ROS1
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.
Full Name
ROS Proto-Oncogene 1, Receptor Tyrosine Kinase
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.
Biological Process
Biological Process cell differentiationISS:UniProtKB
Biological Process columnar/cuboidal epithelial cell developmentISS:UniProtKB
Biological Process positive regulation of kinase activityManual Assertion Based On ExperimentIBA:GO_Central
Biological Process protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of cell growthManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of ERK1 and ERK2 cascadeISS:UniProtKB
Biological Process regulation of TOR signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process spermatogenesisISS:UniProtKB
Biological Process transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Cellular Location
Cell membrane
Involvement in disease
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.
Topology
Extracellular: 28-1859
Helical: 1860-1882
Cytoplasmic: 1883-2347
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.
Loading...
Datasheet