Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003382
UniProt IDP26651
Primary gene name(s)ZFP36
Synonym gene name(s)G0S24, NUP475, RNF162A, TIS11A, TTP
Protein namemRNA decay activator protein ZFP36
Protein functionZinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element, ARE-containing mRNA transcripts by promoting their poly(A tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis, PubMed:9703499, PubMed:10330172, PubMed:10751406, PubMed:11279239, PubMed:12115244, PubMed:12748283, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:27193233, PubMed:23644599, PubMed:25815583. Acts as an 3'-untranslated region, UTR ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery, PubMed:15687258, PubMed:23644599. Recruits deadenylase CNOT7, and probably the CCR4-NOT complex via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation, PubMed:23644599. Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, PubMed:11719186, PubMed:12748283, PubMed:15687258, PubMed:16364915. Self regulates by destabilizing its own mRNA, PubMed:15187101. Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA, PubMed:10330172, PubMed:10751406, PubMed:12115244, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:19188452, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:25815583. Plays a role in anti-inflammatory responses; suppresses tumor necrosis factor, TNF-alpha production by stimulating ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-containing mRNAs in interferon, IFN- and/or lipopolysaccharide, LPS-induced macrophages, By similarity. Plays also a role in the regulation of dendritic cell maturation at the post-transcriptional level, and hence operates as part of a negative feedback loop to limit the inflammatory response, PubMed:18367721. Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia, PubMed:21775632. Positively regulates early adipogenesis of preadipocytes by promoting ARE-mediated mRNA decay of immediate early genes, IEGs, By similarity. Negatively regulates hematopoietic/erythroid cell differentiation by promoting ARE-mediated mRNA decay of the transcription factor STAT5B mRNA, PubMed:20702587. Plays a role in maintaining skeletal muscle satellite cell quiescence by promoting ARE-mediated mRNA decay of the myogenic determination factor MYOD1 mRNA, By similarity. Associates also with and regulates the expression of non-ARE-containing target mRNAs at the post-transcriptional level, such as MHC class I mRNAs, PubMed:18367721. Participates in association with argonaute RISC catalytic components in the ARE-mediated mRNA decay mechanism; assists microRNA, miRNA targeting ARE-containing mRNAs, PubMed:15766526. May also play a role in the regulation of cytoplasmic mRNA decapping; enhances decapping of ARE-containing RNAs, in vitro, PubMed:16364915. Involved in the delivery of target ARE-mRNAs to processing bodies, PBs, PubMed:17369404. In addition to its cytosolic mRNA-decay function, affects nuclear pre-mRNA processing, By similarity. Negatively regulates nuclear poly(A-binding protein PABPN1-stimulated polyadenylation activity on ARE-containing pre-mRNA during LPS-stimulated macrophages, By similarity. Also involved in the regulation of stress granule, SG and P-body, PB formation and fusion, By similarity. Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis, PubMed:27182009. Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells, PubMed:26926077. {ECO:0000250|UniProtKB:P22893, ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:10751406, ECO:0000269|PubMed:11279239, ECO:0000269|PubMed:11719186, ECO:0000269|PubMed:12115244, ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15187101, ECO:0000269|PubMed:15634918, ECO:0000269|PubMed:15687258, ECO:0000269|PubMed:15766526, ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:16702957, ECO:0000269|PubMed:17030620, ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:18367721, ECO:0000269|PubMed:19188452, ECO:0000269|PubMed:20221403, ECO:0000269|PubMed:20702587, ECO:0000269|PubMed:21775632, ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:25815583, ECO:0000269|PubMed:26926077, ECO:0000269|PubMed:27182009, ECO:0000269|PubMed:27193233, ECO:0000269|PubMed:9703499}.; FUNCTION:, Microbial infection Negatively regulates HTLV-1 TAX-dependent transactivation of viral long terminal repeat, LTR promoter. {ECO:0000269|PubMed:14679154}.
Subcellular locationNucleus {ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:27182009}. Cytoplasm {ECO:0000269|PubMed:10330172, ECO:0000269|PubMed:12115244, ECO:0000269|PubMed:14766228, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:20221403}. Cytoplasmic granule {ECO:0000269|PubMed:15014438}. Cytoplasm, P-body {ECO:0000269|PubMed:17369404}. Note=Shuttles between nucleus and cytoplasm in a CRM1-dependent manner, By similarity. Localized predominantly in the cytoplasm in a p38 MAPK- and YWHAB-dependent manner, By similarity. Colocalizes with SH3KBP1 and MAP3K4 in the cytoplasm, PubMed:20221403. Component of cytoplasmic stress granules, SGs, By similarity. Localizes to cytoplasmic stress granules upon energy starvation, PubMed:15014438. Localizes in processing bodies, PBs, PubMed:17369404. Excluded from stress granules in a phosphorylation MAPKAPK2-dependent manner, By similarity. Shuttles in and out of both cytoplasmic P-body and SGs, By similarity. {ECO:0000250|UniProtKB:P22893, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:17369404, ECO:0000269|PubMed:20221403}.;
