Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006779
UniProt IDQ13546
Primary gene name(s)RIPK1
Synonym gene name(s)RIP, RIP1
Protein nameReceptor-interacting serine/threonine-protein kinase 1
Protein functionSerine-threonine kinase which transduces inflammatory and cell-death signals, programmed necrosis following death receptors ligation, activation of pathogen recognition receptors, PRRs, and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex. {ECO:0000269|PubMed:11101870, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513}.
Subcellular locationCytoplasm. Cell membrane {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q13546
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway [GO:0097296];
activation of JUN kinase activity [GO:0007257];
amyloid fibril formation [GO:1990000];
apoptotic process [GO:0006915];
apoptotic signaling pathway [GO:0097190];
cellular protein catabolic process [GO:0044257];
cellular response to growth factor stimulus [GO:0071363];
cellular response to tumor necrosis factor [GO:0071356];
death-inducing signaling complex assembly [GO:0071550];
extrinsic apoptotic signaling pathway [GO:0097191];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
necroptotic process [GO:0070266];
necroptotic signaling pathway [GO:0097527];
negative regulation of extrinsic apoptotic signaling pathway [GO:2001237];
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand [GO:2001240];
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902042];
negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124];
peptidyl-serine autophosphorylation [GO:0036289];
positive regulation of apoptotic process [GO:0043065];
positive regulation of extrinsic apoptotic signaling pathway [GO:2001238];
positive regulation of hydrogen peroxide-induced cell death [GO:1905206];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of interleukin-8 production [GO:0032757];
positive regulation of JNK cascade [GO:0046330];
positive regulation of macrophage differentiation [GO:0045651];
positive regulation of necroptotic process [GO:0060545];
positive regulation of necrotic cell death [GO:0010940];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of programmed cell death [GO:0043068];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of reactive oxygen species metabolic process [GO:2000379];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of tumor necrosis factor production [GO:0032760];
protein autophosphorylation [GO:0046777];
protein heterooligomerization [GO:0051291];
protein homooligomerization [GO:0051260];
regulation of ATP:ADP antiporter activity [GO:0070926];
regulation of extrinsic apoptotic signaling pathway via death domain receptors [GO:1902041];
regulation of necrotic cell death [GO:0010939];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
response to tumor necrosis factor [GO:0034612];
ripoptosome assembly [GO:0097343];
ripoptosome assembly involved in necroptotic process [GO:1901026];
T cell apoptotic process [GO:0070231];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
death domain binding [GO:0070513];
death receptor binding [GO:0005123];
identical protein binding [GO:0042802];
protein complex binding [GO:0032403];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
death-inducing signaling complex [GO:0031264];
membrane raft [GO:0045121];
mitochondrion [GO:0005739];
receptor complex [GO:0043235];
ripoptosome [GO:0097342]
Protein-protein interaction114274
Phylogenetic treeQ13546
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. CD3-0.3347129963359250.3075035842171630.426374794969741
AZA vs. DISU-0.00101741974353160.996791594665270.999297613676408
AZA vs. IL70.04646442629745920.8093587637346230.999311006273513
AZA vs. SAHA-0.6644240061976910.007008971295181740.0771754808645505
DISU vs. CD30.3212897507598340.3759780831047070.510309168442315
DISU vs. IL70.03807850337320380.8798755414949180.977018349573079
DISU vs. SAHA-0.6615811156428310.02443219044566770.182738234345736
DMSO vs. AZA-0.02332132636716160.8896008580659031
DMSO vs. CD30.3005963497339180.3480656147291230.462032644805201
DMSO vs. DISU-0.02399342299545990.9216843122476310.989176058858871
DMSO vs. IL70.07697332429438680.6691643033569730.93213494903488
DMSO vs. SAHA-0.6472532264210390.006515335935472820.0672761860186936
HIV vs. Mock in Activation0.1410817301334590.8206250595733570.999983755607037
HIV vs. Mock in Latency0.05105580220328310.7574387377039390.999834320637052
IL7 vs. CD30.3878009499787230.2287696661763950.357405180169652
SAHA vs. CD3-0.3539322008072740.3212533919377170.436256695382784
SAHA vs. IL7-0.7137604090910870.003670882316386240.0308788393064766
(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) unknown
(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 -0.0975671 0.55473
(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
0.989 1.09 1.062 1.175 1.213
(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
4ITH X-ray 2.2Å A/B=1-294.
4ITI X-ray 2.8Å A/B=1-294.
4ITJ X-ray 1.8Å A/B=1-294.
4NEU X-ray 2.5Å A/B=1-324.
5HX6 X-ray 2.2Å A/B=1-294.

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

HIV Partner Interaction Type PubMed
retropepsin disrupts 26297639
retropepsin cleaves 26297639
26297639
retropepsin binds 26297639
Vpr upregulates 20801175

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
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