Protein detail
TGFB1
Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
Protein symbol TGFB1 | UniProt ID | EVMP score 0.60 |
Frequency 20 | Transmembrane count | Protein classification Human disease related genesPredicted secreted proteins |
Basic Information
Protein Names
Transforming growth factor beta-1 proprotein [Cleaved into: Latency-associated peptide (LAP); Transforming growth factor beta-1 (TGF-beta-1)]
Protein Class
Human disease related genesPredicted secreted proteins
Protein Function
- Human disease related genes:Immune system diseases:Allergies and autoimmune diseases
- Human disease related genes:Congenital disorders of metabolism:Congenital disorders of ion transport and metabolism
- Predicted secreted proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
Ensembl
Entrez Gene Symbol
Gene Synonym
CEDDPD1TGFBTGFbeta
Gene Description
Transforming growth factor beta 1
Chromosome
19
Position
41301587-41353922
Frequency
20
EVMP Score
0.60
Fluorescence & Localization
Tissue SpecificbrainCell SpecificB-cellsSingle-Nuclei Brain Specificmedium spiny neuronBlood Cell Specificmemory B-cellBlood Lineage SpecificB-cells
Function & Pathway
Protein Function
- Human disease related genes:Immune system diseases:Allergies and autoimmune diseases
- Human disease related genes:Congenital disorders of metabolism:Congenital disorders of ion transport and metabolism
- Predicted secreted proteins
- Human disease related genes:Congenital malformations:Congenital malformations of the musculoskeletal system
Cellular Component
- GO:0005576 extracellular region
- GO:0005615 extracellular space
- GO:0005634 nucleus
- GO:0005737 cytoplasm
- GO:0005796 Golgi lumen
- GO:0005886 plasma membrane
- GO:0005902 microvillus
- GO:0009986 cell surface
- GO:0030424 axon
- GO:0031012 extracellular matrix
- GO:0031093 platelet alpha granule lumen
- GO:0043025 neuronal cell body
- GO:0062023 collagen-containing extracellular matrix
- GO:0072562 blood microparticle
Molecular Function
- GO:0005114 type II transforming growth factor beta receptor binding
- GO:0005125 cytokine activity
- GO:0005515 protein binding
- GO:0008083 growth factor activity
- GO:0019899 enzyme binding
- GO:0034713 type I transforming growth factor beta receptor binding
- GO:0034714 type III transforming growth factor beta receptor binding
- GO:0035800 deubiquitinase activator activity
- GO:0042802 identical protein binding
- GO:0043539 protein serine/threonine kinase activator activity
- GO:0044877 protein-containing complex binding
Biological Process
KEGG
- hsa04010 MAPK signaling pathway
- KEGG:hsa04060 Cytokine-cytokine receptor interaction
- KEGG:hsa04068 FoxO signaling pathway
- KEGG:hsa04110 Cell cycle
- KEGG:hsa04148 Efferocytosis
- KEGG:hsa04218 Cellular senescence
- KEGG:hsa04350 TGF-beta signaling pathway
- KEGG:hsa04380 Osteoclast differentiation
- KEGG:hsa04390 Hippo signaling pathway
- KEGG:hsa04518 Integrin signaling
- KEGG:hsa04659 Th17 cell differentiation
- KEGG:hsa04672 Intestinal immune network for IgA production
- KEGG:hsa04926 Relaxin signaling pathway
- KEGG:hsa04932 Non-alcoholic fatty liver disease
- KEGG:hsa04933 AGE-RAGE signaling pathway in diabetic complications
- KEGG:hsa05140 Leishmaniasis
- KEGG:hsa05142 Chagas disease
- KEGG:hsa05144 Malaria
- KEGG:hsa05145 Toxoplasmosis
- KEGG:hsa05146 Amoebiasis
- KEGG:hsa05152 Tuberculosis
- KEGG:hsa05161 Hepatitis B
- KEGG:hsa05166 Human T-cell leukemia virus 1 infection
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05205 Proteoglycans in cancer
- KEGG:hsa05210 Colorectal cancer
