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Protein

Calcium/calmodulin-dependent protein kinase type II subunit delta

Gene

CAMK2D

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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'. 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. 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. 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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei43ATP1
Active sitei136Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi20 – 28ATP9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase type II subunit delta (EC:2.7.11.17)
Short name:
CaM kinase II subunit delta
Short name:
CaMK-II subunit delta
Gene namesi
Name:CAMK2D
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane, Sarcoplasmic reticulum

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002778162 – 488Calcium/calmodulin-dependent protein kinase type II subunit deltaAdd BLAST487

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei287Phosphothreonine; by autocatalysisBy similarity1
Modified residuei306Phosphothreonine; by autocatalysisBy similarity1
Modified residuei307Phosphothreonine; by autocatalysisBy similarity1
Modified residuei315PhosphoserineBy similarity1
Modified residuei317N6-acetyllysineBy similarity1
Modified residuei318PhosphoserineBy similarity1
Modified residuei340PhosphoserineBy similarity1
Modified residuei341PhosphothreonineBy similarity1
Modified residuei343PhosphoserineBy similarity1
Modified residuei346PhosphothreonineBy similarity1
Modified residuei347PhosphothreonineBy similarity1
Modified residuei414PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylation of Thr-287 following activation by Ca2+/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ2HJF7.
PeptideAtlasiQ2HJF7.
PRIDEiQ2HJF7.

Expressioni

Gene expression databases

BgeeiENSBTAG00000014463.
ExpressionAtlasiQ2HJF7. baseline and differential.

Interactioni

Subunit structurei

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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000039621.

Structurei

3D structure databases

ProteinModelPortaliQ2HJF7.
SMRiQ2HJF7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 272Protein kinaseAdd BLAST259

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni283 – 292Autoinhibitory domainBy similarity10
Regioni291 – 301Calmodulin-bindingBy similarityAdd BLAST11

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi331 – 334Poly-Ser4

Domaini

The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0033. Eukaryota.
ENOG410XNRX. LUCA.
GeneTreeiENSGT00760000118944.
HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiQ2HJF7.
KOiK04515.
OMAiCHVNGIV.
OrthoDBiEOG091G0SCS.
TreeFamiTF315229.

Family and domain databases

InterProiView protein in InterPro
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom_sf.
IPR032710. NTF2-like_dom_sf.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF54427. SSF54427. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q2HJF7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASTTTCTRF TDEYQLFEEL GKGAFSVVRR CMKIPTGQEY AAKIINTKKL
60 70 80 90 100
SARDHQKLER EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE
110 120 130 140 150
DIVAREYYSE ADASHCIQQI LESVNHCHLN GIVHRDLKPE NLLLASKSKG
160 170 180 190 200
AAVKLADFGL AIEVQGDQQA WFGFAGTPGY LSPEVLRKDP YGKPVDMWAC
210 220 230 240 250
GVILYILLVG YPPFWDEDQH RLYQQIKAGA YDFPSPEWDT VTPEAKDLIN
260 270 280 290 300
KMLTINPAKR ITASEALKHP WICQRSTVAS MMHRQETVDC LKKFNARRKL
310 320 330 340 350
KGAILTTMLA TRNFSAKSLL KKPDGVKKRK SSSSVQMMES TESSNTTIED
360 370 380 390 400
EDVKARKQEI IKVTEQLIEA INNGDFEAYT KICDPGLTAF EPEALGNLVE
410 420 430 440 450
GMDFHRFYFE NALSKSNKPI HTIILNPHVH LVGDDAACIA YIRLTQYMDG
460 470 480
SGMPKTMQSE ETRVWHRRDG KWQNVHFHRS GSPTVPIN
Length:488
Mass (Da):55,293
Last modified:March 21, 2006 - v1
Checksum:i3D4D3A8D1F778F21
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC105459 mRNA. Translation: AAI05460.1.
RefSeqiNP_001039798.1. NM_001046333.1.
UniGeneiBt.58299.

Genome annotation databases

EnsembliENSBTAT00000039835; ENSBTAP00000039621; ENSBTAG00000014463.
GeneIDi532713.
KEGGibta:532713.

Similar proteinsi

Entry informationi

Entry nameiKCC2D_BOVIN
AccessioniPrimary (citable) accession number: Q2HJF7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: March 21, 2006
Last modified: November 22, 2017
This is version 107 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families