Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

ROS1 (P08922) - Overview - Molecular Target Synopsis


ROS1, Proto-oncogene tyrosine-protein kinase ROS
Enzyme Classification
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.

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.

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,, 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):


(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)