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

CDC42BPA (Q5VT25) - Overview - Molecular Target Synopsis

Protein


CDC42BPA, Serine/threonine-protein kinase MRCK alpha
Enzyme Classification 2.7.11.1
UniProt Q5VT25

Also Known as MRCKA_HUMAN, CDC42BPA, KIAA0451

Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration (PubMed:15723050, PubMed:9418861, PubMed:9092543). Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates: PPP1R12A, LIMK1 and LIMK2 (PubMed:11340065, PubMed:11399775). May play a role in TFRC-mediated iron uptake (PubMed:20188707). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation. Homodimer and homotetramer via the coiled coil regions (PubMed:11283256). Interacts tightly with GTP-bound but not GDP-bound CDC42 (PubMed:9418861). Forms a tripartite complex with MYO18A and LURAP1 with the latter acting as an adapter connecting CDC42BPA and MYO18A. LURAP1 binding results in activation of CDC42BPA by abolition of its negative autoregulation (PubMed:18854160). Interacts with LURAP1. Interacts (via AGC-kinase C-terminal domain) with FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with FAM89B/LRAP25 and LIMK1.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: CDC42BPA is active in the following subcellular-locations: cell projection, cytoplasm, lamellipodium.
GO terms: CDC42BPA is active in the following subcellular-locations: actomyosin, cell leading edge, cell-cell junction, cytoplasm, extracellular exosome, lamellipodium.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project CDC42BPA has gain in 3 cell-lines, loss in 2 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HT29, SNB_75, HOP_92

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: OCUM-1, Panc 04.03, SW 1573

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: NHLF, HSMM, AG445

(see details)

RNA Interference


CDC42BPA was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HCH1, SKOV3. (see details)

3D Structures


At greater than 90% identity similarity to CDC42BPA there are:
1 structures (1 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CDC42BPA has been screened with 735 compounds (1322 bioactivities), 15 compounds have bioactivities that show binding affinity of <= 500nM (16 bioactivities). (see details)