Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000443
UniProt IDQ13557
Primary gene name(s)CAMK2D
Synonym gene name(s)CAMKD
Protein nameCalcium/calmodulin-dependent protein kinase type II subunit delta
Protein functionCalcium/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. 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. 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. {ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:17179159}.
Subcellular locationCell membrane, sarcolemma {ECO:0000305};
Peripheral membrane protein {ECO:0000305};
Cytoplasmic side {ECO:0000305}. Sarcoplasmic reticulum membrane {ECO:0000305};
Peripheral membrane protein {ECO:0000305};
Cytoplasmic side {ECO:0000305}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13557
Gene Ontology
(Biological Process)
Complete annatation
calcium ion transport [GO:0006816];
cardiac muscle cell contraction [GO:0086003];
cell growth involved in cardiac muscle cell development [GO:0061049];
cellular potassium ion homeostasis [GO:0030007];
cellular response to calcium ion [GO:0071277];
endoplasmic reticulum calcium ion homeostasis [GO:0032469];
G1/S transition of mitotic cell cycle [GO:0000082];
interferon-gamma-mediated signaling pathway [GO:0060333];
MAPK cascade [GO:0000165];
negative regulation of sodium ion transmembrane transport [GO:1902306];
negative regulation of sodium ion transmembrane transporter activity [GO:2000650];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
positive regulation of cardiac muscle cell apoptotic process [GO:0010666];
positive regulation of cardiac muscle hypertrophy [GO:0010613];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of Rac protein signal transduction [GO:0035022];
positive regulation of smooth muscle cell migration [GO:0014911];
positive regulation of smooth muscle cell proliferation [GO:0048661];
protein autophosphorylation [GO:0046777];
protein oligomerization [GO:0051259];
protein phosphorylation [GO:0006468];
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel [GO:1902514];
regulation of cardiac muscle cell action potential [GO:0098901];
regulation of cardiac muscle cell action potential involved in regulation of contraction [GO:0098909];
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion [GO:0010881];
regulation of cell communication by electrical coupling [GO:0010649];
regulation of cell communication by electrical coupling involved in cardiac conduction [GO:1901844];
regulation of cell growth [GO:0001558];
regulation of cellular localization [GO:0060341];
regulation of cellular response to heat [GO:1900034];
regulation of G2/M transition of mitotic cell cycle [GO:0010389];
regulation of heart contraction [GO:0008016];
regulation of heart rate by cardiac conduction [GO:0086091];
regulation of histone deacetylase activity [GO:1901725];
regulation of membrane depolarization [GO:0003254];
regulation of relaxation of cardiac muscle [GO:1901897];
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum [GO:0010880];
regulation of ryanodine-sensitive calcium-release channel activity [GO:0060314];
regulation of the force of heart contraction [GO:0002026];
regulation of transcription from RNA polymerase II promoter [GO:0006357];
relaxation of cardiac muscle [GO:0055119];
response to hypoxia [GO:0001666]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
calmodulin binding [GO:0005516];
calmodulin-dependent protein kinase activity [GO:0004683];
ion channel binding [GO:0044325];
protein homodimerization activity [GO:0042803];
protein serine/threonine kinase activity [GO:0004674];
Ras guanyl-nucleotide exchange factor activity [GO:0005088];
sodium channel inhibitor activity [GO:0019871];
titin binding [GO:0031432]
Gene Ontology
(Cellular Component)
Complete annatation
axon initial segment [GO:0043194];
calcium channel complex [GO:0034704];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endocytic vesicle membrane [GO:0030666];
intercalated disc [GO:0014704];
membrane [GO:0016020];
neuromuscular junction [GO:0031594];
neuronal cell body [GO:0043025];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
sarcoplasmic reticulum membrane [GO:0033017];
T-tubule [GO:0030315]
Protein-protein interaction107267
Phylogenetic treeQ13557
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD32.025305323791023.04215475033232e-093.95952991338589e-08
AZA vs. DISU0.09962707634752470.7538826578377180.976021571236163
AZA vs. IL7-0.1915966894834050.3269607267489480.999311006273513
AZA vs. SAHA0.3263439827289590.1847368541821450.548930285815425
DISU vs. CD3-1.937277094612895.12126278939817e-075.30934768138845e-06
DISU vs. IL7-0.2995478367040780.3689744820128320.744119105865344
DISU vs. SAHA0.2271277465528840.4667968398523810.802390587891908
DMSO vs. AZA-0.08437553621063080.6218089688728741
DMSO vs. CD3-2.12060202712742.39790742817547e-103.52778080131479e-09
DMSO vs. DISU-0.1857590601866590.5496940991011720.92277332651041
DMSO vs. IL7-0.1000007289747840.5846554065013130.908907935754077
DMSO vs. SAHA0.403185385209040.09009488146773530.350857870439338
HIV vs. Mock in Activation-0.2724992730066190.6627506364435170.999983755607037
HIV vs. Mock in Latency0.189278862726480.2574587119238450.999834320637052
IL7 vs. CD3-2.208104624952446.80668854613486e-111.48261873491172e-09
SAHA vs. CD3-1.724326694838442.29569861986967e-061.7101422739217e-05
SAHA vs. IL70.5137904155020440.03682850244730380.149314912826966
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.466056 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.033 1.01 1.101 1.312 1.374
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB08039 (3Z)-N,N-DIMETHYL-2-OXO-3-(4,5,6,7-TETRAHYDRO-1H-INDOL-2-YLMETHYLIDENE)-2,3-DIHYDRO-1H-INDOLE-5-SULFONAMIDE experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2VN9 X-ray 2.3Å A/B=11-309.
2W2C X-ray 2.7Å A/B/C/D/E/F/G/H/I/J/K/L/M/N=334-475.
2WEL X-ray 1.9Å A=11-335.
3GP2 X-ray 1.4Å B=294-311.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04020 Calcium signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04114 Oocyte meiosis - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04713 Circadian entrainment - Homo sapiens (human)
hsa04720 Long-term potentiation - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04725 Cholinergic synapse - Homo sapiens (human)
hsa04728 Dopaminergic synapse - Homo sapiens (human)
hsa04740 Olfactory transduction - Homo sapiens (human)
hsa04750 Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
hsa04911 Insulin secretion - Homo sapiens (human)
hsa04912 GnRH signaling pathway - Homo sapiens (human)
hsa04916 Melanogenesis - Homo sapiens (human)
hsa04921 Oxytocin signaling pathway - Homo sapiens (human)
hsa04922 Glucagon signaling pathway - Homo sapiens (human)
hsa04925 Aldosterone synthesis and secretion - Homo sapiens (human)
hsa04971 Gastric acid secretion - Homo sapiens (human)
hsa05031 Amphetamine addiction - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)