Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002980
UniProt IDP36897
Primary gene name(s)TGFBR1
Synonym gene name(s)ALK5, SKR4
Protein nameTGF-beta receptor type-1
Protein functionTransmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, 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 TGFBR1 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. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}.
Subcellular locationCell membrane {ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:9472030};
Single-pass type I membrane protein {ECO:0000269|PubMed:9472030}. Cell junction, tight junction {ECO:0000269|PubMed:15761148}. Cell surface {ECO:0000269|PubMed:25893292}. Membrane raft {ECO:0000269|PubMed:25893292}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P36897
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPKK activity [GO:0000186];
activin receptor signaling pathway [GO:0032924];
angiogenesis involved in coronary vascular morphogenesis [GO:0060978];
anterior/posterior pattern specification [GO:0009952];
apoptotic process [GO:0006915];
artery morphogenesis [GO:0048844];
blastocyst development [GO:0001824];
cardiac epithelial to mesenchymal transition [GO:0060317];
cell cycle arrest [GO:0007050];
cell motility [GO:0048870];
cellular response to transforming growth factor beta stimulus [GO:0071560];
collagen fibril organization [GO:0030199];
coronary artery morphogenesis [GO:0060982];
embryonic cranial skeleton morphogenesis [GO:0048701];
endothelial cell activation [GO:0042118];
endothelial cell migration [GO:0043542];
epicardium morphogenesis [GO:1905223];
epithelial to mesenchymal transition [GO:0001837];
extracellular structure organization [GO:0043062];
germ cell migration [GO:0008354];
heart development [GO:0007507];
intracellular signal transduction [GO:0035556];
in utero embryonic development [GO:0001701];
kidney development [GO:0001822];
lens development in camera-type eye [GO:0002088];
male gonad development [GO:0008584];
mesenchymal cell differentiation [GO:0048762];
negative regulation of chondrocyte differentiation [GO:0032331];
negative regulation of endothelial cell proliferation [GO:0001937];
negative regulation of extrinsic apoptotic signaling pathway [GO:2001237];
negative regulation of transforming growth factor beta receptor signaling pathway [GO:0030512];
neuron fate commitment [GO:0048663];
palate development [GO:0060021];
parathyroid gland development [GO:0060017];
pathway-restricted SMAD protein phosphorylation [GO:0060389];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
pharyngeal system development [GO:0060037];
positive regulation of apoptotic signaling pathway [GO:2001235];
positive regulation of cell growth [GO:0030307];
positive regulation of cell migration [GO:0030335];
positive regulation of cell proliferation [GO:0008284];
positive regulation of cellular component movement [GO:0051272];
positive regulation of endothelial cell proliferation [GO:0001938];
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 filopodium assembly [GO:0051491];
positive regulation of gene expression [GO:0010628];
positive regulation of occluding junction disassembly [GO:1905075];
positive regulation of pathway-restricted SMAD protein phosphorylation [GO:0010862];
positive regulation of protein kinase B signaling [GO:0051897];
positive regulation of SMAD protein import into nucleus [GO:0060391];
positive regulation of stress fiber assembly [GO:0051496];
positive regulation of transcription, DNA-templated [GO:0045893];
post-embryonic development [GO:0009791];
protein phosphorylation [GO:0006468];
regulation of cardiac muscle cell proliferation [GO:0060043];
regulation of epithelial to mesenchymal transition [GO:0010717];
regulation of gene expression [GO:0010468];
regulation of protein binding [GO:0043393];
regulation of protein ubiquitination [GO:0031396];
regulation of transcription, DNA-templated [GO:0006355];
response to cholesterol [GO:0070723];
signal transduction [GO:0007165];
skeletal system development [GO:0001501];
skeletal system morphogenesis [GO:0048705];
thymus development [GO:0048538];
transforming growth factor beta receptor signaling pathway [GO:0007179];
