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

FRK (P42685) - Overview - Molecular Target Synopsis

Protein


FRK, Tyrosine-protein kinase FRK
Enzyme Classification 2.7.10.2
UniProt P42685

Also Known as FRK_HUMAN, FRK, PTK5, RAK

Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor. Interacts (via the SH3-domain) with PTEN. Interacts with RB1.

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
505ENSG00000111816ENST00000606080ENSP00000476145P42685-1
363ENSG00000111816ENST00000538210ENSP00000443075P42685-2

Drugs


FRK is targeted by Approved Drugs Dasatinib, Vandetanib. (see details)
Dasatinib
Vandetanib

Sub-cellular localization


UniProt: FRK is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: FRK is active in the following subcellular-locations: azurophil granule lumen, cytosol, extracellular exosome, extracellular region, extrinsic component of cytoplasmic side of plasma membrane, intracellular, nucleus, specific granule lumen.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project FRK has gain in 0 cell-lines, loss in 8 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, HL_60

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Okajima, DMS 53, BT-20

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: GM12878, SK-N-SH, NHLF

(see details)

RNA Interference


FRK was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAL120, G292. (see details)

3D Structures


At greater than 50% identity similarity to FRK there are:
147 structures (236 chains) solved
137 are solved in complex with at least one small molecule ligand
13 are solved with an approved drug

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

AMP/ADENOSINE PHOSPHATE (3DQX_A, 3DQX_B),
DB8/BOSUTINIB (4MXO_A, 4MXO_B, 4MXX_A, 4MXX_B, 4MXY_A, 4MXY_B, 4MXZ_A, 4MXZ_B),
RXT/RUXOLITINIB (4U5J_A, 4U5J_B),
STI/IMATINIB (2OIQ_A, 2PL0_A, 3OEZ_A, 3OEZ_B, 4CSV_A),
1N1/DASATINIB (2ZVA_A, 3G5D_A, 3G5D_B, 3QLG_A, 3QLG_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


FRK has been screened with 682 compounds (1302 bioactivities), 24 compounds have bioactivities that show binding affinity of <= 500nM (34 bioactivities). (see details)