Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002665
UniProt IDO60880
Primary gene name(s)SH2D1A
Synonym gene name(s)DSHP, SAP
Protein nameSH2 domain-containing protein 1A
Protein functionCytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule, SLAM family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2. Initially it has been proposed that association with SLAMF1 prevents SLAMF1 binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2, PubMed:11806999. However, by simultaneous interactions, recruits FYN which subsequently phosphorylates and activates SLAMF1, PubMed:12458214. Positively regulates CD244/2B4- and CD84-mediated natural killer, NK cell functions. Can also promote CD48-, SLAMF6 -, LY9-, and SLAMF7-mediated NK cell activation. In the context of NK cell-mediated cytotoxicity enhances conjugate formation with target cells, By similarity. May also regulate the activity of the neurotrophin receptors NTRK1, NTRK2 and NTRK3. {ECO:0000250|UniProtKB:O88890, ECO:0000269|PubMed:11806999, ECO:0000269|PubMed:12458214, ECO:0000305|PubMed:21219180}.
Subcellular locationCytoplasm {ECO:0000305}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O60880
Gene Ontology
(Biological Process)
Complete annatation
adaptive immune response [GO:0002250];
cell-cell signaling [GO:0007267];
cellular defense response [GO:0006968];
humoral immune response [GO:0006959];
innate immune response [GO:0045087];
positive regulation of natural killer cell mediated cytotoxicity [GO:0045954];
regulation of immune response [GO:0050776]
Gene Ontology
(Molecular Function)
Complete annatation
SH3/SH2 adaptor activity [GO:0005070]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829]
Protein-protein interaction110246
Phylogenetic treeO60880
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. CD30.5484544358433440.09825970823300250.173476668910368
AZA vs. DISU-0.08270780536238360.7434571763541960.976008954784031
AZA vs. IL7-0.1825444337280180.3421087043662090.999311006273513
AZA vs. SAHA0.007797509417212820.9745008493595560.993683677416353
DISU vs. CD3-0.6443766993090030.07839220230485180.153865111659288
DISU vs. IL7-0.108823035415580.6654001120021680.906543758556953
DISU vs. SAHA0.09126836983720330.7538773680482130.930658150857737
DMSO vs. AZA-0.1518955042426460.3641879568288581
DMSO vs. CD3-0.7134734103823870.02845489601446450.0601224415789492
DMSO vs. DISU-0.07149022109630280.7695122196946450.970807110547067
DMSO vs. IL7-0.02334654807948210.8966944127690420.978020113804905
DMSO vs. SAHA0.1531607116931030.5165545733941390.822115747311956
HIV vs. Mock in Activation-0.08695159057815580.8887634943674420.999983755607037
HIV vs. Mock in Latency-0.004788656646173960.9768223820410090.999834320637052
IL7 vs. CD3-0.7224913420107270.02616460435492330.0649611400826485
SAHA vs. CD3-0.5657606097210840.1116936554012830.190496082718124
SAHA vs. IL70.1865030980466890.4434925418981580.683489068252002
(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 -2.39112409
(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
2.2 0.000146816 1.6 0.007329983 1.6 0.004600474
(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 -0.504354 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
1.03 0.961 0.635 0.672 1.521
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
-0.76 <0.0001 -0.23 0.0934 -0.2 0.0178 Cell growth and proliferation at 4 hpi
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
210116_at 1.56 No upregulated in CD8+ cells

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
1D1Z X-ray 1.4Å A/B/C/D=1-104.
1D4T X-ray 1.1Å A=1-104.
1D4W X-ray 1.8Å A/B=1-104.
1KA6 NMR - A=1-128.
1KA7 NMR - A=1-128.
1M27 X-ray 2.5Å A=1-104.

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
hsa04650 Natural killer cell mediated cytotoxicity - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)