RON_HUMAN » Macrophage-stimulating protein receptor

RON_HUMAN » Macrophage-stimulating protein receptor
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
RON_HUMAN » Macrophage-stimulating protein receptor » MSP receptor; CDw136;Protein-tyrosine kinase 8;p185-Ron;
Hydrophobic Thickness 36.8 ± 2.6 Å
Tilt Angle 1 ± 0°
ΔGtransfer -47.9 kcal/mol
ΔGfold -25.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 954-983 (954-985)
Pathways none
PDB 3pls (1060-1357), 4fww (42-568), 4qt8 (A/B=25-683)
OPM none
Complexes none
Interactions

EPOR, Complex: EPOR:RON, PubMed

FURIN, Complex: RON:FURIN, PubMed

PLXB1, Complex: PLXB1:RON, PubMed

PLXB2, Complex: PLXB2:RON, PubMed

PLXB3, Complex: PLXB3:RON, PubMed

Domains

AA: 60-504, PDBID: 4FWW, Subunit A, Seq Identity:100%, Sema domain

AA: 569-674, PDBID: 4QT8, Subunit B, Seq Identity:100%, IPT/TIG domain

AA: 684-766, PDBID: 2UZY, Subunit B, Seq Identity:31%, IPT/TIG domain

AA: 770-865, PDBID: 2UZY, Subunit B, Seq Identity:26%, IPT/TIG domain

AA: 1082-1341, PDBID: 3PLS, Subunit A, Seq Identity:100%, Protein tyrosine kinase

UniProt annotation for RON_HUMAN » Macrophage-stimulating protein receptor
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.

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

ENZYME REGULATION: 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.

SUBUNIT: 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.

TISSUE SPECIFICITY: Expressed in colon, skin, lung and bone marrow.

UniProt features for RON_HUMAN » Macrophage-stimulating protein receptor
SIGNAL 1 24 Potential.
CHAIN 25 1400 Macrophage-stimulating protein receptor.
CHAIN 25 304 Macrophage-stimulating protein receptor alpha chain (Potential).
CHAIN 310 1400 Macrophage-stimulating protein receptor beta chain (Potential).
DOMAIN 31 522 Sema.
DOMAIN 569 671 IPT/TIG 1.
DOMAIN 684 767 IPT/TIG 2.
DOMAIN 770 860 IPT/TIG 3.
DOMAIN 1082 1345 Protein kinase.
ACT_SITE 1208 1208 Proton acceptor (Probable).
DISULFID 101 104
DISULFID 107 162
DISULFID 135 143
DISULFID 174 177
DISULFID 300 367
DISULFID 385 407
DISULFID 386 422
DISULFID 527 545
DISULFID 533 567
DISULFID 536 552
DISULFID 548 558
Amino Acid Sequence for RON_HUMAN » Macrophage-stimulating protein receptor
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