Gene/Proteome Database (LMPD)
LMPD ID
LMP006777
Gene ID
Species
Homo sapiens (Human)
Gene Name
membrane-bound transcription factor peptidase, site 2
Gene Symbol
Synonyms
BRESEK; IFAP; KFSD; KFSDX; OLMSX; S2P
Alternate Names
membrane-bound transcription factor site-2 protease; endopeptidase S2P; SREBPs intramembrane protease; keratosis follicularis spinulosa decalvans; membrane-bound transcription factor protease, site 2; sterol regulatory element-binding proteins intramembrane protease
Chromosome
X
Map Location
Xp22.12-p22.11
EC Number
3.4.24.85
Summary
This gene encodes a intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response.[provided by RefSeq, Aug 2009]
Orthologs
Proteins
| membrane-bound transcription factor site-2 protease | |
|---|---|
| Refseq ID | NP_056968 |
| Protein GI | 7706693 |
| UniProt ID | O43462 |
| mRNA ID | NM_015884 |
| Length | 519 |
| RefSeq Status | REVIEWED |
| MIPVSLVVVVVGGWTVVYLTDLVLKSSVYFKHSYEDWLENNGLSISPFHIRWQTAVFNRAFYSWGRRKARMLYQWFNFGMVFGVIAMFSSFFLLGKTLMQTLAQMMADSPSSYSSSSSSSSSSSSSSSSSSSSSSSLHNEQVLQVVVPGINLPVNQLTYFFTAVLISGVVHEIGHGIAAIREQVRFNGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALVLLPVILLPFYYTGVGVLITEVAEDSPAIGPRGLFVGDLVTHLQDCPVTNVQDWNECLDTIAYEPQIGYCISASTLQQLSFPVRAYKRLDGSTECCNNHSLTDVCFSYRNNFNKRLHTCLPARKAVEATQVCRTNKDCKKSSSSSFCIIPSLETHTRLIKVKHPPQIDMLYVGHPLHLHYTVSITSFIPRFNFLSIDLPVVVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFLDATLTSVIGDNDVKDLIGFFILLGGSVLLAANVTLGLWMVTAR | |
Gene Information
Entrez Gene ID
Gene Name
membrane-bound transcription factor peptidase, site 2
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0000139 | TAS:Reactome | C | Golgi membrane |
| GO:0005737 | IDA:UniProtKB | C | cytoplasm |
| GO:0016021 | TAS:ProtInc | C | integral component of membrane |
| GO:0046872 | IEA:UniProtKB-KW | F | metal ion binding |
| GO:0004222 | TAS:ProtInc | F | metalloendopeptidase activity |
| GO:0006987 | TAS:Reactome | P | activation of signaling protein activity involved in unfolded protein response |
| GO:0044267 | TAS:Reactome | P | cellular protein metabolic process |
| GO:0008203 | TAS:ProtInc | P | cholesterol metabolic process |
| GO:0030968 | TAS:Reactome | P | endoplasmic reticulum unfolded protein response |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa04141 | Protein processing in endoplasmic reticulum |
| ko04141 | Protein processing in endoplasmic reticulum |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_147797 | Regulation of cholesterol biosynthesis by SREBP (SREBF) |
Domain Information
UniProt Annotations
Entry Information
Gene Name
membrane-bound transcription factor peptidase, site 2
Protein Entry
MBTP2_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Catalytic Activity | Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site 477-DRSRILL-|- CVLTFLCLSFNPLTSLLQWGGA-505. The residues Asn-Pro, 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced. |
| Cofactor | Name=Zn(2+); Xref=ChEBI |
| Disease | IFAP syndrome with or without BRESHECK syndrome (IFAPS) [MIM |
| Disease | Keratosis follicularis spinulosa decalvans X-linked (KFSDX) [MIM |
| Disease | Olmsted syndrome, X-linked (OLMSX) [MIM |
| Function | Intramembrane proteolysis of sterol-regulatory element- binding proteins (SREBPs) within the first transmembrane segment thereby releasing the N-terminal segment with a portion of the transmembrane segment attached. Site-2 cleavage comes after site-1 cleavage which takes place in the lumenal loop. |
| Similarity | Belongs to the peptidase M50A family. |
| Subcellular Location | Membrane ; Multi-pass membrane protein . Cytoplasm . |
| Tissue Specificity | Expressed in heart, brain, placenta, lung, liver, muscle, kidney and pancreas. |
Identical and Related Proteins
Unique RefSeq proteins for LMP006777 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 7706693 | RefSeq | NP_056968 | 519 | membrane-bound transcription factor site-2 protease |
Identical Sequences to LMP006777 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:7706693 | DBBJ | BAG11437.1 | 519 | membrane-bound transcription factor site-2 protease, partial [synthetic construct] |
| GI:7706693 | GenBank | AAC51937.1 | 519 | S2P [Homo sapiens] |
| GI:7706693 | GenBank | EAW98982.1 | 519 | membrane-bound transcription factor peptidase, site 2 [Homo sapiens] |
| GI:7706693 | RefSeq | XP_003819612.1 | 519 | PREDICTED: membrane-bound transcription factor site-2 protease [Pan paniscus] |
| GI:7706693 | SwissProt | O43462.1 | 519 | RecName: Full=Membrane-bound transcription factor site-2 protease; AltName: Full=Endopeptidase S2P; AltName: Full=Sterol regulatory element-binding proteins intramembrane protease; Short=SREBPs intramembrane protease [Homo sapiens] |
Related Sequences to LMP006777 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:7706693 | DBBJ | BAF85622.1 | 519 | unnamed protein product [Homo sapiens] |
| GI:7706693 | GenBank | ACM86230.1 | 552 | Sequence 11728 from patent US 6812339 |
| GI:7706693 | GenBank | JAA04855.1 | 521 | membrane-bound transcription factor peptidase, site 2 [Pan troglodytes] |
| GI:7706693 | GenBank | JAA19115.1 | 521 | membrane-bound transcription factor peptidase, site 2 [Pan troglodytes] |
| GI:7706693 | GenBank | JAA23418.1 | 521 | membrane-bound transcription factor peptidase, site 2 [Pan troglodytes] |
| GI:7706693 | GenBank | JAA43253.1 | 521 | membrane-bound transcription factor peptidase, site 2 [Pan troglodytes] |