MBTPS1: Membrane-Bound Transcription Factor Peptidase, Site 1
Key regulator of cholesterol homeostasis and ER stress response via SREBP activation
Gene Information Card
| Symbol | MBTPS1 |
|---|---|
| Full Name | Membrane-Bound Transcription Factor Peptidase, Site 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q23.3-q24.1 |
| NCBI Gene ID | 8720 ncbi.nlm.nih.gov/gene/8720 |
| Ensembl ID | ENSG00000140943 |
| UniProt ID | Q14703 |
| OMIM ID | 603355 |
| HGNC ID | 15456 |
| Aliases | S1P, PCSK8, SKI-1 |
Description
MBTPS1 encodes site-1 protease (S1P), a subtilisin-like proprotein convertase localized to the Golgi membrane. It cleaves membrane-bound transcription factors such as SREBPs (sterol regulatory element-binding proteins) and ATF6, regulating cholesterol biosynthesis, fatty acid metabolism, and the unfolded protein response. Loss-of-function mutations cause a syndromic form of lipodystrophy with spondyloepiphyseal dysplasia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spondyloepiphyseal dysplasia, MBTPS1-related | Impaired SREBP cleavage leads to defective chondrocyte differentiation and lipid metabolism | OMIM #618392 |
| Lipodystrophy, congenital generalized, type 5 | Loss of S1P activity disrupts adipocyte differentiation and lipid storage | OMIM #618393 |
| Nonalcoholic fatty liver disease (NAFLD) | Dysregulated SREBP processing contributes to hepatic steatosis | ClinVar, PMID: 28886345 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Adipose tissue | 8.3 | Medium |
| Pancreas | 6.1 | Low |
| Brain | 4.7 | Low |
| Kidney | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocyte line |
| 3T3-L1 | 9.8 | Adipocyte precursor |
| HEK293 | 7.5 | Embryonic kidney |
| HeLa | 5.1 | Cervical carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.304C>T (p.Arg102*) | Nonsense | <0.01% | Loss of function; truncation of catalytic domain |
| c.1129G>A (p.Gly377Arg) | Missense | <0.01% | Impaired autocatalytic processing |
| c.1996C>T (p.Arg666Cys) | Missense | <0.01% | Reduced SREBP cleavage activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations impairing catalytic activity or autocatalytic processing lead to loss of S1P function, causing lipodystrophy and skeletal dysplasia.
Gain of Function (GOF)
Not reported in MBTPS1.
Dominant Negative (DN)
Not reported; all known pathogenic mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Regulation of cholesterol biosynthesis by SREBP (SREBP signaling)
• Unfolded protein response (ATF6-alpha pathway)
• Proprotein convertase processing
Protein Summary
Site-1 protease (S1P) is a 1052-amino-acid Golgi-resident serine protease that cleaves SREBP transcription factors, releasing their N-terminal domains to activate genes involved in cholesterol and fatty acid synthesis. It also processes ATF6 during ER stress. The enzyme undergoes autocatalytic activation and requires a calcium ion for activity. Mutations cause a rare autosomal recessive disorder combining lipodystrophy and spondyloepiphyseal dysplasia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MBTPS1 Knockout HEK293 Cell Line | EDJ-KQ1067 | Human | 8720 | Details Get a Quote |
| MBTPS1 Knockout HCT 116 Cell Line | EDJ-KQ20199 | Human | 8720 | Details Get a Quote |
| MBTPS1 Knockout HeLa Cell Line | EDJ-KQ20200 | Human | 8720 | Details Get a Quote |
| MBTPS1 Knockout A-549 Cell Line | EDJ-KQ63472 | Human | 8720 | Details Get a Quote |
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