Human Gene MST1R (ENST00000296474.8) from GENCODE V44
  Description: Homo sapiens macrophage stimulating 1 receptor (MST1R), transcript variant 4, non-coding RNA. (from RefSeq NR_134919)
RefSeq Summary (NM_002447): This gene encodes a cell surface receptor for macrophage-stimulating protein (MSP) with tyrosine kinase activity. The mature form of this protein is a heterodimer of disulfide-linked alpha and beta subunits, generated by proteolytic cleavage of a single-chain precursor. The beta subunit undergoes tyrosine phosphorylation upon stimulation by MSP. This protein is expressed on the ciliated epithelia of the mucociliary transport apparatus of the lung, and together with MSP, thought to be involved in host defense. Alternative splicing generates multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Jan 2016].
Gencode Transcript: ENST00000296474.8
Gencode Gene: ENSG00000164078.14
Transcript (Including UTRs)
   Position: hg38 chr3:49,887,002-49,903,873 Size: 16,872 Total Exon Count: 20 Strand: -
Coding Region
   Position: hg38 chr3:49,887,307-49,903,609 Size: 16,303 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:49,887,002-49,903,873)mRNA (may differ from genome)Protein (1400 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: RON_HUMAN
DESCRIPTION: RecName: Full=Macrophage-stimulating protein receptor; Short=MSP receptor; EC=2.7.10.1; AltName: Full=CDw136; AltName: Full=Protein-tyrosine kinase 8; AltName: Full=p185-Ron; AltName: CD_antigen=CD136; Contains: RecName: Full=Macrophage-stimulating protein receptor alpha chain; Contains: RecName: Full=Macrophage-stimulating protein receptor beta chain; Flags: Precursor;
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.
INTERACTION: O43157:PLXNB1; NbExp=3; IntAct=EBI-2637518, EBI-1111488; O15031:PLXNB2; NbExp=2; IntAct=EBI-2637518, EBI-722004; Q9ULL4:PLXNB3; NbExp=2; IntAct=EBI-2637518, EBI-311073;
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
TISSUE SPECIFICITY: Expressed in colon, skin, lung and bone marrow.
PTM: Proteolytic processing yields the two subunits.
PTM: 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.
PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family.
SIMILARITY: Contains 3 IPT/TIG domains.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 Sema domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/RONID287.html";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: MST1R
Diseases sorted by gene-association score: nasopharyngeal carcinoma 3* (904), nasopharyngeal carcinoma (20), renal oncocytoma (9), papillary adenocarcinoma (7), adenocarcinoma (4), breast cancer (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 19.08 RPKM in Colon - Transverse
Total median expression: 147.17 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -129.80264-0.492 Picture PostScript Text
3' UTR -112.30305-0.368 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013783 - Ig-like_fold
IPR014756 - Ig_E-set
IPR002909 - IPT_TIG_rcpt
IPR011009 - Kinase-like_dom
IPR003659 - Plexin-like
IPR016201 - Plexin-like_fold
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001627 - Semaphorin/CD100_Ag
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

Pfam Domains:
PF07714 - Protein tyrosine kinase
PF01403 - Sema domain
PF01833 - IPT/TIG domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3PLS - X-ray MuPIT 4FWW - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q04912
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005011 macrophage colony-stimulating factor receptor activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019899 enzyme binding

Biological Process:
GO:0002376 immune system process
GO:0006468 protein phosphorylation
GO:0006952 defense response
GO:0007165 signal transduction
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007338 single fertilization
GO:0008284 positive regulation of cell proliferation
GO:0009615 response to virus
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0038145 macrophage colony-stimulating factor signaling pathway
GO:0043406 positive regulation of MAP kinase activity
GO:0045087 innate immune response
GO:0048012 hepatocyte growth factor receptor signaling pathway
GO:0051897 positive regulation of protein kinase B signaling

Cellular Component:
GO:0001725 stress fiber
GO:0005773 vacuole
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  JN983806 - Homo sapiens RON variant E2E3 mRNA, complete cds.
X70040 - H.sapiens RON mRNA for tyrosine kinase.
LF213760 - JP 2014500723-A/21263: Polycomb-Associated Non-Coding RNAs.
MA449337 - JP 2018138019-A/21263: Polycomb-Associated Non-Coding RNAs.
LF208619 - JP 2014500723-A/16122: Polycomb-Associated Non-Coding RNAs.
MA444196 - JP 2018138019-A/16122: Polycomb-Associated Non-Coding RNAs.
JD053493 - Sequence 34517 from Patent EP1572962.
JD467316 - Sequence 448340 from Patent EP1572962.
JD148833 - Sequence 129857 from Patent EP1572962.
JD210143 - Sequence 191167 from Patent EP1572962.
AK303234 - Homo sapiens cDNA FLJ50323 complete cds, highly similar to Macrophage-stimulating protein receptor precursor (EC 2.7.10.1).
JD347003 - Sequence 328027 from Patent EP1572962.
JD278005 - Sequence 259029 from Patent EP1572962.
JD152721 - Sequence 133745 from Patent EP1572962.
JD152720 - Sequence 133744 from Patent EP1572962.
JD193430 - Sequence 174454 from Patent EP1572962.
JD424391 - Sequence 405415 from Patent EP1572962.
JD256467 - Sequence 237491 from Patent EP1572962.
HQ908652 - Homo sapiens RON variant 21 (RON) mRNA, partial cds, alternatively spliced.
JN689381 - Homo sapiens MST1R variant RON30 mRNA, complete cds, alternatively spliced.
JN689382 - Homo sapiens MST1R variant RON62 mRNA, complete cds, alternatively spliced.
CQ873711 - Sequence 130 from Patent WO2004076622.
DD413548 - Regulation of Mammalian Cells.
KY320166 - Homo sapiens cell line A549 macrophage stimulating 1 receptor variant (MST1R) mRNA, partial sequence.
EU826584 - Homo sapiens soluble RON variant 3 (RON) mRNA, complete cds, alternatively spliced.
EU826583 - Homo sapiens soluble RON variant 2 (RON) mRNA, complete cds, alternatively spliced.
EU826585 - Homo sapiens soluble RON variant 4 (RON) mRNA, complete cds, alternatively spliced.
EU826582 - Homo sapiens soluble RON variant 1 (RON) mRNA, complete cds, alternatively spliced.
LF212312 - JP 2014500723-A/19815: Polycomb-Associated Non-Coding RNAs.
MA447889 - JP 2018138019-A/19815: Polycomb-Associated Non-Coding RNAs.
LF378456 - JP 2014500723-A/185959: Polycomb-Associated Non-Coding RNAs.
MA614033 - JP 2018138019-A/185959: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_mspPathway - Msp/Ron Receptor Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein Q04912 (Reactome details) participates in the following event(s):

R-HSA-6800315 MST1 binds MST1R
R-HSA-8852522 MST1 dimer:MST1R dimer binds MST1R dimer
R-HSA-8852552 MST1R autophosphorylates
R-HSA-8852405 Signaling by MST1
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B5A944, B5A945, B5A946, B5A947, ENST00000296474.1, ENST00000296474.2, ENST00000296474.3, ENST00000296474.4, ENST00000296474.5, ENST00000296474.6, ENST00000296474.7, NR_134919, PTK8, Q04912, RON, RON_HUMAN, uc003cxy.1, uc003cxy.2, uc003cxy.3, uc003cxy.4, uc003cxy.5, uc003cxy.6
UCSC ID: ENST00000296474.8
RefSeq Accession: NM_002447
Protein: Q04912 (aka RON_HUMAN)
CCDS: CCDS2807.1, CCDS58833.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.