InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CAMK2D

Summary

InnateDB Protein

IDBP-34994.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CAMK2D

Protein Name

calcium/calmodulin-dependent protein kinase II delta

Synonyms

CAMKD;

Species

Homo sapiens

Ensembl Protein

ENSP00000369098

InnateDB Gene

IDBG-34988 (CAMK2D)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:16690701, ECO:0000269PubMed:17179159}.

Subcellular Localization

Cell membrane, sarcolemma {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Sarcoplasmic reticulum membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}.

Disease Associations

Tissue Specificity

Expressed in cardiac muscle and skeletal muscle. Isoform Delta 3, isoform Delta 2, isoform Delta 8 and isoform Delta 9 are expressed in cardiac muscle. Isoform Delta 11 is expressed in skeletal muscle. {ECO:0000269PubMed:10189359, ECO:0000269PubMed:16690701}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 40 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.

Experimentally validated
Total	40 [view]
Protein-Protein	38 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	6 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004683	calmodulin-dependent protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005516	calmodulin binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017080	sodium channel regulator activity
GO:0031432	titin binding
GO:0044325	ion channel binding

Biological Process

GO:0001558	regulation of cell growth
GO:0002026	regulation of the force of heart contraction
GO:0003254	regulation of membrane depolarization
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006468	protein phosphorylation
GO:0007268	synaptic transmission
GO:0008016	regulation of heart contraction
GO:0010613	positive regulation of cardiac muscle hypertrophy
GO:0010881	regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0019221	cytokine-mediated signaling pathway
GO:0046777	protein autophosphorylation
GO:0055119	relaxation of cardiac muscle
GO:0060314	regulation of ryanodine-sensitive calcium-release channel activity
GO:0060333	interferon-gamma-mediated signaling pathway
GO:0060341	regulation of cellular localization
GO:0071277	cellular response to calcium ion
GO:0086003	cardiac muscle cell contraction
GO:0086091	regulation of heart rate by cardiac conduction
GO:1901725	regulation of histone deacetylase activity
GO:1901897	regulation of relaxation of cardiac muscle
GO:1902305	regulation of sodium ion transmembrane transport
GO:2000649	regulation of sodium ion transmembrane transporter activity

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005954	calcium- and calmodulin-dependent protein kinase complex
GO:0016020	membrane
GO:0030666	endocytic vesicle membrane
GO:0033017	sarcoplasmic reticulum membrane
GO:0034704	calcium channel complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR013543 Calcium/calmodulin-dependent protein kinase II, association-domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF08332

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt