Proto-oncogene tyrosine-protein kinase ROS

UniProt P08922 Organism Homo sapiens Gene MCF3, ROS, ROS1 EC 2.7.10.1

Also known as: MCF3, ROS, ROS1

Function

Receptor tyrosine kinase (RTK) that plays a role in epithelial cell differentiation and regionalization of the proximal epididymal epithelium. NELL2 is an endogenous ligand for ROS1. Upon endogenous stimulation by NELL2, ROS1 activates the intracellular signaling pathway and triggers epididymal epithelial differentiation and subsequent sperm maturation (By similarity). 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.

Classification

Family (Pfam): PF00041 fn3, PF28033 Fn3_ROS1, PF07714 PK_Tyr_Ser-Thr
InterPro: 6-blade_b-propeller_TolB-like, FN3_dom, FN3_sf, Ig-like_fold, Kinase-like_dom_sf, LDLR_classB_rpt, Prot_kinase_dom, Protein_kinase_ATP_BS, RTK, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_rcpt_2_CS
Functional cluster: Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 5

3ZBF X-ray 2.20A
4UXL X-ray 2.40A
7Z5W X-ray 2.25A
7Z5X X-ray 2.04A
9QEK X-ray 2.21A

A predicted model is available from AlphaFold.

Gene Ontology · 15

Drugs targeting this protein · 4

ENTRECTINIB inhibitor
REPOTRECTINIB inhibitor
TALETRECTINIB inhibitor
CRIZOTINIB inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Proto-oncogene tyrosine-protein kinase ROS 2 shared papers
Sodium-dependent phosphate transport protein 2B 1 shared papers
Guanine nucleotide exchange factor VAV3 1 shared papers
Tyrosine-protein phosphatase non-receptor type 11 1 shared papers
HLA class II histocompatibility antigen gamma chain 1 shared papers
Golgi-associated PDZ and coiled-coil motif-containing protein 1 shared papers
Tyrosine-protein phosphatase non-receptor type 11 1 shared papers
Tyrosine-protein phosphatase non-receptor type 11 1 shared papers

Literature · 10 cited papers

Patterns of somatic mutation in human cancer genomes. Nature · 2007
ROS fusion tyrosine kinase activates a SH2 domain-containing phosphatase-2/phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling axis to form glioblastoma in mice. Cancer Res. · 2006
The DNA sequence and analysis of human chromosome 6. Nature · 2003
Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21). Genes Chromosomes Cancer · 2003
Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma. Proc. Natl. Acad. Sci. U.S.A. · 2003
Vav3 mediates receptor protein tyrosine kinase signaling, regulates GTPase activity, modulates cell morphology, and induces cell transformation. Mol. Cell. Biol. · 2000
Analysis of oncogene expression in primary human gliomas: evidence for increased expression of the ros oncogene. Cancer Genet. Cytogenet. · 1994
Characterization of an activated human ros gene. Mol. Cell. Biol. · 1986
Human c-ros-1 gene homologous to the v-ros sequence of UR2 sarcoma virus encodes for a transmembrane receptorlike molecule. Mol. Cell. Biol. · 1986
Characterization of ROS1 cDNA from a human glioblastoma cell line. Proc. Natl. Acad. Sci. U.S.A. · 1990

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