Reviewed, UniProtKB/Swiss-Prot P56819 (BACE1_RAT)

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
    Aspartyl protease 2
      Short name=Asp 2
      Short name=ASP2

Gene names

Name:	Bace1
Synonyms:	Bace

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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.
Sequence similarities	Belongs to the peptidase A1 family.

Ontologies

Keywords
Cellular component	Membrane
Domain	Signal Transmembrane
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Glycoprotein Zymogen
Gene Ontology (GO)
Biological process	beta-amyloid metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from sequence or structural similarity. Source: UniProtKB endosome Inferred from sequence or structural similarity. Source: UniProtKB
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
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 45	24	Potential
	Chain	46 – 501	456	Beta-secretase 1
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)
	P56819-1 [UniParc]. Last modified May 30, 2000. Version 1. Checksum: 24B445BC8BE87DE3	FASTA	501	55,807
	10 20 30 40 50 60 MAPALRWLLL WVGSGMLPAQ GTHLGIRLPL RSGLAGPPLG LRLPRETDEE PEEPGRRGSF 70 80 90 100 110 120 VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA VGAAPHPFLH RYYQRQLSST 130 140 150 160 170 180 YRDLRKSVYV PYTQGKWEGE LGTDLVSIPH GPNVTVRANI AAITESDKFF INGSNWEGIL 190 200 210 220 230 240 GLAYAEIARP DDSLEPFFDS LVKQTHIPNI FSLQLCGAGF PLNQTEALAS VGGSMIIGGI 250 260 270 280 290 300 DHSLYTGSLW 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 YKFAVSQSST GTVMGAVIME GFYVVFDRAR KRIGFAVSAC 430 440 450 460 470 480 HVHDEFRTAA VEGPFVTADM EDCGYNIPQT DESTLMTIAY VMAAICALFM LPLCLMVCQW 490 500 RCLRCLRHQH DDFADDISLL K

References

[1]

"Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE." Vassar R., Bennett B.D., Babu-Khan S., Kahn S., Mendiaz E.A., Denis P., Teplow D.B., Ross S., Amarante P., Loeloff R., Luo Y., Fisher S., