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P15791 · KCC2D_RAT

  • Protein
    Calcium/calmodulin-dependent protein kinase type II subunit delta
  • Gene
    Camk2d
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

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
IDPosition(s)Description
Binding site20-28ATP (UniProtKB | ChEBI)
Binding site43ATP (UniProtKB | ChEBI)
Active site136Proton acceptor

GO annotations

AspectTerm
Cellular Componentaxon initial segment
Cellular Componentcalcium- and calmodulin-dependent protein kinase complex
Cellular Componentcochlear hair cell ribbon synapse
Cellular Componentcytoplasm
Cellular Componentintercalated disc
Cellular Componentneuromuscular junction
Cellular Componentneuron projection
Cellular Componentneuronal cell body
Cellular Componentnucleus
Cellular Componentperinuclear region of cytoplasm
Cellular Componentpostsynaptic cytosol
Cellular Componentprotein-containing complex
Cellular Componentsarcoplasmic reticulum membrane
Cellular ComponentT-tubule
Molecular FunctionATP binding
Molecular Functioncalcium/calmodulin-dependent protein kinase activity
Molecular Functioncalmodulin binding
Molecular Functionidentical protein binding
Molecular Functionnitric-oxide synthase binding
Molecular Functionprotein homodimerization activity
Molecular Functionprotein kinase activity
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Molecular Functionsodium channel inhibitor activity
Molecular Functiontitin binding
Molecular Functiontransmembrane transporter binding
Biological Processcalcium ion transport
Biological Processcardiac muscle cell contraction
Biological Processcardiac muscle contraction
Biological Processcell growth involved in cardiac muscle cell development
Biological Processendoplasmic reticulum calcium ion homeostasis
Biological ProcessG1/S transition of mitotic cell cycle
Biological Processintracellular potassium ion homeostasis
Biological Processnegative regulation of sodium ion transmembrane transport
Biological Processpeptidyl-serine phosphorylation
Biological Processpeptidyl-threonine phosphorylation
Biological Processpositive regulation of cardiac muscle cell apoptotic process
Biological Processpositive regulation of cardiac muscle hypertrophy
Biological Processpositive regulation of DNA biosynthetic process
Biological Processpositive regulation of ERK1 and ERK2 cascade
Biological Processpositive regulation of G2/M transition of mitotic cell cycle
Biological Processpositive regulation of Rac protein signal transduction
Biological Processpositive regulation of smooth muscle cell migration
Biological Processpositive regulation of vascular associated smooth muscle cell proliferation
Biological Processprotein phosphorylation
Biological Processregulation of calcium ion transmembrane transport via high voltage-gated calcium channel
Biological Processregulation of cardiac muscle cell action potential
Biological Processregulation of cardiac muscle cell action potential involved in regulation of contraction
Biological Processregulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
Biological Processregulation of cell communication by electrical coupling
Biological Processregulation of cell communication by electrical coupling involved in cardiac conduction
Biological Processregulation of cellular localization
Biological Processregulation of membrane depolarization
Biological Processregulation of protein localization to plasma membrane
Biological Processregulation of relaxation of cardiac muscle
Biological Processregulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
Biological Processregulation of sodium ion transport
Biological Processrelaxation of cardiac muscle
Biological Processresponse to hypoxia

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Calcium/calmodulin-dependent protein kinase type II subunit delta
  • EC number
  • Short names
    CaM kinase II subunit delta; CaMK-II subunit delta

Gene names

    • Name
      Camk2d

Organism names

  • Taxonomic identifier
  • Strain
    • Sprague-Dawley
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P15791
  • Secondary accessions
    • P97915
    • P97916
    • Q3B7L0
    • Q63904
    • Q63905

Proteomes

Organism-specific databases

Phenotypes & Variants

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain.

Type
IDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00000861002-533Calcium/calmodulin-dependent protein kinase type II subunit delta
Modified residue287Phosphothreonine; by autocatalysis
Modified residue306Phosphothreonine; by autocatalysis
Modified residue307Phosphothreonine; by autocatalysis
Modified residue315Phosphoserine
Modified residue318N6-acetyllysine
Modified residue319Phosphoserine
Modified residue364Phosphoserine
Modified residue365Phosphothreonine
Modified residue367Phosphoserine
Modified residue370Phosphothreonine
Modified residue371Phosphothreonine
Modified residue524Phosphoserine
Modified residue528Phosphoserine

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

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
IDPosition(s)Description
Domain14-272Protein kinase
Region283-292Autoinhibitory domain
Region291-301Calmodulin-binding
Compositional bias337-367Polar residues
Region337-375Disordered

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

Align isoforms (7)
  • Sequence status
    Complete

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.

  • Name
    Delta 1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    533
  • Mass (Da)
    60,081
  • Last updated
    1990-04-01 v1
  • MD5 Checksum
    F9CE598B706977C6C29970DF73D914DD
MASTTTCTRFTDEYQLFEELGKGAFSVVRRCMKIPTGQEYAAKIINTKKLSARDHQKLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDLVTGGELFEDIVAREYYSEADASHCIQQILESVNHCHLNGIVHRDLKPENLLLASKSKGAAVKLADFGLAIEVQGDQQAWFGFAGTPGYLSPEVLRKDPYGKPVDMWACGVILYILLVGYPPFWDEDQHRLYQQIKAGAYDFPSPEWDTVTPEAKDLINKMLTINPAKRITASEALKHPWICQRSTVASMMHRQETVDCLKKFNARRKLKGAILTTMLATRNFSAAKSLLKKPDGVKINNKANVVTSPKENIPTPALEPQTTVIHNPDGNKESTESSNTTIEDEDVKARKQEIIKVTEQLIEAINNGDFEAYTKICDPGLTAFEPEALGNLVEGMDFHRFYFENALPKINKPIHTIILNPHVHLVGDDAACIAYIRLTQYMDGNGMPKTMQSEETRVWHRRDGKWQNIHFHRSGSPTVPIKPPCIPNGKENFSGGTSLWQNI

P15791-2

  • Name
    Delta 2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P15791-3

P15791-4

  • Name
    Delta 4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P15791-5

  • Name
    Delta 5
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P15791-6

  • Name
    Delta 6
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P15791-7

  • Name
    Delta 7
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 7 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I6AL07A0A8I6AL07_RATCamk2d492
A0A8I6AT87A0A8I6AT87_RATCamk2d498
A0A8L2QW89A0A8L2QW89_RATCamk2d515
A0A8I6A1N4A0A8I6A1N4_RATCamk2d488
A0A8I5YBF2A0A8I5YBF2_RATCamk2d436
A0A8I6A550A0A8I6A550_RATCamk2d512
A0A8I5ZUY3A0A8I5ZUY3_RATCamk2d429

Features

Showing features for alternative sequence, compositional bias.

Type
IDPosition(s)Description
Alternative sequenceVSP_004785329-335in isoform Delta 3
Alternative sequenceVSP_004784329-362in isoform Delta 2 and isoform Delta 5
Alternative sequenceVSP_004786337-359in isoform Delta 3
Compositional bias337-367Polar residues
Alternative sequenceVSP_004788349-362in isoform Delta 4 and isoform Delta 7
Alternative sequenceVSP_004787360-362in isoform Delta 3
Alternative sequenceVSP_012043512-533in isoform Delta 5, isoform Delta 6 and isoform Delta 7

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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