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

Camk2d (Q6PHZ2) - Overview - Molecular Target Synopsis

Protein


Camk2d, Calcium/calmodulin-dependent protein kinase type II subunit delta
Enzyme Classification 2.7.11.17
UniProt Q6PHZ2

Also Known as KCC2D_MOUSE, Camk2d, Kiaa4163

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. Interacts with RRAD (By similarity). Interacts with CACNB2.

6BAB
THE STRUCTURE OF HUMAN CAMKII WITH BOUND INHIBITOR
RCSB/PDB
Inspect Structure
See all 3D Structures for Camk2d

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
512Q6PHZ2-5
499ENSG00000145349ENST00000342666ENSP00000339740Q6PHZ2-1, Q13557-1
492Q6PHZ2-4

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: axon initial segment, cytoplasm, cytosol, intercalated disc, neuromuscular junction, neuron projection, neuronal cell body, nucleus, perinuclear region of cytoplasm, protein-containing complex, sarcoplasmic reticulum, sarcoplasmic reticulum membrane, T-tubule.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project Camk2d has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures


For Camk2d there are:
1 structures (4 chains) solved
1 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 compounds ( bioactivities). (see details)