MBTPS2 (Membrane Bound Transcription Factor Peptidase, Site 2)
Key regulator of SREBP processing and cholesterol homeostasis
Gene Information Card
| Symbol | MBTPS2 |
|---|---|
| Full Name | Membrane Bound Transcription Factor Peptidase, Site 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.12 |
| NCBI Gene ID | 51360 ncbi.nlm.nih.gov/gene/51360 |
| Ensembl ID | ENSG00000112144 |
| UniProt ID | O43462 |
| OMIM ID | 300294 |
| HGNC ID | 15455 |
| Aliases | S2P, KIAA1791, BRESHECK, IFAP |
Description
MBTPS2 encodes site-2 protease (S2P), a zinc metalloprotease localized in the Golgi membrane. S2P cleaves membrane-bound transcription factors such as SREBPs (sterol regulatory element-binding proteins) and ATF6, releasing their N-terminal domains to regulate cholesterol biosynthesis, lipid metabolism, and the unfolded protein response. Mutations in MBTPS2 cause X-linked disorders including ichthyosis follicularis with atrichia and photophobia (IFAP) and BRESHECK syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ichthyosis follicularis with atrichia and photophobia (IFAP) | Loss-of-function mutations impair SREBP processing, leading to defective cholesterol homeostasis and skin barrier dysfunction | ClinVar, OMIM #308205 |
| BRESHECK syndrome | Hypomorphic mutations reduce S2P activity, causing intellectual disability, skeletal abnormalities, and ichthyosis | OMIM #300294, PMID: 19559398 |
| Keratosis follicularis spinulosa decalvans (KFSD) | Missense variants alter S2P catalytic activity, disrupting epidermal differentiation | ClinVar, PMID: 24387992 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Brain | 6.1 | Low |
| Kidney | 7.9 | Medium |
| Testis | 9.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.1 | Cervical cancer cell line |
| HEK293 | 8.7 | Embryonic kidney cells |
| HepG2 | 9.5 | Hepatocellular carcinoma cells |
| K562 | 6.3 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1286A>G (p.Asn429Ser) | Missense | Rare | Reduced S2P activity; associated with IFAP syndrome |
| c.1523C>T (p.Pro508Leu) | Missense | Rare | Impaired SREBP cleavage; BRESHECK syndrome |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of function; severe IFAP phenotype |
| c.1022T>C (p.Leu341Pro) | Missense | Rare | Dominant-negative effect; KFSD |
Mutation functional classification
Loss of Function (LOF)
Most MBTPS2 mutations are loss-of-function, reducing or abolishing S2P protease activity, leading to impaired SREBP and ATF6 processing.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MBTPS2.
Dominant Negative (DN)
Some missense variants (e.g., p.Leu341Pro) may exert dominant-negative effects by interfering with wild-type S2P dimerization or substrate access.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SREBP signaling pathway (Reactome: R-HSA-1655829)
• Unfolded Protein Response (UPR) (Reactome: R-HSA-381119)
• Cholesterol biosynthesis (KEGG: hsa00100)
Protein Summary
Site-2 protease (S2P) is a 519-amino-acid zinc metalloprotease with multiple transmembrane domains. It resides in the Golgi membrane and cleaves the luminal loop of SREBPs and ATF6 after site-1 protease (S1P) cleavage, releasing their cytosolic transcription factor domains. S2P activity is essential for cholesterol sensing and ER stress response. The protein contains a HEXXH zinc-binding motif critical for catalysis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MBTPS2 Knockout HEK293 Cell Line | EDJ-KQ2239 | Human | 51360 | Details Get a Quote |
| MBTPS2 Knockout A-549 Cell Line | EDJ-KQ22533 | Human | 51360 | Details Get a Quote |
| MBTPS2 Knockout HCT 116 Cell Line | EDJ-KQ22534 | Human | 51360 | Details Get a Quote |
| MBTPS2 Knockout HeLa Cell Line | EDJ-KQ22535 | Human | 51360 | Details Get a Quote |
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