UniProt:P15791 Camk2d

chain
  • initiator methionine:1
  • chain:2-533
checksum E41BCB2B5A00E7CA
comment
  • 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' (PubMed:17923476). 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 (PubMed:17923476). 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 (PubMed:10825152). 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 (By similarity).CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.SUBUNIT CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with RRAD and CACNB2.SUBCELLULAR LOCATION Isoform Delta 1 is the predominant form in the brain, isoform Delta 2 and isoform Delta 3 predominate in the aorta and isoform Delta 4 in skeletal muscle.INDUCTION By cocaine in cardiomyocytes.DOMAIN The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.PTM Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state (By similarity).SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
crossReference
databaseName UniProt
dbId 93734
description
  • recommendedName: Calcium/calmodulin-dependent protein kinase type II subunit delta shortName: CaM kinase II subunit delta shortName: CaMK-II subunit delta ecNumber: 2.7.11.17
displayName UniProt:P15791 Camk2d
geneName
  • Camk2d
identifier P15791
isSequenceChanged false
keyword
  • Acetylation
  • Alternative splicing
  • ATP-binding
  • Calmodulin-binding
  • Cell membrane
  • Kinase
  • Membrane
  • Nucleotide-binding
  • Nucleus
  • Phosphoprotein
  • Reference proteome
  • Sarcoplasmic reticulum
  • Serine/threonine-protein kinase
  • Transferase
modified [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType Protein
name
  • Camk2d
otherIdentifier
  • 10818920
  • 1371263_a_at
  • 17742540
  • 24246
  • 5627416
  • 5683038
  • 5702967
  • 5732333
  • 5901933
  • 5925055
  • 5941144
  • 5985067
  • 6025236
  • 6154328
  • 6179297
  • 6255868
  • 6258133
  • 6387058
  • 6425557
  • 6458104
  • 6511160
  • 6524925
  • 6560418
  • 6565067
  • 6607960
  • 6627296
  • 6656017
  • 6660098
  • 6709314
  • 6739393
  • A_44_P873329
  • A_64_P002053
  • A_64_P158505
  • GE1180657
  • GO:0000166
  • GO:0003824
  • GO:0004672
  • GO:0004674
  • GO:0004683
  • GO:0005516
  • GO:0005524
  • GO:0006468
  • GO:0016301
  • GO:0016740
  • GO:0043226
  • GO:0065008
  • GO:0140096
  • GO:1903076
  • L13406_s_at
  • PH_rn_0012311
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • KCC2D_RAT
  • P97915
  • P97916
  • Q3B7L0
  • Q63904
  • Q63905
  • Q63906
  • Q63907
  • Q63908
sequenceLength 533
species [Species:48895] Rattus norvegicus
stId uniprot:P15791
url http://purl.uniprot.org/uniprot/P15791
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