Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000569
UniProt IDQ15078
Primary gene name(s)CDK5R1
Synonym gene name(s)CDK5R, NCK5A
Protein nameCyclin-dependent kinase 5 activator 1
Protein functionp35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution. {ECO:0000269|PubMed:24235147}.
Subcellular locationCyclin-dependent kinase 5 activator 1, p35: Cell membrane {ECO:0000305};
Lipid-anchor {ECO:0000305};
Cytoplasmic side {ECO:0000305}. Note=In the primary cortical neurons, p35 is present in the peripheries and nerve terminals.;
SUBCELLULAR LOCATION: Cyclin-dependent kinase 5 activator 1, p25: Nucleus. Cytoplasm, perinuclear region. Note=The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions. In the primary cortical neurons, p25 is primarily concentrated in the cell soma and is largely absent from neurites.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q15078
Gene Ontology
(Biological Process)
Complete annatation
axonal fasciculation [GO:0007413];
axon guidance [GO:0007411];
brain development [GO:0007420];
cell proliferation [GO:0008283];
cerebellum development [GO:0021549];
embryo development [GO:0009790];
ephrin receptor signaling pathway [GO:0048013];
G-protein coupled acetylcholine receptor signaling pathway [GO:0007213];
hippocampus development [GO:0021766];
ionotropic glutamate receptor signaling pathway [GO:0035235];
layer formation in cerebral cortex [GO:0021819];
negative regulation of axon extension [GO:0030517];
negative regulation of transcription, DNA-templated [GO:0045892];
neuron cell-cell adhesion [GO:0007158];
neuron differentiation [GO:0030182];
neuron migration [GO:0001764];
neuron projection development [GO:0031175];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
positive regulation of cell cycle arrest [GO:0071158];
positive regulation of neuron apoptotic process [GO:0043525];
positive regulation of protein targeting to membrane [GO:0090314];
regulation of actin cytoskeleton organization [GO:0032956];
regulation of cyclin-dependent protein serine/threonine kinase activity [GO:0000079];
regulation of dendritic spine morphogenesis [GO:0061001];
regulation of macroautophagy [GO:0016241];
regulation of microtubule cytoskeleton organization [GO:0070507];
regulation of neuron differentiation [GO:0045664];
regulation of signal transduction by p53 class mediator [GO:1901796];
rhythmic process [GO:0048511];
serine phosphorylation of STAT3 protein [GO:0033136];
superior olivary nucleus maturation [GO:0021722]
Gene Ontology
(Molecular Function)
Complete annatation
cadherin binding [GO:0045296];
calcium ion binding [GO:0005509];
cyclin-dependent protein kinase 5 activator activity [GO:0016534];
cyclin-dependent protein serine/threonine kinase activity [GO:0004693];
kinase activity [GO:0016301];
protein kinase activity [GO:0004672];
protein kinase binding [GO:0019901];
protein serine/threonine kinase activator activity [GO:0043539]
Gene Ontology
(Cellular Component)
Complete annatation
axon [GO:0030424];
contractile fiber [GO:0043292];
cyclin-dependent protein kinase 5 holoenzyme complex [GO:0016533];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
dendrite [GO:0030425];
dendritic spine [GO:0043197];
growth cone [GO:0030426];
intracellular membrane-bounded organelle [GO:0043231];
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];
postsynaptic density [GO:0014069]
Protein-protein interaction114376
Phylogenetic treeQ15078
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD3-1.587544575923323.14324891037554e-062.18519592145665e-05
AZA vs. DISU-0.05728380798591460.8232500956966050.98478550430575
AZA vs. IL7-0.6357280802064980.001413930062989840.104471410977676
AZA vs. SAHA-0.6146082327520640.01403266096495910.121918346620054
DISU vs. CD31.5172673831695.57478368736763e-050.000339807073608491
DISU vs. IL7-0.5873416880480820.0221871914007090.189231373641956
DISU vs. SAHA-0.5560532433561120.06022350246353130.309770786903713
DMSO vs. AZA0.08237316693748150.634205299941161
DMSO vs. CD31.65669581555116.30680829005748e-074.71758028250824e-06
DMSO vs. DISU0.1375154469229230.5784220298724760.932467317571925
DMSO vs. IL7-0.7110319335090620.0001393568117865620.0150057424120173
DMSO vs. SAHA-0.7027180871811360.003697433077871180.0447223225654868
HIV vs. Mock in Activation-0.1888805917205390.7653768616898050.999983755607037
HIV vs. Mock in Latency-0.02980231346397280.8616256596113940.999834320637052
IL7 vs. CD30.959022343127920.003835125516265410.0134340801549311
SAHA vs. CD30.9482219398596350.009477150611063580.0244938117421308
SAHA vs. IL70.01723080356269140.9449382438322570.978348126071593
(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 0.598117 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
unknown unknown unknown unknown unknown
(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
DB07364 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE experimental unknown unknown
DB02052 Indirubin-3&,39;-Monoxime experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1H4L X-ray 2.6Å D/E=147-293.
1UNG X-ray 2.3Å D/E=100-307.
1UNH X-ray 2.3Å D/E=100-307.
1UNL X-ray 2.2Å D/E=100-307.
3O0G X-ray 1.9Å D/E=145-293.

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

HIV Partner Interaction Type PubMed
Tat modulates 18247371
Tat downregulates 12491158
1824737118247371

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa05010 Alzheimer's disease - Homo sapiens (human)
hsa05030 Cocaine addiction - Homo sapiens (human)
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