Reviewed, UniProtKB/Swiss-Prot Q0III2 (MBTP2_BOVIN)

Names and origin

Protein names

Recommended name:
    Membrane-bound transcription factor site-2 protease
      Short name=Site-2 protease
    EC=3.4.24.85
Alternative name(s):
    S2P endopeptidase

Gene names

Name:

MBTPS2

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	516 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript level.

General annotation (Comments)

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 By similarity.
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	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Membrane; Multi-pass membrane protein Probable.
Sequence similarities	Belongs to the peptidase M50A family.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism
Cellular component	Membrane
Domain	Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	cholesterol metabolic process Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 516	516	Membrane-bound transcription factor site-2 protease		PRO_0000261591
Regions
	Topological domain	1 – 3	3	Cytoplasmic By similarity
	Transmembrane	4 – 24	21	Potential
	Topological domain	25 – 74	50	Lumenal By similarity
	Transmembrane	75 – 95	21	Potential
	Transmembrane	96 – 107	12	Potential
	Topological domain	108 – 141	34	Lumenal By similarity
	Transmembrane	142 – 166	25	Potential
	Transmembrane	171 – 183	13	Potential
	Transmembrane	184 – 206	23	Potential
	Transmembrane	226 – 248	23	Potential
	Topological domain	249 – 443	195	Lumenal By similarity
	Transmembrane	444 – 461	18	Potential
	Transmembrane	462 – 473	12	Potential
	Topological domain	474 – 489	16	Lumenal Potential
	Transmembrane	490 – 510	21	Potential
	Topological domain	511 – 516	6	Cytoplasmic Potential
	Compositional bias	109 – 133	25	Poly-Ser
	Compositional bias	282 – 383	102	Cys-rich
	Compositional bias	377 – 381	5	Poly-Ser
Sites
	Active site	169	1	By similarity
	Metal binding	168	1	Zinc; catalytic By similarity
	Metal binding	172	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	334	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q0III2-1 [UniParc]. Last modified October 3, 2006. Version 1. Checksum: F2E18EC52C644074	FASTA	516	57,214
	10 20 30 40 50 60 MIPVSLVVVV VGGWTAVYLT DLVLKSSVYF KHSYEDWLEN NGLSISPFHI RWQTAVFNRA 70 80 90 100 110 120 FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLIQ TLGQMMADSS YSSSSSSSSH 130 140 150 160 170 180 SSSSSSSSSS SSSLYNEQVL QVVVPGINLP VNQLTYFFAA VLISGVVHEI GHGIAAIREQ 190 200 210 220 230 240 VRFNGFGIFL FIIYPGAFVD LFTTHLQLIS PVQQLRIFCA GIWHNFILAL LGILALILLP 250 260 270 280 290 300 VILLPFYYTG VGVLITEVAE DSPAIGPRGL FVGDLVTHLQ DCPVTNVQDW NECLDTITYE 310 320 330 340 350 360 PQIGYCISAS TLQQLSFPVR AYKRLDGSTE CCNNHSLTDV CFSYRNNFNK RLHTCLPARK 370 380 390 400 410 420 AVEATQVCRT NKDCKKSSSS SFCIIPSLET HTRLIKVKHP PQIDMLYVGH PLHLHYTVSI 430 440 450 460 470 480 TSFIPRFKFL SIDLPVVVET FVKYLISLSG ALAIVNAVPC FALDGQWILN SFLDATLTSV 490 500 510 IGDNDVKDLI GFFILLGGSI LLAANVALGL WMVTAR

References

[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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	BC122628 mRNA. Translation: AAI22629.1.
IPI	IPI00686868.
RefSeq	NP_001069449.1.
UniGene	Bt.38187
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q0III2.
Protein family/group databases
MEROPS	M50.001.
Genome annotation databases
Ensembl	ENSBTAT00000010764; ENSBTAP00000010764; ENSBTAG00000008183; Bos taurus. [Genome view]
GeneID	533134.
KEGG	bta:533134.
Organism-specific databases
CTD	533134.
Phylogenomic databases
HOVERGEN	Q0III2.
OMA	VVVETFV.
Enzyme and pathway databases
BRENDA	3.4.24.85. 251.
Family and domain databases
InterPro	IPR001193. Pept_M50_SREBP. IPR006025. Pept_M_Zn_BS. IPR008915. Peptidase_M50. [Graphical view]
Pfam	PF02163. Peptidase_M50. 1 hit. [Graphical view]
PRINTS	PR01000. SREBPS2PTASE.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

MBTP2_BOVIN

Accession

Primary (citable) accession number: Q0III2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	October 3, 2006
Last modified:	November 3, 2009
This is version 27 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)