Q9WTZ3 · MBTP1_RAT
- ProteinMembrane-bound transcription factor site-1 protease
- GeneMbtps1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1052 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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. 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. Catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Also mediates the first step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B). Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes. 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. Involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. It is required for the activation of CREB3L2/BBF2H7, a transcriptional activator of MIA3/TANGO and other genes controlling mega vesicle formation. Therefore, it plays a key role in the regulation of mega vesicle-mediated collagen trafficking. 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.
Catalytic activity
Cofactor
Activity regulation
Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments. Inhibited by 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), a serine protease inhibitor.
Features
Showing features for site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 186-187 | Cleavage; by autolysis | ||||
Sequence: LR | ||||||
Active site | 218 | Charge relay system | ||||
Sequence: D | ||||||
Active site | 249 | Charge relay system | ||||
Sequence: H | ||||||
Active site | 414 | Charge relay system | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | Golgi apparatus | |
Cellular Component | Golgi membrane | |
Cellular Component | Golgi stack | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | cholesterol metabolic process | |
Biological Process | lipid metabolic process | |
Biological Process | lysosome organization | |
Biological Process | membrane protein intracellular domain proteolysis | |
Biological Process | mitotic G2 DNA damage checkpoint signaling | |
Biological Process | protein maturation | |
Biological Process | protein processing | |
Biological Process | proteolysis | |
Biological Process | regulation of vesicle-mediated transport |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameMembrane-bound transcription factor site-1 protease
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ9WTZ3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass type I membrane protein
Golgi apparatus membrane ; Single-pass type I membrane protein
Note: May sort to other organelles, including lysosomal and/or endosomal compartments.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 187-999 | Lumenal | ||||
Sequence: RAIPRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNERTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKKIDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGGIDFEDNIARFSSRGMTTWELPGGYGRVKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVVAGAVTLLVSTVQKRELVNPASVKQALIASARRLPGVNMFEQGHGKLDLLRAYQILSSYKPQASLSPSYIDLTECPYMWPYCSQPIYYGGMPTIVNVTILNGMGVTGRIVDKPEWRPYLPQNGDNIEVAFSYSSVLWPWSGYLAISISVTKKAASWEGIAQGHIMITVASPAETELKNGAEHTSTVKLPIKVKIIPTPPRSKRVLWDQYHNLRYPPGYFPRDNLRMKNDPLDWNGDHVHTNFRDMYQHLRSMGYFVEVLGAPFTCFDATQYGTLLMVDSEEEYFPEEIAKLRRDVDNGLSLVVFSDWYNTSVMRKVKFYDENTRQWWMPDTGGANVPALNELLSVWNMGFSDGLYEGEFALANHDMYYASGCSIARFPEDGVVITQTFKDQGLEVLKQETAVVDNVPILGLYQIPAEGGGRIVLYGDSNCLDDSHRQKDCFWLLDALLQYTSYGVTPPSLSHSGNRQRPPSGAGLAPPERMEGNHLHRYSKVLEAHLGDPKPRPLPACPHLSWAKPQPLNETAPSNLWKHQKLLSIDLDKVVLPNFRSNRPQVRPLSPGESGAWDIPGGIMPGRYNQEVG | ||||||
Transmembrane | 1000-1022 | Helical | ||||
Sequence: QTIPVFAFLGAMVALAFFVVQIS | ||||||
Topological domain | 1023-1052 | Cytoplasmic | ||||
Sequence: KAKSRPKRRRPRAKRPQLAQQAHPARTPSV |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for signal, propeptide, glycosylation, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-17 | |||||
Sequence: MKLVNIWLLLLVVLLCG | ||||||
Propeptide | PRO_0000027055 | 18-186 | ||||
Sequence: KKHLGDRLGKKAFEKAPCPSCSHLTLKVEFSSTVVEYEYIVAFNGYFTAKARNSFISSALKSSEVDNWRIIPRNNPSSDYPSDFEVIQIKEKQKAGLLTLEDHPNIKRVTPQRKVFRSLKFAESDPIVPCNETRWSQKWQSSRPLKRASLSLGSGFWHATGRHSSRRLL | ||||||
