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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei43 – 431ATPPROSITE-ProRule annotation
Active sitei136 – 1361Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi20 – 289ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-BTA-3371571. HSF1-dependent transactivation.
R-BTA-399719. Trafficking of AMPA receptors.
R-BTA-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-BTA-442729. CREB phosphorylation through the activation of CaMKII.
R-BTA-442742. CREB phosphorylation through the activation of Ras.
R-BTA-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-BTA-5576892. Phase 0 - rapid depolarisation.
R-BTA-5578775. Ion homeostasis.
R-BTA-5673001. RAF/MAP kinase cascade.
R-BTA-877300. Interferon gamma signaling.
R-BTA-936837. Ion transport by P-type ATPases.

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Sarcoplasmic reticulum

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 488487Calcium/calmodulin-dependent protein kinase type II subunit deltaPRO_0000277816Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei287 – 2871Phosphothreonine; by autocatalysisBy similarity
Modified residuei306 – 3061Phosphothreonine; by autocatalysisBy similarity
Modified residuei307 – 3071Phosphothreonine; by autocatalysisBy similarity
Modified residuei315 – 3151PhosphoserineBy similarity
Modified residuei317 – 3171N6-acetyllysineBy similarity
Modified residuei318 – 3181PhosphoserineBy similarity
Modified residuei340 – 3401PhosphoserineBy similarity
Modified residuei341 – 3411PhosphothreonineBy similarity
Modified residuei343 – 3431PhosphoserineBy similarity
Modified residuei346 – 3461PhosphothreonineBy similarity
Modified residuei347 – 3471PhosphothreonineBy similarity
Modified residuei414 – 4141PhosphoserineBy similarity

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.
PRIDEiQ2HJF7.

Expressioni

Gene expression databases

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000039621.

Structurei

3D structure databases

ProteinModelPortaliQ2HJF7.
SMRiQ2HJF7. Positions 8-484.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini14 – 272259Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni283 – 29210Autoinhibitory domainBy similarity
Regioni291 – 30111Calmodulin-bindingBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi331 – 3344Poly-Ser

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0033. Eukaryota.
ENOG410XNRX. LUCA.
GeneTreeiENSGT00760000118944.
HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiQ2HJF7.
KOiK04515.
OMAiEEIRIVC.
TreeFamiTF315229.

Family and domain databases

Gene3Di3.10.450.50. 1 hit.
InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR032710. NTF2-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54427. SSF54427. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliQ2HJF7.
SMRiQ2HJF7. Positions 8-484.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000039621.

Proteomic databases

PaxDbiQ2HJF7.
PRIDEiQ2HJF7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi817.

Phylogenomic databases

eggNOGiKOG0033. Eukaryota.
ENOG410XNRX. LUCA.
GeneTreeiENSGT00760000118944.
HOGENOMiHOG000233016.
HOVERGENiHBG108055.
InParanoidiQ2HJF7.
KOiK04515.
OMAiEEIRIVC.
TreeFamiTF315229.

Enzyme and pathway databases

ReactomeiR-BTA-3371571. HSF1-dependent transactivation.
R-BTA-399719. Trafficking of AMPA receptors.
R-BTA-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-BTA-442729. CREB phosphorylation through the activation of CaMKII.
R-BTA-442742. CREB phosphorylation through the activation of Ras.
R-BTA-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-BTA-5576892. Phase 0 - rapid depolarisation.
R-BTA-5578775. Ion homeostasis.
R-BTA-5673001. RAF/MAP kinase cascade.
R-BTA-877300. Interferon gamma signaling.
R-BTA-936837. Ion transport by P-type ATPases.

Gene expression databases

ExpressionAtlasiQ2HJF7. baseline and differential.

Family and domain databases

Gene3Di3.10.450.50. 1 hit.
InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR032710. NTF2-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 1 hit.
PfamiPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54427. SSF54427. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Heart ventricle.

Entry informationi

Entry nameiKCC2D_BOVIN
AccessioniPrimary (citable) accession number: Q2HJF7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: March 21, 2006
Last modified: June 8, 2016
This is version 94 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.