Hmdb loader

Showing Protein Transforming growth factor beta-1 proprotein (HMDBP14468)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP14468
Secondary Accession Numbers None
Name Transforming growth factor beta-1 proprotein
Synonyms Not Available
Gene Name TGFB1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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.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.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. Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (By similarity).
Pathways
  • AGE-RAGE signaling pathway in diabetic complications
  • Amoebiasis
  • Cell cycle
  • Cellular senescence
  • Chagas disease
  • Chronic myeloid leukemia
  • Colorectal cancer
  • Cytokine-cytokine receptor interaction
  • Diabetic cardiomyopathy
  • Dilated cardiomyopathy
  • FoxO signaling pathway
  • Gastric cancer
  • Hepatitis B
  • Hepatocellular carcinoma
  • Hippo signaling pathway
  • Human T-cell leukemia virus 1 infection
  • Hypertrophic cardiomyopathy
  • Inflammatory bowel disease
  • Intestinal immune network for IgA production
  • Leishmaniasis
  • Malaria
  • MAPK signaling pathway
  • Non-alcoholic fatty liver disease
  • Osteoclast differentiation
  • Pancreatic cancer
  • Proteoglycans in cancer
  • Relaxin signaling pathway
  • Renal cell carcinoma
  • Rheumatoid arthritis
  • TGF-beta signaling pathway
  • Th17 cell differentiation
  • Toxoplasmosis
  • Tuberculosis
Reactions Not Available
GO Classification
Biological Process
cell-cell junction organization
negative regulation of cell cycle
positive regulation of bone mineralization
regulation of cell proliferation
ATP biosynthetic process
response to progesterone stimulus
positive regulation of protein dephosphorylation
positive regulation of cell migration
cell cycle arrest
positive regulation of cell proliferation
negative regulation of fat cell differentiation
chondrocyte differentiation
positive regulation of phosphatidylinositol 3-kinase activity
positive regulation of protein import into nucleus
negative regulation of blood vessel endothelial cell migration
cell migration
negative regulation of epithelial cell proliferation
SMAD protein signal transduction
inflammatory response
positive regulation of protein secretion
positive regulation of superoxide anion generation
response to wounding
BMP signaling pathway
hyaluronan catabolic process
ossification involved in bone remodeling
positive regulation of pathway-restricted SMAD protein phosphorylation
positive regulation of collagen biosynthetic process
regulation of SMAD protein signal transduction
positive regulation of epithelial to mesenchymal transition
positive regulation of protein phosphorylation
positive regulation of interleukin-17 production
protein kinase B signaling cascade
epithelial to mesenchymal transition
salivary gland morphogenesis
protein export from nucleus
positive regulation of blood vessel endothelial cell migration
negative regulation of mitotic cell cycle
positive regulation of ERK1 and ERK2 cascade
positive regulation of peptidyl-threonine phosphorylation
cellular response to organic cyclic compound
negative regulation of protein phosphorylation
hematopoietic progenitor cell differentiation
positive regulation of cellular protein metabolic process
negative regulation of transcription, DNA-dependent
positive regulation of transcription, DNA-dependent
positive regulation of protein kinase B signaling cascade
positive regulation of transcription from RNA polymerase II promoter
response to cholesterol
MAPK cascade
negative regulation of cell growth
positive regulation of fibroblast migration
phosphate-containing compound metabolic process
positive regulation of SMAD protein signal transduction
regulation of transforming growth factor beta receptor signaling pathway
SMAD protein complex assembly
transforming growth factor beta receptor signaling pathway
negative regulation of cell proliferation
lipopolysaccharide-mediated signaling pathway
positive regulation of gene expression
positive regulation of protein complex assembly
positive regulation of cell division
response to estradiol stimulus
cellular response to transforming growth factor beta stimulus
positive regulation of MAP kinase activity
negative regulation of macrophage cytokine production
negative regulation of gene expression
common-partner SMAD protein phosphorylation
extracellular matrix assembly
positive regulation of peptidyl-serine phosphorylation
extrinsic apoptotic signaling pathway
membrane protein intracellular domain proteolysis
negative regulation of myoblast differentiation
negative regulation of cell-cell adhesion
negative regulation of hyaluronan biosynthetic process
negative regulation of skeletal muscle tissue development
pathway-restricted SMAD protein phosphorylation
positive regulation of isotype switching to IgA isotypes
positive regulation of microglia differentiation
positive regulation of NAD+ ADP-ribosyltransferase activity
positive regulation of transcription regulatory region DNA binding
receptor catabolic process
epidermal growth factor receptor signaling pathway
positive regulation of chemotaxis
Cellular Component
cell surface
cytoplasm
blood microparticle
nucleus
extracellular space
Molecular Function
growth factor activity
antigen binding
type II transforming growth factor beta receptor binding
type III transforming growth factor beta receptor binding
cytokine activity
type I transforming growth factor beta receptor binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 390
Molecular Weight 44184.575
Theoretical pI 8.708
Pfam Domain Function
Signals
  • 1-29;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P54831
UniProtKB/Swiss-Prot Entry Name TGFB1_CANLF
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Manning AM, Auchampach JA, Drong RF, Slightom JL: Cloning of a canine cDNA homologous to the human transforming growth factor-beta 1-encoding gene. Gene. 1995 Apr 3;155(2):307-8. doi: 10.1016/0378-1119(94)00903-6. [PubMed:7721110 ]