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

CAMK2D (Q13557) - Overview - Molecular Target Synopsis


CAMK2D, Calcium/calmodulin-dependent protein kinase type II subunit delta
Enzyme Classification
UniProt Q13557


Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program. Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis. May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (PubMed:14722083). Interacts with RRAD and CACNB2.

Inspect Structure
See all 3D Structures for CAMK2D

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: CAMK2D is active in the following subcellular-locations: cell membrane, sarcolemma, sarcoplasmic reticulum membrane.
GO terms: CAMK2D is active in the following subcellular-locations: cytoplasm, cytosol, endocytic vesicle membrane, membrane, neuron projection, nucleoplasm, nucleus, plasma membrane, sarcolemma, sarcoplasmic reticulum membrane.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project CAMK2D has gain in 1 cell-lines, loss in 2 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: IGROV1, SR, COLO205

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: Daudi, MKN-45, Toledo

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

CAMK2D was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HCC202, KNS42. (see details)

3D Structures

For CAMK2D there are:
7 structures (26 chains) solved
5 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

CAMK2D has been screened with 1069 compounds (1798 bioactivities), 82 compounds have bioactivities that show binding affinity of <= 500nM (103 bioactivities). (see details)