN MCGQQKECPG SWQQDHCPPK LTEFHPHSGP LRGSTRLTLC GSNFYLHPSG LVPEGTHQVT VGQSPCRPLP KDSSKLRPVP RKDFVEEFEC ELEPLGTQAV GPTNVSLTVT NMPPGKHFRV DGTSVLRGFS FMEPVLIAVQ PLFGPRAGGT CLTLEGQSLS VGTSRAVLVN GTECLLARVS EGQLLCATPP GATVASVPLS LQVGGAQVPG SWTFQYREDP VVLSISPNCG YINSHITICG QHLTSAWHLV LSFHDGLRAV ESRCERQLPE QQLCRLPEYV VRDPQGWVAG NLSARGDGAA GFTLPGFRFL PPPHPPSANL VPLKPEEHAI KFEYIGLGAV ADCVGINVTV GGESCQHEFR GDMVVCPLPP SLQLGQDGAP LQVCVDGECH ILGRVVRPGP DGVPQSTLLG ILLPLLLLVA ALATALVFSY WWRRKQLVLP PNLNDLASLD QTAGATPLPI LYSGSDYRSG LALPAIDGLD STTCVHGASF SDSEDESCVP LLRKESIQLR DLDSALLAEV KDVLIPHERV VTHSDRVIGK GHFGVVYHGE YIDQAQNRIQ CAIKSLSRIT EMQQVEAFLR EGLLMRGLNH PNVLALIGIM LPPEGLPHVL LPYMCHGDLL QFIRSPQRNP TVKDLISFGL QVARSMEYLA EQKFVHRDLA ARNCMLDESF TVKVADFGLA RDILDREYYS VQQHRHARLP VKWMALESLQ TYRFTTKSDV WSFGVLLWEL LTRGAPPYRH IDPFDLTHFL AQGRRLPQPE YCPDSLYQVM QQCWEADPAV RPTFRVLVGE VEQIVSALLG DHYVQLPATY MNLGPSTSHE MNVRPEQPQF SPMPGNVRRP RPLSEPPRPT //