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Q04912

- RON_HUMAN

UniProt

Q04912 - RON_HUMAN

Protein

Macrophage-stimulating protein receptor

Gene

MST1R

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 158 (01 Oct 2014)
      Sequence version 2 (20 Apr 2010)
      Previous versions | rss
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    Functioni

    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.3 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Enzyme regulationi

    In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei1114 – 11141ATP
    Active sitei1208 – 12081Proton acceptor1 Publication
    Binding sitei1212 – 12121ATP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1088 – 10969ATP
    Nucleotide bindingi1161 – 11644ATP

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. enzyme binding Source: UniProtKB
    3. macrophage colony-stimulating factor receptor activity Source: ProtInc
    4. protein binding Source: IntAct

    GO - Biological processi

    1. cellular component movement Source: ProtInc
    2. defense response Source: ProtInc
    3. innate immune response Source: UniProtKB-KW
    4. macrophage colony-stimulating factor signaling pathway Source: GOC
    5. multicellular organismal development Source: InterPro
    6. positive regulation of cell proliferation Source: ProtInc
    7. positive regulation of MAP kinase activity Source: UniProtKB
    8. positive regulation of protein kinase B signaling Source: UniProtKB
    9. response to virus Source: UniProtKB
    10. signal transduction Source: ProtInc
    11. single fertilization Source: ProtInc
    12. transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    SignaLinkiQ04912.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Macrophage-stimulating protein receptor (EC:2.7.10.1)
    Short name:
    MSP receptor
    Alternative name(s):
    CDw136
    Protein-tyrosine kinase 8
    p185-Ron
    CD_antigen: CD136
    Cleaved into the following 2 chains:
    Gene namesi
    Name:MST1R
    Synonyms:PTK8, RON
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:7381. MST1R.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. stress fiber Source: Ensembl

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA31186.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Chaini25 – 14001376Macrophage-stimulating protein receptorPRO_0000024452Add
    BLAST
    Chaini25 – 304280Macrophage-stimulating protein receptor alpha chainSequence AnalysisPRO_0000024453Add
    BLAST
    Chaini310 – 14001091Macrophage-stimulating protein receptor beta chainSequence AnalysisPRO_0000024454Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi66 – 661N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi101 ↔ 1041 PublicationPROSITE-ProRule annotation
    Disulfide bondi107 ↔ 1621 PublicationPROSITE-ProRule annotation
    Disulfide bondi135 ↔ 1431 PublicationPROSITE-ProRule annotation
    Disulfide bondi174 ↔ 1771 PublicationPROSITE-ProRule annotation
    Disulfide bondi300 ↔ 3671 PublicationPROSITE-ProRule annotation
    Disulfide bondi385 ↔ 4071 PublicationPROSITE-ProRule annotation
    Disulfide bondi386 ↔ 4221 PublicationPROSITE-ProRule annotation
    Glycosylationi419 – 4191N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi458 – 4581N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi488 – 4881N-linked (GlcNAc...)1 Publication
    Disulfide bondi527 ↔ 5451 PublicationPROSITE-ProRule annotation
    Disulfide bondi533 ↔ 5671 PublicationPROSITE-ProRule annotation
    Disulfide bondi536 ↔ 5521 PublicationPROSITE-ProRule annotation
    Disulfide bondi548 ↔ 5581 PublicationPROSITE-ProRule annotation
    Glycosylationi654 – 6541N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi720 – 7201N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi841 – 8411N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi897 – 8971N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1238 – 12381Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei1239 – 12391Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei1353 – 13531Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei1360 – 13601Phosphotyrosine; by autocatalysis1 Publication

    Post-translational modificationi

    Proteolytic processing yields the two subunits.
    Autophosphorylated in response to ligand binding on Tyr-1238 and Tyr-1239 in the kinase domain leading to further phosphorylation of Tyr-1353 and Tyr-1360 in the C-terminal multifunctional docking site.2 Publications
    Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation.1 Publication

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ04912.
    PaxDbiQ04912.
    PRIDEiQ04912.

    PTM databases

    PhosphoSiteiQ04912.

