UniProt functional annotation for Q04912



	UniProt functional annotation for Q04912

UniProt code: Q04912.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:18836480, ECO:0000269|PubMed:7939629, ECO:0000269|PubMed:9764835}.

Catalytic activity: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};

Activity 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. {ECO:0000269|PubMed:15632155}.

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. {ECO:0000269|PubMed:10222149, ECO:0000269|PubMed:10514476, ECO:0000269|PubMed:12676986, ECO:0000269|PubMed:15184888, ECO:0000269|PubMed:20726546, ECO:0000269|PubMed:21784853, ECO:0000269|PubMed:7687741}.

Subcellular location: Membrane; Single-pass type I membrane protein.

Tissue specificity: Expressed in colon, skin, lung and bone marrow. {ECO:0000269|PubMed:8062829}.

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. {ECO:0000269|PubMed:15632155, ECO:0000269|PubMed:20726546}.

Ptm: Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. {ECO:0000269|PubMed:12802274}.

Disease: Nasopharyngeal carcinoma, 3 (NPCA3) [MIM:617075]: A form of nasopharyngeal carcinoma, a malignant neoplasm that originates in the nasopharyngeal epithelium and includes 4 subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and papillary adenocarcinoma. {ECO:0000269|PubMed:26951679}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Miscellaneous: [Isoform Delta-RON]: Lacks part of the extracellular domain, oligomerizes and is constitutively activated. Expressed at higher level in cancer cells. {ECO:0000303|PubMed:26951679}.

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:18836480, ECO:0000269\|PubMed:7939629, ECO:0000269\|PubMed:9764835}.


Catalytic activity:		Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255\|PROSITE-ProRule:PRU10028};
Activity 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. {ECO:0000269\|PubMed:15632155}.
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. {ECO:0000269\|PubMed:10222149, ECO:0000269\|PubMed:10514476, ECO:0000269\|PubMed:12676986, ECO:0000269\|PubMed:15184888, ECO:0000269\|PubMed:20726546, ECO:0000269\|PubMed:21784853, ECO:0000269\|PubMed:7687741}.
Subcellular location:		Membrane; Single-pass type I membrane protein.
Tissue specificity:		Expressed in colon, skin, lung and bone marrow. {ECO:0000269\|PubMed:8062829}.
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. {ECO:0000269\|PubMed:15632155, ECO:0000269\|PubMed:20726546}.
Ptm:		Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. {ECO:0000269\|PubMed:12802274}.
Disease:		Nasopharyngeal carcinoma, 3 (NPCA3) [MIM:617075]: A form of nasopharyngeal carcinoma, a malignant neoplasm that originates in the nasopharyngeal epithelium and includes 4 subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and papillary adenocarcinoma. {ECO:0000269\|PubMed:26951679}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform Delta-RON]: Lacks part of the extracellular domain, oligomerizes and is constitutively activated. Expressed at higher level in cancer cells. {ECO:0000303\|PubMed:26951679}.
Similarity:		Belongs to the protein kinase superfamily. Tyr protein kinase family. {ECO:0000255\|PROSITE-ProRule:PRU00159}.