P15791 · KCC2D_RAT
- ProteinCalcium/calmodulin-dependent protein kinase type II subunit delta
- GeneCamk2d
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids533 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca2+ homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca2+ influx into the myocyte, Ca2+ release from the sarcoplasmic reticulum (SR), SR Ca2+ 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 Ca2+ release via direct phosphorylation of RYR2 Ca2+ 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 Ca2+ influx to myocytes by binding and phosphorylating the L-type Ca2+ channel subunit beta-2 CACNB2. In addition to Ca2+ 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 Ca2+ 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 Ca2+ 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).
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 Ca2+ influx to myocytes by binding and phosphorylating the L-type Ca2+ channel subunit beta-2 CACNB2. In addition to Ca2+ 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 Ca2+ 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 Ca2+ 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+
Activity regulation
Activated by Ca2+/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 Ca2+-independent activity.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 20-28 | ATP (UniProtKB | ChEBI) | |||
Binding site | 43 | ATP (UniProtKB | ChEBI) | |||
Active site | 136 | Proton acceptor | |||
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCalcium/calmodulin-dependent protein kinase type II subunit delta
- EC number
- Short namesCaM kinase II subunit delta; CaMK-II subunit delta
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP15791
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane, sarcolemma ; Peripheral membrane protein
Sarcoplasmic reticulum membrane ; Peripheral membrane protein
Isoform Delta 1
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Initiator methionine | 1 | Removed | |||
Modified residue | 2 | N-acetylalanine | |||
Chain | PRO_0000086100 | 2-533 | Calcium/calmodulin-dependent protein kinase type II subunit delta | ||
Modified residue | 287 | Phosphothreonine; by autocatalysis | |||
Modified residue | 306 | Phosphothreonine; by autocatalysis | |||
Modified residue | 307 | Phosphothreonine; by autocatalysis | |||
Modified residue | 315 | Phosphoserine | |||
Modified residue | 318 | N6-acetyllysine | |||
Modified residue | 319 | Phosphoserine | |||
Modified residue | 364 | Phosphoserine | |||
Modified residue | 365 | Phosphothreonine | |||
Modified residue | 367 | Phosphoserine | |||
Modified residue | 370 | Phosphothreonine | |||
Modified residue | 371 | Phosphothreonine | |||
Modified residue | 524 | Phosphoserine | |||
Modified residue | 528 | Phosphoserine | |||
Post-translational modification
Autophosphorylation of Thr-287 following activation by Ca2+/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Gene expression databases
Interaction
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.
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 14-272 | Protein kinase | |||
Region | 283-292 | Autoinhibitory domain | |||
Region | 291-301 | Calmodulin-binding | |||
Compositional bias | 337-367 | Polar residues | |||
Region | 337-375 | Disordered | |||
Domain
The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 7 isoforms produced by Alternative splicing.
P15791-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameDelta 1
- Length533
- Mass (Da)60,081
- Last updated1990-04-01 v1
- MD5 ChecksumF9CE598B706977C6C29970DF73D914DD
P15791-2
- NameDelta 2
- Differences from canonical
- 329-362: Missing
P15791-3
- NameDelta 3
P15791-4
- NameDelta 4
- Differences from canonical
- 349-362: Missing
P15791-5
- NameDelta 5
P15791-6
- NameDelta 6
- Differences from canonical
- 512-533: KPPCIPNGKENFSGGTSLWQNI → N
P15791-7
- NameDelta 7
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AL07 | A0A8I6AL07_RAT | Camk2d | 492 | ||
A0A8I6AT87 | A0A8I6AT87_RAT | Camk2d | 498 | ||
A0A8L2QW89 | A0A8L2QW89_RAT | Camk2d | 515 | ||
A0A8I6A1N4 | A0A8I6A1N4_RAT | Camk2d | 488 | ||
A0A8I5YBF2 | A0A8I5YBF2_RAT | Camk2d | 436 | ||
A0A8I6A550 | A0A8I6A550_RAT | Camk2d | 512 | ||
A0A8I5ZUY3 | A0A8I5ZUY3_RAT | Camk2d | 429 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Alternative sequence | VSP_004785 | 329-335 | in isoform Delta 3 | ||
Alternative sequence | VSP_004784 | 329-362 | in isoform Delta 2 and isoform Delta 5 | ||
Alternative sequence | VSP_004786 | 337-359 | in isoform Delta 3 | ||
Compositional bias | 337-367 | Polar residues | |||
Alternative sequence | VSP_004788 | 349-362 | in isoform Delta 4 and isoform Delta 7 | ||
Alternative sequence | VSP_004787 | 360-362 | in isoform Delta 3 | ||
Alternative sequence | VSP_012043 | 512-533 | in isoform Delta 5, isoform Delta 6 and isoform Delta 7 | ||
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
J05072 EMBL· GenBank· DDBJ | AAA40866.1 EMBL· GenBank· DDBJ | mRNA | ||
BC107562 EMBL· GenBank· DDBJ | AAI07563.1 EMBL· GenBank· DDBJ | mRNA | ||
L13406 EMBL· GenBank· DDBJ | AAA41479.1 EMBL· GenBank· DDBJ | mRNA | ||
L13407 EMBL· GenBank· DDBJ | AAA41480.1 EMBL· GenBank· DDBJ | mRNA | ||
L13408 EMBL· GenBank· DDBJ | AAA41481.1 EMBL· GenBank· DDBJ | mRNA | ||
X77192 EMBL· GenBank· DDBJ | CAA54412.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X77193 EMBL· GenBank· DDBJ | CAA54413.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X77194 EMBL· GenBank· DDBJ | CAA54414.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X77195 EMBL· GenBank· DDBJ | CAA54415.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X75774 EMBL· GenBank· DDBJ | CAA53395.1 EMBL· GenBank· DDBJ | Genomic DNA |