    Expressioni

    Tissue specificityi

    Expressed in colon, skin, lung and bone marrow.1 Publication

    Gene expression databases

    ArrayExpressiQ04912.
    BgeeiQ04912.
    CleanExiHS_MST1R.
    GenevestigatoriQ04912.

    Organism-specific databases

    HPAiCAB008972.
    HPA007657.
    HPA008180.

    Interactioni

    Subunit structurei

    Heterodimer of an alpha chain and a beta chain which are disulfide linked. Binds PLXNB1. Associates with and is negatively regulated by HYAL2. Interacts when phosphorylated with downstream effectors including PIK3R1, PCLG1, GRB2 and GAB1. Interacts with integrin beta1/ITGB1 in a ligand-independent fashion.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PLXNB1O431573EBI-2637518,EBI-1111488
    PLXNB2O150312EBI-2637518,EBI-722004
    PLXNB3Q9ULL42EBI-2637518,EBI-311073

    Protein-protein interaction databases

    BioGridi110592. 19 interactions.
    DIPiDIP-6029N.
    IntActiQ04912. 9 interactions.
    MINTiMINT-6539690.
    STRINGi9606.ENSP00000296474.

    Structurei

    Secondary structure

    1
    1400
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi43 – 453
    Beta strandi48 – 503
    Beta strandi55 – 628
    Beta strandi68 – 747
    Beta strandi77 – 815
    Beta strandi87 – 926
    Helixi102 – 1054
    Beta strandi108 – 1103
    Beta strandi120 – 1267
    Turni127 – 1304
    Beta strandi131 – 1388
    Helixi139 – 1413
    Beta strandi143 – 1519
    Beta strandi154 – 1574
    Beta strandi184 – 1918
    Beta strandi194 – 2018
    Helixi205 – 2084
    Beta strandi209 – 2113
    Beta strandi215 – 2217
    Beta strandi233 – 2353
    Helixi239 – 2424
    Beta strandi248 – 2558
    Beta strandi258 – 26811
    Beta strandi275 – 28814
    Beta strandi294 – 3029
    Beta strandi316 – 3183
    Beta strandi320 – 3289
    Helixi331 – 3377
    Beta strandi344 – 3518
    Beta strandi365 – 3706
    Helixi371 – 38616
    Beta strandi387 – 3893
    Turni399 – 4013
    Helixi422 – 4243
    Beta strandi433 – 4364
    Turni438 – 4458
    Beta strandi448 – 4569
    Beta strandi459 – 4668
    Beta strandi469 – 4757
    Beta strandi485 – 4917
    Beta strandi503 – 5053
    Beta strandi508 – 5136
    Beta strandi516 – 5216
    Helixi527 – 5293
    Helixi533 – 5386
    Helixi541 – 5433
    Beta strandi549 – 5535
    Helixi555 – 5573
    Turni559 – 5613
    Helixi1064 – 10696
    Helixi1071 – 10733
    Helixi1077 – 10793
    Beta strandi1080 – 109112
    Beta strandi1094 – 11029
    Beta strandi1104 – 11063
    Beta strandi1108 – 11169
    Helixi1122 – 113615
    Beta strandi1148 – 11503
    Beta strandi1153 – 11553
    Beta strandi1158 – 11614
    Helixi1169 – 11746
    Helixi1182 – 120120
    Helixi1211 – 12133
    Beta strandi1214 – 12163
    Beta strandi1222 – 12243
    Turni1232 – 12354
    Helixi1236 – 12394
    Helixi1250 – 12534
    Helixi1256 – 12594
    Helixi1266 – 128217
    Turni1287 – 12904
    Helixi1293 – 12953
    Helixi1296 – 13016
    Helixi1314 – 132310
    Helixi1328 – 13303
    Helixi1334 – 134714

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3PLSX-ray2.24A1060-1357[»]
    4FWWX-ray1.85A42-568[»]
    ProteinModelPortaliQ04912.
    SMRiQ04912. Positions 42-769, 1060-1377.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini25 – 957933ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini979 – 1400422CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei958 – 97821HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini31 – 522492SemaPROSITE-ProRule annotationAdd
    BLAST
    Domaini569 – 671103IPT/TIG 1Add
    BLAST
    Domaini684 – 76784IPT/TIG 2Add
    BLAST
    Domaini770 – 86091IPT/TIG 3Add
    BLAST
    Domaini1082 – 1345264Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi306 – 3094Poly-Arg
    Compositional biasi962 – 9687Poly-Leu

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation
    Contains 3 IPT/TIG domains.Curated
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 Sema domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000220900.
    HOVERGENiHBG104342.
    InParanoidiQ04912.
    KOiK05100.
    OMAiHFGVVYH.
    OrthoDBiEOG7J70DR.
    PhylomeDBiQ04912.
    TreeFamiTF317402.