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14679154}. Cytoplasm {ECO:0000269|PubMed:14679154}. Note=(Microbial infection Colocalizes with HTLV-1 TAX in the nucleus and the cytoplasm in a region surrounding the nucleus. {ECO:0000269|PubMed:14679154}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P26651
Gene Ontology
(Biological Process)
Complete annatation
3'-UTR-mediated mRNA destabilization [GO:0061158];
3'-UTR-mediated mRNA stabilization [GO:0070935];
cellular response to epidermal growth factor stimulus [GO:0071364];
cellular response to fibroblast growth factor stimulus [GO:0044344];
cellular response to glucocorticoid stimulus [GO:0071385];
cellular response to granulocyte macrophage colony-stimulating factor stimulus [GO:0097011];
cellular response to lipopolysaccharide [GO:0071222];
cellular response to tumor necrosis factor [GO:0071356];
MAPK cascade [GO:0000165];
miRNA mediated inhibition of translation [GO:0035278];
mRNA catabolic process [GO:0006402];
mRNA transport [GO:0051028];
negative regulation of erythrocyte differentiation [GO:0045647];
negative regulation of interleukin-2 biosynthetic process [GO:0045085];
negative regulation of polynucleotide adenylyltransferase activity [GO:1904246];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of viral transcription [GO:0032897];
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay [GO:0000288];
nuclear-transcribed mRNA catabolic process, deadenylation-independent decay [GO:0031086];
nuclear-transcribed mRNA poly(A tail shortening [GO:0000289];
p38MAPK cascade [GO:0038066];
positive regulation of deadenylation-independent decapping of nuclear-transcribed mRNA [GO:1901835];
positive regulation of fat cell differentiation [GO:0045600];
positive regulation of gene silencing by miRNA [GO:2000637];
positive regulation of intracellular mRNA localization [GO:1904582];
positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay [GO:1900153];
positive regulation of nuclear-transcribed mRNA poly(A tail shortening [GO:0060213];
regulation of keratinocyte apoptotic process [GO:1902172];
regulation of keratinocyte differentiation [GO:0045616];
regulation of keratinocyte proliferation [GO:0010837];
regulation of mRNA stability [GO:0043488];
regulation of tumor necrosis factor production [GO:0032680];
response to starvation [GO:0042594];
response to wounding [GO:0009611]
Gene Ontology
(Molecular Function)
Complete annatation
14-3-3 protein binding [GO:0071889];
AU-rich element binding [GO:0017091];
C-C chemokine binding [GO:0019957];
DNA binding [GO:0003677];
enzyme binding [GO:0019899];
metal ion binding [GO:0046872];
mRNA 3'-UTR AU-rich region binding [GO:0035925];
mRNA binding [GO:0003729];
poly(A RNA binding [GO:0044822];
protein kinase binding [GO:0019901];
single-stranded RNA binding [GO:0003727]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytoplasmic stress granule [GO:0010494];
cytosol [GO:0005829];
nucleus [GO:0005634]
Protein-protein interaction113370
Phylogenetic treeP26651
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. CD3-1.843899924082131.97304349036642e-061.43314272225555e-05
AZA vs. DISU0.3147883515759320.2144112520378690.802236854010993
AZA vs. IL7-0.3198875602484870.09841936790501850.833343590495724
AZA vs. SAHA-0.1258256608544180.6079040270275970.871447782308868
DISU vs. CD32.145692531067991.63105034367561e-071.8971028457227e-06
DISU vs. IL7-0.6439216673181540.01114953879775620.125525987584895
DISU vs. SAHA-0.4382703243071080.1353394729457170.472655986983727
DMSO vs. AZA0.02706375758097560.8724551414762811
DMSO vs. CD31.857342226653281.02937751855769e-067.38455824622461e-06
DMSO vs. DISU-0.2901793749451190.2355803324206340.752889792172352
DMSO vs. IL7-0.3391630014881650.06095846316482150.474873299629768
DMSO vs. SAHA-0.1580524109966530.5042585006790340.817230311314925
HIV vs. Mock in Activation-0.005404911536600530.994862591413570.999983755607037
HIV vs. Mock in Latency-0.6704187781070650.0002259447694854530.0205174184049622
IL7 vs. CD31.530187216418127.02499115654565e-050.000428868739176235
SAHA vs. CD31.693909202389161.07442155098392e-056.69348192365756e-05
SAHA vs. IL70.1903688006052910.436075288215990.676902367888768
(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
-1.7 0.014815652 -1.7 0.001104518 -2.1 0.056460179
(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 -0.714655 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

PDB Accession Method Resolution Chain Structure Preview
4J8S X-ray 1.5Å B=312-326.

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

HIV Partner Interaction Type PubMed
Tat upregulates 25943894

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa05166 HTLV-I infection - Homo sapiens (human)