Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001788
UniProt IDQ8IZD2
Primary gene name(s)KMT2E
Synonym gene name(s)MLL5
Protein nameHistone-lysine N-methyltransferase 2E
Protein functionHistone methyltransferase that specifically mono- and dimethylates 'Lys-4' of histone H3, H3K4me1 and H3K4me2. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell, HSCs self-renewal by a mechanism that involves DNA methylation. Plays an essential role in retinoic-acid-induced granulopoiesis by acting as a coactivator of RAR-alpha, RARA in target gene promoters. Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages. Required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells. Overexpression inhibits cell cycle progression, while knockdown induces cell cycle arrest at both the G1 and G2/M phases.; FUNCTION: Isoform NKp44L: Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity.
Subcellular locationNucleus speckle {ECO:0000269|PubMed:14718661}. Note=Absent from the nucleolus. {ECO:0000269|PubMed:14718661}.;
SUBCELLULAR LOCATION: Isoform NKp44L: Cytoplasm {ECO:0000269|PubMed:23958951}. Cell membrane {ECO:0000269|PubMed:23958951};
Peripheral membrane protein {ECO:0000269|PubMed:23958951}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8IZD2
Gene Ontology
(Biological Process)
Complete annatation
cell cycle arrest [GO:0007050];
cellular response to retinoic acid [GO:0071300];
DNA methylation [GO:0006306];
erythrocyte differentiation [GO:0030218];
histone H3-K4 methylation [GO:0051568];
neutrophil activation [GO:0042119];
neutrophil mediated immunity [GO:0002446];
positive regulation of granulocyte differentiation [GO:0030854];
positive regulation of transcription, DNA-templated [GO:0045893];
retinoic acid receptor signaling pathway [GO:0048384];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
enzyme binding [GO:0019899];
histone-lysine N-methyltransferase activity [GO:0018024];
histone methyltransferase activity, H3-K4 specific [GO:0042800];
transcription coactivator activity [GO:0003713];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
intercellular bridge [GO:0045171];
intracellular membrane-bounded organelle [GO:0043231];
MLL5-L complex [GO:0070688];
nuclear speck [GO:0016607];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886]
Protein-protein interaction120990
Phylogenetic treeQ8IZD2
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. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activationunknownunknownunknown
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
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 -0.17603 0.312491
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2LV9 NMR - A=109-188.
4L58 X-ray 1.4Å A=117-181.

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

HIV Partner Interaction Type PubMed
Envelope transmembrane glycoprotein gp41 interacts with 23696512
Envelope transmembrane glycoprotein gp41 enhances 16046540
16954720
Envelope transmembrane glycoprotein gp41 upregulates 16046540

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00310 Lysine degradation - Homo sapiens (human)
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