    Family and domain databases

    Gene3Di2.130.10.10. 1 hit.
    2.60.40.10. 4 hits.
    InterProiIPR013783. Ig-like_fold.
    IPR014756. Ig_E-set.
    IPR002909. IPT.
    IPR011009. Kinase-like_dom.
    IPR016201. Plexin-like_fold.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001627. Semap_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016244. Tyr_kinase_HGF/MSP_rcpt.
    IPR015943. WD40/YVTN_repeat-like_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF01403. Sema. 1 hit.
    PF01833. TIG. 2 hits.
    [Graphical view]
    PIRSFiPIRSF000617. TyrPK_HGF-R. 1 hit.
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00429. IPT. 3 hits.
    SM00423. PSI. 1 hit.
    SM00630. Sema. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF101912. SSF101912. 1 hit.
    SSF103575. SSF103575. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF81296. SSF81296. 3 hits.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS51004. SEMA. 1 hit.
    [Graphical view]

    Sequences (6)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 6 isoformsi produced by alternative splicing. Align

    Isoform RON (identifier: Q04912-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MELLPPLPQS FLLLLLLPAK PAAGEDWQCP RTPYAASRDF DVKYVVPSFS     50
    AGGLVQAMVT YEGDRNESAV FVAIRNRLHV LGPDLKSVQS LATGPAGDPG 100
    CQTCAACGPG PHGPPGDTDT KVLVLDPALP ALVSCGSSLQ GRCFLHDLEP 150
    QGTAVHLAAP ACLFSAHHNR PDDCPDCVAS PLGTRVTVVE QGQASYFYVA 200
    SSLDAAVAAS FSPRSVSIRR LKADASGFAP GFVALSVLPK HLVSYSIEYV 250
    HSFHTGAFVY FLTVQPASVT DDPSALHTRL ARLSATEPEL GDYRELVLDC 300
    RFAPKRRRRG APEGGQPYPV LRVAHSAPVG AQLATELSIA EGQEVLFGVF 350
    VTGKDGGPGV GPNSVVCAFP IDLLDTLIDE GVERCCESPV HPGLRRGLDF 400
    FQSPSFCPNP PGLEALSPNT SCRHFPLLVS SSFSRVDLFN GLLGPVQVTA 450
    LYVTRLDNVT VAHMGTMDGR ILQVELVRSL NYLLYVSNFS LGDSGQPVQR 500
    DVSRLGDHLL FASGDQVFQV PIQGPGCRHF LTCGRCLRAW HFMGCGWCGN 550
    MCGQQKECPG SWQQDHCPPK LTEFHPHSGP LRGSTRLTLC GSNFYLHPSG 600
    LVPEGTHQVT VGQSPCRPLP KDSSKLRPVP RKDFVEEFEC ELEPLGTQAV 650
    GPTNVSLTVT NMPPGKHFRV DGTSVLRGFS FMEPVLIAVQ PLFGPRAGGT 700
    CLTLEGQSLS VGTSRAVLVN GTECLLARVS EGQLLCATPP GATVASVPLS 750
    LQVGGAQVPG SWTFQYREDP VVLSISPNCG YINSHITICG QHLTSAWHLV 800
    LSFHDGLRAV ESRCERQLPE QQLCRLPEYV VRDPQGWVAG NLSARGDGAA 850
    GFTLPGFRFL PPPHPPSANL VPLKPEEHAI KFEYIGLGAV ADCVGINVTV 900
    GGESCQHEFR GDMVVCPLPP SLQLGQDGAP LQVCVDGECH ILGRVVRPGP 950
    DGVPQSTLLG ILLPLLLLVA ALATALVFSY WWRRKQLVLP PNLNDLASLD 1000
    QTAGATPLPI LYSGSDYRSG LALPAIDGLD STTCVHGASF SDSEDESCVP 1050
    LLRKESIQLR DLDSALLAEV KDVLIPHERV VTHSDRVIGK GHFGVVYHGE 1100
    YIDQAQNRIQ CAIKSLSRIT EMQQVEAFLR EGLLMRGLNH PNVLALIGIM 1150
    LPPEGLPHVL LPYMCHGDLL QFIRSPQRNP TVKDLISFGL QVARSMEYLA 1200
    EQKFVHRDLA ARNCMLDESF TVKVADFGLA RDILDREYYS VQQHRHARLP 1250
    VKWMALESLQ TYRFTTKSDV WSFGVLLWEL LTRGAPPYRH IDPFDLTHFL 1300
    AQGRRLPQPE YCPDSLYQVM QQCWEADPAV RPTFRVLVGE VEQIVSALLG 1350
    DHYVQLPATY MNLGPSTSHE MNVRPEQPQF SPMPGNVRRP RPLSEPPRPT 1400
    Length:1,400
    Mass (Da):152,271
    Last modified:April 20, 2010 - v2
    Checksum:iEB5CA79ABC69A882
    GO
    Isoform Delta-RON (identifier: Q04912-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         884-932: Missing.

