The following text describes a protein:
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 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. Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (By similarity). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (By similarity).
Subcellular Localization:
[Latency-associated peptide]: Secreted, extracellular space, extracellular matrix; [Transforming growth factor beta-1]: Secreted.
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-54 and Tyr-101/Tyr-102; [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. 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.
Sequence:
MRVESLLLALQCLLGFVHYSGALSTCSPLDLELIKRKRIEAIRGQILSKLRLSKEPEVDEEKESQNIPAELISVYNSTVELNEEQAAPPEQPKEDPVEEEYYAKEVHKFTIKLMEKNPDKFLWFNITDISQTLGLNRIISQVELRLLITTFPDGSEQRLELYQVIGNKSRYLESRFIPNQRKWLSFDVTQTLKDWLQRSEAEQGFQLKMADNCDPQKTFQLKIPGLVLVRGDTETLAVNMPRPHILVMSLPLDGNNSSKSRRKRQTETDQVCTDKSDGCCVRSLYIDFRKDLGWKWIHEPSGYYANYCTGSCSFVWTSENKYSQVLALYKHHNPGASAQPCRVPQVLNPLPIFYYVGRQHKVEQLSNMIVKTCKCC