CAMK2D (calcium/calmodulin dependent protein kinase II delta)

Gene

• Entrez ID: 817
• Gene name: Calcium/calmodulin dependent protein kinase II delta
• Gene symbol: CAMK2D
• Synonyms: CAMKD
• Chromosome: 4
• Chromosome location: 4q26
• Summary: The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns.[provided by RefSeq, Nov 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025927	hsa-miR-7-5p	Microarray	19073608
MIRT041998	hsa-miR-484	CLASH	23622248
MIRT052455	hsa-let-7a-5p	CLASH	23622248
MIRT733579	hsa-miR-30c-5p	Luciferase reporter assay, qRT-PCR, Western blot	27199283
MIRT735111	hsa-miR-185-5p	Luciferase reporter assay, qRT-PCR, Western blot	25767890

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001558	Process	Regulation of cell growth	NAS	9060999
GO:0002026	Process	Regulation of the force of heart contraction	TAS	23283722
GO:0003254	Process	Regulation of membrane depolarization	IDA	22514276
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	22514276
GO:0004683	Function	Calmodulin-dependent protein kinase activity	IBA	21873635
GO:0004683	Function	Calmodulin-dependent protein kinase activity	IDA	22514276, 23283722
GO:0005515	Function	Protein binding	IPI	20668654, 22514276, 25416956, 25852190, 27519799, 29426014, 31515488, 31980649, 32873725
GO:0005516	Function	Calmodulin binding	IBA	21873635
GO:0005516	Function	Calmodulin binding	IPI	20668654
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	ISS	12676814
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	ISS	12676814
GO:0005829	Component	Cytosol	TAS
GO:0005954	Component	Calcium- and calmodulin-dependent protein kinase complex	IDA	20668654
GO:0006357	Process	Regulation of transcription by RNA polymerase II	TAS	23283722
GO:0006468	Process	Protein phosphorylation	IDA	17179159, 23283722
GO:0008016	Process	Regulation of heart contraction	TAS	17157285
GO:0010613	Process	Positive regulation of cardiac muscle hypertrophy	IMP	17179159
GO:0010649	Process	Regulation of cell communication by electrical coupling	ISS
GO:0010666	Process	Positive regulation of cardiac muscle cell apoptotic process	ISS
GO:0010880	Process	Regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	ISS
GO:0010881	Process	Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	IC	12676813
GO:0010881	Process	Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion	TAS	17157285
GO:0016020	Component	Membrane	HDA	19946888
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	22514276, 23283722
GO:0018107	Process	Peptidyl-threonine phosphorylation	IDA	22514276, 23283722
GO:0019871	Function	Sodium channel inhibitor activity	IDA	22514276
GO:0030666	Component	Endocytic vesicle membrane	TAS
GO:0031432	Function	Titin binding	IPI	23283722
GO:0032469	Process	Endoplasmic reticulum calcium ion homeostasis	ISS
GO:0033017	Component	Sarcoplasmic reticulum membrane	IEA
GO:0042383	Component	Sarcolemma	IEA
GO:0042802	Function	Identical protein binding	IPI	20668654, 25416956, 31515488
GO:0042803	Function	Protein homodimerization activity	IPI	20668654
GO:0043005	Component	Neuron projection	IBA	21873635
GO:0044325	Function	Ion channel binding	IPI	22514276
GO:0044325	Function	Ion channel binding	ISS	12676814
GO:0046777	Process	Protein autophosphorylation	IDA	22514276
GO:0055119	Process	Relaxation of cardiac muscle	ISS	12676814
GO:0060314	Process	Regulation of ryanodine-sensitive calcium-release channel activity	TAS	12676813, 19482609
GO:0060333	Process	Interferon-gamma-mediated signaling pathway	TAS
GO:0060341	Process	Regulation of cellular localization	IMP	17179159
GO:0071277	Process	Cellular response to calcium ion	TAS	23283722
GO:0086003	Process	Cardiac muscle cell contraction	ISS	12676814
GO:0086091	Process	Regulation of heart rate by cardiac conduction	IC	22514276
GO:0098901	Process	Regulation of cardiac muscle cell action potential	ISS
GO:0098909	Process	Regulation of cardiac muscle cell action potential involved in regulation of contraction	IC	12676813
GO:1900034	Process	Regulation of cellular response to heat	TAS
GO:1901725	Process	Regulation of histone deacetylase activity	TAS	23283722
GO:1901844	Process	Regulation of cell communication by electrical coupling involved in cardiac conduction	IC	12676813
GO:1901897	Process	Regulation of relaxation of cardiac muscle	IDA	23283722
GO:1902306	Process	Negative regulation of sodium ion transmembrane transport	IDA	22514276
GO:1902514	Process	Regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	ISS
GO:2000650	Process	Negative regulation of sodium ion transmembrane transporter activity	IDA	22514276

Other IDs

• MIM: 607708
• HGNC: 1462
• e!Ensembl: ENSG00000145349

Protein

• UniProt ID: Q13557
• Protein name: Calcium/calmodulin-dependent protein kinase type II subunit delta (CaM kinase II subunit delta) (CaMK-II subunit delta) (EC 2.7.11.17)
• Protein 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.
• PDB: 2VN9, 2W2C, 2WEL, 3GP2, 5VLO, 6AYW
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	14 → 272	Protein kinase domain	Domain
  PF08332	CaMKII_AD	346 → 473	Calcium/calmodulin dependent protein kinase II association domain	Domain

• Sequence:

  MASTTTCTRFTDEYQLFEELGKGAFSVVRRCMKIPTGQEYAAKIINTKKLSARDHQKLER
  EARICRLLKHPNIVRLHDSISEEGFHYLVFDLVTGGELFEDIVAREYYSEADASHCIQQI
  LESVNHCHLNGIVHRDLKPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGY
  LSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDEDQHRLYQQIKAGAYDFPSPEWDT
  VTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASMMHRQETVDCLKKFNARRKL
  KGAILTTMLATRNFSAAKSLLKKPDGVKESTESSNTTIEDEDVKARKQEIIKVTEQLIEA
  INNGDFEAYTKICDPGLTAFEPEALGNLVEGMDFHRFYFENALSKSNKPIHTIILNPHVH
  LVGDDAACIAYIRLTQYMDGSGMPKTMQSEETRVWHRRDGKWQNVHFHRSGSPTVPIKPP
  CIPNGKENFSGGTSLWQNI

• Sequence length: 499