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Protein

Macrophage-stimulating protein receptor

Gene

Mst1r

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1091ATPPROSITE-ProRule annotation1
Active sitei1185Proton acceptorPROSITE-ProRule annotation1
Binding sitei1189ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1065 – 1073ATPPROSITE-ProRule annotation9
Nucleotide bindingi1138 – 1141ATPPROSITE-ProRule annotation4

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Host-virus interaction, Immunity, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage-stimulating protein receptor (EC:2.7.10.1)
Short name:
MSP receptor
Alternative name(s):
Stem cell-derived tyrosine kinase
p185-Ron
CD_antigen: CD136
Cleaved into the following 2 chains:
Gene namesi
Name:Mst1r
Synonyms:Ron, Stk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:99614. Mst1r.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 960ExtracellularSequence analysisAdd BLAST936
Transmembranei961 – 981HelicalSequence analysisAdd BLAST21
Topological domaini982 – 1378CytoplasmicSequence analysisAdd BLAST397

GO - Cellular componenti

  • cell surface Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: MGI
  • stress fiber Source: MGI
  • vacuole Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show increased inflammation in an IFN-gamma-mediated delayed-type hypersensitivity reaction and increased susceptibility to lipopolysaccharide-induced endotoxic shock.1 Publication

Chemistry databases

ChEMBLiCHEMBL1795170.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000002445524 – 1378Macrophage-stimulating protein receptorAdd BLAST1355
ChainiPRO_000002445625 – 305Macrophage-stimulating protein receptor alpha chainSequence analysisAdd BLAST281
ChainiPRO_0000024457311 – 1378Macrophage-stimulating protein receptor beta chainSequence analysisAdd BLAST1068

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi91N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi102 ↔ 105PROSITE-ProRule annotation
Disulfide bondi108 ↔ 163PROSITE-ProRule annotation
Disulfide bondi136 ↔ 144PROSITE-ProRule annotation
Disulfide bondi175 ↔ 178PROSITE-ProRule annotation
Disulfide bondi301 ↔ 368PROSITE-ProRule annotation
Disulfide bondi386 ↔ 409PROSITE-ProRule annotation
Disulfide bondi387 ↔ 424PROSITE-ProRule annotation
Glycosylationi391N-linked (GlcNAc...)Sequence analysis1
Glycosylationi460N-linked (GlcNAc...)Sequence analysis1
Glycosylationi490N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi529 ↔ 547PROSITE-ProRule annotation
Disulfide bondi535 ↔ 569PROSITE-ProRule annotation
Disulfide bondi538 ↔ 554PROSITE-ProRule annotation
Disulfide bondi550 ↔ 560PROSITE-ProRule annotation
Glycosylationi656N-linked (GlcNAc...)Sequence analysis1
Glycosylationi722N-linked (GlcNAc...)Sequence analysis1
Glycosylationi845N-linked (GlcNAc...)Sequence analysis1
Glycosylationi901N-linked (GlcNAc...)Sequence analysis1
Modified residuei1215Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1216Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1330Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei1337Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Proteolytic processing yields the two subunits.By similarity
Autophosphorylated in response to ligand binding on Tyr-1215 and Tyr-1216 in the kinase domain leading to further phosphorylation of Tyr-1330 and Tyr-1337 in the C-terminal multifunctional docking site.By similarity
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity).By similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiQ62190.
PRIDEiQ62190.

PTM databases

iPTMnetiQ62190.
PhosphoSitePlusiQ62190.

Expressioni

Tissue specificityi

Expressed in liver, skin, lung, brain, testis and kidney.1 Publication

Gene expression databases

BgeeiENSMUSG00000032584.
ExpressionAtlasiQ62190. baseline and differential.
GenevisibleiQ62190. MM.

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. Isoform sf-Stk forms covalent heterodimers with friend spleen focus-forming virus (FSFFV) gp55.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ62190. 1 interactor.
STRINGi10090.ENSMUSP00000035203.

Chemistry databases

BindingDBiQ62190.

