Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002663
UniProt IDQ9NRF2
Primary gene name(s)SH2B1
Synonym gene name(s)KIAA1299, SH2B
Protein nameSH2B adapter protein 1
Protein functionAdapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase, JAK and receptor tyrosine kinases, including the receptors of insulin, INS, insulin-like growth factor I, IGF1, nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, glial cell line-derived neurotrophic factor, GDNF, platelet-derived growth factor, PDGF and fibroblast growth factors, FGFs. In growth hormone, GH signaling, autophosphorylated, 'Tyr-813' JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin, LEP signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity. Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis, By similarity. {ECO:0000250, ECO:0000269|PubMed:11827956, ECO:0000269|PubMed:14565960, ECO:0000269|PubMed:15767667, ECO:0000269|PubMed:16569669, ECO:0000269|PubMed:17471236, ECO:0000269|PubMed:9694882, ECO:0000269|PubMed:9742218}.
Subcellular locationCytoplasm {ECO:0000250}. Membrane {ECO:0000305}. Nucleus {ECO:0000250}. Note=Shuttles between the nucleus and the cytoplasm. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9NRF2
Gene Ontology
(Biological Process)
Complete annatation
blood coagulation [GO:0007596];
intracellular signal transduction [GO:0035556];
lamellipodium assembly [GO:0030032];
positive regulation of mitotic nuclear division [GO:0045840];
regulation of DNA biosynthetic process [GO:2000278]
Gene Ontology
(Molecular Function)
Complete annatation
signaling adaptor activity [GO:0035591];
signal transducer activity [GO:0004871]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
membrane [GO:0016020];
nucleus [GO:0005634]
Protein-protein interaction117455
Phylogenetic treeQ9NRF2
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. CD3-0.8259075886777190.01241318850471340.0313386226370252
AZA vs. DISU0.0231754221443720.9269781913627170.995042856396371
AZA vs. IL7-0.2555003480050550.1843051438475780.952505417553304
AZA vs. SAHA-0.1388475268183370.5691802259079690.856334320630286
DISU vs. CD30.8358626295631430.02202062500425850.0557224947648468
DISU vs. IL7-0.2880103595825230.2532827164151770.639376849213207
DISU vs. SAHA-0.1594687420588630.5840901371539880.866504819081381
DMSO vs. AZA0.08317515655194850.619630993502411
DMSO vs. CD30.8950724666572210.005592263294713070.0150954034285706
DMSO vs. DISU0.05759802091571240.8133269769018410.97968488065788
DMSO vs. IL7-0.3309627213386730.06602934839347170.491334685900506
DMSO vs. SAHA-0.22665077370290.3363545783826050.68996867439829
HIV vs. Mock in Activation0.05085945484833010.9348470968281330.999983755607037
HIV vs. Mock in Latency-0.04883435619614410.7671073957088670.999834320637052
IL7 vs. CD30.5762155207908990.07467342507764130.151080877341649
SAHA vs. CD30.6636255324829110.06189078166975460.118302141015119
SAHA vs. IL70.1136296751308360.6407689396954850.8229744967942
(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) 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 0.125131 0.958506
(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

not found

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
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)