Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000745
UniProt IDP53355
Primary gene name(s)DAPK1
Synonym gene name(s)DAPK
Protein nameDeath-associated protein kinase 1
Protein functionCalcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+ influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing.
Subcellular locationIsoform 1: Cytoplasm. Cytoplasm, cytoskeleton. Note=Colocalizes with MAP1B in the microtubules and cortical actin fibers.;
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Cytoplasm, cytoskeleton.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P53355
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
apoptotic signaling pathway [GO:0097190];
cellular response to interferon-gamma [GO:0071346];
extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625];
intracellular signal transduction [GO:0035556];
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042];
negative regulation of translation [GO:0017148];
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
regulation of apoptotic process [GO:0042981];
regulation of autophagy [GO:0010506];
regulation of N-methyl-D-aspartate selective glutamate receptor activity [GO:2000310]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
calmodulin binding [GO:0005516];
calmodulin-dependent protein kinase activity [GO:0004683];
GTP binding [GO:0005525];
identical protein binding [GO:0042802];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
syntaxin-1 binding [GO:0017075]
Gene Ontology
(Cellular Component)
Complete annatation
actin cytoskeleton [GO:0015629];
cytoplasm [GO:0005737];
plasma membrane [GO:0005886]
Protein-protein interaction107982
Phylogenetic treeP53355
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. CD34.864504689761754.19457801825729e-106.52432197019338e-09
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3-4.624319263185141.05246311665752e-092.09298535890441e-08
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3-4.694122286232741.52919055196321e-091.90705758818922e-08
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activation-0.7410232768722220.5291014581950120.999983755607037
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3-5.379144855541597.50280948480508e-111.6271920484096e-09
SAHA vs. CD3-4.324676226491631.35074494922449e-071.36615613320893e-06
SAHA vs. IL7unknownunknownunknown
(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 1.15449 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
1.106 0.973 1.404 1.441 1.07
(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
DB04069 5,6-Dihydro-Benzo[H]Cinnolin-3-Ylamine experimental unknown unknown
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown unknown
DB07444 6-(3-AMINOPROPYL)-4,9-DIMETHYLPYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONE experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1IG1 X-ray 1.8Å A=2-285.
1JKK X-ray 2.4Å A=2-285.
1JKL X-ray 1.6Å A=2-285.
1JKS X-ray 1.5Å A=2-285.
1JKT X-ray 3.5Å A/B=2-285.
1P4F X-ray 1.9Å A=2-285.
1WVW X-ray 2.4Å A=1-278.
1WVX X-ray 2.6Å A=1-278.
1WVY X-ray 2.8Å A=1-278.
1YR5 X-ray 1.7Å B=302-320.
2W4J X-ray 1.3Å A=1-277.
2W4K X-ray 1.9Å A=1-302.
2X0G X-ray 2.2Å A=1-334.
2XUU X-ray 1.8Å A=1-334.
2XZS X-ray 2.0Å A/B=2-312.
2Y0A X-ray 2.6Å A=2-304.
2Y4P X-ray 2.6Å A/B/C/D=1-285.
2Y4V X-ray 1.8Å B=302-320.
2YAK X-ray 2.2Å A=1-285.
3DFC X-ray 1.9Å B=1-285.
3DGK X-ray 1.7Å A=1-285.
3EH9 X-ray 1.7Å A=2-285.
3EHA X-ray 1.6Å A=2-285.
3F5G X-ray 1.8Å A=2-285.
3F5U X-ray 2.0Å A=1-285.
3GU4 X-ray 1.3Å A=1-285.
3GU5 X-ray 1.6Å A=1-285.
3GU6 X-ray 1.4Å A=1-285.
3GU7 X-ray 1.9Å A=1-285.
3GU8 X-ray 1.6Å A=1-285.
3GUB X-ray 1.7Å A=1-285.
3ZXT X-ray 2.6Å A/B/C/D=1-285.
4B4L X-ray 1.7Å A=1-334.
4PF4 X-ray 1.1Å A=1-277.
4TL0 X-ray 2.7Å A=1-334.
4TXC X-ray 1.9Å A=1-285.
4UV0 X-ray 2.4Å A=1-321.
4YO4 X-ray 1.6Å A=2-285.
4YPD X-ray 1.4Å A=2-285.
5AUT X-ray 1.7Å A=1-285.
5AUU X-ray 1.7Å A=1-285.
5AUV X-ray 1.5Å A=1-285.
5AUW X-ray 1.5Å A=1-285.
5AUX X-ray 1.5Å A=1-285.
5AUY X-ray 2.0Å A=1-285.
5AUZ X-ray 1.6Å A=1-285.
5AV0 X-ray 1.8Å A=1-285.
5AV1 X-ray 1.5Å A=1-285.
5AV2 X-ray 1.5Å A=1-285.
5AV3 X-ray 1.9Å A=1-285.
5AV4 X-ray 1.4Å A=1-285.

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
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05219 Bladder cancer - Homo sapiens (human)