Structurei

3D structure databases

ProteinModelPortaliQ62190.
SMRiQ62190.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 524SemaPROSITE-ProRule annotationAdd BLAST492
Domaini571 – 673IPT/TIG 1Add BLAST103
Domaini686 – 769IPT/TIG 2Add BLAST84
Domaini772 – 864IPT/TIG 3Add BLAST93
Domaini1059 – 1322Protein kinasePROSITE-ProRule annotationAdd BLAST264

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi307 – 310Poly-Arg4

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

eggNOGiKOG1095. Eukaryota.
KOG3610. Eukaryota.
ENOG410XRIK. LUCA.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiQ62190.
KOiK05100.
OMAiEQKFVHR.
OrthoDBiEOG091G0751.
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.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016201. PSI.
IPR001627. Semap_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform RON (identifier: Q62190-1) [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

        10         20         30         40         50
MGLPLPLLQS SLLLMLLLRL SAASTNLNWQ CPRIPYAASR DFSVKYVVPS
60 70 80 90 100
FSAGGRVQAT AAYEDSTNSA VFVATRNHLH VLGPDLQFIE NLTTGPIGNP
110 120 130 140 150
GCQTCASCGP GPHGPPKDTD TLVLVMEPGL PALVSCGSTL QGRCFLHELE
160 170 180 190 200
PRGKALHLAA PACLFSANNN KPEACTDCVA SPLGTRVTVV EQGHASYFYV
210 220 230 240 250
ASSLDPELAA SFSPRSVSIR RLKSDTSGFQ PGFPSLSVLP KYLASYLIKY
260 270 280 290 300
VYSFHSGDFV YFLTVQPISV TSPPSALHTR LVRLNAVEPE IGDYRELVLD
310 320 330 340 350
CHFAPKRRRR GAPEGTQPYP VLQAAHSAPV DAKLAVELSI SEGQEVLFGV
360 370 380 390 400
FVTVKDGGSG MGPNSVVCAF PIYHLNILIE EGVEYCCHSS NSSSLLSRGL
410 420 430 440 450
DFFQTPSFCP NPPGGEASGP SSRCHYFPLM VHASFTRVDL FNGLLGSVKV
460 470 480 490 500
TALHVTRLGN VTVAHMGTVD GRVLQVEIAR SLNYLLYVSN FSLGSSGQPV
510 520 530 540 550
HRDVSRLGND LLFASGDQVF KVPIQGPGCR HFLTCWRCLR AQRFMGCGWC
560 570 580 590 600
GDRCDRQKEC PGSWQQDHCP PEISEFYPHS GPLRGTTRLT LCGSNFYLRP
610 620 630 640 650
DDVVPEGTHQ ITVGQSPCRL LPKDSSSPRP GSLKEFIQEL ECELEPLVTQ
660 670 680 690 700
AVGTTNISLV ITNMPAGKHF RVEGISVQEG FSFVEPVLTS IKPDFGPRAG
710 720 730 740 750
GTYLTLEGQS LSVGTSRAVL VNGTQCRLEQ VNEEQILCVT PPGAGTARVP
760 770 780 790 800
LHLQIGGAEV PGSWTFHYKE DPIVLDISPK CGYSGSHIMI HGQHLTSAWH
810 820 830 840 850
FTLSFHDGQS TVESRCAGQF VEQQQRRCRL PEYVVRNPQG WATGNLSVWG
860 870 880 890 900
DGAAGFTLPG FRFLPPPSPL RAGLVELKPE EHSVKVEYVG LGAVADCVTV
910 920 930 940 950
NMTVGGEVCQ HELRGDVVIC PLPPSLQLGK DGVPLQVCVD GGCHILSQVV
960 970 980 990 1000
RSSPGRASQR ILLIALLVLI LLVAVLAVAL IFNSRRRKKQ LGAHSLSPTT
1010 1020 1030 1040 1050
LSDINDTASG APNHEESSES RDGTSVPLLR TESIRLQDLD RMLLAEVKDV
1060 1070 1080 1090 1100
LIPHEQVVIH TDQVIGKGHF GVVYHGEYTD GAQNQTHCAI KSLSRITEVQ
1110 1120 1130 1140 1150
EVEAFLREGL LMRGLHHPNI LALIGIMLPP EGLPRVLLPY MRHGDLLHFI
1160 1170 1180 1190 1200
RSPQRNPTVK DLVSFGLQVA CGMEYLAEQK FVHRDLAARN CMLDESFTVK
1210 1220 1230 1240 1250
VADFGLARGV LDKEYYSVRQ HRHARLPVKW MALESLQTYR FTTKSDVWSF
1260 1270 1280 1290 1300
GVLLWELLTR GAPPYPHIDP FDLSHFLAQG RRLPQPEYCP DSLYHVMLRC
1310 1320 1330 1340 1350
WEADPAARPT FRALVLEVKQ VVASLLGDHY VQLTAAYVNV GPRAVDDGSV
1360 1370
PPEQVQPSPQ HCRSTSKPRP LSEPPLPT
Length:1,378
Mass (Da):150,519
Last modified:July 27, 2011 - v3
Checksum:i5899D3A17F95F76D
GO
Isoform sf-Stk (identifier: Q62190-2)
Sequence is not available
Note: Lacks part of the extracellular domain, oligomerizes and is constitutively activated. This isoform confers host susceptibility to Friend disease.
Length:
Mass (Da):

