ID   RON_HUMAN               Reviewed;        1400 AA.
AC   Q04912;
DT   01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1994, sequence version 1.
DT   10-JUL-2007, entry version 84.
DE   Macrophage-stimulating protein receptor precursor (EC 2.7.10.1) (MSP
DE   receptor) (p185-Ron) (CD136 antigen) (CDw136) [Contains: Macrophage-
DE   stimulating protein receptor alpha chain; Macrophage-stimulating
DE   protein receptor beta chain].
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].
RC   TISSUE=Keratinocyte;
RX   MEDLINE=93241719; 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   MEDLINE=96413302; 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   FUNCTION.
RX   MEDLINE=95025877; PubMed=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   [4]
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   [5]
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).
CC   -!- FUNCTION: Receptor for macrophage stimulating protein (MSP). Has a
CC       tyrosine-protein kinase activity.
CC   -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC       [protein]-L-tyrosine phosphate.
CC   -!- SUBUNIT: Heterodimer formed of an alpha chain and a beta chain
CC       which are disulfide linked. Binds PLXNB1. Associates with and is
CC       negatively regulated by HYAL2.
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC       protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
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   -!- TISSUE SPECIFICITY: Keratinocytes and lung.
CC   -!- PTM: Proteolytic processing yields the two subunits.
CC   -!- PTM: Phosphorylated in response to ligand binding (Probable).
CC   -!- SIMILARITY: Belongs to the Tyr protein 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".
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DR   EMBL; X70040; CAA49634.1; -; mRNA.
DR   PIR; I38185; I38185.
DR   UniGene; Hs.517973; -.
DR   HSSP; P11362; 1FGK.
DR   DIP; DIP:6029N; -.
DR   Ensembl; ENSG00000164078; Homo sapiens.
DR   KEGG; hsa:4486; -.
DR   HGNC; HGNC:7381; MST1R.
DR   MIM; 600168; gene.
DR   PharmGKB; PA31186; -.
DR   ArrayExpress; Q04912; -.
DR   GermOnline; ENSG00000164078; Homo sapiens.
DR   GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR   GO; GO:0005011; F:macrophage colony stimulating factor recept...; TAS:ProtInc.
DR   GO; GO:0006928; P:cell motility; TAS:ProtInc.
DR   GO; GO:0006952; P:defense response; TAS:ProtInc.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0007338; P:single fertilization; TAS:ProtInc.
DR   InterPro; IPR002909; IPT_TIG_rcpt.
DR   InterPro; IPR003659; Plexin-like.
DR   InterPro; IPR002165; Plexin_repeat.
DR   InterPro; IPR000719; Prot_kinase.
DR   InterPro; IPR001627; Sema.
DR   InterPro; IPR001245; Tyr_pkinase.
DR   InterPro; IPR008266; Tyr_pkinase_AS.
DR   Pfam; PF07714; Pkinase_Tyr; 1.
DR   Pfam; PF01437; PSI; 1.
DR   Pfam; PF01403; Sema; 1.
DR   Pfam; PF01833; TIG; 3.
DR   PRINTS; PR00109; TYRKINASE.
DR   ProDom; PD000001; Prot_kinase; 1.
DR   SMART; SM00429; IPT; 3.
DR   SMART; SM00423; PSI; 1.
DR   SMART; SM00630; Sema; 1.
DR   SMART; SM00219; TyrKc; 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.
KW   Alternative splicing; ATP-binding; Cleavage on pair of basic residues;
KW   Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphorylation;
KW   Polymorphism; Receptor; Repeat; Signal; Transferase; Transmembrane;
KW   Tyrosine-protein kinase.
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       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 (By similarity).
FT   COMPBIAS    306    309       Poly-Arg.
FT   ACT_SITE   1208   1208       Proton acceptor (By similarity).
FT   BINDING    1114   1114       ATP (By similarity).
FT   MOD_RES    1353   1353       Phosphotyrosine; by autocatalysis (By
FT                                similarity).
FT   MOD_RES    1360   1360       Phosphotyrosine; by autocatalysis (By
FT                                similarity).
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...) (Potential).
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   VAR_SEQ     884    932       Missing (in isoform Delta-RON).
FT                                /FTId=VSP_005007.
FT   VARIANT     322    322       Q -> R.
FT                                /FTId=VAR_006350.
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    1335   1335       R -> G (in dbSNP:rs1062633).
FT                                /FTId=VAR_024577.
SQ   SEQUENCE   1400 AA;  152227 MW;  EE782D07E4D2568A CRC64;
     MELLPPLPQS FLLLLLLPAK PAAGEDWQCP RTPYAASRDF DVKYVVPSFS AGGLVQAMVT
     YEGDRNESAV FVAIRNRLHV LGPDLKSVQS LATGPAGDPG CQTCAACGPG PHGPPGDTDT
     KVLVLDPALP ALVSCGSSLQ GRCFLHDLEP QGTAVHLAAP ACLFSAHHNR PDDCPDCVAS
     PLGTRVTVVE QGQASYFYVA SSLDAAVAGS FSPRSVSIRR LKADASGFAP GFVALSVLPK
     HLVSYSIEYV HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC
     RFAPKRRRRG APEGGQPYPV LQVAHSAPVG AQLATELSIA EGQEVLFGVF VTGKDGGPGV
     GPNSVVCAFP IDLLDTLIDE GVERCCESPV HPGLRRGLDF FQSPSFCPNP PGLEALSPNT
     SCRHFPLLVS SSFSRVDLFN GLLGPVQVTA LYVTRLDNVT VAHMGTMDGR ILQVELVRSL
     NYLLYVSNFS LGDSGQPVQR DVSRLGDHLL FASGDQVFQV PIRGPGCRHF 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 QVARGMEYLA
     EQKFVHRDLA ARNCMLDESF TVKVADFGLA RDILDREYYS VQQHRHARLP VKWMALESLQ
     TYRFTTKSDV WSFGVLLWEL LTRGAPPYRH IDPFDLTHFL AQGRRLPQPE YCPDSLYQVM
     QQCWEADPAV RPTFRVLVGE VEQIVSALLG DHYVQLPATY MNLGPSTSHE MNVRPEQPQF
     SPMPGNVRRP RPLSEPPRPT
//