Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002981
UniProt IDP37173
Primary gene name(s)TGFBR2
Synonym gene name(s)unknown
Protein nameTGF-beta receptor type-2
Protein functionTransmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. {ECO:0000269|PubMed:7774578}.
Subcellular locationCell membrane {ECO:0000269|PubMed:1310899, ECO:0000269|PubMed:25893292};
Single-pass type I membrane protein {ECO:0000269|PubMed:1310899}. Membrane raft {ECO:0000269|PubMed:25893292}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P37173
Gene Ontology
(Biological Process)
Complete annatation
activation of protein kinase activity [GO:0032147];
aging [GO:0007568];
animal organ regeneration [GO:0031100];
apoptotic process [GO:0006915];
atrioventricular valve morphogenesis [GO:0003181];
blood vessel development [GO:0001568];
brain development [GO:0007420];
bronchus morphogenesis [GO:0060434];
cardiac left ventricle morphogenesis [GO:0003214];
common-partner SMAD protein phosphorylation [GO:0007182];
digestive tract development [GO:0048565];
embryo implantation [GO:0007566];
embryonic cranial skeleton morphogenesis [GO:0048701];
embryonic hemopoiesis [GO:0035162];
endocardial cushion fusion [GO:0003274];
gastrulation [GO:0007369];
growth plate cartilage chondrocyte growth [GO:0003430];
heart development [GO:0007507];
heart looping [GO:0001947];
in utero embryonic development [GO:0001701];
lens development in camera-type eye [GO:0002088];
lens fiber cell apoptotic process [GO:1990086];
lung lobe morphogenesis [GO:0060463];
mammary gland morphogenesis [GO:0060443];
membranous septum morphogenesis [GO:0003149];
myeloid dendritic cell differentiation [GO:0043011];
negative regulation of cardiac muscle cell proliferation [GO:0060044];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
Notch signaling pathway [GO:0007219];
outflow tract morphogenesis [GO:0003151];
outflow tract septum morphogenesis [GO:0003148];
palate development [GO:0060021];
pathway-restricted SMAD protein phosphorylation [GO:0060389];
patterning of blood vessels [GO:0001569];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
positive regulation of angiogenesis [GO:0045766];
positive regulation of B cell tolerance induction [GO:0002663];
positive regulation of cell proliferation [GO:0008284];
positive regulation of epithelial cell migration [GO:0010634];
positive regulation of epithelial to mesenchymal transition [GO:0010718];
positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation [GO:1905007];
positive regulation of mesenchymal cell proliferation [GO:0002053];
positive regulation of NK T cell differentiation [GO:0051138];
positive regulation of reactive oxygen species metabolic process [GO:2000379];
positive regulation of skeletal muscle tissue regeneration [GO:0043415];
positive regulation of smooth muscle cell proliferation [GO:0048661];
positive regulation of T cell tolerance induction [GO:0002666];
positive regulation of tolerance induction to self antigen [GO:0002651];
protein phosphorylation [GO:0006468];
receptor-mediated endocytosis [GO:0006898];
regulation of cell proliferation [GO:0042127];
regulation of gene expression [GO:0010468];
response to cholesterol [GO:0070723];
response to drug [GO:0042493];
response to estrogen [GO:0043627];
response to glucose [GO:0009749];
response to hypoxia [GO:0001666];
response to mechanical stimulus [GO:0009612];
response to nutrient [GO:0007584];
response to steroid hormone [GO:0048545];
smoothened signaling pathway [GO:0007224];
trachea formation [GO:0060440];
transforming growth factor beta receptor signaling pathway [GO:0007179];
tricuspid valve morphogenesis [GO:0003186];
vasculogenesis [GO:0001570];
ventricular septum morphogenesis [GO:0060412];
wound healing [GO:0042060]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
glycosaminoglycan binding [GO:0005539];
metal ion binding [GO:0046872];
receptor signaling protein serine/threonine kinase activity [GO:0004702];
SMAD binding [GO:0046332];
transforming growth factor beta-activated receptor activity [GO:0005024];
transforming growth factor beta binding [GO:0050431];
transforming growth factor beta receptor activity, type II [GO:0005026];
transmembrane receptor protein serine/threonine kinase activity [GO:0004675];
type III transforming growth factor beta receptor binding [GO:0034714];
type I transforming growth factor beta receptor binding [GO:0034713]
Gene Ontology
(Cellular Component)
Complete annatation
caveola [GO:0005901];
cytosol [GO:0005829];
external side of plasma membrane [GO:0009897];
integral component of membrane [GO:0016021];
membrane raft [GO:0045121];
plasma membrane [GO:0005886];
receptor complex [GO:0043235];
transforming growth factor beta receptor homodimeric complex [GO:0070022]
Protein-protein interaction112906
Phylogenetic treeP37173
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. CD3-0.9835490299622590.002940136068056990.00925903276593291
AZA vs. DISU0.01867407100031910.9411246951741270.996198528027442
AZA vs. IL7-0.3032923085515770.114029183089450.866573954993761
AZA vs. SAHA-0.06881832904724080.7775471147312420.941353350035522
DISU vs. CD30.9902672795389020.007184086376449070.022019706799226
DISU vs. IL7-0.3311987751440530.188553238937760.562712734426718
DISU vs. SAHA-0.08629085651221880.7667109978002490.933821031828637
DMSO vs. AZA-0.04594167142387210.7831259691469641
DMSO vs. CD30.9253783190201460.004140198028539040.0116889211581598
DMSO vs. DISU-0.06670626388308970.784435608348730.973040230101706
DMSO vs. IL7-0.2499851423373560.1635344778941030.670192409500264
DMSO vs. SAHA-0.02914127227320580.9014611610654640.976350783932275
HIV vs. Mock in Activation-0.06693038708819540.9143400198478370.999983755607037
HIV vs. Mock in Latency0.1047789575036510.5239592090617270.999834320637052
IL7 vs. CD30.6877923136762040.03351411218001670.0795347817664546
SAHA vs. CD30.8901341776131160.01277772743973640.0315001394596478
SAHA vs. IL70.2309898654081940.3421300383728320.591572333140522
(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 -0.395084 0.00241278
(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
208944_at 1.6 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB04077 Glycerol experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1KTZ X-ray 2.1Å B=38-159.
1M9Z X-ray 1.0Å A=49-159.
1PLO NMR - A=38-159.
2PJY X-ray 3.0Å B=42-149.
3KFD X-ray 3.0Å E/F/G/H=38-153.
4P7U X-ray 1.5Å A=49-159.
4XJJ X-ray 1.4Å A=50-159.
5E8V X-ray 1.6Å A=237-549.
5E8Y X-ray 2.0Å A=237-549.
5E91 X-ray 2.4Å A=237-549.
5E92 X-ray 2.0Å A=237-549.

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

HIV Partner Interaction Type PubMed
Vpu interacts with 24551192
Pr55(Gag) interacts with 24447338

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04350 TGF-beta signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04390 Hippo signaling pathway - Homo sapiens (human)
hsa04520 Adherens junction - 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)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
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