Gene/Proteome Database (LMPD)

LMPD ID
LMP002884
Gene ID
8720
Species
Homo sapiens (Human)
Gene Name
membrane-bound transcription factor peptidase, site 1
Gene Symbol
MBTPS1
Synonyms
PCSK8; S1P; SKI-1
Alternate Names
membrane-bound transcription factor site-1 protease; site-1 protease; endopeptidase S1P; subtilisin/kexin isozyme-1; proprotein convertase subtilisin/kexin type 8
Chromosome
16
Map Location
16q24
EC Number
3.4.21.112
Summary
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to the cis/medial-Golgi where a second autocatalytic event takes place and the catalytic activity is acquired. It encodes a type 1 membrane bound protease which is ubiquitously expressed and regulates cholesterol or lipid homeostasis via cleavage of substrates at non-basic residues. Mutations in this gene may be associated with lysosomal dysfunction. [provided by RefSeq, Feb 2014]
Orthologs
View orthologs and multiple alignments for MBTPS1

Proteins

membrane-bound transcription factor site-1 protease preproprotein
Refseq ID NP_003782
Protein GI 4506775
UniProt ID Q14703
mRNA ID NM_003791
Length 1052
RefSeq Status REVIEWED
MKLVNIWLLLLVVLLCGKKHLGDRLEKKSFEKAPCPGCSHLTLKVEFSSTVVEYEYIVAFNGYFTAKARNSFISSALKSSEVDNWRIIPRNNPSSDYPSDFEVIQIKEKQKAGLLTLEDHPNIKRVTPQRKVFRSLKYAESDPTVPCNETRWSQKWQSSRPLRRASLSLGSGFWHATGRHSSRRLLRAIPRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNERTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKKIDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGGIDFEDNIARFSSRGMTTWELPGGYGRMKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVVAGAVTLLVSTVQKRELVNPASMKQALIASARRLPGVNMFEQGHGKLDLLRAYQILNSYKPQASLSPSYIDLTECPYMWPYCSQPIYYGGMPTVVNVTILNGMGVTGRIVDKPDWQPYLPQNGDNIEVAFSYSSVLWPWSGYLAISISVTKKAASWEGIAQGHVMITVASPAETESKNGAEQTSTVKLPIKVKIIPTPPRSKRVLWDQYHNLRYPPGYFPRDNLRMKNDPLDWNGDHIHTNFRDMYQHLRSMGYFVEVLGAPFTCFDASQYGTLLMVDSEEEYFPEEIAKLRRDVDNGLSLVIFSDWYNTSVMRKVKFYDENTRQWWMPDTGGANIPALNELLSVWNMGFSDGLYEGEFTLANHDMYYASGCSIAKFPEDGVVITQTFKDQGLEVLKQETAVVENVPILGLYQIPAEGGGRIVLYGDSNCLDDSHRQKDCFWLLDALLQYTSYGVTPPSLSHSGNRQRPPSGAGSVTPERMEGNHLHRYSKVLEAHLGDPKPRPLPACPRLSWAKPQPLNETAPSNLWKHQKLLSIDLDKVVLPNFRSNRPQVRPLSPGESGAWDIPGGIMPGRYNQEVGQTIPVFAFLGAMVVLAFFVVQINKAKSRPKRRKPRVKRPQLMQQVHPPKTPSV
sig_peptide: 1..17 experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q14703.1) calculated_mol_wt: 1941 peptide sequence: MKLVNIWLLLLVVLLCG mat_peptide: 187..1052 product: Membrane-bound transcription factor site-1 protease experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q14703.1) calculated_mol_wt: 96430 peptide sequence: RAIPRQVAQTLQADVLWQMGYTGANVRVAVFDTGLSEKHPHFKNVKERTNWTNERTLDDGLGHGTFVAGVIASMRECQGFAPDAELHIFRVFTNNQVSYTSWFLDAFNYAILKKIDVLNLSIGGPDFMDHPFVDKVWELTANNVIMVSAIGNDGPLYGTLNNPADQMDVIGVGGIDFEDNIARFSSRGMTTWELPGGYGRMKPDIVTYGAGVRGSGVKGGCRALSGTSVASPVVAGAVTLLVSTVQKRELVNPASMKQALIASARRLPGVNMFEQGHGKLDLLRAYQILNSYKPQASLSPSYIDLTECPYMWPYCSQPIYYGGMPTVVNVTILNGMGVTGRIVDKPDWQPYLPQNGDNIEVAFSYSSVLWPWSGYLAISISVTKKAASWEGIAQGHVMITVASPAETESKNGAEQTSTVKLPIKVKIIPTPPRSKRVLWDQYHNLRYPPGYFPRDNLRMKNDPLDWNGDHIHTNFRDMYQHLRSMGYFVEVLGAPFTCFDASQYGTLLMVDSEEEYFPEEIAKLRRDVDNGLSLVIFSDWYNTSVMRKVKFYDENTRQWWMPDTGGANIPALNELLSVWNMGFSDGLYEGEFTLANHDMYYASGCSIAKFPEDGVVITQTFKDQGLEVLKQETAVVENVPILGLYQIPAEGGGRIVLYGDSNCLDDSHRQKDCFWLLDALLQYTSYGVTPPSLSHSGNRQRPPSGAGSVTPERMEGNHLHRYSKVLEAHLGDPKPRPLPACPRLSWAKPQPLNETAPSNLWKHQKLLSIDLDKVVLPNFRSNRPQVRPLSPGESGAWDIPGGIMPGRYNQEVGQTIPVFAFLGAMVVLAFFVVQINKAKSRPKRRKPRVKRPQLMQQVHPPKTPSV

