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Protein

Membrane-bound transcription factor site-2 protease

Gene

MBTPS2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 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 (By similarity).By similarity

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 bindingi168 – 1681Zinc; catalyticPROSITE-ProRule annotation
Active sitei169 – 1691PROSITE-ProRule annotation
Metal bindingi172 – 1721Zinc; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

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

ReactomeiR-BTA-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-BTA-381033. ATF6-alpha activates chaperones.

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
Gene namesi
Name:MBTPS2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome X

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 – 14134LumenalBy similarityAdd
BLAST
Transmembranei142 – 16625HelicalSequence analysisAdd
BLAST
Transmembranei171 – 18313HelicalSequence analysisAdd
BLAST
Transmembranei184 – 20623HelicalSequence analysisAdd
BLAST
Transmembranei226 – 24823HelicalSequence analysisAdd
BLAST
Topological domaini249 – 443195LumenalBy similarityAdd
BLAST
Transmembranei444 – 46118HelicalSequence analysisAdd
BLAST
Transmembranei462 – 47312HelicalSequence analysisAdd
BLAST
Topological domaini474 – 48916LumenalSequence analysisAdd
BLAST
Transmembranei490 – 51021HelicalSequence analysisAdd
BLAST
Topological domaini511 – 5166CytoplasmicSequence analysis

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 516516Membrane-bound transcription factor site-2 proteasePRO_0000261591Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi334 – 3341N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ0III2.

Interactioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000010764.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi109 – 13325Poly-SerAdd
BLAST
Compositional biasi282 – 383102Cys-richAdd
BLAST
Compositional biasi377 – 3815Poly-Ser

Sequence similaritiesi

Belongs to the peptidase M50A family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2921. Eukaryota.
COG0750. LUCA.
GeneTreeiENSGT00510000048066.
HOGENOMiHOG000231255.
HOVERGENiHBG006397.
InParanoidiQ0III2.
KOiK07765.
OMAiTELSHDH.
OrthoDBiEOG7WMCJB.
TreeFamiTF314478.

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.

Q0III2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIPVSLVVVV VGGWTAVYLT DLVLKSSVYF KHSYEDWLEN NGLSISPFHI
60 70 80 90 100
RWQTAVFNRA FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLIQ
110 120 130 140 150
TLGQMMADSS YSSSSSSSSH SSSSSSSSSS SSSLYNEQVL QVVVPGINLP
160 170 180 190 200
VNQLTYFFAA VLISGVVHEI GHGIAAIREQ VRFNGFGIFL FIIYPGAFVD
210 220 230 240 250
LFTTHLQLIS PVQQLRIFCA GIWHNFILAL LGILALILLP VILLPFYYTG
260 270 280 290 300
VGVLITEVAE DSPAIGPRGL FVGDLVTHLQ DCPVTNVQDW NECLDTITYE
310 320 330 340 350
PQIGYCISAS TLQQLSFPVR AYKRLDGSTE CCNNHSLTDV CFSYRNNFNK
360 370 380 390 400
RLHTCLPARK AVEATQVCRT NKDCKKSSSS SFCIIPSLET HTRLIKVKHP
410 420 430 440 450
PQIDMLYVGH PLHLHYTVSI TSFIPRFKFL SIDLPVVVET FVKYLISLSG
460 470 480 490 500
ALAIVNAVPC FALDGQWILN SFLDATLTSV IGDNDVKDLI GFFILLGGSI
510
LLAANVALGL WMVTAR
Length:516
Mass (Da):57,214
Last modified:October 3, 2006 - v1
Checksum:iF2E18EC52C644074
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC122628 mRNA. Translation: AAI22629.1.
RefSeqiNP_001069449.1. NM_001075981.1.
UniGeneiBt.38187.

Genome annotation databases

EnsembliENSBTAT00000010764; ENSBTAP00000010764; ENSBTAG00000008183.
GeneIDi533134.
KEGGibta:533134.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC122628 mRNA. Translation: AAI22629.1.
RefSeqiNP_001069449.1. NM_001075981.1.
UniGeneiBt.38187.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000010764.

Protein family/group databases

MEROPSiM50.001.

Proteomic databases

PaxDbiQ0III2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000010764; ENSBTAP00000010764; ENSBTAG00000008183.
GeneIDi533134.
KEGGibta:533134.

Organism-specific databases

CTDi51360.

Phylogenomic databases

eggNOGiKOG2921. Eukaryota.
COG0750. LUCA.
GeneTreeiENSGT00510000048066.
HOGENOMiHOG000231255.
HOVERGENiHBG006397.
InParanoidiQ0III2.
KOiK07765.
OMAiTELSHDH.
OrthoDBiEOG7WMCJB.
TreeFamiTF314478.

Enzyme and pathway databases

ReactomeiR-BTA-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).
R-BTA-381033. ATF6-alpha activates chaperones.

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. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Basal ganglia.

Entry informationi

Entry nameiMBTP2_BOVIN
AccessioniPrimary (citable) accession number: Q0III2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: October 3, 2006
Last modified: June 8, 2016
This is version 67 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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.