Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002083
UniProt IDQ13153
Primary gene name(s)PAK1
Synonym gene name(s)unknown
Protein nameSerine/threonine-protein kinase PAK 1
Protein functionProtein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction, NMJ. Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin, CFL1 and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation. Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion, PubMed:25766321. {ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:16278681, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:25766321}. Cell junction, focal adhesion. Cell membrane. Cell projection, ruffle membrane. Cell projection, invadopodium {ECO:0000269|PubMed:25766321}. Note=Colocalizes with RUFY3, F-actin and other core migration components in invadopodia at the cell periphery, PubMed:25766321. Recruited to the cell membrane by interaction with CDC42 and RAC1. Recruited to focal adhesions upon activation. Colocalized with CIB1 within membrane ruffles during cell spreading upon readhesion to fibronectin. {ECO:0000269|PubMed:25766321}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13153
Gene Ontology
(Biological Process)
Complete annatation
actin cytoskeleton reorganization [GO:0031532];
apoptotic process [GO:0006915];
axonogenesis [GO:0007409];
branching morphogenesis of an epithelial tube [GO:0048754];
cellular response to insulin stimulus [GO:0032869];
ephrin receptor signaling pathway [GO:0048013];
exocytosis [GO:0006887];
Fc-epsilon receptor signaling pathway [GO:0038095];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
negative regulation of cell proliferation involved in contact inhibition [GO:0060244];
neuron projection morphogenesis [GO:0048812];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of intracellular estrogen receptor signaling pathway [GO:0033148];
positive regulation of JUN kinase activity [GO:0043507];
positive regulation of peptidyl-serine phosphorylation [GO:0033138];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of stress fiber assembly [GO:0051496];
protein autophosphorylation [GO:0046777];
protein phosphorylation [GO:0006468];
response to hypoxia [GO:0001666];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
T cell costimulation [GO:0031295];
T cell receptor signaling pathway [GO:0050852];
wound healing [GO:0042060]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
collagen binding [GO:0005518];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
receptor signaling protein serine/threonine kinase activity [GO:0004702]
Gene Ontology
(Cellular Component)
Complete annatation
axon [GO:0030424];
cell-cell junction [GO:0005911];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
dendrite [GO:0030425];
focal adhesion [GO:0005925];
Golgi apparatus [GO:0005794];
intercalated disc [GO:0014704];
invadopodium [GO:0071437];
nuclear membrane [GO:0031965];
plasma membrane [GO:0005886];
protein complex [GO:0043234];
ruffle [GO:0001726];
ruffle membrane [GO:0032587];
Z disc [GO:0030018]
Protein-protein interaction111095
Phylogenetic treeQ13153
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. CD30.7916466716787530.01662599754822510.0399341888520875
AZA vs. DISU-0.6060487535229560.01798078084945510.318977034644305
AZA vs. IL70.8869375307103785.86448216699509e-060.00192163781963298
AZA vs. SAHA0.3130201091299530.2045498827454160.572035079910209
DISU vs. CD3-1.409904490159690.000139894067479940.00075854790402612
DISU vs. IL71.483103119201491.03593674749547e-083.0270583347617e-06
DISU vs. SAHA0.921467880861760.001844947221581020.0319233060579191
DMSO vs. AZA-0.0223835566350360.8957321762761911
DMSO vs. CD3-0.823353120037190.01320407092704480.0315544620107756
DMSO vs. DISU0.5825481447341480.01833770003460870.278017242979429
DMSO vs. IL70.9159699205962495.90881291895329e-070.000222688386883052
DMSO vs. SAHA0.3296849148591350.1661054980666890.492140687192555
HIV vs. Mock in Activation0.8380043975045190.1899719226968060.999983755607037
HIV vs. Mock in Latency0.1344565157745630.5092127951192530.999834320637052
IL7 vs. CD30.1004069282695680.7619100178131230.841508114652213
SAHA vs. CD3-0.5020597713893070.1567628972832580.249331594940231
SAHA vs. IL7-0.574230070541320.02047157913105850.102012754982339
(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 0.464115 0.00241278
(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
0.983 1.02 1.134 1.203 1.271
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1F3M X-ray 2.3Å A/B=70-149# C/D=249-545.
1YHV X-ray 1.8Å A=249-545.
1YHW X-ray 1.8Å A=249-545.
1ZSG NMR - B=183-204.
2HY8 X-ray 2.0Å 1=249-545.
2QME X-ray 1.7Å I=74-109.
3DVP X-ray 2.5Å C/D=212-221.
3FXZ X-ray 1.6Å A=249-545.
3FY0 X-ray 2.3Å A=249-545.
3Q4Z X-ray 1.8Å A/B=248-545.
3Q52 X-ray 1.8Å A=248-545.
3Q53 X-ray 2.0Å A=248-545.
4DAW X-ray 2.0Å A=249-545.
4EQC X-ray 2.0Å A=249-545.
4O0R X-ray 2.4Å A/B=249-545.
4O0T X-ray 2.6Å A/B=249-545.
4P90 X-ray 2.4Å A/B=249-545.
4ZJI X-ray 1.9Å A/B/C/D=249-545.
4ZJJ X-ray 2.2Å A/B/C/D=249-545.
4ZLO X-ray 2.5Å A/B=249-545.
4ZY4 X-ray 2.6Å A/B=249-545.
4ZY5 X-ray 2.3Å A/B=249-545.
4ZY6 X-ray 2.1Å A/B=249-545.
5DEW X-ray 1.9Å A/B=249-545.
5DEY X-ray 2.1Å A/B=249-545.
5DFP X-ray 2.2Å A=249-545.
5IME X-ray 2.2Å A/B=249-545.
5KBQ X-ray 2.5Å A/B=254-542.
5KBR X-ray 2.3Å A/B=254-542.

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

HIV Partner Interaction Type PubMed
Nef interacts with 19146681
Nef inhibits 23317503
Nef associates with 8108442
Tat regulated by 22465675
Envelope surface glycoprotein gp120 activates 21562048
Nef activates 10559302
Tat interacts with 14694110

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04392 Hippo signaling pathway -multiple species - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04650 Natural killer cell mediated cytotoxicity - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)
hsa04810 Regulation of actin cytoskeleton - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)