Glycosylation | 148 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 168 | Phosphoserine | ||||
Sequence: S | ||||||
Chain | PRO_0000027056 | 187-1052 | Membrane-bound transcription factor site-1 protease | |||
Sequence: RAIPRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNERTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKKIDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGGIDFEDNIARFSSRGMTTWELPGGYGRVKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVVAGAVTLLVSTVQKRELVNPASVKQALIASARRLPGVNMFEQGHGKLDLLRAYQILSSYKPQASLSPSYIDLTECPYMWPYCSQPIYYGGMPTIVNVTILNGMGVTGRIVDKPEWRPYLPQNGDNIEVAFSYSSVLWPWSGYLAISISVTKKAASWEGIAQGHIMITVASPAETELKNGAEHTSTVKLPIKVKIIPTPPRSKRVLWDQYHNLRYPPGYFPRDNLRMKNDPLDWNGDHVHTNFRDMYQHLRSMGYFVEVLGAPFTCFDATQYGTLLMVDSEEEYFPEEIAKLRRDVDNGLSLVVFSDWYNTSVMRKVKFYDENTRQWWMPDTGGANVPALNELLSVWNMGFSDGLYEGEFALANHDMYYASGCSIARFPEDGVVITQTFKDQGLEVLKQETAVVDNVPILGLYQIPAEGGGRIVLYGDSNCLDDSHRQKDCFWLLDALLQYTSYGVTPPSLSHSGNRQRPPSGAGLAPPERMEGNHLHRYSKVLEAHLGDPKPRPLPACPHLSWAKPQPLNETAPSNLWKHQKLLSIDLDKVVLPNFRSNRPQVRPLSPGESGAWDIPGGIMPGRYNQEVGQTIPVFAFLGAMVALAFFVVQISKAKSRPKRRRPRAKRPQLAQQAHPARTPSV | ||||||
Glycosylation | 236 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 305 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 515 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 728 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 939 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
The 148 kDa zymogen is processed progressively into two membrane-bound 120 and 106 kDa forms in the endoplasmic reticulum, and late into a secreted 98 kDa form. The propeptide is autocatalytically removed through an intramolecular cleavage after Leu-186. Further cleavage generates 14, 10, and 8 kDa intermediates.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed (PubMed:9990022).
In adult rat, highly expressed in anterior pituitary, thyroid and adrenal glands and in liver (PubMed:9990022).
In 2-day old rat, detected in developing skin, striated muscles, cardiac muscles, bones, teeth and internal organs (PubMed:9990022).
Highly expressed in retina, cerebellum, pituitary, submaxillary, thyroid and adrenal glands, molars, thymus, kidney and intestine (PubMed:9990022).
In adult rat, highly expressed in anterior pituitary, thyroid and adrenal glands and in liver (PubMed:9990022).
In 2-day old rat, detected in developing skin, striated muscles, cardiac muscles, bones, teeth and internal organs (PubMed:9990022).
Highly expressed in retina, cerebellum, pituitary, submaxillary, thyroid and adrenal glands, molars, thymus, kidney and intestine (PubMed:9990022).
Gene expression databases
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 190-472 | Peptidase S8 | ||||
Sequence: PRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNERTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKKIDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGGIDFEDNIARFSSRGMTTWELPGGYGRVKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVVAGAVTLLVSTVQKRELVNPASVKQALIASARRLPGVNMFEQGHGKLDLLRAY | ||||||
Region | 877-900 | Disordered | ||||
Sequence: PSLSHSGNRQRPPSGAGLAPPERM | ||||||
Region | 1026-1052 | Disordered | ||||
Sequence: SRPKRRRPRAKRPQLAQQAHPARTPSV |
Sequence similarities
Belongs to the peptidase S8 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length1,052
- Mass (Da)117,462
- Last updated2014-04-16 v2
- Checksum417A6FEE4DEAB2B6
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I5XW81 | A0A8I5XW81_RAT | Mbtps1 | 964 | ||
A0A8L2R475 | A0A8L2R475_RAT | Mbtps1 | 1066 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 301 | in Ref. 1; AAD27011 | ||||
Sequence: I → M |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF094821 EMBL· GenBank· DDBJ | AAD27011.1 EMBL· GenBank· DDBJ | mRNA | ||
AABR06099111 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH473972 EMBL· GenBank· DDBJ | EDL92670.1 EMBL· GenBank· DDBJ | Genomic DNA |