    Note: Lacks part of the extracellular domain, oligomerizes and is constitutively activated.

    Show »
    Length:1,351
    Mass (Da):147,277
    Checksum:i23ACE5B9330EEA0B
    GO
    Isoform RON-1 (identifier: Q04912-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         475-495: ELVRSLNYLLYVSNFSLGDSG → GPHPHSPLALGPCLHPHFAHI
         496-1400: Missing.

    Show »
    Length:495
    Mass (Da):52,519
    Checksum:i3F99D0A454B25721
    GO
    Isoform RON-2 (identifier: Q04912-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         411-516: Missing.
         628-647: PVPRKDFVEEFECELEPLGT → YNLVPPLPFPEGGNQAAPSP
         648-1400: Missing.

    Show »
    Length:541
    Mass (Da):57,721
    Checksum:i9BC028F4170B1BFC
    GO
    Isoform RON-3 (identifier: Q04912-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         884-907: YIGLGAVADCVGINVTVGGESCQH → VSVRDRGRDSWGSESRGQPTGWSS
         908-1400: Missing.

    Show »
    Length:907
    Mass (Da):97,315
    Checksum:iDDC3A5776146ECCB
    GO
    Isoform RON-4 (identifier: Q04912-6) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         628-647: PVPRKDFVEEFECELEPLGT → YNLVPPLPFPEGGNQAAPSP
         648-1400: Missing.

    Show »
    Length:647
    Mass (Da):69,265
    Checksum:iBE4234918FE98C33
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti209 – 2091A → G in CAA49634. (PubMed:8386824)Curated
    Sequence conflicti813 – 8131R → RQ in ACF47620. (PubMed:18593464)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti75 – 751R → S.1 Publication
    Corresponds to variant rs35887539 [ dbSNP | Ensembl ].
    VAR_041768
    Natural varianti95 – 951P → T.1 Publication
    Corresponds to variant rs55908300 [ dbSNP | Ensembl ].
    VAR_041769
    Natural varianti185 – 1851R → C.1 Publication
    Corresponds to variant rs55633379 [ dbSNP | Ensembl ].
    VAR_041770
    Natural varianti322 – 3221R → Q.2 Publications
    Corresponds to variant rs2230593 [ dbSNP | Ensembl ].
    VAR_006350
    Natural varianti356 – 3561G → D.1 Publication
    Corresponds to variant rs35924402 [ dbSNP | Ensembl ].
    VAR_041771
    Natural varianti434 – 4341S → L.1 Publication
    Corresponds to variant rs2230591 [ dbSNP | Ensembl ].
    VAR_029238
    Natural varianti440 – 4401N → S.
    Corresponds to variant rs2230592 [ dbSNP | Ensembl ].
    VAR_029239
    Natural varianti465 – 4651G → D.1 Publication
    Corresponds to variant rs34564898 [ dbSNP | Ensembl ].
    VAR_041772
    Natural varianti504 – 5041R → C.1 Publication
    Corresponds to variant rs34350470 [ dbSNP | Ensembl ].
    VAR_041773
    Natural varianti523 – 5231Q → R.2 Publications
    Corresponds to variant rs2230590 [ dbSNP | Ensembl ].
    VAR_041774
    Natural varianti613 – 6131Q → P.1 Publication
    Corresponds to variant rs35986685 [ dbSNP | Ensembl ].
    VAR_041775
    Natural varianti900 – 9001V → M.1 Publication
    Corresponds to variant rs56091918 [ dbSNP | Ensembl ].
    VAR_041776
    Natural varianti1195 – 11951S → G.1 Publication
    Corresponds to variant rs7433231 [ dbSNP | Ensembl ].
    VAR_061749
    Natural varianti1304 – 13041R → G.1 Publication
    VAR_041777
    Natural varianti1335 – 13351R → G.1 Publication
    Corresponds to variant rs1062633 [ dbSNP | Ensembl ].
    VAR_024577
    Natural varianti1360 – 13601Y → C.1 Publication
    Corresponds to variant rs56330223 [ dbSNP | Ensembl ].
    VAR_041778

