Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

ROS1 (P08922) - Overview - Molecular Target Synopsis

Protein


ROS1, Proto-oncogene tyrosine-protein kinase ROS
Enzyme Classification 2.7.10.1
UniProt P08922

Also Known as ROS1_HUMAN, ROS1, MCF3, ROS

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. 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.

4UXL
STRUCTURE OF HUMAN ROS1 KINASE DOMAIN IN COMPLEX WITH PF-06463922
RCSB/PDB
Inspect Structure
See all 3D Structures for ROS1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: ROS1 is active in the following subcellular-locations: cell membrane.
GO terms: ROS1 is active in the following subcellular-locations: cell surface, integral component of plasma membrane, membrane, perinuclear region of cytoplasm, receptor complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project ROS1 has gain in 1 cell-lines, loss in 6 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MCF7, SK_OV_3, TK_10

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: G142, MCF10DCIS.com, SUM 159PT

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, HMEC, NHLF

(see details)

RNA Interference


ROS1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: NY, 93VU. (see details)

3D Structures


For ROS1 there are:
2 structures (2 chains) solved
2 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

ROS1 is solved in complex with the approved drug(s):

VGH/CRIZOTINIB (3ZBF_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


ROS1 has been screened with 842 compounds (1466 bioactivities), 74 compounds have bioactivities that show binding affinity of <= 500nM (89 bioactivities). (see details)