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Protein

Membrane-bound transcription factor site-2 protease

Gene

MBTPS2

Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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.

Catalytic activityi

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.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi162 – 1621Zinc; catalyticPROSITE-ProRule annotation
Active sitei163 – 1631PROSITE-ProRule annotation
Metal bindingi166 – 1661Zinc; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • cholesterol metabolic process Source: UniProtKB-KW
  • membrane protein intracellular domain proteolysis Source: ParkinsonsUK-UCL
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: ParkinsonsUK-UCL
  • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.85. 1309.

Protein family/group databases

MEROPSiM50.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Membrane-bound transcription factor site-2 protease (EC:3.4.24.85)
Alternative name(s):
Endopeptidase S2P
Sterol regulatory element-binding proteins intramembrane protease
Short name:
SREBPs intramembrane protease
Gene namesi
Name:MBTPS2
Synonyms:S2P
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 33CytoplasmicBy similarity
Transmembranei4 – 2421HelicalSequence analysisAdd
BLAST
Topological domaini25 – 7450LumenalBy similarityAdd
BLAST
Transmembranei75 – 9521HelicalSequence analysisAdd
BLAST
Transmembranei96 – 10712HelicalSequence analysisAdd
BLAST
Topological domaini108 – 13528LumenalBy similarityAdd
BLAST
Transmembranei136 – 16025HelicalSequence analysisAdd
BLAST
Transmembranei165 – 17713HelicalSequence analysisAdd
BLAST
Transmembranei178 – 20023HelicalSequence analysisAdd
BLAST
Transmembranei220 – 24223HelicalSequence analysisAdd
BLAST
Topological domaini243 – 437195LumenalBy similarityAdd
BLAST
Transmembranei438 – 45518HelicalSequence analysisAdd
BLAST
Transmembranei456 – 46712HelicalSequence analysisAdd
BLAST
Topological domaini468 – 48316LumenalSequence analysisAdd
BLAST
Transmembranei484 – 50421HelicalSequence analysisAdd
BLAST
Topological domaini505 – 5106CytoplasmicSequence analysis

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 510510Membrane-bound transcription factor site-2 proteasePRO_0000088481Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi328 – 3281N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi109 – 12719Poly-SerAdd
BLAST
Compositional biasi276 – 377102Cys-richAdd
BLAST
Compositional biasi371 – 3755Poly-Ser

Sequence similaritiesi

Belongs to the peptidase M50A family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG006397.
KOiK07765.

Family and domain databases

InterProiIPR001193. MBTPS2.
IPR001478. PDZ.
IPR008915. Peptidase_M50.
[Graphical view]
PANTHERiPTHR13325. PTHR13325. 1 hit.
PfamiPF02163. Peptidase_M50. 1 hit.
[Graphical view]
PRINTSiPR01000. SREBPS2PTASE.
SUPFAMiSSF50156. SSF50156. 1 hit.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O54862-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIPVSLVVVV VGGWTAVYLA DLVLKSSVYF KHSYEDWLEK NGLSISPFHI
60 70 80 90 100
RWQTSVFNRA FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLMQ
110 120 130 140 150
TLAQMMADSP SSSSSSSSSS SSSSSSSIHN EQVLQVVVPG INLPVNQLTY
160 170 180 190 200
FFAAVLISGV VHEIGHGIAA IREQVRFNGF GIFLFIIYPG AFVDLFTTHL
210 220 230 240 250
QLISPVQQLR IFCAGIWHNF VLALLGILAL VLLPVILLPF YYTGVGVLIT
260 270 280 290 300
EVAEDSPAIG PRGLFVGDLV THLQDCPVTN VQDWNECLDT IAYEPQIGYC
310 320 330 340 350
ISASTLQQLS FPVRAYKRLD GSTECCNNHS LTDVCFSYRN NFNKRLHTCL
360 370 380 390 400
PARKAVEATQ VCRTNKDCKT SSSSSFCIVP SLETHTRLIK VKHPPQIDML
410 420 430 440 450
YVGHPLHLHY TVSITSFIPR FNFLSIDLPV IVETFVKYLI SLSGALAIVN
460 470 480 490 500
AVPCFALDGQ WILNSFLDAT LTSVIGDNDV KDLIGFFILL GGSVLLAANV
510
TLGLWMVTAR
Length:510
Mass (Da):56,499
Last modified:June 1, 1998 - v1
Checksum:i12B6B2257C0DA7A4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019611 mRNA. Translation: AAC53526.1.
RefSeqiNP_001231018.1. NM_001244089.1.

Genome annotation databases

GeneIDi100689085.
KEGGicge:100689085.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF019611 mRNA. Translation: AAC53526.1.
RefSeqiNP_001231018.1. NM_001244089.1.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiM50.001.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100689085.
KEGGicge:100689085.

Organism-specific databases

CTDi51360.

Phylogenomic databases

HOVERGENiHBG006397.
KOiK07765.

Enzyme and pathway databases

BRENDAi3.4.24.85. 1309.

Family and domain databases

InterProiIPR001193. MBTPS2.
IPR001478. PDZ.
IPR008915. Peptidase_M50.
[Graphical view]
PANTHERiPTHR13325. PTHR13325. 1 hit.
PfamiPF02163. Peptidase_M50. 1 hit.
[Graphical view]
PRINTSiPR01000. SREBPS2PTASE.
SUPFAMiSSF50156. SSF50156. 1 hit.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs."
    Rawson R.B., Zelenski N.G., Nijhawan D., Ye J., Sakai J., Hasan M.T., Chang T.Y., Brown M.S., Goldstein J.L.
    Mol. Cell 1:47-57(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiMBTP2_CRIGR
AccessioniPrimary (citable) accession number: O54862
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: March 4, 2015
This is version 76 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.