Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0012927
UniProt IDP51617
Primary gene name(s)IRAK1
Synonym gene name(s)IRAK
Protein nameInterleukin-1 receptor-associated kinase 1
Protein functionSerine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor, TLR and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins, PELI1, PELI2 and PELI3 to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs, CHUK/IKKA and IKBKB/IKKB leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7, IRF7 to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:16690127}. Nucleus {ECO:0000269|PubMed:16690127}. Lipid droplet {ECO:0000250}. Note=Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P51617
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
activation of NF-kappaB-inducing kinase activity [GO:0007250];
aging [GO:0007568];
cellular response to heat [GO:0034605];
cellular response to hypoxia [GO:0071456];
innate immune response [GO:0045087];
interleukin-1-mediated signaling pathway [GO:0070498];
JNK cascade [GO:0007254];
lipopolysaccharide-mediated signaling pathway [GO:0031663];
MyD88-dependent toll-like receptor signaling pathway [GO:0002755];
negative regulation of apoptotic process [GO:0043066];
negative regulation of NF-kappaB transcription factor activity [GO:0032088];
nucleotide-binding oligomerization domain containing signaling pathway [GO:0070423];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of MAP kinase activity [GO:0043406];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of smooth muscle cell proliferation [GO:0048661];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of type I interferon production [GO:0032481];
protein autophosphorylation [GO:0046777];
protein oligomerization [GO:0051259];
protein phosphorylation [GO:0006468];
regulation of cytokine-mediated signaling pathway [GO:0001959];
response to interleukin-1 [GO:0070555];
response to lipopolysaccharide [GO:0032496];
signal transduction [GO:0007165];
toll-like receptor 2 signaling pathway [GO:0034134];
toll-like receptor 4 signaling pathway [GO:0034142];
toll-like receptor 9 signaling pathway [GO:0034162];
toll-like receptor signaling pathway [GO:0002224];
transmembrane receptor protein serine/threonine kinase signaling pathway [GO:0007178]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
kinase activity [GO:0016301];
NF-kappaB-inducing kinase activity [GO:0004704];
protein heterodimerization activity [GO:0046982];
protein homodimerization activity [GO:0042803];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endosome membrane [GO:0010008];
interleukin-1 receptor complex [GO:0045323];
lipid particle [GO:0005811];
nucleus [GO:0005634];
plasma membrane [GO:0005886]
Protein-protein interaction109863
Phylogenetic treeP51617
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. CD30.6002825560611230.06824094576913990.128614172143613
AZA vs. DISU-0.1643191494109870.5156366348495380.938437432475966
AZA vs. IL70.1135989678046260.55419348548270.999311006273513
AZA vs. SAHA-1.140649198727890.0004195273452943790.0113945138792207
DISU vs. CD3-0.7768289043276590.03319429615723990.0777335436188029
DISU vs. IL70.268514796190820.2861659551369680.673003396831481
DISU vs. SAHA-0.9741520679278390.003008399569758850.0452490917323708
DMSO vs. AZA0.02606147934122590.8762172025685851
DMSO vs. CD3-0.5869371918603430.06785819308064070.124196927025672
DMSO vs. DISU0.1881271821369610.4403494956743890.884575846873152
DMSO vs. IL70.09518459909732390.5961184572288150.911685679489133
DMSO vs. SAHA-1.17199881747730.000237004240127070.00651804909298371
HIV vs. Mock in Activation0.1705205165723440.7840366603130980.999983755607037
HIV vs. Mock in Latency-0.01776518738270770.9142388885948880.999834320637052
IL7 vs. CD3-0.4805198595978420.1358658510766710.240054621179071
SAHA vs. CD3-1.764480280997392.19941132684198e-061.64819138217348e-05
SAHA vs. IL7-1.257074416279510.0001030066465551590.00200610102089467
(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 0.530959 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

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

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

HIV Partner Interaction Type PubMed
Tat downregulates 25472883

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa05133 Pertussis - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)