MBTPS1
GeneName
MBTPS1
Summary
MBTPS1, also known as S1P, SKI-1, or SKI1, is a 118 kDa serine-type endopeptidase that is predominantly localised in the endoplasmic reticulum and Golgi apparatus. It plays a critical role in the processing of membrane proteins and the regulation of cholesterol metabolism. MBTPS1 is involved in the ATF6-mediated unfolded protein response, which is essential for maintaining cellular homeostasis under stress conditions. Additionally, it participates in various biological processes such as lysosome organisation, protein maturation, and the response to endoplasmic reticulum stress, highlighting its importance in cellular function and integrity.
Importance
MBTPS1 is relevant to: - The unfolded protein response, which is vital for cellular adaptation to stress and has implications in various diseases, including neurodegenerative disorders. - Cholesterol metabolism and homeostasis, contributing to understanding metabolic diseases and cardiovascular health. - The regulation of vesicle-mediated transport, which is crucial for intracellular trafficking and organelle communication. - DNA damage response mechanisms, providing insights into cancer biology and therapeutic targets.
Top Products
For researchers investigating MBTPS1, we recommend the well-cited polyclonal antibody, Anti-S1P antibody (ab140592). This antibody has garnered 15 citations, reflecting its reliability and trust within the scientific community. It is particularly effective for Western blotting (WB), making it an excellent choice for those looking to study MBTPS1 in detail.
Abcam Product Citation Summary
The MBTPS1 gene has been investigated in the context of experimental autoimmune encephalomyelitis using mouse spinal cord tissues. The use of western blotting indicates a focus on protein expression levels in this model.
Abcam Product Citation Table
Function
Serine protease that cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4: known substrates include SREBF1/SREBP1, SREBF2/SREBP2, BDNF, GNPTAB, ATF6, ATF6B and FAM20C (PubMed:10644685, PubMed:12782636, PubMed:21719679, PubMed:34349020). Cleaves substrates after Arg-Ser-Val-Leu (SREBP2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu (PubMed:10644685, PubMed:21719679). Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:12782636). Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) (PubMed:12782636). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes (PubMed:21719679). Cleaves the propeptide from FAM20C which is required for FAM20C secretion from the Golgi apparatus membrane and for enhancement of FAM20C kinase activity, promoting osteoblast differentiation and biomineralization (PubMed:34349020). Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes (PubMed:21719679, PubMed:30046013). It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation (PubMed:30046013). Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking (PubMed:30046013). Promotes FAD binding to the ETFA/ETFB complex and is therefore involved in mitochondrial respiratory chain regulation (PubMed:35362222). In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the first step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression (PubMed:16417584).
Involvement in disease
Spondyloepiphyseal dysplasia, Kondo-Fu type
SEDKF
A disorder characterized by severely retarded growth, spondyloepiphyseal dysplasia, reduced bone mineral density, and markedly elevated plasma levels of various lysosomal enzymes. Additional features include pectus carinatum, kyphosis, a waddling gait, brachydactyly and dysmorphic facial features. SEDKF transmission pattern is consistent with autosomal recessive inheritance.
None
The disease is caused by variants affecting the gene represented in this entry.
Cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome
CAOP
An autosomal recessive disorder characterized by early-onset bilateral lens cataract, generalized non-scarring alopecia, oral mucosal disorder, and severe psoriasiform skin lesions affecting the scalp, facial, inguinal region, buttocks, and lower extremities.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and into a secreted 98 kDa form (PubMed:10644685, PubMed:9990022). The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates (PubMed:10644685).
Sequence Similarities
Belongs to the peptidase S8 family.
Tissue Specificity
Widely expressed.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass type I membrane protein
- Golgi apparatus membrane
- Single-pass type I membrane protein
- Secreted
- Mitochondrion
- May sort to other organelles, including lysosomal and/or endosomal compartments. The 98 kDa form is secreted.
Alternative names
KIAA0091, S1P, SKI1, MBTPS1, Membrane-bound transcription factor site-1 protease, Endopeptidase S1P, Subtilisin/kexin-isozyme 1, SKI-1