ventricular compact myocardium morphogenesis [GO:0003223];
ventricular septum morphogenesis [GO:0060412];
ventricular trabecula myocardium morphogenesis [GO:0003222];
wound healing [GO:0042060]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
I-SMAD binding [GO:0070411];
metal ion binding [GO:0046872];
protein kinase activity [GO:0004672];
protein serine/threonine kinase activity [GO:0004674];
receptor signaling protein activity [GO:0005057];
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 I [GO:0005025];
type II transforming growth factor beta receptor binding [GO:0005114]
Gene Ontology
(Cellular Component)
Complete annatation
bicellular tight junction [GO:0005923];
cell [GO:0005623];
cell surface [GO:0009986];
endosome [GO:0005768];
intracellular [GO:0005622];
membrane [GO:0016020];
membrane raft [GO:0045121];
plasma membrane [GO:0005886];
receptor complex [GO:0043235];
transforming growth factor beta receptor homodimeric complex [GO:0070022]
Protein-protein interaction112904
Phylogenetic treeP36897
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. CD3-0.8918926271094610.006876437699453450.0189785147420184
AZA vs. DISU-0.3136913283297790.2146511393212530.802236854010993
AZA vs. IL70.5670522555359590.003202021725902560.171087139430647
AZA vs. SAHA-0.08848867089387750.7167038321016550.920551528487789
DISU vs. CD30.5675474352237690.1187449903597530.213497374127257
DISU vs. IL70.8710430776748530.0005862081800840360.0186830619762512
DISU vs. SAHA0.2262616105064860.4373100929895080.783163714726641
DMSO vs. AZA-0.1122529769370360.5018722401372981
DMSO vs. CD30.7736124233055310.01615414799255950.0373656133130523
DMSO vs. DISU0.2010086108852580.4095107405159690.870383340329923
DMSO vs. IL70.68589183918770.0001407805567587020.0150515382492016
DMSO vs. SAHA0.0159276120034480.9461218791430960.987406241330154
HIV vs. Mock in Activation0.3494466249578540.575770813760290.999983755607037
HIV vs. Mock in Latency0.1941945904257120.2564541256722490.999834320637052
IL7 vs. CD31.465570325967017.66532811058429e-066.12291948123143e-05
SAHA vs. CD30.7792541385800410.02897608181170950.0629751302137961
SAHA vs. IL7-0.6582223580217260.007119277613531930.0494771741569296
(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 -1.230343344
(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) 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 -0.0204384 0.918071
(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
1.122 1.01 0.82 1.318 1.563
(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
DB04434 Naphthyridine Inhibitor experimental unknown unknown
DB07152 N-[4-(5-fluoro-6-methylpyridin-2-yl)-5-quinoxalin-6-yl-1H-imidazol-2-yl]acetamide experimental unknown unknown
DB04480 3-(4-Fluorophenyl)-2-(6-Methylpyridin-2-Yl)-5,6-Dihydro-4h-Pyrrolo[1,2-B]Pyrazole experimental unknown unknown
DB07267 2-(6-methylpyridin-2-yl)-N-pyridin-4-ylquinazolin-4-amine experimental unknown unknown
DB03921 4-(3-Pyridin-2-Yl-1h-Pyrazol-4-Yl)Quinoline experimental unknown unknown
DB08450 N-1H-indazol-5-yl-2-(6-methylpyridin-2-yl)quinazolin-4-amine experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1B6C X-ray 2.6Å B/D/F/H=162-503.
1IAS X-ray 2.9Å A/B/C/D/E=162-503.
1PY5 X-ray 2.3Å A=175-500.
1RW8 X-ray 2.4Å A=200-500.
1TBI Model - A=34-114.
1VJY X-ray 2.0Å A=201-503.
2L5S NMR - A=31-115.
2PJY X-ray 3.0Å C=33-111.
2WOT X-ray 1.8Å A=200-503.
2WOU X-ray 2.3Å A=200-503.
2X7O X-ray 3.7Å A/B/C/D/E=162-503.
3FAA X-ray 3.3Å A/B/C/D/E=162-503.
3GXL X-ray 1.8Å A=201-503.
3HMM X-ray 1.7Å A=201-503.
3KCF X-ray 2.8Å A/B/C/D/E=162-503.
3KFD X-ray 3.0Å I/J/K/L=31-115.
3TZM X-ray 1.7Å A=200-503.
4X0M X-ray 1.6Å A=200-503.
4X2F X-ray 1.4Å A=200-503.
4X2G X-ray 1.5Å A=200-503.
4X2J X-ray 1.6Å A=200-503.
4X2K X-ray 1.6Å A=200-503.
4X2N X-ray 1.8Å A=200-503.
5E8S X-ray 1.4Å A=200-503.
5E8T X-ray 1.7Å A=200-503.
5E8U X-ray 2.0Å A=200-503.
5E8W X-ray 1.8Å A=200-503.
5E8X X-ray 1.4Å A=200-503.
5E8Z X-ray 1.5Å A=200-503.
5E90 X-ray 2.0Å A=200-503.
5FRI X-ray 2.0Å A=200-498.

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

HIV Partner Interaction Type PubMed
Vpu interacts with 24551192

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)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)