O54862 (MBTP2_CRIGR) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	MBTPS2
Synonyms:	S2P

Organism

Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)

Taxonomic identifier

10029 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Cricetidae › Cricetinae › Cricetulus

Protein attributes

Sequence length	510 AA.
Sequence status	Complete.
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.
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. Cytoplasm By similarity.
Sequence similarities	Belongs to the peptidase M50A family.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism
Cellular component	Cytoplasm Membrane
Domain	Transmembrane Transmembrane helix
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: UniProtKB-KW
Cellular component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 510	510	Membrane-bound transcription factor site-2 protease		PRO_0000088481
Regions
	Topological domain	1 – 3	3	Cytoplasmic By similarity
	Transmembrane	4 – 24	21	Helical; Potential
	Topological domain	25 – 74	50	Lumenal By similarity
	Transmembrane	75 – 95	21	Helical; Potential
	Transmembrane	96 – 107	12	Helical; Potential
	Topological domain	108 – 135	28	Lumenal By similarity
	Transmembrane	136 – 160	25	Helical; Potential
	Transmembrane	165 – 177	13	Helical; Potential
	Transmembrane	178 – 200	23	Helical; Potential
	Transmembrane	220 – 242	23	Helical; Potential
	Topological domain	243 – 437	195	Lumenal By similarity
	Transmembrane	438 – 455	18	Helical; Potential
	Transmembrane	456 – 467	12	Helical; Potential
	Topological domain	468 – 483	16	Lumenal Potential
	Transmembrane	484 – 504	21	Helical; Potential
	Topological domain	505 – 510	6	Cytoplasmic Potential
	Compositional bias	109 – 127	19	Poly-Ser
	Compositional bias	276 – 377	102	Cys-rich
	Compositional bias	371 – 375	5	Poly-Ser
Sites
	Active site	163	1	By similarity
	Metal binding	162	1	Zinc; catalytic By similarity
	Metal binding	166	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	328	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	O54862 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 12B6B2257C0DA7A4	FASTA	510	56,499
	10 20 30 40 50 60 MIPVSLVVVV VGGWTAVYLA DLVLKSSVYF KHSYEDWLEK NGLSISPFHI RWQTSVFNRA 70 80 90 100 110 120 FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLMQ TLAQMMADSP SSSSSSSSSS 130 140 150 160 170 180 SSSSSSSIHN EQVLQVVVPG INLPVNQLTY FFAAVLISGV VHEIGHGIAA IREQVRFNGF 190 200 210 220 230 240 GIFLFIIYPG AFVDLFTTHL QLISPVQQLR IFCAGIWHNF VLALLGILAL VLLPVILLPF 250 260 270 280 290 300 YYTGVGVLIT EVAEDSPAIG PRGLFVGDLV THLQDCPVTN VQDWNECLDT IAYEPQIGYC 310 320 330 340 350 360 ISASTLQQLS FPVRAYKRLD GSTECCNNHS LTDVCFSYRN NFNKRLHTCL PARKAVEATQ 370 380 390 400 410 420 VCRTNKDCKT SSSSSFCIVP SLETHTRLIK VKHPPQIDML YVGHPLHLHY TVSITSFIPR 430 440 450 460 470 480 FNFLSIDLPV IVETFVKYLI SLSGALAIVN AVPCFALDGQ WILNSFLDAT LTSVIGDNDV 490 500 510 KDLIGFFILL GGSVLLAANV TLGLWMVTAR

References

[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: 9659902] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF019611 mRNA. Translation: AAC53526.1.
RefSeq	NP_001231018.1. NM_001244089.1.
3D structure databases
ModBase	Search...
Protein family/group databases
MEROPS	M50.001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100689085.
Phylogenomic databases
HOVERGEN	HBG006397.
Enzyme and pathway databases
BRENDA	3.4.24.85. 1309.
Family and domain databases
InterPro	IPR001193. Pept_M50_SREBP. 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_CRIGR

Accession

Primary (citable) accession number: O54862

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 1, 1998
Last modified:	January 25, 2012
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program