Reviewed, UniProtKB/Swiss-Prot Q1KLR6 (BACE1_CAVPO)

Names and origin

Protein names

Recommended name:
    Beta-secretase 1
    EC=3.4.23.46
Alternative name(s):
    Beta-site amyloid precursor protein cleaving enzyme 1
      Short name=Beta-site APP cleaving enzyme 1
    Membrane-associated aspartic protease 2
    Memapsin-2

Gene names

Name:

BACE1

Organism

Cavia porcellus (Guinea pig)

Taxonomic identifier

10141 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Hystricognathi › Caviidae › Cavia

Protein attributes

Sequence length	473 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level.

General annotation (Comments)

Function	Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase By similarity.
Catalytic activity	Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein.
Enzyme regulation	Inhibited by RTN3 and RTN4 By similarity.
Subunit structure	Monomer. Interacts with GGA1, GGA2 and GGA3. Interacts with RTN3 and RTN4 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein. Golgi apparatus › trans-Golgi network By similarity. Endoplasmic reticulum By similarity. Endosome By similarity. Cell surface By similarity. Note: Predominantly localized to the later Golgi/trans-Golgi network (TGN) and minimally detectable in the early Golgi compartments. A small portion is also found in the endoplasmic reticulum, endosomes and on the cell surface By similarity.
Domain	The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP By similarity.
Post-translational modification	Glycosylated By similarity.
Sequence similarities	Belongs to the peptidase A1 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Endosome Golgi apparatus Membrane
Domain	Signal Transmembrane
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Disulfide bond Glycoprotein Zymogen
Gene Ontology (GO)
Biological process	beta-amyloid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB cell surface Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aspartic-type endopeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 45	24	By similarity		PRO_0000245804
	Chain	46 – 473	428	Beta-secretase 1		PRO_0000245805
Regions
	Topological domain	22 – 429	408	Extracellular Potential
	Transmembrane	430 – 450	21	Potential
	Topological domain	451 – 473	23	Cytoplasmic Potential
	Region	451 – 473	23	Interaction with RTN3 By similarity
Sites
	Active site	90	1	By similarity
	Active site	261	1	By similarity
Amino acid modifications
	Glycosylation	150	1	N-linked (GlcNAc...) Potential
	Glycosylation	169	1	N-linked (GlcNAc...) Potential
	Glycosylation	195	1	N-linked (GlcNAc...) Potential
	Glycosylation	326	1	N-linked (GlcNAc...) Potential
	Disulfide bond	188 ↔ 392		By similarity
	Disulfide bond	250 ↔ 415		By similarity
	Disulfide bond	302 ↔ 352		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q1KLR6-1 [UniParc]. Last modified May 30, 2006. Version 1. Checksum: F9583693A13F86E9	FASTA	473	52,576
	10 20 30 40 50 60 MAPALPWLLL WVGSGVLPVH GTQDGIRLPL RSGLAGAPLG LRLPRETDEE PGRRGSFVEM 70 80 90 100 110 120 VDNLRGKSGQ GYYVEMTVGS PPQTLNILVD TGSSNFAVGA APHPFLHRYY QRQRSSTYRD 130 140 150 160 170 180 LRKGVYVPYT QGKWEGELGT DLVSIPHGPN VTVRANIAAI TESDKFFING SNWEGILGLA 190 200 210 220 230 240 YAEIARLCGA GFPLNQSEAV ASVGGSMIIG GIDHSLYTGN LWYTPIRREW YYEVIIVRVE 250 260 270 280 290 300 INGQDLKMDC KEYNYDKSIV DSGTTNLRLP KKVFEAAVKS IKAASSTEKF PDGFWLGEQL 310 320 330 340 350 360 VCWQAGTTPW NIFPVISLYL MGEVTNQSFR ITILPQQYLR PVEDVATSQD DCYKFAISQS 370 380 390 400 410 420 STGTVMGAVI MEGFYVVFDR ARKRIGFAVS ACHVHDEFRT ATVEGPFVTP DMEDCGYNIP 430 440 450 460 470 QTDESTLMTI AYVMAAICAL FMLPLCLMVC QWRCLRCLRH QHDDFADDIS LLK

References

[1]	"Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) mRNA from guinea pig." Christensen S. Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ471956 mRNA. Translation: ABF13340.1.
3D structure databases
SMR	Q1KLR6. Positions 52-419.
ModBase	Search...
Genome annotation databases
Ensembl	ENSCPOT00000012877; ENSCPOP00000011476; ENSCPOG00000012754; Cavia porcellus. [Genome view]
Phylogenomic databases
eggNOG	roNOG14885.
HOVERGEN	Q1KLR6.
InParanoid	Q1KLR6.
OMA	SFVEMVD.
OrthoDB	EOG9DV85X.
Enzyme and pathway databases
BRENDA	3.4.23.46. 44.
Family and domain databases
InterPro	IPR009119. Pept_A1_BACE. IPR009120. Pept_A1_BACE1. IPR001461. Peptidase_A1. IPR021109. Peptidase_aspartic. IPR001969. Peptidase_aspartic_AS. IPR009007. Peptidase_aspartic_catalytic. [Graphical view]
Gene3D	G3DSA:2.40.70.10. Pept_Aspartc_cat. 2 hits.
PANTHER	PTHR13683. Peptidase_A1. 1 hit.
Pfam	PF00026. Asp. 2 hits. [Graphical view]
PRINTS	PR01816. BACE1. PR01815. BACEFAMILY. PR00792. PEPSIN.
PROSITE	PS00141. ASP_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

BACE1_CAVPO

Accession

Primary (citable) accession number: Q1KLR6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2006
Last sequence update:	May 30, 2006
Last modified:	February 9, 2010
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)