Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001786
UniProt IDQ8NB16
Primary gene name(s)MLKL
Synonym gene name(s)unknown
Protein nameMixed lineage kinase domain-like protein
Protein functionPseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process. Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. Does not have protein kinase activity. {ECO:0000269|PubMed:22265413, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:22421439, ECO:0000269|PubMed:24316671}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:24316671}. Cell membrane {ECO:0000269|PubMed:24316671}. Note=Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q8NB16
Gene Ontology
(Biological Process)
Complete annatation
necroptotic process [GO:0070266];
protein homotrimerization [GO:0070207];
protein phosphorylation [GO:0006468]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
protein complex binding [GO:0032403]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
plasma membrane [GO:0005886]
Protein-protein interaction128244
Phylogenetic treeQ8NB16
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. CD3-0.3708677096520420.2667087177693290.381316049537026
AZA vs. DISU-0.2030944126096620.429607151246610.915321300055321
AZA vs. IL70.19657428200790.3194056110225010.999311006273513
AZA vs. SAHA-0.9010631901572510.1113363515041540.425642145306662
DISU vs. CD30.1569432685775580.6711225686973160.767389941632659
DISU vs. IL70.3893484663524780.1284031812577170.469255262414567
DISU vs. SAHA-0.6957256543057640.2308922015618650.608596418256017
DMSO vs. AZA0.06226780012061060.7202128908040751
DMSO vs. CD30.4242221669616650.1931191505473350.290875825134533
DMSO vs. DISU0.2642069902742340.2865135352599840.799733094344871
DMSO vs. IL70.1409995258971620.4450680802271150.866847714395834
DMSO vs. SAHA-0.9691757886478430.08775026493571540.346136076067688
HIV vs. Mock in Activation0.1933378228626110.7579290100378410.999983755607037
HIV vs. Mock in Latency0.2108023722853870.2102353268588780.999834320637052
IL7 vs. CD30.5732314784960510.07902799154777150.157856999284331
SAHA vs. CD3-0.5517876916955050.3474589078803770.463545125863782
SAHA vs. IL7-1.09877734749260.05105317869604080.187062619266922
(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 0.258876 0.076146
(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
2MSV NMR - A=1-154.
4M67 X-ray 1.9Å A=179-471.
4MWI X-ray 1.7Å A=183-471.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04668 TNF signaling pathway - Homo sapiens (human)