- KEGG:hsa05211 Renal cell carcinoma
- KEGG:hsa05212 Pancreatic cancer
- KEGG:hsa05220 Chronic myeloid leukemia
- KEGG:hsa05225 Hepatocellular carcinoma
- KEGG:hsa05226 Gastric cancer
- KEGG:hsa05321 Inflammatory bowel disease
- KEGG:hsa05323 Rheumatoid arthritis
- KEGG:hsa05410 Hypertrophic cardiomyopathy
- KEGG:hsa05414 Dilated cardiomyopathy
- KEGG:hsa05415 Diabetic cardiomyopathy
Reactome
- R-hsa-9843745 adipogenesis
- R-hsa-202733 cell surface interactions at the vascular wall
- R-hsa-1280215 cytokine signaling in immune system
- R-hsa-5688426 deubiquitination
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-2173788 downregulation of tgf beta receptor signaling
- R-hsa-3000178 ecm proteoglycans
- R-hsa-1566948 elastic fibre formation
- R-hsa-1474244 extracellular matrix organization
- R-hsa-109582 hemostasis
- R-hsa-5663205 infectious disease
- R-hsa-168255 influenza infection
- R-hsa-6785807 interleukin 4 and interleukin 13 signaling
- R-hsa-3304349 loss of function of smad2 3 in cancer
- R-hsa-2129379 molecules associated with elastic fibres
- R-hsa-3000171 non integrin membrane ecm interactions
- R-hsa-76002 platelet activation signaling and aggregation
- R-hsa-597592 post translational protein modification
- R-hsa-8941858 regulation of runx3 expression and activity
- R-hsa-76005 response to elevated platelet cytosolic ca2
- R-hsa-73857 rna polymerase ii transcription
- R-hsa-8941855 runx3 regulates cdkn1a transcription
- R-hsa-8951936 runx3 regulates p14 arf
- R-hsa-449147 signaling by interleukins
- R-hsa-9839373 signaling by tgfbr3
- R-hsa-9006936 signaling by tgfb family members
- R-hsa-170834 signaling by tgf beta receptor complex
- R-hsa-3304351 signaling by tgf beta receptor complex in cancer
- R-hsa-3000170 syndecan interactions
- R-hsa-9839389 tgfbr3 regulates tgf beta signaling
- R-hsa-2173789 tgf beta receptor signaling activates smads
- R-hsa-2173791 tgf beta receptor signaling in emt epithelial to mesenchymal transition
- R-hsa-8878159 transcriptional regulation by runx3
- R-hsa-381340 transcriptional regulation of white adipocyte differentiation
- R-hsa-5689603 uch proteinases
- R-hsa-9824446 viral infection pathways
Mediation Categories
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
0 records.
Ligand-Receptor Signaling
49 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| ligand | ligand | scConnect | Yes | No | Yes | No | No |
| ligand | ligand | connectomeDB2020 | Yes | No | Yes | No | No |
| ligand | ligand | Matrisome | Yes | No | Yes | No | No |
| ligand | ligand | CellCall | Yes | No | Yes | No | No |
| growth_factor | ligand | UniProt_keyword | Yes | No | Yes | No | No |
| ligand | ligand | iTALK | Yes | No | Yes | No | No |
| growth_factor | ligand | iTALK | Yes | No | Yes | No | No |
| ligand | ligand | EMBRACE | Yes | No | Yes | No | No |
| transforming_growth_factor_beta | ligand | HGNC | Yes | No | Yes | No | No |
| ligand | ligand | HGNC | Yes | No | Yes | No | No |
Regulatory Interaction Network
13 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| TDGF1 | P13385 | TGFB1 | P01137 | Yes | No | Yes | WangSIGNOR | SIGNOR:17030617 |
| MMP9 | P14780 | TGFB1 | P01137 | Yes | Yes | No | WangLit-BM-17SIGNORACSN | Lit-BM-17:25241761SIGNOR:10652271ACSN:21900405Lit-BM-17:10652271 |
| LTBP1 | Q14766 | TGFB1 | P01137 | Yes | Yes | Yes | SIGNORHINTIntActDIPWangCellChatDB-cofactors | SIGNOR:8432736HINT:12429738HINT:10930463DIP:21677751IntAct:21677751HINT:21677751 |
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Protein Complex Composition
