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

PRKACB (P22694) - Overview - Molecular Target Synopsis

Protein


PRKACB, cAMP-dependent protein kinase catalytic subunit beta
Enzyme Classification 2.7.11.11
UniProt P22694

Also Known as KAPCB_HUMAN, PRKACB

Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits (By similarity). The cAMP-dependent protein kinase catalytic subunit binds PJA2 (PubMed:21423175). Interacts with GPKOW (PubMed:21880142).

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PRKACB is active in the following subcellular-locations: cell membrane, cytoplasm, membrane, nucleus.
GO terms: PRKACB is active in the following subcellular-locations: cAMP-dependent protein kinase complex, centrosome, ciliary base, cytosol, extracellular exosome, intercellular bridge, nucleoplasm, perinuclear region of cytoplasm, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRKACB has gain in 7 cell-lines, loss in 1 cell-lines and no signal in 997 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HS578T, HCT_116, MDA_MB_231

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: RPMI 2650, KP4, LNCAP

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


PRKACB 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, MFM223. (see details)

3D Structures


At greater than 90% identity similarity to PRKACB there are:
224 structures (250 chains) solved
203 are solved in complex with at least one small molecule ligand
4 are solved with an approved drug

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

AMP/ADENOSINE PHOSPHATE (6EH2_A, 6ESA_A),
IPH/PHENOL (3NX8_A),
NCA/NIACINAMIDE (5N3H_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRKACB has been screened with 891 compounds (1022 bioactivities), 88 compounds have bioactivities that show binding affinity of <= 500nM (115 bioactivities). (see details)