Reviewed,
UniProtKB/Swiss-Prot Q04912 (RON_HUMAN)
Last modified
June 16, 2009.
Version 103.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Macrophage-stimulating protein receptor Short name=MSP receptor EC=2.7.10.1 Alternative name(s): p185-Ron CDw136 CD_antigen=CD136 Cleaved into the following 2 chains: 1- Recommended name: Macrophage-stimulating protein receptor alpha chain 2- Recommended name: Macrophage-stimulating protein receptor beta chain | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1400 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Receptor for macrophage stimulating protein (MSP). Has a tyrosine-protein kinase activity. Ref.3 |
| Catalytic activity | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. |
| Subunit structure | Heterodimer formed of an alpha chain and a beta chain which are disulfide linked. Binds PLXNB1. Associates with and is negatively regulated by HYAL2. |
| Subcellular location | |
| Tissue specificity | Keratinocytes and lung. |
| Post-translational modification | Proteolytic processing yields the two subunits. Phosphorylated in response to ligand binding Probable. |
| Sequence similarities | Belongs to the protein kinase superfamily. Tyr protein kinase family. Contains 3 IPT/TIG domains. Contains 1 protein kinase domain. Contains 1 Sema domain. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform RON (identifier: Q04912-1) 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. | ||||||
| Isoform Delta-RON (identifier: Q04912-2) 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. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 24 | 24 | Potential | ||||||
| Chain | 25 – 1400 | 1376 | Macrophage-stimulating protein receptor | PRO_0000024452 | |||||
| Chain | 25 – 304 | 280 | Macrophage-stimulating protein receptor alpha chain Potential | PRO_0000024453 | |||||
| Chain | 310 – 1400 | 1091 | Macrophage-stimulating protein receptor beta chain Potential | PRO_0000024454 | |||||
Regions | |||||||||
| Topological domain | 25 – 957 | 933 | Extracellular Potential | ||||||
| Transmembrane | 958 – 978 | 21 | Potential | ||||||
| Topological domain | 979 – 1400 | 422 | Cytoplasmic Potential | ||||||
| Domain | 31 – 522 | 492 | Sema | ||||||
| Domain | 569 – 671 | 103 | IPT/TIG 1 | ||||||
| Domain | 684 – 767 | 84 | IPT/TIG 2 | ||||||
| Domain | 770 – 860 | 91 | IPT/TIG 3 | ||||||
| Domain | 1082 – 1345 | 264 | Protein kinase | ||||||
| Nucleotide binding | 1088 – 1096 | 9 | ATP By similarity | ||||||
| Compositional bias | 306 – 309 | 4 | Poly-Arg | ||||||
Sites | |||||||||
| Active site | 1208 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 1114 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 1353 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||
| Modified residue | 1360 | 1 | Phosphotyrosine; by autocatalysis By similarity | ||||||
| Glycosylation | 66 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 419 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 458 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 488 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 654 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 720 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 841 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 897 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 884 – 932 | 49 | Missing in isoform Delta-RON. | VSP_005007 | |||||
| Natural variant | 75 | 1 | R → S Ref.6 | VAR_041768 | |||||
| Natural variant | 95 | 1 | P → T Ref.6 | VAR_041769 | |||||
| Natural variant | 185 | 1 | R → C Ref.6 | VAR_041770 | |||||
| Natural variant | 322 | 1 | Q → R Ref.6 | VAR_006350 | |||||
| Natural variant | 356 | 1 | G → D Ref.6 | VAR_041771 | |||||
| Natural variant | 434 | 1 | S → L: dbSNP rs2230591. Ref.6 | VAR_029238 | |||||
| Natural variant | 440 | 1 | N → S: dbSNP rs2230592. | VAR_029239 | |||||
| Natural variant | 465 | 1 | G → D Ref.6 | VAR_041772 | |||||
| Natural variant | 504 | 1 | R → C Ref.6 | VAR_041773 | |||||
| Natural variant | 523 | 1 | R → Q Ref.6 | VAR_041774 | |||||
| Natural variant | 613 | 1 | Q → P Ref.6 | VAR_041775 | |||||
| Natural variant | 900 | 1 | V → M Ref.6 | VAR_041776 | |||||
| Natural variant | 1304 | 1 | R → G Ref.6 | VAR_041777 | |||||
| Natural variant | 1335 | 1 | R → G: dbSNP rs1062633. Ref.6 | VAR_024577 | |||||
| Natural variant | 1360 | 1 | Y → C Ref.6 | VAR_041778 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [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: 8386824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 8816464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. |
| [3] | "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: 7939629] [Abstract] Cited for: FUNCTION. |
| [4] | "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: 12676986] [Abstract] Cited for: INTERACTION WITH HYAL2. |
| [5] | "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: 15184888] [Abstract] Cited for: INTERACTION WITH PLXNB1. |
| [6] | "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. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-75; THR-95; CYS-185; ARG-322; ASP-356; LEU-434; ASP-465; CYS-504; GLN-523; PRO-613; MET-900; GLY-1304; GLY-1335 AND CYS-1360. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| X70040 mRNA. Translation: CAA49634.1. | |
| IPI | IPI00030273. IPI00219706. |
| PIR | I38185. |
| RefSeq | NP_002438.2. |
| UniGene | Hs.517973 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1FGK based on UniProtKB P11362. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP:6029N. |
PTM databases | |
| PhosphoSite | Q04912. |
Proteomic databases | |
| PRIDE | Q04912. |
Genome annotation databases | |
| Ensembl | ENSG00000164078. Homo sapiens. [Contig view] |
| GeneID | 4486. |
| KEGG | hsa:4486. |
Organism-specific databases | |
| GeneCards | GC03M049899. |
| H-InvDB | HIX0030873. |
| HGNC | HGNC:7381. MST1R. |
| HPA | CAB008972. HPA007657. HPA008180. |
| MIM | 600168. gene. |
| PharmGKB | PA31186. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q04912. |
| HOVERGEN | Q04912. |
Enzyme and pathway databases | |
| BRENDA | 2.7.10.1. 247. |
| Pathway_Interaction_DB | a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling. amb2_neutrophils_pathway. amb2 Integrin signaling. |
Gene expression databases | |
| ArrayExpress | Q04912. |
| Bgee | Q04912. |
| CleanEx | HS_MST1R. |
| GermOnline | ENSG00000164078. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR002909. IPT_TIG_rcpt. IPR003659. Plexin-like. IPR002165. Plexin_repeat. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR001627. Semaphorin/CD100_Ag. IPR001245. Tyr_pkinase. IPR008266. Tyr_pkinase_AS. IPR016244. TyrPK_HGF-R. [Graphical view] |
| Pfam | PF07714. Pkinase_Tyr. 1 hit. PF01437. PSI. 1 hit. PF01403. Sema. 1 hit. PF01833. TIG. 3 hits. [Graphical view] |
| PIRSF | PIRSF000617. TyrPK_HGF-R. 1 hit. |
| PRINTS | PR00109. TYRKINASE. |
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| SMART | SM00429. IPT. 3 hits. SM00423. PSI. 1 hit. SM00630. Sema. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view] |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS51004. SEMA. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 17355. |
| SOURCE | Search... |
Entry information
| Entry name | RON_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q04912 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human cell differentiation molecules CD nomenclature of surface proteins of human leucocytes and list of entries |
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

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