Gene Information

Entrez Gene ID
8720
Gene Name
membrane-bound transcription factor peptidase, site 1
Gene Symbol
MBTPS1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005788 TAS:ProtInc C endoplasmic reticulum lumen
GO:0005794 IBA:RefGenome C Golgi apparatus
GO:0000139 TAS:Reactome C Golgi membrane
GO:0005795 IEA:Ensembl C Golgi stack
GO:0016021 IEA:UniProtKB-KW C integral component of membrane
GO:0004252 IMP:UniProtKB F serine-type endopeptidase 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 IEA:UniProtKB-KW P cholesterol metabolic process
GO:0030968 TAS:Reactome P endoplasmic reticulum unfolded protein response
GO:0006629 IBA:RefGenome P lipid metabolic process
GO:0007040 IMP:UniProtKB P lysosome organization
GO:0006508 IMP:UniProtKB P proteolysis
GO:0042990 IEA:Ensembl P regulation of transcription factor import into nucleus
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

InterPro Annotations

Accession Description
IPR000209 Peptidase S8/S53 domain
IPR022398 Peptidase S8, subtilisin, His-active site
IPR015500 Peptidase S8, subtilisin-related
IPR023828 Peptidase S8, subtilisin, Ser-active site

UniProt Annotations

Entry Information

Gene Name
membrane-bound transcription factor peptidase, site 1
Protein Entry
MBTP1_HUMAN
UniProt ID
Q14703
Species
Human

Comments

Comment Type Description
Catalytic Activity Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3.
Cofactor Name=Ca(2+); Xref=ChEBI
Enzyme Regulation Inhibited by divalent copper and zinc ions, but not by nickel or cobalt. Inhibited by its prosegment, but not smaller fragments thereof.
Function Serine protease that catalyzes the first step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs). Other known substrates are BDNF, GNPTAB and ATF6. Cleaves after hydrophobic or small residues, provided that Arg or Lys is in position P4. Cleaves known substrates after Arg- Ser-Val-Leu (SERBP-2), Arg-His-Leu-Leu (ATF6), Arg-Gly-Leu-Thr (BDNF) and its own propeptide after Arg-Arg-Leu-Leu. Mediates the protein cleavage of GNPTAB into subunit alpha and beta, thereby participating in biogenesis of lysosomes.
Induction Down-regulated by sterols.
Ptm 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.
Sequence Caution Sequence=BAA07653.2; Type=Erroneous initiation; Evidence= ;
Similarity Belongs to the peptidase S8 family.
Similarity Contains 1 peptidase S8 domain.
Subcellular Location 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.
Tissue Specificity Widely expressed.

Identical and Related Proteins

Unique RefSeq proteins for LMP002884 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
4506775 RefSeq NP_003782 1052 membrane-bound transcription factor site-1 protease preproprotein

Identical Sequences to LMP002884 proteins

Reference Database Accession Length Protein Name
GI:4506775 DBBJ BAG09601.1 1052 membrane-bound transcription factor site-1 protease precursor, partial [synthetic construct]
GI:4506775 GenBank ABH81879.1 1052 Sequence 4 from patent US 7045294
GI:4506775 GenBank EAW95505.1 1052 membrane-bound transcription factor peptidase, site 1, isoform CRA_a [Homo sapiens]
GI:4506775 GenBank ABT02356.1 1052 Sequence 6 from patent US 7211424
GI:4506775 GenBank ACM80915.1 1052 Sequence 6413 from patent US 6812339
GI:4506775 GenBank AHD73122.1 1052 Sequence 10190 from patent US 8586006

Related Sequences to LMP002884 proteins

Reference Database Accession Length Protein Name
GI:4506775 DBBJ BAA07653.2 1058 KIAA0091, partial [Homo sapiens]
GI:4506775 DBBJ BAF84462.1 1052 unnamed protein product [Homo sapiens]
GI:4506775 GenBank ACM85189.1 1058 Sequence 10687 from patent US 6812339
GI:4506775 GenBank JAA08031.1 1052 membrane-bound transcription factor peptidase, site 1 [Pan troglodytes]
GI:4506775 GenBank JAA17127.1 1052 membrane-bound transcription factor peptidase, site 1 [Pan troglodytes]
GI:4506775 GenBank JAA30722.1 1052 membrane-bound transcription factor peptidase, site 1 [Pan troglodytes]