Human Gene ROS1 (ENST00000368508.7) from GENCODE V44
Description: Homo sapiens ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), transcript variant 1, mRNA. (from RefSeq NM_002944) RefSeq Summary (NM_002944): This proto-oncogene, highly-expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000368508.7 Gencode Gene: ENSG00000047936.11 Transcript (Including UTRs) Position: hg38 chr6:117,288,300-117,425,855 Size: 137,556 Total Exon Count: 43 Strand: - Coding Region Position: hg38 chr6:117,288,492-117,425,656 Size: 137,165 Coding Exon Count: 43
ID:ROS1_HUMAN DESCRIPTION: RecName: Full=Proto-oncogene tyrosine-protein kinase ROS; EC=2.7.10.1; AltName: Full=Proto-oncogene c-Ros; AltName: Full=Proto-oncogene c-Ros-1; AltName: Full=Receptor tyrosine kinase c-ros oncogene 1; AltName: Full=c-Ros receptor tyrosine kinase; Flags: Precursor; FUNCTION: Orphan receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. May activate several downstream signaling pathways related to cell differentiation, proliferation, growth and survival including the PI3 kinase-mTOR signaling pathway. Mediates the phosphorylation of PTPN11, an activator of this pathway. May also phosphorylate and activate the transcription factor STAT3 to control anchorage-independent cell growth. Mediates the phosphorylation and the activation of VAV3, a guanine nucleotide exchange factor regulating cell morphology. May activate other downstream signaling proteins including AKT1, MAPK1, MAPK3, IRS1 and PLCG2. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ENZYME REGULATION: Inhibited by dephosphorylation by PTPN6 (By similarity). SUBUNIT: Interacts with PTPN6 (via SH2 1 domain); the interaction is direct and promotes ROS1 dephosphorylation (By similarity). Interacts with PTPN11; may activate the PI3 kinase-mTOR signaling pathway. Interacts with VAV3; constitutive interaction mediating VAV3 phosphorylation. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein (Probable). TISSUE SPECIFICITY: Expressed in brain. Expression is increased in primary gliomas. PTM: Phosphorylated. Probably autophosphorylates. Phosphorylation at Tyr-2274 is required for the interaction with PTPN6 that mediates ROS1 dephosphorylation (By similarity). Phosphorylation at Tyr-2274 stimulates the kinase activity and the activation of the ERK1 signaling cascade (By similarity). Phosphorylation at Tyr-2274 and/or Tyr-2334 recruits PTPN11. DISEASE: Note=A chromosomal aberration involving ROS1 is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which is localized to the Golgi and has a constitutive receptor tyrosine kinase activity. A SLC34A2-ROS1 chimeric protein produced in non-small cell lung cancer cells also retains a constitutive kinase activity. A third type of chimeric protein CD74-ROS1 was also identified in those cells. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily. SIMILARITY: Contains 9 fibronectin type-III domains. SIMILARITY: Contains 1 protein kinase domain.
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.
Pfam Domains: PF00041 - Fibronectin type III domain PF07714 - Protein tyrosine kinase
ModBase Predicted Comparative 3D Structure on P08922
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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.
Biological Process: GO:0001558 regulation of cell growth GO:0002066 columnar/cuboidal epithelial cell development GO:0006468 protein phosphorylation GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007283 spermatogenesis GO:0008283 cell proliferation GO:0010629 negative regulation of gene expression GO:0010966 regulation of phosphate transport GO:0016310 phosphorylation GO:0023014 signal transduction by protein phosphorylation GO:0030154 cell differentiation GO:0032006 regulation of TOR signaling GO:0038083 peptidyl-tyrosine autophosphorylation GO:0070372 regulation of ERK1 and ERK2 cascade
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