P07200 · TGFB1_PIG
- ProteinTransforming growth factor beta-1 proprotein
- GeneTGFB1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids390 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
Latency-associated peptide
Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix. Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1. Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia. Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1.
Transforming growth factor beta-1
Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity).
Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus. TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1. Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity).
While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules'. Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. 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 (By similarity).
Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes (By similarity).
Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (By similarity).
Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix. At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF-beta-1 and maintain it in a latent state during storage in extracellular milieus. TGF-beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1. Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity).
While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency-associated peptide chain (LAP) and 'milieu molecules'. Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts. 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 (By similarity).
Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus. Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes (By similarity).
Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 278-279 | Cleavage; by FURIN | ||||
Sequence: RA |
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTransforming growth factor beta-1 proprotein
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus
Accessions
- Primary accessionP07200
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Latency-associated peptide
Transforming growth factor beta-1
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 103 | Results in spontaneous, non integrin-dependent activation. | ||||
Sequence: Y → A, K, or T | ||||||
Mutagenesis | 104 | Results in spontaneous, non integrin-dependent activation. | ||||
Sequence: Y → A, C, S, or T | ||||||
Natural variant | 114 | |||||
Sequence: V → L |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 7 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-29 | |||||
Sequence: MPPSGLRLLPLLLPLLWLLVLTPGRPAAG | ||||||
Chain | PRO_0000033768 | 30-278 | Latency-associated peptide | |||
Sequence: LSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQGDVPPGPLPEAVLALYNSTRDRVAGESVEPEPEPEADYYAKEVTRVLMVESGNQIYDKFKGTPHSLYMLFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNDSWRYLSNRLLAPSDSPEWLSFDVTGVVRQWLTRREAIEGFRLSAHCSCDSKDNTLHVEINGFNSGRRGDLATIHGMNRPFLLLMATPLERAQHLHSSRHRR | ||||||
Disulfide bond | 33 | Interchain (with C-? in LTBP1 TB3 domain); in inactive form | ||||
Sequence: C | ||||||
Glycosylation | 82 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 136 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 176 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 223 | Interchain (with C-225) | ||||
Sequence: C | ||||||
Disulfide bond | 225 | Interchain (with C-223) | ||||
Sequence: C | ||||||
Chain | PRO_0000033769 | 279-390 | Transforming growth factor beta-1 | |||
Sequence: ALDTNYCFSSTEKNCCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQALEPLPIVYYVGRKPKVEQLSNMIVRSCKCS | ||||||
Disulfide bond | 285↔294 | |||||
Sequence: CFSSTEKNCC | ||||||
Disulfide bond | 293↔356 | |||||
Sequence: CCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCC | ||||||
Disulfide bond | 322↔387 | |||||
Sequence: CLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQALEPLPIVYYVGRKPKVEQLSNMIVRSC | ||||||
Disulfide bond | 326↔389 | |||||
Sequence: CPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQALEPLPIVYYVGRKPKVEQLSNMIVRSCKC | ||||||
Disulfide bond | 355 | Interchain | ||||
Sequence: C |
Post-translational modification
Transforming growth factor beta-1 proprotein: The precursor proprotein is cleaved in the Golgi apparatus by FURIN to form Transforming growth factor beta-1 (TGF-beta-1) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-1 inactive.
Latency-associated peptide
N-glycosylated. Deglycosylation leads to activation of Transforming growth factor beta-1 (TGF-beta-1); mechanisms triggering deglycosylation-driven activation of TGF-beta-1 are however unclear.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
Homodimer; disulfide-linked. Interacts with the serine proteases, HTRA1 and HTRA3: the interaction with either inhibits TGFB1-mediated signaling and the HTRA protease activity is required for this inhibition. May interact with THSD4; this interaction may lead to sequestration by FBN1 microfibril assembly and attenuation of TGFB signaling. Interacts with CD109, DPT and ASPN. Interacts with EFEMP2. Interacts with TSKU; the interaction contributes to regulation of the hair cycle.
Latency-associated peptide
Homodimer; disulfide-linked. Interacts with transforming growth factor beta-1 (TGF-beta-1) chain; interaction is non-covalent and maintains TGF-beta-1 in a latent state; each latency-associated peptide (LAP) monomer interacts with TGF-beta-1 in the other monomer. Interacts with LTBP1; leading to regulation of TGF-beta-1 activation. Interacts with LRRC32/GARP; leading to regulation of TGF-beta-1 activation on the surface of activated regulatory T-cells (Tregs). Interacts with LRRC33/NRROS; leading to regulation of TGF-beta-1 activation in macrophages and microglia. Interacts (via cell attachment site) with integrins ITGAV and ITGB6 (ITGAV:ITGB6), leading to release of the active TGF-beta-1. Interacts with NREP; the interaction results in a decrease in TGFB1 autoinduction. Interacts with HSP90AB1; inhibits latent TGFB1 activation.
Transforming growth factor beta-1
Homodimer; disulfide-linked. Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P07200 | Emilin1 Q99K41 | 2 | EBI-907660, EBI-906561 | |
BINARY | P07200 | TGFB1 P07200 | 2 | EBI-907660, EBI-907660 | |
XENO | P07200 | TGFBR2 P37173 | 2 | EBI-907660, EBI-296151 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 30-74 | Straightjacket domain | ||||
Sequence: LSTCKTIDMELVKRKRIEAIRGQILSKLRLASPPSQGDVPPGPLP | ||||||
Region | 75-271 | Arm domain | ||||
Sequence: EAVLALYNSTRDRVAGESVEPEPEPEADYYAKEVTRVLMVESGNQIYDKFKGTPHSLYMLFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNDSWRYLSNRLLAPSDSPEWLSFDVTGVVRQWLTRREAIEGFRLSAHCSCDSKDNTLHVEINGFNSGRRGDLATIHGMNRPFLLLMATPLERAQHL | ||||||
Region | 226-252 | Bowtie tail | ||||
Sequence: DSKDNTLHVEINGFNSGRRGDLATIHG | ||||||
Motif | 244-246 | Cell attachment site | ||||
Sequence: RGD |
Domain
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.
Latency-associated peptide
The cell attachment site motif mediates binding to integrins (ITGAV:ITGB6 or ITGAV:ITGB8). The motif locates to a long loop in the arm domain called the bowtie tail. Integrin-binding stabilizes an alternative conformation of the bowtie tail (PubMed:21677751).
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 (By similarity).
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 (By similarity).
Sequence similarities
Belongs to the TGF-beta family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length390
- Mass (Da)44,280
- Last updated2018-10-10 v2
- ChecksumA9FC32859BA6AF06
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 6-7 | in Ref. 3; CAA30933 | ||||
Sequence: LR → PG | ||||||
Sequence conflict | 180 | in Ref. 3; CAA30933 | ||||
Sequence: R → G | ||||||
Sequence conflict | 237 | in Ref. 3; CAA30933 | ||||
Sequence: N → NA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y00111 EMBL· GenBank· DDBJ | CAA68291.1 EMBL· GenBank· DDBJ | mRNA | ||
M23703 EMBL· GenBank· DDBJ | AAA64616.1 EMBL· GenBank· DDBJ | mRNA | ||
X12373 EMBL· GenBank· DDBJ | CAA30933.1 EMBL· GenBank· DDBJ | mRNA | ||
AF461808 EMBL· GenBank· DDBJ | AAL57902.1 EMBL· GenBank· DDBJ | mRNA | ||
AEMK02000041 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |