UniProt Accession

 KCC2D_HUMAN; Q13557; A8MVS8; Q52PK4; Q59G21; Q8N553; Q9UGH6; Q9UQE9 

Genbank Protein ID

 AF071569; AK055642; AB209288; AY987011; AC004056; AC004168; AC093900; AC107386; BC032784; AJ252239; U50361 

Genbank Nucleotide ID

 AAD20442.1; BAG51545.1; BAD92525.1; AAX88806.1; AAH32784.1; CAB65123.1; AAB16866.1 

Protein Name

 Calcium/calmodulin-dependent protein kinase type II subunit delta 

Protein Synonyms/Alias

 CaM kinase II subunit delta; CaMK-II subunit delta 

Gene Name

 CAMK2D 

Gene Synonyms/Alias

 CAMKD 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
251	EAKDLINKMLTINPA	ubiquitination	[1]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 14 272 Protein kinase.
 NP_BIND 20 28 ATP (By similarity).
 REGION 283 292 Autoinhibitory domain (By similarity).
 REGION 291 301 Calmodulin-binding (By similarity).
 ACT_SITE 136 136 Proton acceptor (By similarity).
 BINDING 43 43 ATP (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 231 231 Phosphotyrosine (By similarity).
 MOD_RES 287 287 Phosphothreonine; by autocatalysis.
 MOD_RES 306 306 Phosphothreonine; by autocatalysis
 MOD_RES 307 307 Phosphothreonine; by autocatalysis
 MOD_RES 319 319 Phosphoserine.
 MOD_RES 330 330 Phosphoserine (By similarity).
 MOD_RES 337 337 Phosphothreonine (By similarity).
 MOD_RES 404 404 Phosphoserine.
 MOD_RES 490 490 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; ATP-binding; Calmodulin-binding; Cell membrane; Complete proteome; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Sarcoplasmic reticulum; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 499 AA 

Protein Sequence

Gene Ontology

 GO:0043194; C:axon initial segment; IEA:Compara.
 GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; TAS:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
 GO:0014704; C:intercalated disc; IEA:Compara.
 GO:0031594; C:neuromuscular junction; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
 GO:0030315; C:T-tubule; IEA:Compara.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0004683; F:calmodulin-dependent protein kinase activity; IEA:EC.
 GO:0006816; P:calcium ion transport; IEA:Compara.
 GO:0060048; P:cardiac muscle contraction; IEA:Compara.
 GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Compara.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0018105; P:peptidyl-serine phosphorylation; IEA:Compara.
 GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
 GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; TAS:UniProtKB.
 GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
 GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; TAS:UniProtKB.
 GO:0002028; P:regulation of sodium ion transport; IEA:Compara.
 GO:0007268; P:synaptic transmission; TAS:Reactome. 

Interpro

 IPR020636; Ca/CaM-dep_Ca-dep_prot_Kinase.
 IPR013543; Ca/CaM-dep_prot_kinase-assoc.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF08332; CaMKII_AD
 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS