Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0011111
UniProt IDP01137
Primary gene name(s)TGFB1
Synonym gene name(s)TGFB
Protein nameTransforming growth factor beta-1
Protein functionMultifunctional protein that controls proliferation, differentiation and other functions in many cell types. Many cells synthesize TGFB1 and have specific receptors for it. It positively and negatively regulates many other growth factors. It plays an important role in bone remodeling as it is a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts, By similarity. Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis, RIP, PubMed:25310401. Can promote either T-helper 17 cells, Th17 or regulatory T-cells, Treg lineage differentiation in a concentration-dependent manner. At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development. At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells. Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus, PubMed:25893292. Can induce epithelial-to-mesenchymal transition, EMT and cell migration in various cell types, PubMed:25893292. {ECO:0000250|UniProtKB:P04202, ECO:0000269|PubMed:25310401, ECO:0000269|PubMed:25893292}.
Subcellular locationSecreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:17827158}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P01137
Gene Ontology
(Biological Process)
Complete annatation
active induction of host immune response by virus [GO:0046732];
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains [GO:0002460];
aging [GO:0007568];
ATP biosynthetic process [GO:0006754];
branch elongation involved in mammary gland duct branching [GO:0060751];
cell-cell junction organization [GO:0045216];
cell cycle arrest [GO:0007050];
cell growth [GO:0016049];
cell migration [GO:0016477];
cellular calcium ion homeostasis [GO:0006874];
cellular response to dexamethasone stimulus [GO:0071549];
cellular response to insulin-like growth factor stimulus [GO:1990314];
cellular response to ionizing radiation [GO:0071479];
cellular response to mechanical stimulus [GO:0071260];
cellular response to organic cyclic compound [GO:0071407];
cellular response to transforming growth factor beta stimulus [GO:0071560];
chondrocyte differentiation [GO:0002062];
common-partner SMAD protein phosphorylation [GO:0007182];
connective tissue replacement involved in inflammatory response wound healing [GO:0002248];
defense response to fungus, incompatible interaction [GO:0009817];
digestive tract development [GO:0048565];
embryonic liver development [GO:1990402];
endoderm development [GO:0007492];
epidermal growth factor receptor signaling pathway [GO:0007173];
epithelial to mesenchymal transition [GO:0001837];
evasion or tolerance of host defenses by virus [GO:0019049];
extracellular matrix assembly [GO:0085029];
extrinsic apoptotic signaling pathway [GO:0097191];
face morphogenesis [GO:0060325];
female pregnancy [GO:0007565];
frontal suture morphogenesis [GO:0060364];
germ cell migration [GO:0008354];
heart development [GO:0007507];
heart valve morphogenesis [GO:0003179];
hematopoietic progenitor cell differentiation [GO:0002244];
hyaluronan catabolic process [GO:0030214];
inflammatory response [GO:0006954];
inner ear development [GO:0048839];
lens fiber cell differentiation [GO:0070306];
lipopolysaccharide-mediated signaling pathway [GO:0031663];
liver regeneration [GO:0097421];
lymph node development [GO:0048535];
macrophage derived foam cell differentiation [GO:0010742];
mammary gland branching involved in thelarche [GO:0060744];
MAPK cascade [GO:0000165];
membrane protein intracellular domain proteolysis [GO:0031293];
mitotic cell cycle checkpoint [GO:0007093];
mononuclear cell proliferation [GO:0032943];
myelination [GO:0042552];
myeloid dendritic cell differentiation [GO:0043011];
negative regulation of blood vessel endothelial cell migration [GO:0043537];
negative regulation of cell-cell adhesion [GO:0022408];
negative regulation of cell cycle [GO:0045786];
negative regulation of cell differentiation [GO:0045596];
negative regulation of cell growth [GO:0030308];
negative regulation of cell proliferation [GO:0008285];
negative regulation of DNA replication [GO:0008156];
negative regulation of epithelial cell proliferation [GO:0050680];
negative regulation of extracellular matrix disassembly [GO:0010716];
negative regulation of fat cell differentiation [GO:0045599];
negative regulation of gene expression [GO:0010629];
negative regulation of gene silencing by miRNA [GO:0060965];
negative regulation of hyaluronan biosynthetic process [GO:1900126];
negative regulation of interleukin-17 production [GO:0032700];
negative regulation of macrophage cytokine production [GO:0010936];
negative regulation of mitotic cell cycle [GO:0045930];
negative regulation of myoblast differentiation [GO:0045662];
negative regulation of neuroblast proliferation [GO:0007406];
negative regulation of ossification [GO:0030279];
negative regulation of phagocytosis [GO:0050765];
negative regulation of production of miRNAs involved in gene silencing by miRNA [GO:1903799];
negative regulation of protein localization to plasma membrane [GO:1903077];
negative regulation of protein phosphorylation [GO:0001933];
negative regulation of release of sequestered calcium ion into cytosol [GO:0051280];
negative regulation of skeletal muscle tissue development [GO:0048642];
negative regulation of T cell proliferation [GO:0042130];
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];
neural tube closure [GO:0001843];
neural tube development [GO:0021915];
Notch signaling pathway [GO:0007219];
oligodendrocyte development [GO:0014003];
ossification involved in bone remodeling [GO:0043932];
pathway-restricted SMAD protein phosphorylation [GO:0060389];
phosphate-containing compound metabolic process [GO:0006796];
platelet degranulation [GO:0002576];
positive regulation of apoptotic process [GO:0043065];
positive regulation of blood vessel endothelial cell migration [GO:0043536];
positive regulation of bone mineralization [GO:0030501];
positive regulation of branching involved in ureteric bud morphogenesis [GO:0090190];
positive regulation of cardiac muscle cell differentiation [GO:2000727];
positive regulation of cell cycle arrest [GO:0071158];
positive regulation of cell division [GO:0051781];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of cellular protein metabolic process [GO:0032270];
positive regulation of chemotaxis [GO:0050921];
positive regulation of collagen biosynthetic process [GO:0032967];
positive regulation of epithelial cell proliferation [GO:0050679];
positive regulation of epithelial to mesenchymal transition [GO:0010718];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of exit from mitosis [GO:0031536];
positive regulation of extracellular matrix assembly [GO:1901203];
positive regulation of fibroblast migration [GO:0010763];
positive regulation of fibroblast proliferation [GO:0048146];
positive regulation of gene expression [GO:0010628];
positive regulation of histone acetylation [GO:0035066];
positive regulation of histone deacetylation [GO:0031065];
positive regulation of interleukin-17 production [GO:0032740];
positive regulation of isotype switching to IgA isotypes [GO:0048298];
positive regulation of MAP kinase activity [GO:0043406];
positive regulation of mononuclear cell migration [GO:0071677];
positive regulation of NAD+ ADP-ribosyltransferase activity [GO:1901666];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of odontogenesis [GO:0042482];
positive regulation of pathway-restricted SMAD protein phosphorylation [GO:0010862];
positive regulation of peptidyl-serine phosphorylation [GO:0033138];
positive regulation of peptidyl-threonine phosphorylation [GO:0010800];
positive regulation of peptidyl-tyrosine phosphorylation [GO:0050731];
positive regulation of phosphatidylinositol 3-kinase activity [GO:0043552];
positive regulation of pri-miRNA transcription from RNA polymerase II promoter [GO:1902895];
positive regulation of protein complex assembly [GO:0031334];
positive regulation of protein dephosphorylation [GO:0035307];
positive regulation of protein import into nucleus [GO:0042307];
positive regulation of protein kinase B signaling [GO:0051897];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of protein secretion [GO:0050714];
positive regulation of receptor clustering [GO:1903911];
positive regulation of regulatory T cell differentiation [GO:0045591];
positive regulation of SMAD protein import into nucleus [GO:0060391];
positive regulation of smooth muscle cell differentiation [GO:0051152];
positive regulation of superoxide anion generation [GO:0032930];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transcription regulatory region DNA binding [GO:2000679];
positive regulation of vascular endothelial growth factor production [GO:0010575];
positive regulation of vascular permeability [GO:0043117];
protein export from nucleus [GO:0006611];
protein import into nucleus, translocation [GO:0000060];
protein kinase B signaling [GO:0043491];
protein phosphorylation [GO:0006468];
receptor catabolic process [GO:0032801];
regulation of actin cytoskeleton reorganization [GO:2000249];
regulation of apoptotic process [GO:0042981];
regulation of binding [GO:0051098];
regulation of blood vessel remodeling [GO:0060312];
regulation of branching involved in mammary gland duct morphogenesis [GO:0060762];
regulation of cartilage development [GO:0061035];
regulation of cell migration [GO:0030334];
regulation of DNA binding [GO:0051101];
regulation of interleukin-23 production [GO:0032667];
regulation of protein import into nucleus [GO:0042306];
regulation of SMAD protein import into nucleus [GO:0060390];
regulation of sodium ion transport [GO:0002028];
regulation of striated muscle tissue development [GO:0016202];
regulation of transforming growth factor beta receptor signaling pathway [GO:0017015];
regulatory T cell differentiation [GO:0045066];
response to cholesterol [GO:0070723];
response to drug [GO:0042493];
response to estradiol [GO:0032355];
response to glucose [GO:0009749];
response to hypoxia [GO:0001666];
response to immobilization stress [GO:0035902];
response to laminar fluid shear stress [GO:0034616];
response to progesterone [GO:0032570];
response to vitamin D [GO:0033280];
response to wounding [GO:0009611];
salivary gland morphogenesis [GO:0007435];
SMAD protein complex assembly [GO:0007183];
SMAD protein import into nucleus [GO:0007184];
SMAD protein signal transduction [GO:0060395];
T cell homeostasis [GO:0043029];
tolerance induction to self antigen [GO:0002513];
transforming growth factor beta receptor signaling pathway [GO:0007179];
transforming growth factor beta receptor signaling pathway involved in heart development [GO:1905313];
ureteric bud development [GO:0001657];
vasculogenesis [GO:0001570];
ventricular cardiac muscle tissue morphogenesis [GO:0055010]
Gene Ontology
(Molecular Function)
Complete annatation
antigen binding [GO:0003823];
cytokine activity [GO:0005125];
enzyme binding [GO:0019899];
glycoprotein binding [GO:0001948];
protein serine/threonine kinase activator activity [GO:0043539];
transforming growth factor beta receptor binding [GO:0005160];
type III transforming growth factor beta receptor binding [GO:0034714];
type II transforming growth factor beta receptor binding [GO:0005114];
type I transforming growth factor beta receptor binding [GO:0034713]
Gene Ontology
(Cellular Component)
Complete annatation
axon [GO:0030424];
blood microparticle [GO:0072562];
cell surface [GO:0009986];
cytoplasm [GO:0005737];
extracellular region [GO:0005576];
extracellular space [GO:0005615];
Golgi lumen [GO:0005796];
neuronal cell body [GO:0043025];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
platelet alpha granule lumen [GO:0031093];
proteinaceous extracellular matrix [GO:0005578]
Protein-protein interaction112898
Phylogenetic treeP01137
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. CD3-0.329159502362350.4210652130472530.542696672742277
AZA vs. DISU-0.2953655574704070.2652068874192440.843224767128808
AZA vs. IL7-0.1874807687326490.3297545996754940.999311006273513
AZA vs. SAHA-0.04899156508144960.8408097712039360.962221666045162
DISU vs. CD30.02322646853109360.9596556061810630.974196821844794
DISU vs. IL70.09793236242455120.7110823117209690.925936412645211
DISU vs. SAHA0.2487695970198360.4017936146460080.761132318037086
DMSO vs. AZA-0.08824219465709080.613282129065711
DMSO vs. CD30.232937602387880.5745707575769920.674503893313909
DMSO vs. DISU0.2060689356168490.4379254017588780.882432295026854
DMSO vs. IL7-0.09209181151221840.608256116150720.91420348464328
DMSO vs. SAHA0.03324300216218840.8880804956129820.972686978140092
HIV vs. Mock in Activation0.276768543550680.7430303384850620.999983755607037
HIV vs. Mock in Latency0.03652175674015470.8309220573857230.999834320637052
IL7 vs. CD30.1467334290410790.7198855302861760.811338013907846
SAHA vs. CD30.2574152133192140.5433718421766560.648500329579647
SAHA vs. IL70.1362945184310290.5775091319645690.782083609310387
(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 -0.353531 0.0214182
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00070 Hyaluronidase approved, investigational unknown inhibitor
DB06205 Hyaluronidase (Human Recombinant) approved unknown Inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1KLA NMR - A/B=279-390.
1KLC NMR - A/B=279-390.
1KLD NMR - A/B=279-390.
3KFD X-ray 3.0Å A/B/C/D=279-390.
4KV5 X-ray 3.0Å A/B/C/D=279-390.

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

HIV Partner Interaction Type PubMed
Vpu interacts with 24551192
Envelope surface glycoprotein gp120 interacts with 16179804
24162774
Envelope surface glycoprotein gp160; precursor upregulates 8811049
Tat upregulates 12202226
127581671281686
7695626
7803268
8264131
8294518
8336945
9383706
9670843
9987082
10431160
1585750818457978
2441836425943894
Vpr modulates 18417583
23986795
capsid interacts with 25354152
Tat interacts with 22412921
Tat regulates 22859956
Envelope surface glycoprotein gp160; precursor interacts with 7495302
capsid regulated by 18060582
Tat inhibited by 10376933
Vpu activates 24551192
Envelope surface glycoprotein gp120 upregulates 16179804
8551249
Envelope surface glycoprotein gp120 enhances 18325393

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)
hsa04110 Cell cycle - 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)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04672 Intestinal immune network for IgA production - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05144 Malaria - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05146 Amoebiasis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05161 Hepatitis B - 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)
hsa05211 Renal cell carcinoma - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)
hsa05323 Rheumatoid arthritis - Homo sapiens (human)
hsa05410 Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
hsa05414 Dilated cardiomyopathy - Homo sapiens (human)
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