5 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| TGF-beta-1 complex | TGFB1 | P01137 | 2 | ComplexPortalPDB | PDB:6p7jPDB:8udzPDB:4kv5PDB:1klcPDB:5vqpPDB:1kldPDB:1klaintact:EBI-12501958 | 2397970729109152252091761206575614755292867961313338882020773822943793 |
| CDC45MCM10MCM2MCM3MCM4MCM6MCM7ORC2ORC4SMAD2TGFB1 | O43929O75419P01137P25205P33991P33993P49736Q13416Q14566Q15796Q7L590 | 1:1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC7295 | ||
| TGFB1TGFB3 | P01137P10600 | 0:0 | hu.MAP2 | |||
| BMP3TGFB1WFIKKN1WFIKKN2 | P01137P12645Q8TEU8Q96NZ8 | 1:1:1:1 | CompleatCFinder | Compleat:HC5891 | ||
| NRROSTGFB1 | P01137Q86YC3 | 2:1 | PDB | PDB:7y1r |
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Mass spectrometry [LTQ-FT Ultra] | 0 |
Sequence, Structure & Domains
Sequences
Length
390
Mass
44,325
Sequence
MPPSGLRLLPLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEIYDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWRYLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFTTGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQALEPLPIVYYVGRKPKVEQLSNMIVRSCKCS
3D Structural Models
Turn
120..122; 123..126; 282..284; 337..341; 344..346
Helix
38..56; 75..85; 116..119; 137..143; 147..149; 201..207; 265..268; 285..288; 302..306
Beta Strand
70..72; 106..112; 131..136; 144..146; 150..157; 166..170; 175..177; 179..181; 184..187; 196..199; 214..221; 224..230; 232..235; 242..244; 245..248; 251..254; 257..262; 294..296; 299..301; 311..313; 315..318; 321..323; 330..332; 347..349; 350..353; 355..370; 373..390
3D Structure
Electron microscopy (7); NMR spectroscopy (3); X-ray crystallography (7)
Domain & Motif Annotations
Motif
244..246; Cell attachment site
Domain (CC)
[Latency-associated peptide]: The 'straitjacket' and 'arm' domains encircle the Transforming growth factor beta-1 (TGF-beta-1) monomers and are fastened together by strong bonding between Lys-56 and Tyr-103/Tyr-104..; DOMAIN: [Latency-associated peptide]: The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8) (PubMed:28117447). The motif locates to a long loop in the arm domain called the bowtie tail (PubMed:28117447). Integrin-binding stabilizes an alternative conformation of the bowtie tail (PubMed:28117447). Activation by integrin requires force application by the actin cytoskeleton, which is resisted by the 'milieu molecules' (such as LTBP1, LRRC32/GARP and/or LRRC33/NRROS), resulting in distortion of the prodomain and release of the active TGF-beta-1 (PubMed:28117447).
Region
30..74; Straightjacket domain; 75..271; Arm domain; 226..252; Bowtie tail
Protein Families
TGF-beta family
Sequence Similarities
Belongs to the TGF-beta family.
Clinical Relevance
Related Diseases
Biomarker
Phase 2/3; Phase 1/2; Approved; Discontinued in Phase 2; Phase 2; Investigative; Phase 1; Phase 3; IND submitted
Drug Targets
Clinical trial targetSuccessful target
Drugs
SANDOSTATINTOREMIFENEVITAMIN EINTERFERON ALFA-2BTAMOXIFENADRIAMYCINNICOTINE POLACRILEXEMODINASPIRINSILYMARINBINTRAFUSP ALFAESTRADIOL VALERATEINOSITOLFRESOLIMUMABPROTEASOME INHIBITORPIOGLITAZONE HYDROCHLORIDEIDOXURIDINERETINOIC ACID AGENTTESTOSTERONERITUXIMABETOPOSIDENULLGALLIUM NITRATEVACTOSERTIBAMIFOSTINE ANHYDROUSDOXORUBICIN HYDROCHLORIDEPIRFENIDONEGENISTEINATENOLOLHYDROCORTISONE BUTYRATEH2O2STREPTOZOCINIRINOTECAN HYDROCHLORIDEFENRETINIDEGOSSYPOLCLADRIBINETRETINOINGLATIRAMERNISEVOKITUGANTIOXIDANTISOTRETINOINANTISENSE OLIGONUCLEOTIDESKEYHOLE LIMPET HEMOCYANINDISITERTIDETRIAMCINOLONEGALUNISERTIBMELATONINSOTATERCEPTRAMIPRILMETELIMUMABLY-2382770TCDDVERAPAMILTHERAPEUTIC ANDROGENBROXURIDINEBOVINE CARTILAGELUSPATERCEPT-AAMTALPHA-TOCOPHEROLHEPARAN SULFATE