Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009998
UniProt IDP19438
Primary gene name(s)TNFRSF1A
Synonym gene name(s)TNFAR, TNFR1
Protein nameTumor necrosis factor receptor superfamily member 1A
Protein functionReceptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex, DISC performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases, aspartate-specific cysteine proteases mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.
Subcellular locationCell membrane {ECO:0000269|PubMed:22801493};
Single-pass type I membrane protein {ECO:0000269|PubMed:22801493}. Golgi apparatus membrane {ECO:0000269|PubMed:22801493};
Single-pass type I membrane protein {ECO:0000269|PubMed:22801493}. Secreted {ECO:0000269|PubMed:22801493}. Note=A secreted form is produced through proteolytic processing.;
SUBCELLULAR LOCATION: Isoform 4: Secreted. Note=Lacks a Golgi-retention motif, is not membrane bound and therefore is secreted.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P19438
Gene Ontology
(Biological Process)
Complete annatation
cellular response to mechanical stimulus [GO:0071260];
cytokine-mediated signaling pathway [GO:0019221];
death-inducing signaling complex assembly [GO:0071550];
defense response to bacterium [GO:0042742];
establishment of protein localization to plasma membrane [GO:0090002];
extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
immune response [GO:0006955];
inflammatory response [GO:0006954];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
negative regulation of inflammatory response [GO:0050728];
positive regulation of ceramide biosynthetic process [GO:2000304];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of inflammatory response [GO:0050729];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of tyrosine phosphorylation of Stat1 protein [GO:0042511];
prostaglandin metabolic process [GO:0006693];
regulation of apoptotic process [GO:0042981];
regulation of cell proliferation [GO:0042127];
regulation of establishment of endothelial barrier [GO:1903140];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
response to lipopolysaccharide [GO:0032496];
tumor necrosis factor-mediated signaling pathway [GO:0033209];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
tumor necrosis factor-activated receptor activity [GO:0005031];
tumor necrosis factor binding [GO:0043120]
Gene Ontology
(Cellular Component)
Complete annatation
cell surface [GO:0009986];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
Golgi membrane [GO:0000139];
integral component of plasma membrane [GO:0005887];
membrane raft [GO:0045121];
mitochondrion [GO:0005739];
plasma membrane [GO:0005886];
receptor complex [GO:0043235]
Protein-protein interaction112986
Phylogenetic treeP19438
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. CD30.2762792131880630.4006461122009310.522139057768477
AZA vs. DISU-0.04089713715993810.8721849726528110.991631204917382
AZA vs. IL7-0.2418563312232790.2133475302408240.980124146089588
AZA vs. SAHA-0.1535150088697320.5315407921932320.83847278165768
DISU vs. CD3-0.3295508360689030.3640243124815490.498123529952242
DISU vs. IL7-0.2111217557374620.405662150838180.766431498168388
DISU vs. SAHA-0.1095841165114340.7077499635133730.913563472598201
DMSO vs. AZA0.01095270751696220.9484930348681371
DMSO vs. CD3-0.2750309400271690.391905136789510.506437715365755
DMSO vs. DISU0.05027958501448210.8375853192112250.981983099464226
DMSO vs. IL7-0.2457214177453890.1764241762769540.686524124257893
DMSO vs. SAHA-0.1699524784697090.473538755939890.798734751916841
HIV vs. Mock in Activation0.03122054183540270.9600491261859920.999983755607037
HIV vs. Mock in Latency0.05153898588151920.7573051272611980.999834320637052
IL7 vs. CD3-0.5131094654209810.1136109264872550.20927013258492
SAHA vs. CD3-0.4526807339442140.2018005521827810.304265564921912
SAHA vs. IL70.08653138402328040.7243087099482320.873775619047951
(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 -0.439906 0.00199466
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB03507 6-[3-(4-Morpholinyl)Propyl]-2-(3-Nitrophenyl)-5-Thioxo-5,6,-Dihydro-7h-Thienol[2&,39;,3&,39;:4,5]Pyrrolo[1,2-C]Imidazol-7-One experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1EXT X-ray 1.8Å A/B=41-201.
1FT4 X-ray 2.9Å A/B=41-201.
1ICH NMR - A=345-455.
1NCF X-ray 2.2Å A/B=41-201.
1TNR X-ray 2.8Å R=44-182.

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

HIV Partner Interaction Type PubMed
Nef downregulates 25275127
Tat upregulates 11522182
capsid interacts with 25840914

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04215 Apoptosis - multiple species - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05010 Alzheimer's disease - Homo sapiens (human)
hsa05014 Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)