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei411 – 516106Missing in isoform RON-2. 1 PublicationVSP_038919Add
    BLAST
    Alternative sequencei475 – 49521ELVRS…LGDSG → GPHPHSPLALGPCLHPHFAH I in isoform RON-1. 1 PublicationVSP_038920Add
    BLAST
    Alternative sequencei496 – 1400905Missing in isoform RON-1. 1 PublicationVSP_038921Add
    BLAST
    Alternative sequencei628 – 64720PVPRK…EPLGT → YNLVPPLPFPEGGNQAAPSP in isoform RON-2 and isoform RON-4. 1 PublicationVSP_038922Add
    BLAST
    Alternative sequencei648 – 1400753Missing in isoform RON-2 and isoform RON-4. 1 PublicationVSP_038923Add
    BLAST
    Alternative sequencei884 – 93249Missing in isoform Delta-RON. CuratedVSP_005007Add
    BLAST
    Alternative sequencei884 – 90724YIGLG…ESCQH → VSVRDRGRDSWGSESRGQPT GWSS in isoform RON-3. 1 PublicationVSP_038924Add
    BLAST
    Alternative sequencei908 – 1400493Missing in isoform RON-3. 1 PublicationVSP_038925Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X70040 mRNA. Translation: CAA49634.1.
    EU826582 mRNA. Translation: ACF47618.1.
    EU826583 mRNA. Translation: ACF47619.1.
    EU826584 mRNA. Translation: ACF47620.1.
    EU826585 mRNA. Translation: ACF47621.1.
    AC105935 Genomic DNA. No translation available.
    CCDSiCCDS2807.1. [Q04912-1]
    CCDS58833.1. [Q04912-2]
    PIRiI38185.
    RefSeqiNP_001231866.1. NM_001244937.1.
    NP_002438.2. NM_002447.2.
    UniGeneiHs.517973.

    Genome annotation databases

    EnsembliENST00000296474; ENSP00000296474; ENSG00000164078. [Q04912-1]
    ENST00000344206; ENSP00000341325; ENSG00000164078. [Q04912-2]
    GeneIDi4486.
    KEGGihsa:4486.
    UCSCiuc003cxy.4. human. [Q04912-1]
    uc011bdc.2. human. [Q04912-2]
    uc011bdd.2. human. [Q04912-5]
    uc011bde.1. human. [Q04912-6]
    uc011bdf.1. human. [Q04912-4]
    uc011bdg.2. human. [Q04912-3]

    Polymorphism databases

    DMDMi294862462.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X70040 mRNA. Translation: CAA49634.1 .
    EU826582 mRNA. Translation: ACF47618.1 .
    EU826583 mRNA. Translation: ACF47619.1 .
    EU826584 mRNA. Translation: ACF47620.1 .
    EU826585 mRNA. Translation: ACF47621.1 .
    AC105935 Genomic DNA. No translation available.
    CCDSi CCDS2807.1. [Q04912-1 ]
    CCDS58833.1. [Q04912-2 ]
    PIRi I38185.
    RefSeqi NP_001231866.1. NM_001244937.1.
    NP_002438.2. NM_002447.2.
    UniGenei Hs.517973.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3PLS X-ray 2.24 A 1060-1357 [» ]
    4FWW X-ray 1.85 A 42-568 [» ]
    ProteinModelPortali Q04912.
    SMRi Q04912. Positions 42-769, 1060-1377.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110592. 19 interactions.
    DIPi DIP-6029N.
    IntActi Q04912. 9 interactions.
    MINTi MINT-6539690.
    STRINGi 9606.ENSP00000296474.

