Reviewed, UniProtKB/Swiss-Prot Q5RAC8 (MBTP2_PONAB)

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

Pongo abelii (Sumatran orangutan)

Taxonomic identifier

9601 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pongo

Protein attributes

Sequence length	521 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 – 521	521	Membrane-bound transcription factor site-2 protease		PRO_0000261593
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 – 146	39	Lumenal By similarity
	Transmembrane	147 – 171	25	Potential
	Transmembrane	176 – 188	13	Potential
	Transmembrane	189 – 211	23	Potential
	Transmembrane	231 – 253	23	Potential
	Topological domain	254 – 448	195	Lumenal By similarity
	Transmembrane	449 – 466	18	Potential
	Transmembrane	467 – 478	12	Potential
	Topological domain	479 – 494	16	Lumenal Potential
	Transmembrane	495 – 515	21	Potential
	Topological domain	516 – 521	6	Cytoplasmic Potential
	Compositional bias	111 – 138	28	Poly-Ser
	Compositional bias	287 – 388	102	Cys-rich
	Compositional bias	382 – 386	5	Poly-Ser
Sites
	Active site	174	1	By similarity
	Metal binding	173	1	Zinc; catalytic By similarity
	Metal binding	177	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	339	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q5RAC8-1 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: A24D71CD3073E58C	FASTA	521	57,561
	10 20 30 40 50 60 MIPVSLVVVV VGGWTVVYLT DLVLKSSVYF KHSYEDWLES NGLSISPFHI RWQTAVFNRA 70 80 90 100 110 120 FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLMQ TLAQMMADSP SSYSSSSSSS 130 140 150 160 170 180 SSSSSSSSSS SSSSSSSSLH NEQVLQVVVP GINLPVNQLT YFFAAVLISG VVHEIGHGIA 190 200 210 220 230 240 AIREQVRFNG FGIFLFIIYP GAFVDLFTTH LQLISPVQQL RIFCAGIWHN FVLALLGILA 250 260 270 280 290 300 LVLLPVILLP FYYTGVGVLI TEVAEDSPAI GPRGLFVGDL VTHLQDCPVT NVQDWNECLD 310 320 330 340 350 360 TIAYEPQIGY CISASTLQQL SFPVRAYKRL DGSTECCNNH SLTDVCFSYR NNFNKRLHTC 370 380 390 400 410 420 LPARKAVEAT QVCRTNKDCK KSSSSSFCII PSLETHTRLI KVKHPPQIDM LYVGHPLHLH 430 440 450 460 470 480 YTVSITSFIP RFNFLSIDLP VVVETFVKYL ISLSGALAIV NAVPCFALDG QWILNSFLDA 490 500 510 520 TLTSVIGDND VKDLIGFFIL LGGSVLLAAN VTLGLWMVTA R

References

[1]	The German cDNA consortium Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain cortex.

Cross-references

Sequence databases
EMBLGenBankDDBJ	CR859090 mRNA. Translation: CAH91282.1.
UniGene	Pab.19081
3D structure databases
ModBase	Search...
Protein family/group databases
MEROPS	M50.001.
Phylogenomic databases
HOVERGEN	Q5RAC8.
Enzyme and pathway databases
BRENDA	3.4.24.85. 269192.
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_PONAB

Accession

Primary (citable) accession number: Q5RAC8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	December 21, 2004
Last modified:	October 13, 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)