Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001849
UniProt IDP52701
Primary gene name(s)MSH6
Synonym gene name(s)GTBP
Protein nameDNA mismatch repair protein Msh6
Protein functionComponent of the post-replicative DNA mismatch repair system, MMR. Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops, IDL in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3, H3K36me3: early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}.
Subcellular locationNucleus {ECO:0000269|PubMed:23622243}. Chromosome {ECO:0000269|PubMed:23622243}. Note=Associates with H3K36me3 via its PWWP domain.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P52701
Gene Ontology
(Biological Process)
Complete annatation
determination of adult lifespan [GO:0008340];
DNA repair [GO:0006281];
intrinsic apoptotic signaling pathway [GO:0097193];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
isotype switching [GO:0045190];
meiotic mismatch repair [GO:0000710];
mismatch repair [GO:0006298];
negative regulation of DNA recombination [GO:0045910];
positive regulation of helicase activity [GO:0051096];
positive regulation of isotype switching [GO:0045830];
reciprocal meiotic recombination [GO:0007131];
response to UV [GO:0009411];
somatic hypermutation of immunoglobulin genes [GO:0016446];
somatic recombination of immunoglobulin gene segments [GO:0016447];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
chromatin binding [GO:0003682];
damaged DNA binding [GO:0003684];
guanine/thymine mispair binding [GO:0032137];
methylated histone binding [GO:0035064];
mismatched DNA binding [GO:0030983]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
Golgi apparatus [GO:0005794];
intracellular membrane-bounded organelle [GO:0043231];
MutSalpha complex [GO:0032301];
nuclear chromatin [GO:0000790];
nuclear chromosome [GO:0000228];
nucleoplasm [GO:0005654];
plasma membrane [GO:0005886]
Protein-protein interaction109211
Phylogenetic treeP52701
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. CD32.125597815164731.82500858869616e-092.48253875891955e-08
AZA vs. DISU0.06860746441035880.7877580311704270.980024090198827
AZA vs. IL70.4511109005517930.01997928254196060.457671315737039
AZA vs. SAHA0.292232303630220.2336426937858410.605016103417904
DISU vs. CD3-2.068713769856184.70743738434365e-086.25197454903931e-07
DISU vs. IL70.3738492986254840.1389040557539050.486692808633567
DISU vs. SAHA0.2240915228094240.4495405093596130.791852463961566
DMSO vs. AZA-0.08169219054866470.6284856226176121
DMSO vs. CD3-2.217696804906871.82150405869663e-102.735888199827e-09
DMSO vs. DISU-0.1519292388365550.536482194540510.92112338311561
DMSO vs. IL70.5398953910765680.002932737726762390.104765543884407
DMSO vs. SAHA0.3660971595527370.1228863545579390.418441086656732
HIV vs. Mock in Activation-0.07814336689508310.9188046665998630.999983755607037
HIV vs. Mock in Latency-0.0825705108594970.6194322121108790.999834320637052
IL7 vs. CD3-1.665450658185864.20011756196992e-063.5337025225059e-05
SAHA vs. CD3-1.858945251653144.35991007752268e-063.02086643072491e-05
SAHA vs. IL7-0.1627705952326860.5094505137740530.734638987215784
(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 -1.035528626
(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 0.133093 0.449361
(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
1.012 0.791 0.661 0.62 0.81
(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
2GFU NMR - A=68-201.
2O8B X-ray 2.7Å B=341-1360.
2O8C X-ray 3.3Å B=341-1360.
2O8D X-ray 3.0Å B=341-1360.
2O8E X-ray 3.3Å B=341-1360.
2O8F X-ray 3.2Å B=341-1360.

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
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa03430 Mismatch repair - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
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