    Chemistry

    BindingDBi Q04912.
    ChEMBLi CHEMBL2689.
    GuidetoPHARMACOLOGYi 1816.

    PTM databases

    PhosphoSitei Q04912.

    Polymorphism databases

    DMDMi 294862462.

    Proteomic databases

    MaxQBi Q04912.
    PaxDbi Q04912.
    PRIDEi Q04912.

    Protocols and materials databases

    DNASUi 4486.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296474 ; ENSP00000296474 ; ENSG00000164078 . [Q04912-1 ]
    ENST00000344206 ; ENSP00000341325 ; ENSG00000164078 . [Q04912-2 ]
    GeneIDi 4486.
    KEGGi hsa:4486.
    UCSCi uc003cxy.4. human. [Q04912-1 ]
    uc011bdc.2. human. [Q04912-2 ]
    uc011bdd.2. human. [Q04912-5 ]
    uc011bde.1. human. [Q04912-6 ]
    uc011bdf.1. human. [Q04912-4 ]
    uc011bdg.2. human. [Q04912-3 ]

    Organism-specific databases

    CTDi 4486.
    GeneCardsi GC03M049924.
    HGNCi HGNC:7381. MST1R.
    HPAi CAB008972.
    HPA007657.
    HPA008180.
    MIMi 600168. gene.
    neXtProti NX_Q04912.
    PharmGKBi PA31186.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000220900.
    HOVERGENi HBG104342.
    InParanoidi Q04912.
    KOi K05100.
    OMAi HFGVVYH.
    OrthoDBi EOG7J70DR.
    PhylomeDBi Q04912.
    TreeFami TF317402.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    SignaLinki Q04912.

    Miscellaneous databases

    ChiTaRSi MST1R. human.
    GeneWikii MST1R.
    GenomeRNAii 4486.
    NextBioi 17355.
    PROi Q04912.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q04912.
    Bgeei Q04912.
    CleanExi HS_MST1R.
    Genevestigatori Q04912.

