Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000703
UniProt IDP41240
Primary gene name(s)CSK
Synonym gene name(s)unknown
Protein nameTyrosine-protein kinase CSK
Protein functionNon-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases, SFKs including LCK, SRC, HCK, FYN, LYN or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor, TCR and B-cell receptor, BCR by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK. {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:9281320}.
Subcellular locationCytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}. Note=Mainly cytoplasmic, also present in lipid rafts. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P41240
Gene Ontology
(Biological Process)
Complete annatation
adaptive immune response [GO:0002250];
adherens junction organization [GO:0034332];
brain development [GO:0007420];
cell differentiation [GO:0030154];
cell migration [GO:0016477];
cellular response to peptide hormone stimulus [GO:0071375];
central nervous system development [GO:0007417];
epidermal growth factor receptor signaling pathway [GO:0007173];
innate immune response [GO:0045087];
negative regulation of bone resorption [GO:0045779];
negative regulation of cell proliferation [GO:0008285];
negative regulation of ERK1 and ERK2 cascade [GO:0070373];
negative regulation of Golgi to plasma membrane protein transport [GO:0042997];
negative regulation of interleukin-6 production [GO:0032715];
negative regulation of kinase activity [GO:0033673];
negative regulation of low-density lipoprotein particle clearance [GO:0010989];
negative regulation of phagocytosis [GO:0050765];
oligodendrocyte differentiation [GO:0048709];
peptidyl-tyrosine autophosphorylation [GO:0038083];
positive regulation of MAP kinase activity [GO:0043406];
protein phosphorylation [GO:0006468];
regulation of cell proliferation [GO:0042127];
regulation of cytokine production [GO:0001817];
regulation of Fc receptor mediated stimulatory signaling pathway [GO:0060368];
T cell costimulation [GO:0031295];
T cell receptor signaling pathway [GO:0050852];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
identical protein binding [GO:0042802];
kinase activity [GO:0016301];
metal ion binding [GO:0046872];
non-membrane spanning protein tyrosine kinase activity [GO:0004715];
protein C-terminus binding [GO:0008022];
protein kinase A catalytic subunit binding [GO:0034236];
protein tyrosine kinase activity [GO:0004713];
receptor binding [GO:0005102]
Gene Ontology
(Cellular Component)
Complete annatation
cell-cell junction [GO:0005911];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
extrinsic component of cytoplasmic side of plasma membrane [GO:0031234];
membrane raft [GO:0045121];
plasma membrane [GO:0005886]
Protein-protein interaction107832
Phylogenetic treeP41240
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. CD3-0.6688607260886440.04307168826443160.0881195175134402
AZA vs. DISU-0.3295036003260940.1923886492658180.780368775323152
AZA vs. IL70.009450452825823850.9607166904281820.999311006273513
AZA vs. SAHA-0.3986271296997010.1032743078599680.407421333860548
DISU vs. CD30.3281388893158320.3690983455798130.503009534514972
DISU vs. IL70.3293172989759630.1912413500396380.5650904110186
DISU vs. SAHA-0.06670635534593850.8194766600717680.953692976769741
DMSO vs. AZA0.03566710278554220.8309482487685021
DMSO vs. CD30.6926412555174630.03155469827128220.0654971272766053
DMSO vs. DISU0.3631673937127590.1366698593387580.627210114056366
DMSO vs. IL7-0.01872796477907010.9168311429841760.982877932049955
DMSO vs. SAHA-0.4392848057835160.06283928654600220.288999355366127
HIV vs. Mock in Activation0.01692344245673380.9782962753323330.999983755607037
HIV vs. Mock in Latency-0.02304644530607110.8887029652357640.999834320637052
IL7 vs. CD30.6842034624570280.0342850460655530.0810378703694654
SAHA vs. CD30.2474317275511870.4835900438229580.593619054987496
SAHA vs. IL7-0.410198435331920.09234603640160710.274452711497994
(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) FALSE
(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 -0.709663 0.00322755
(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
0.955 0.892 0.854 0.868 0.873
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
-1.46 0.004 -0.37 0.7174 0.3 0.5255 Cell growth and proliferation at 4 hpi
(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
DB02010 Staurosporine experimental unknown unknown
DB05075 TG100801 investigational unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BYG X-ray 2.4Å A=173-450.
1CSK X-ray 2.5Å A/B/C/D=1-71.
3D7T X-ray 2.9Å A=188-450.
3D7U X-ray 4.1Å A/C=188-450.
3EAC X-ray 1.3Å A=73-178.
3EAZ X-ray 1.3Å A=73-178.

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

HIV Partner Interaction Type PubMed
Tat activates 9621077
Envelope surface glycoprotein gp120 activates 21562048

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)