CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004375
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
  
Created Date
 July 27, 2013 
Organism
 Rattus norvegicus (Rat) 
NCBI Taxa ID
 10116 
Lysine Modification
Position
Peptide
Type
References
43TGQEYAAKIINTKKLubiquitination[1]
Reference
 [1] Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis.
 Na CH, Jones DR, Yang Y, Wang X, Xu Y, Peng J.
 J Proteome Res. 2012 Sep 7;11(9):4722-32. [PMID: 22871113] 
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 (By similarity). 
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 (By similarity).
 MOD_RES 231 231 Phosphotyrosine (By similarity).
 MOD_RES 287 287 Phosphothreonine; by autocatalysis (By
 MOD_RES 306 306 Phosphothreonine; by autocatalysis (By
 MOD_RES 307 307 Phosphothreonine; by autocatalysis (By
 MOD_RES 319 319 Phosphoserine (By similarity).
 MOD_RES 364 364 Phosphoserine (By similarity).
 MOD_RES 371 371 Phosphothreonine (By similarity).
 MOD_RES 524 524 Phosphoserine (By similarity).  
Keyword
 Acetylation; Alternative splicing; ATP-binding; Calmodulin-binding; Cell membrane; Complete proteome; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Sarcoplasmic reticulum; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 533 AA 
Protein Sequence
MASTTTCTRF TDEYQLFEEL GKGAFSVVRR CMKIPTGQEY AAKIINTKKL SARDHQKLER 60
EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIQQI 120
LESVNHCHLN GIVHRDLKPE NLLLASKSKG AAVKLADFGL AIEVQGDQQA WFGFAGTPGY 180
LSPEVLRKDP YGKPVDMWAC GVILYILLVG YPPFWDEDQH RLYQQIKAGA YDFPSPEWDT 240
VTPEAKDLIN KMLTINPAKR ITASEALKHP WICQRSTVAS MMHRQETVDC LKKFNARRKL 300
KGAILTTMLA TRNFSAAKSL LKKPDGVKIN NKANVVTSPK ENIPTPALEP QTTVIHNPDG 360
NKESTESSNT TIEDEDVKAR KQEIIKVTEQ LIEAINNGDF EAYTKICDPG LTAFEPEALG 420
NLVEGMDFHR FYFENALPKI NKPIHTIILN PHVHLVGDDA ACIAYIRLTQ YMDGNGMPKT 480
MQSEETRVWH RRDGKWQNIH FHRSGSPTVP IKPPCIPNGK ENFSGGTSLW QNI 533 
Gene Ontology
 GO:0043194; C:axon initial segment; IEA:Compara.
 GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; TAS:UniProtKB.
 GO:0014704; C:intercalated disc; IEA:Compara.
 GO:0031594; C:neuromuscular junction; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
 GO:0030315; C:T-tubule; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 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:0018105; P:peptidyl-serine phosphorylation; IEA:Compara.
 GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
 GO:0060341; P:regulation of cellular localization; ISS:UniProtKB.
 GO:0002028; P:regulation of sodium ion transport; IEA:Compara. 
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