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Details on Person UniProt:Q13557 CAMK2D

Class:Id	ReferenceGeneProduct:57907
_chainChangeLog	initiator methionine:1 added on Sat February 7 2015;chain:2-499 added on Sat February 7 2015;initiator methionine:1 for 57907 removed on Fri Nov 03 2023;initiator methionine: for 57907 added on Fri Nov 03 2023;initiator methionine: for 57907 removed on Fri Aug 15 2025;initiator methionine:1 for 57907 added on Fri Aug 15 2025
_displayName	UniProt:Q13557 CAMK2D
_timestamp	2025-08-15 21:38:47
chain	initiator methionine:1 chain:2-499
checksum	62999FBAB98120CE
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'. 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:17179159). 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:16690701). 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 (PubMed:14722083). Interacts with RRAD and CACNB2 (By similarity).INTERACTION Expressed in cardiac muscle and skeletal muscle. Isoform Delta 3, isoform Delta 2, isoform Delta 8 and isoform Delta 9 are expressed in cardiac muscle. Isoform Delta 11 is expressed in skeletal muscle.INDUCTION Activity is induced in skeletal muscle during exercise.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.MISCELLANEOUS Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy in PubMed:10189359.SIMILARITY Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.SEQUENCE CAUTION Extended N-terminus.
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
geneName	CAMK2D CAMKD
identifier	Q13557
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing ATP-binding Calmodulin-binding Cell membrane Kinase Membrane Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Sarcoplasmic reticulum Serine/threonine-protein kinase Transferase
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	CAMK2D
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:9000649] ENSEMBL:ENSG00000145349 CAMK2D [Homo sapiens]
secondaryIdentifier	KCC2D_HUMAN A8MVS8 Q52PK4 Q59G21 Q8N553 Q9UGH6 Q9UQE9
sequenceLength	499
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:149261] UniProt:Q13557-3 CAMK2D [Homo sapiens] [ReferenceIsoform:149262] UniProt:Q13557-4 CAMK2D [Homo sapiens] [ReferenceIsoform:149263] UniProt:Q13557-5 CAMK2D [Homo sapiens] [ReferenceIsoform:149264] UniProt:Q13557-6 CAMK2D [Homo sapiens] [ReferenceIsoform:234113] UniProt:Q13557-8 CAMK2D [Homo sapiens] [ReferenceIsoform:234114] UniProt:Q13557-9 CAMK2D [Homo sapiens] [ReferenceIsoform:234115] UniProt:Q13557-10 CAMK2D [Homo sapiens] [ReferenceIsoform:234116] UniProt:Q13557-11 CAMK2D [Homo sapiens] [ReferenceIsoform:405635] UniProt:Q13557-1 CAMK2D [Homo sapiens] [ReferenceIsoform:8964833] UniProt:Q13557-12 CAMK2D [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:417002] p-T287-CAMK2D [endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:432794] p-T287-CAMK2D [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:444785] p-T287-CAMK2D [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:445370] p-T287-CAMK2D [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9611357] CAMK2D [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9948086] p-T287-CAMK2D [endoplasmic reticulum membrane] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:420987] O-phospho-L-threonine at 287
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No pathways have been reviewed or authored by UniProt:Q13557 CAMK2D (57907)