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti713 – 714VG → IA in CAA52754 (PubMed:8193352).Curated2
Sequence conflicti719V → A in CAA52754 (PubMed:8193352).Curated1
Sequence conflicti1148H → R in CAA52754 (PubMed:8193352).Curated1
Sequence conflicti1148H → R in AAC39953 (PubMed:9467940).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74736 mRNA. Translation: CAA52754.1.
U65949 Genomic DNA. Translation: AAC39953.1.
AL731808 Genomic DNA. No translation available.
CCDSiCCDS23509.1. [Q62190-1]
PIRiI48751.
RefSeqiNP_033100.2. NM_009074.2. [Q62190-1]
UniGeneiMm.3901.

Genome annotation databases

EnsembliENSMUST00000035203; ENSMUSP00000035203; ENSMUSG00000032584. [Q62190-1]
GeneIDi19882.
KEGGimmu:19882.
UCSCiuc009rni.1. mouse. [Q62190-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X74736 mRNA. Translation: CAA52754.1.
U65949 Genomic DNA. Translation: AAC39953.1.
AL731808 Genomic DNA. No translation available.
CCDSiCCDS23509.1. [Q62190-1]
PIRiI48751.
RefSeqiNP_033100.2. NM_009074.2. [Q62190-1]
UniGeneiMm.3901.

3D structure databases

ProteinModelPortaliQ62190.
SMRiQ62190.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ62190. 1 interactor.
STRINGi10090.ENSMUSP00000035203.

Chemistry databases

BindingDBiQ62190.
ChEMBLiCHEMBL1795170.

PTM databases

iPTMnetiQ62190.
PhosphoSitePlusiQ62190.

Proteomic databases

PaxDbiQ62190.
PRIDEiQ62190.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000035203; ENSMUSP00000035203; ENSMUSG00000032584. [Q62190-1]
GeneIDi19882.
KEGGimmu:19882.
UCSCiuc009rni.1. mouse. [Q62190-1]

Organism-specific databases

CTDi4486.
MGIiMGI:99614. Mst1r.

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG3610. Eukaryota.
ENOG410XRIK. LUCA.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiQ62190.
KOiK05100.
OMAiEQKFVHR.
OrthoDBiEOG091G0751.
TreeFamiTF317402.

Enzyme and pathway databases

BRENDAi2.7.10.1. 3474.

Miscellaneous databases

PROiQ62190.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032584.
ExpressionAtlasiQ62190. baseline and differential.
GenevisibleiQ62190. MM.

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.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016201. PSI.
IPR001627. Semap_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiRON_MOUSE
AccessioniPrimary (citable) accession number: Q62190
Secondary accession number(s): E9QMZ4, Q62555
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 167 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Interaction with FSFFV envelope-like membrane glycoprotein gp55 results in constitutive tyrosine phosphorylation and activation of isoform sf-Stk.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.