Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0007146
UniProt IDQ15796
Primary gene name(s)SMAD2
Synonym gene name(s)MADH2, MADR2
Protein nameMothers against decapentaplegic homolog 2
Protein functionReceptor-regulated SMAD, R-SMAD that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta, transforming growth factor and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. May act as a tumor suppressor in colorectal carcinoma. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:9892009}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:9865696}. Nucleus {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:21599657, ECO:0000269|PubMed:22781750, ECO:0000269|PubMed:9865696}. Note=Cytoplasmic and nuclear in the absence of TGF-beta. On TGF-beta stimulation, migrates to the nucleus when complexed with SMAD4, PubMed:9865696. On dephosphorylation by phosphatase PPM1A, released from the SMAD2/SMAD4 complex, and exported out of the nucleus by interaction with RANBP1, PubMed:16751101, PubMed:19289081. {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:9865696}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q15796
Gene Ontology
(Biological Process)
Complete annatation
activin receptor signaling pathway [GO:0032924];
anterior/posterior pattern specification [GO:0009952];
cell fate commitment [GO:0045165];
common-partner SMAD protein phosphorylation [GO:0007182];
embryonic cranial skeleton morphogenesis [GO:0048701];
embryonic foregut morphogenesis [GO:0048617];
endoderm formation [GO:0001706];
gastrulation [GO:0007369];
insulin secretion [GO:0030073];
intracellular signal transduction [GO:0035556];
in utero embryonic development [GO:0001701];
lung development [GO:0030324];
mesoderm formation [GO:0001707];
negative regulation of cell proliferation [GO:0008285];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
nodal signaling pathway [GO:0038092];
organ growth [GO:0035265];
palate development [GO:0060021];
pancreas development [GO:0031016];
paraxial mesoderm morphogenesis [GO:0048340];
pericardium development [GO:0060039];
positive regulation of BMP signaling pathway [GO:0030513];
positive regulation of epithelial to mesenchymal transition [GO:0010718];
positive regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry [GO:1900224];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
post-embryonic development [GO:0009791];
primary miRNA processing [GO:0031053];
regulation of binding [GO:0051098];
regulation of transforming growth factor beta receptor signaling pathway [GO:0017015];
response to cholesterol [GO:0070723];
response to glucose [GO:0009749];
signal transduction involved in regulation of gene expression [GO:0023019];
SMAD protein complex assembly [GO:0007183];
SMAD protein signal transduction [GO:0060395];
somatic stem cell population maintenance [GO:0035019];
transforming growth factor beta receptor signaling pathway [GO:0007179];
ureteric bud development [GO:0001657];
zygotic specification of dorsal/ventral axis [GO:0007352]
Gene Ontology
(Molecular Function)
Complete annatation
activating transcription factor binding [GO:0033613];
chromatin binding [GO:0003682];
co-SMAD binding [GO:0070410];
double-stranded DNA binding [GO:0003690];
enhancer binding [GO:0035326];
I-SMAD binding [GO:0070411];
metal ion binding [GO:0046872];
phosphatase binding [GO:0019902];
RNA polymerase II core promoter proximal region sequence-specific DNA binding [GO:0000978];
R-SMAD binding [GO:0070412];
SMAD binding [GO:0046332];
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001077];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription factor binding [GO:0008134];
transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity [GO:0030618];
transforming growth factor beta receptor binding [GO:0005160];
type I transforming growth factor beta receptor binding [GO:0034713];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
activin responsive factor complex [GO:0032444];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nuclear chromatin [GO:0000790];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
SMAD2-SMAD3 protein complex [GO:0071144];
SMAD protein complex [GO:0071141];
transcription factor complex [GO:0005667]
Protein-protein interaction110262
Phylogenetic treeQ15796
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. CD31.501264054843097.23743864949888e-064.618233502339e-05
AZA vs. DISU0.1025524829611370.68523833831260.968067733057557
AZA vs. IL70.003756264093757360.9844152721667960.999311006273513
AZA vs. SAHA-0.08574380009177780.725297883425670.923407119489742
DISU vs. CD3-1.410844677150960.0001306902709468090.000716577616198145
DISU vs. IL7-0.1076750379919650.6689872431112130.908307220773913
DISU vs. SAHA-0.1877807782505110.5190922797414260.835726925326677
DMSO vs. AZA-0.05020766574453290.7645604586266261
DMSO vs. CD3-1.562937730167911.80379017489241e-061.22626800472717e-05
DMSO vs. DISU-0.1546577394465390.5263907823029010.91669822417263
DMSO vs. IL70.06117799890466930.7337793373163830.946333083680773
DMSO vs. SAHA-0.04298713539979620.8553548684086630.962018897148281
HIV vs. Mock in Activation-0.08063385867482520.8968594935772040.999983755607037
HIV vs. Mock in Latency0.06808707368363830.6800655178530260.999834320637052
IL7 vs. CD3-1.488839408758965.59541692057852e-064.59366662548366e-05
SAHA vs. CD3-1.612556983028148.23696779761462e-065.29343730106833e-05
SAHA vs. IL7-0.09386748933243850.6998340107980870.86070440729666
(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) unknown
(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 -0.460875 0.00657227
(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
0.96 1.015 0.955 1.005 1.18
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB04522 Phosphonoserine experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1DEV X-ray 2.2Å A/C=261-456.
1KHX X-ray 1.8Å A=241-467.
1U7V X-ray 2.7Å A/C=270-467.
2LB3 NMR - B=217-224.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat enhances 19420158
Tat downregulates 24008158
Envelope surface glycoprotein gp120 induces phosphorylation of 16179804

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04350 TGF-beta signaling pathway - Homo sapiens (human)
hsa04390 Hippo signaling pathway - Homo sapiens (human)
hsa04520 Adherens junction - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)