    Family and domain databases

    Gene3Di 2.130.10.10. 1 hit.
    2.60.40.10. 4 hits.
    InterProi IPR013783. Ig-like_fold.
    IPR014756. Ig_E-set.
    IPR002909. IPT.
    IPR011009. Kinase-like_dom.
    IPR016201. Plexin-like_fold.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001627. Semap_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR016244. Tyr_kinase_HGF/MSP_rcpt.
    IPR015943. WD40/YVTN_repeat-like_dom.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF01403. Sema. 1 hit.
    PF01833. TIG. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF000617. TyrPK_HGF-R. 1 hit.
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00429. IPT. 3 hits.
    SM00423. PSI. 1 hit.
    SM00630. Sema. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF101912. SSF101912. 1 hit.
    SSF103575. SSF103575. 1 hit.
    SSF56112. SSF56112. 1 hit.
    SSF81296. SSF81296. 3 hits.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS51004. SEMA. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel putative receptor protein tyrosine kinase of the met family."
      Ronsin C., Muscatelli F., Mattei M.-G., Breathnach R.
      Oncogene 8:1195-1202(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM RON), VARIANTS GLN-322; ARG-523 AND GLY-1195.
      Tissue: Keratinocyte.
    2. "A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype."
      Collesi C., Santoro M.M., Gaudino G., Comoglio P.M.
      Mol. Cell. Biol. 16:5518-5526(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
    3. "Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis."
      Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.
      Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS RON-1; RON-2; RON-3 AND RON-4).
    4. "The DNA sequence, annotation and analysis of human chromosome 3."
      Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
      , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
      Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor."
      Ponzetto C., Bardelli A., Maina F., Longati P., Panayotou G., Dhand R., Waterfield M.D., Comoglio P.M.
      Mol. Cell. Biol. 13:4600-4608(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIK3R1.
    6. "RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP."
      Gaudino G., Follenzi A., Naldini L., Collesi C., Santoro M., Gallo K.A., Godowski P.J., Comoglio P.M.
      EMBO J. 13:3524-3532(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    7. "Identification of the ron gene product as the receptor for the human macrophage stimulating protein."
      Wang M.-H., Ronsin C., Gesnel M.-C., Coupey L., Skeel A., Leonard E.J., Breatnach R.
      Science 266:117-119(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury."
      Nanney L.B., Skeel A., Luan J., Polis S., Richmond A., Wang M.H., Leonard E.J.
      J. Invest. Dermatol. 111:573-581(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN WOUND HEALING RESPONSE.
    9. "Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism."
      Danilkovitch A., Skeel A., Leonard E.J.
      Exp. Cell Res. 248:575-582(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ITGB1.
    10. "Interaction of macrophage-stimulating protein with its receptor. Residues critical for beta chain binding and evidence for independent alpha chain binding."
      Danilkovitch A., Miller M., Leonard E.J.
      J. Biol. Chem. 274:29937-29943(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MST1.
    11. "Macrophage-stimulating protein and RON receptor tyrosine kinase: potential regulators of macrophage inflammatory activities."
      Wang M.H., Zhou Y.Q., Chen Y.Q.
      Scand. J. Immunol. 56:545-553(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    12. "c-Cbl is a critical modulator of the Ron tyrosine kinase receptor."
      Penengo L., Rubin C., Yarden Y., Gaudino G.
      Oncogene 22:3669-3679(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    13. "Hyaluronidase 2 negatively regulates RON receptor tyrosine kinase and mediates transformation of epithelial cells by jaagsiekte sheep retrovirus."
      Danilkovitch-Miagkova A., Duh F.-M., Kuzmin I., Angeloni D., Liu S.-L., Miller A.D., Lerman M.I.
      Proc. Natl. Acad. Sci. U.S.A. 100:4580-4585(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HYAL2.
    14. "Interplay between scatter factor receptors and B plexins controls invasive growth."
      Conrotto P., Corso S., Gamberini S., Comoglio P.M., Giordano S.
      Oncogene 23:5131-5137(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PLXNB1.
    15. "The C terminus of RON tyrosine kinase plays an autoinhibitory role."
      Yokoyama N., Ischenko I., Hayman M.J., Miller W.T.
      J. Biol. Chem. 280:8893-8900(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-1238; TYR-1239; TYR-1353 AND TYR-1360, ENZYME REGULATION.
    16. "The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells."
      Feres K.J., Ischenko I., Hayman M.J.
      Oncogene 28:279-288(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET."
      Chaudhuri A., Xie M.H., Yang B., Mahapatra K., Liu J., Marsters S., Bodepudi S., Ashkenazi A.
      J. Biol. Chem. 286:32762-32774(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GAB1 AND GRB2.
    19. "The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis."
      Wang J., Steinbacher S., Augustin M., Schreiner P., Epstein D., Mulvihill M.J., Crew A.P.
      Biochemistry 49:7972-7974(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 1060-1357 IN COMPLEX WITH AMP-PNP AND MAGNESIUM, ACTIVE SITE, PHOSPHORYLATION AT TYR-1238.
    20. "Crystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase."
      Chao K.L., Tsai I.W., Chen C., Herzberg O.
      PLoS ONE 7:E41912-E41912(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 42-568, GLYCOSYLATION AT ASN-488, DISULFIDE BONDS.
    21. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-75; THR-95; CYS-185; GLN-322; ASP-356; LEU-434; ASP-465; CYS-504; ARG-523; PRO-613; MET-900; GLY-1304; GLY-1335 AND CYS-1360.

    Entry informationi

    Entry nameiRON_HUMAN
    AccessioniPrimary (citable) accession number: Q04912
    Secondary accession number(s): B5A944
    , B5A945, B5A946, B5A947
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1994
    Last sequence update: April 20, 2010
    Last modified: October 1, 2014
    This is version 158 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3