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

PRKX (P51817) - Overview - Molecular Target Synopsis

Protein


PRKX, cAMP-dependent protein kinase catalytic subunit PRKX
Enzyme Classification 2.7.11.1
UniProt P51817

Also Known as PRKX_HUMAN, PRKX, PKX1

Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation. Like other cAMP-dependent protein kinases, the inactive holoenzyme is probably composed of 2 PRKX catalytic subunits and a dimer of regulatory subunits. Interacts (cAMP-dependent) specifically with the regulatory subunits PRKAR1A and PRKAR1B. Compared to other cAMP-dependent serine/threonine protein kinases, does not interact with the 2 other PKA regulatory subunits PRKAR2A and PRKAR2B. Interacts with cAMP-dependent protein kinase inhibitor/PKI proteins; inhibits PRKX. Interacts with GPKOW. Interacts with SMAD6. Interacts with PKD1; involved in differentiation and controlled morphogenesis of the kidney. Interacts with PIN1 (via WW domain).

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
358ENSG00000183943ENST00000262848ENSP00000262848P51817-1

Sub-cellular localization


UniProt: PRKX is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: PRKX is active in the following subcellular-locations: cytoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRKX has gain in 1 cell-lines, loss in 57 cell-lines and no signal in 946 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SW_620, K_562, CCRF_CEM

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SCC-3, TK, OAW28

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: NHEK, HSMM, HMEC

(see details)

RNA Interference


PRKX was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: TE1, KPD. (see details)

3D Structures


At greater than 50% identity similarity to PRKX there are:
211 structures (250 chains) solved
179 are solved in complex with at least one small molecule ligand
6 are solved with an approved drug

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

A/ADENOSINE PHOSPHATE (1BKX_A),
AMP/ADENOSINE PHOSPHATE (6EH2_A, 6ESA_A),
IPH/PHENOL (3NX8_A),
NCA/NIACINAMIDE (5N3H_A),
ADN/ADENOSINE (1FMO_E).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRKX has been screened with 712 compounds (1309 bioactivities), 5 compounds have bioactivities that show binding affinity of <= 500nM (8 bioactivities). (see details)