Search Results

Overview

Uniprot IDQ6PHZ2
Protein NameCalcium/calmodulin-dependent protein kinase type II subunit delta
Gene NameCamk2d
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
322 SAAKSLLKKPDGVKE

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 (PubMed:12676814, PubMed:15456698, PubMed:17124532). 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 (PubMed:12676814, PubMed:19179290, PubMed:19381018). Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808' (PubMed:20194790). 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 (PubMed:15793582). 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 (PubMed:17124532). 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. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023)

Protein Sequence

10 MASTTTCTRF 20 TDEYQLFEEL 30 GKGAFSVVRR 40 CMKIPTGQEY 50 AAKIINTKKL 60 SARDHQKLER 70 EARICRLLKH 80 PNIVRLHDSI 90 SEEGFHYLVF 100 DLVTGGELFE 110 DIVAREYYSE 120 ADASHCIQQI 130 LESVNHCHLN 140 GIVHRDLKPE 150 NLLLASKSKG 160 AAVKLADFGL 170 AIEVQGDQQA 180 WFGFAGTPGY 190 LSPEVLRKDP 200 YGKPVDMWAC 210 GVILYILLVG 220 YPPFWDEDQH 230 RLYQQIKAGA 240 YDFPSPEWDT 250 VTPEAKDLIN 260 KMLTINPAKR 270 ITASEALKHP 280 WICQRSTVAS 290 MMHRQETVDC 300 LKKFNARRKL 310 KGAILTTMLA 320 TRNFSAAKSL 330 LKKPDGVKES 340 TESSNTTIED 350 EDVKARKQEI 360 IKVTEQLIEA 370 INNGDFEAYT 380 KICDPGLTAF 390 EPEALGNLVE 400 GMDFHRFYFE 410 NALSKSNKPI 420 HTIILNPHVH 430 LVGDDAACIA 440 YIRLTQYMDG 450 SGMPKTMQSE 460 ETRVWHRRDG 470 KWQNVHFHRS 480 GSPTVPIKPP 490 CIPNGKENFS GGTSLWQNI

Gene Ontology

Classification GO ID Description
Cellular Component GO:0043194 axon initial segment
Cellular Component GO:0005954 calcium- and calmodulin-dependent protein kinase complex
Cellular Component GO:0098683 cochlear hair cell ribbon synapse
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0014704 intercalated disc
Cellular Component GO:0031594 neuromuscular junction
Cellular Component GO:0043005 neuron projection
Cellular Component GO:0043025 neuronal cell body
Cellular Component GO:0005634 nucleus
Cellular Component GO:0048471 perinuclear region of cytoplasm
Cellular Component GO:0099524 postsynaptic cytosol
Cellular Component GO:0014069 postsynaptic density
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0016529 sarcoplasmic reticulum
Cellular Component GO:0033017 sarcoplasmic reticulum membrane
Cellular Component GO:0030315 T-tubule
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0004683 calcium/calmodulin-dependent protein kinase activity
Molecular Function GO:0005516 calmodulin binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0050998 nitric-oxide synthase binding
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0106310 protein serine kinase activity
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0019871 sodium channel inhibitor activity
Molecular Function GO:0031432 titin binding
Molecular Function GO:0044325 transmembrane transporter binding
Biological Process GO:0006816 calcium ion transport
Biological Process GO:0086003 cardiac muscle cell contraction
Biological Process GO:0060048 cardiac muscle contraction
Biological Process GO:0061049 cell growth involved in cardiac muscle cell development
Biological Process GO:0032469 endoplasmic reticulum calcium ion homeostasis
Biological Process GO:0000082 G1/S transition of mitotic cell cycle
Biological Process GO:0030007 intracellular potassium ion homeostasis
Biological Process GO:1902306 negative regulation of sodium ion transmembrane transport
Biological Process GO:0018105 peptidyl-serine phosphorylation
Biological Process GO:0010666 positive regulation of cardiac muscle cell apoptotic process
Biological Process GO:0010613 positive regulation of cardiac muscle hypertrophy
Biological Process GO:2000573 positive regulation of DNA biosynthetic process
Biological Process GO:0070374 positive regulation of ERK1 and ERK2 cascade
Biological Process GO:0010971 positive regulation of G2/M transition of mitotic cell cycle
Biological Process GO:0035022 positive regulation of Rac protein signal transduction
Biological Process GO:0014911 positive regulation of smooth muscle cell migration
Biological Process GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
Biological Process GO:0046777 protein autophosphorylation
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:1902514 regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
Biological Process GO:0098901 regulation of cardiac muscle cell action potential
Biological Process GO:0010649 regulation of cell communication by electrical coupling
Biological Process GO:0060341 regulation of cellular localization
Biological Process GO:0003254 regulation of membrane depolarization
Biological Process GO:0048168 regulation of neuronal synaptic plasticity
Biological Process GO:1903076 regulation of protein localization to plasma membrane
Biological Process GO:1901897 regulation of relaxation of cardiac muscle
Biological Process GO:0010880 regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
Biological Process GO:0002028 regulation of sodium ion transport
Biological Process GO:0055119 relaxation of cardiac muscle
Biological Process GO:0001666 response to hypoxia

Reference

[1] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.