Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000966
UniProt IDO95278
Primary gene name(s)EPM2A
Synonym gene name(s)unknown
Protein nameLaforin
Protein functionHas both dual-specificity protein phosphatase and glucan phosphatase activities. Together with the E3 ubiquitin ligase NHLRC1/malin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. Dephosphorylates phosphotyrosine, phosphoserine and phosphothreonine substrates in vitro. Has also been shown to dephosphorylate MAPT. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates. Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system, UPS. Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin. Also promotes proteasome-independent protein degradation through the macroautophagy pathway. Isoform 2, an inactive phosphatase, could function as a dominant-negative regulator for the phosphatase activity of isoform 1. {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11220751, ECO:0000269|PubMed:16901901, ECO:0000269|PubMed:18070875, ECO:0000269|PubMed:18617530, ECO:0000269|PubMed:19036738, ECO:0000269|PubMed:20453062, ECO:0000269|PubMed:23624058}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11220751, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:17908927, ECO:0000269|PubMed:18617530}. Note=Under glycogenolytic conditions localizes to the nucleus.;
SUBCELLULAR LOCATION: Isoform 1: Endoplasmic reticulum. Cell membrane. Note=Primarily associated with polyribosomes at the endoplasmic reticulum, also found at the plasma membrane.;
SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum {ECO:0000269|PubMed:11883934}. Cell membrane {ECO:0000269|PubMed:11883934}. Nucleus {ECO:0000269|PubMed:11883934}. Note=Also found in the nucleus.;
SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. Nucleus.;
SUBCELLULAR LOCATION: Isoform 5: Cytoplasm. Nucleus.;
SUBCELLULAR LOCATION: Isoform 7: Cytoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O95278
Gene Ontology
(Biological Process)
Complete annatation
autophagy [GO:0006914];
glycogen biosynthetic process [GO:0005978];
glycogen metabolic process [GO:0005977];
habituation [GO:0046959];
nervous system development [GO:0007399];
positive regulation of macroautophagy [GO:0016239];
protein dephosphorylation [GO:0006470]
Gene Ontology
(Molecular Function)
Complete annatation
carbohydrate phosphatase activity [GO:0019203];
protein serine/threonine phosphatase activity [GO:0004722];
protein tyrosine/serine/threonine phosphatase activity [GO:0008138];
protein tyrosine phosphatase activity [GO:0004725];
starch binding [GO:2001070]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
polysome [GO:0005844]
Protein-protein interaction113679
Phylogenetic treeO95278
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. CD31.299515252436480.0001496796483826390.0006886360379802
AZA vs. DISU0.1620135820358790.5541760625657380.947911194249955
AZA vs. IL70.3845869470984680.08017198993437040.784187153978432
AZA vs. SAHA-1.248027316138550.01684777274095140.137351717845917
DISU vs. CD3-1.150783692927430.002151338549904790.00797571994620384
DISU vs. IL70.2149617569884150.4248304499393820.78074494315426
DISU vs. SAHA-1.41094713211590.009605864284640720.100814749745
DMSO vs. AZA-0.01335410451245270.9474686730333181
DMSO vs. CD3-1.326482398880767.41994447965855e-050.000345324261927884
DMSO vs. DISU-0.1772437638779920.5015724942316210.908929488219426
DMSO vs. IL70.4037266964346150.07142094906097140.511159517037691
DMSO vs. SAHA-1.2429134344480.01885095692272880.136522235359176
HIV vs. Mock in Activation-0.2493084087984880.6925927902819030.999983755607037
HIV vs. Mock in Latency-0.2842797765542050.150259158517760.999834320637052
IL7 vs. CD3-0.9015558450532330.006634643659245270.021245800695943
SAHA vs. CD3-2.574921015398166.29169286336939e-075.37504600062226e-06
SAHA vs. IL7-1.645781375126890.002126690512636480.0205498287099245
(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 -0.115245 0.486668
(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
4R30 X-ray 2.3Å A/B/C/D=148-331.
4RKK X-ray 2.4Å A/C=1-329.

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
not found