Detailed Information

Protein Information (annotations from UniProt)

Database ID	HIV0001931
UniProt ID	P51955
Primary gene name(s)	NEK2
Synonym gene name(s)	NEK2A, NLK1
Protein name	Serine/threonine-protein kinase Nek2
Protein function	Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation, essential for the formation of bipolar spindles and high-fidelity chromosome separation by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly, PubMed:24554434. NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis, PubMed:25704143. Involved in the regulation of centrosome disjunction, PubMed:26220856. {ECO:0000269\|PubMed:11742531, ECO:0000269\|PubMed:12857871, ECO:0000269\|PubMed:14978040, ECO:0000269\|PubMed:15358203, ECO:0000269\|PubMed:15388344, ECO:0000269\|PubMed:17283141, ECO:0000269\|PubMed:17621308, ECO:0000269\|PubMed:17626005, ECO:0000269\|PubMed:18086858, ECO:0000269\|PubMed:18297113, ECO:0000269\|PubMed:20034488, ECO:0000269\|PubMed:21076410, ECO:0000269\|PubMed:24554434, ECO:0000269\|PubMed:25704143, ECO:0000269\|PubMed:26220856}.; FUNCTION: Isoform 1: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269\|PubMed:15161910}.; FUNCTION: Isoform 2: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269\|PubMed:15161910}.
Subcellular location	Isoform 1: Nucleus. Nucleus, nucleolus {ECO:0000269\|PubMed:15161910}. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:26220856}. Cytoplasm, cytoskeleton, spindle pole. Chromosome, centromere, kinetochore. Chromosome, centromere {ECO:0000250}. Note=STK3/MST2 and SAV1 are required for its targeting to the centrosome. Colocalizes with SGO1 and MAD1L1 at the kinetochore. Not associated with kinetochore in the interphase but becomes associated with it upon the breakdown of the nuclear envelope. Has a nucleolar targeting/ retention activity via a coiled-coil domain at the C-terminal end.; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Note=Predominantly cytoplasmic.; SUBCELLULAR LOCATION: Isoform 4: Nucleus. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Predominantly nuclear.
ECO code	Click here for more information.
Amino acid sequence FASTA format: P51955
Gene Ontology (Biological Process) Complete annatation	blastocyst development [GO:0001824]; cell division [GO:0051301]; centrosome separation [GO:0051299]; chromosome segregation [GO:0007059]; G2/M transition of mitotic cell cycle [GO:0000086]; meiotic cell cycle [GO:0051321]; mitotic nuclear division [GO:0007067]; mitotic sister chromatid segregation [GO:0000070]; mitotic spindle assembly [GO:0090307]; negative regulation of centriole-centriole cohesion [GO:1903126]; negative regulation of DNA binding [GO:0043392]; positive regulation of telomerase activity [GO:0051973]; positive regulation of telomere capping [GO:1904355]; positive regulation of telomere maintenance via telomerase [GO:0032212]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; regulation of attachment of spindle microtubules to kinetochore [GO:0051988]; regulation of mitotic centrosome separation [GO:0046602]; regulation of mitotic nuclear division [GO:0007088]; spindle assembly [GO:0051225]
Gene Ontology (Molecular Function) Complete annatation	ATP binding [GO:0005524]; metal ion binding [GO:0046872]; protein kinase activity [GO:0004672]; protein phosphatase binding [GO:0019903]; protein serine/threonine kinase activity [GO:0004674]
Gene Ontology (Cellular Component) Complete annatation	centrosome [GO:0005813]; condensed chromosome kinetochore [GO:0000777]; condensed nuclear chromosome [GO:0000794]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; kinetochore [GO:0000776]; microtubule [GO:0005874]; midbody [GO:0030496]; nucleolus [GO:0005730]; nucleus [GO:0005634]; protein complex [GO:0043234]; spindle pole [GO:0000922]
Protein-protein interaction	110826
Phylogenetic tree	P51955
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	-0.534336222234717	0.699614071959931	0.785736459953806
AZA vs. DISU	-0.0200010358699199	0.973850689747274	0.997811953897277
AZA vs. IL7	-0.0179956642574994	0.976742206972112	0.999311006273513
AZA vs. SAHA	-0.443033101272265	0.432625762529713	0.781755064058127
DISU vs. CD3	0.503782917471303	0.712230544063723	0.798168405413469
DISU vs. IL7	-0.0076701501075511	0.989570114241844	0.999065831444279
DISU vs. SAHA	-0.423489038277031	0.425036995882693	0.776890584262731
DMSO vs. AZA	-0.0303054549484143	0.958645950444682	1
DMSO vs. CD3	0.484903048405091	0.727166670340856	0.801255550664497
DMSO vs. DISU	-0.0152538358129691	0.977799580900349	0.995772380333035
DMSO vs. IL7	0.0208110997753617	0.970243429674904	0.993912727803016
DMSO vs. SAHA	-0.418378098360063	0.394826252647238	0.739030076461782
HIV vs. Mock in Activation	-0.30788233346154	0.895566844560839	0.999983755607037
HIV vs. Mock in Latency	0.360493994618932	0.536962235634309	0.999834320637052
IL7 vs. CD3	0.526771187992053	0.700152711884702	0.796904162669948
SAHA vs. CD3	0.0641269711297706	0.964187928082991	0.976031639691618
SAHA vs. IL7	-0.428166323281722	0.426658423375322	0.669106229084436

(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
3.1	0.000804265	1.8	0.038955253	2	0.11310395

(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	0.336271	0.015495

(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
0.018	0.008

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
2.014	1.751	3.39	5.087	1.857

(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
204641_at	4.76	Yes	upregulated in CD4+ cells
204641_at	8.98	Yes	upregulated in CD8+ cells

Protein Overview top

Drug-protein Interaction (annotations from DrugBank) top

Drugbank ID	Drug Name	Drug Status	Pharmacological Action	Drug Action
DB07180	5-[(Z)-(5-CHLORO-2-OXO-1,2-DIHYDRO-3H-INDOL-3-YLIDENE)METHYL]-N-(DIETHYLAMINO)ETHYL]-2,4-DIMETHYL-1H-PYRROLE-3-CARBOXAMIDE	experimental	unknown	unknown

Protein Secondary Structure (annotations from PDB) top

PDB Accession	Method	Resolution	Chain
2JAV	X-ray	2.2Å	A=1-271.
2W5A	X-ray	1.5Å	A=1-271.
2W5B	X-ray	2.4Å	A=1-271.
2W5H	X-ray	2.3Å	A=1-271.
2WQO	X-ray	2.1Å	A=1-271.
2XK3	X-ray	2.2Å	A=1-271.
2XK4	X-ray	2.1Å	A=1-271.
2XK6	X-ray	2.2Å	A=1-271.
2XK7	X-ray	1.9Å	A=1-271.
2XK8	X-ray	2.0Å	A=1-271.
2XKC	X-ray	2.5Å	A=1-271.
2XKD	X-ray	1.9Å	A=1-271.
2XKE	X-ray	2.2Å	A=1-271.
2XKF	X-ray	2.3Å	A=1-271.
2XNM	X-ray	1.8Å	A=1-271.
2XNN	X-ray	2.5Å	A=1-271.
2XNO	X-ray	1.9Å	A=1-271.
2XNP	X-ray	1.9Å	A=1-271.
4A4X	X-ray	2.4Å	A=1-271.
4AFE	X-ray	2.6Å	A=1-271.