Gene Ontology annotation through association of InterPro records with GO terms

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

Combined Automated Annotation using Multiple IEA Methods

ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.

IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.

The endoplasmic reticulum stress response in aging and age-related diseases.

MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta.

Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs.

Regulation of cholesterol biosynthesis by SREBP (SREBF)

S2P hydrolyzes SREBP1A,1C,2

ATF6 (ATF6-alpha) activates chaperones

Unfolded Protein Response (UPR)

MBTPS2 (S2P) cleaves ATF6 (ATF6-alpha)

MBTPS2 (S2P) cleaves ATF6B (ATF6-beta)

ATF6B (ATF6-beta) activates chaperones

MBTPS2 (S2P) cleaves CREB3L3

Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment.

Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease.

Membrane topology of S2P, a protein required for intramembranous cleavage of sterol regulatory element-binding proteins.

Cleavage of the membrane-bound transcription factor OASIS in response to endoplasmic reticulum stress.

UniProt entry O43462 (MBTP2_HUMAN)