Reviewed, UniProtKB/Swiss-Prot Q2HJ40 (BACE1_BOVIN)

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

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	501 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_0000245802
	Chain	46 – 501	456	Beta-secretase 1		PRO_0000245803
Regions
	Topological domain	22 – 457	436	Extracellular Potential
	Transmembrane	458 – 478	21	Potential
	Topological domain	479 – 501	23	Cytoplasmic Potential
	Region	479 – 501	23	Interaction with RTN3 By similarity
Sites
	Active site	93	1	By similarity
	Active site	289	1	By similarity
Amino acid modifications
	Glycosylation	153	1	N-linked (GlcNAc...) Potential
	Glycosylation	172	1	N-linked (GlcNAc...) Potential
	Glycosylation	223	1	N-linked (GlcNAc...) Potential
	Glycosylation	354	1	N-linked (GlcNAc...) Potential
	Disulfide bond	216 ↔ 420		By similarity
	Disulfide bond	278 ↔ 443		By similarity
	Disulfide bond	330 ↔ 380		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q2HJ40-1 [UniParc]. Last modified March 21, 2006. Version 1. Checksum: 8E5EA730FC91C295	FASTA	501	55,725
	10 20 30 40 50 60 MAQALPWLLL WMGSGVLPAH GSQPGIRLPL RSGLGGAPLG LRLPRETDEE SEEPGRRGSF 70 80 90 100 110 120 VEMVDNLRGK SGQGYYVEMT LGSPPQTLNI LVDTGSSNFA VGAAPHPFLH RYYQRQLSST 130 140 150 160 170 180 YRDLRKGVYV PYTQGKWEGE LGTDLVSIPH GPNVTVRANI AAITESDKFF INGSNWEGIL 190 200 210 220 230 240 GLAYAEIARP DDSLEPFFDS LVKQTHVPNL FSLQLCGAGF PLNQSEALAS VGGSMIIGGI 250 260 270 280 290 300 DHSLYMGSLW YTPIRREWYY EVIIVRVEIN GQDLKMDCKE YNYDKSIVDS GTTNLRLPKK 310 320 330 340 350 360 VFEAAVKSIK AASSTEKFPD GFWLGEQLVC WQAGTTPWNI FPVISLYLMG EVTNQSFRIT 370 380 390 400 410 420 ILPQQYLRPV EDVATSQDDC YKFAISQSST GTVMGAVIME GFYVVFDRAR KRIGFAVSAC 430 440 450 460 470 480 HVHDEFRTAA VEGPFVTPDM EDCGYNIPQT DESTLMTIAY VMAAICALFM LPLCLMVCQW 490 500 RCLRCLRHQH DDFADDISLL K

References

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

Cross-references

Sequence databases
EMBLGenBankDDBJ	BC113325 mRNA. Translation: AAI13326.1.
IPI	IPI00691457.
RefSeq	NP_001039996.1.
UniGene	Bt.28273
3D structure databases
SMR	Q2HJ40. Positions 56-446.
ModBase	Search...
Protein-protein interaction databases
STRING	Q2HJ40.
Genome annotation databases
Ensembl	ENSBTAT00000040056; ENSBTAP00000039837; ENSBTAG00000019365; Bos taurus. [Genome view]
GeneID	614333.
KEGG	bta:614333.
Organism-specific databases
CTD	614333.
Phylogenomic databases
HOVERGEN	Q2HJ40.
OMA	SFVEMVD
OrthoDB	EOG9DV85X
Enzyme and pathway databases
BRENDA	3.4.23.46. 251.
Family and domain databases
InterPro	IPR009119. Pept_A1_BACE. IPR009120. Pept_A1_BACE1. IPR001461. Peptidase_A1. 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. 1 hit. [Graphical view]
PRINTS	PR01816. BACE1. PR01815. BACEFAMILY. PR00792. PEPSIN.
PROSITE	PS00141. ASP_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

BACE1_BOVIN

Accession

Primary (citable) accession number: Q2HJ40

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2006
Last sequence update:	March 21, 2006
Last modified:	November 24, 2009
This is version 31 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)