Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000652
UniProt IDA5YKK6
Primary gene name(s)CNOT1
Synonym gene name(s)CDC39, KIAA1007, NOT1
Protein nameCCR4-NOT transcription complex subunit 1
Protein functionScaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element, ARE-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of emryonic stem, ES cell identity. {ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065, ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759, ECO:0000269|PubMed:23644599}.
Subcellular locationCytoplasm, P-body {ECO:0000269|PubMed:21976065}. Nucleus {ECO:0000305|PubMed:21976065}. Note=NANOS2 promotes its localization to P-body. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: A5YKK6
Gene Ontology
(Biological Process)
Complete annatation
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
gene silencing by miRNA [GO:0035195];
multicellular organism development [GO:0007275];
negative regulation of intracellular estrogen receptor signaling pathway [GO:0033147];
negative regulation of retinoic acid receptor signaling pathway [GO:0048387];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of translation [GO:0017148];
nuclear-transcribed mRNA poly(A tail shortening [GO:0000289];
positive regulation of cytoplasmic mRNA processing body assembly [GO:0010606];
positive regulation of mRNA catabolic process [GO:0061014];
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 stem cell population maintenance [GO:2000036];
RNA phosphodiester bond hydrolysis, exonucleolytic [GO:0090503];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
armadillo repeat domain binding [GO:0070016];
estrogen receptor binding [GO:0030331];
poly(A RNA binding [GO:0044822];
protein complex scaffold [GO:0032947];
protein domain specific binding [GO:0019904];
retinoic acid receptor binding [GO:0042974]
Gene Ontology
(Cellular Component)
Complete annatation
CCR4-NOT complex [GO:0030014];
CCR4-NOT core complex [GO:0030015];
cytoplasm [GO:0005737];
cytoplasmic mRNA processing body [GO:0000932];
cytosol [GO:0005829];
extracellular space [GO:0005615];
intracellular membrane-bounded organelle [GO:0043231];
membrane [GO:0016020];
nucleus [GO:0005634];
peroxisomal membrane [GO:0005778]
Protein-protein interaction116660
Phylogenetic treeA5YKK6
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. CD30.6246552626494210.05703525163959330.1114816901455
AZA vs. DISU0.2088013288300730.4086384358936360.908113198395223
AZA vs. IL70.1242946130917160.5167783572220230.999311006273513
AZA vs. SAHA-0.05257435656195030.8289450538745490.959284914894791
DISU vs. CD3-0.4284612191667220.2370049747565550.362040229983817
DISU vs. IL7-0.09364261073781050.709456392448210.925147623623488
DISU vs. SAHA-0.259732379737720.3727936143685420.742974419749841
DMSO vs. AZA0.03470964636147410.8352006102446081
DMSO vs. CD3-0.6010397259774570.06059753446791770.11320707549097
DMSO vs. DISU-0.1758656652571620.4702886024106790.896439316763082
DMSO vs. IL70.09681632014339740.5890359012185560.909845858619163
DMSO vs. SAHA-0.09390279121401350.6897617805505020.904340999971867
HIV vs. Mock in Activation0.2677936856649560.6682484268016620.999983755607037
HIV vs. Mock in Latency0.1182229225666380.4719911485626460.999834320637052
IL7 vs. CD3-0.4932811348778410.1247151886441750.224403967820657
SAHA vs. CD3-0.7016913584602360.04791622640470880.0955914127507231
SAHA vs. IL7-0.1800877560481330.4590661200228640.695823297458486
(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 -0.0808263 0.674525
(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
1.017 0.961 0.957 0.975 0.959
(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
4C0D X-ray 3.2Å A=1565-2371.
4CQO X-ray 2.8Å A/C=1833-2361.
4CRU X-ray 1.6Å A=1356-1607.
4CRV X-ray 2.0Å A=1356-1607.
4CRW X-ray 1.7Å A=1093-1317.
4CT4 X-ray 2.3Å A/C=1063-1314.
4CT6 X-ray 2.1Å A=1352-1594.
4CT7 X-ray 1.9Å A=1352-1594.
4GMJ X-ray 2.7Å A/C/E=1093-1317.
4GML X-ray 2.9Å A/B/C/D/E/F=1093-1317.
4J8S X-ray 1.5Å A=800-1004.
5ANR X-ray 2.1Å A=1063-1314.
5FU6 X-ray 2.9Å A/D=1833-2361.
5FU7 X-ray 3.1Å A/E=1833-2361.

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
hsa03018 RNA degradation - Homo sapiens (human)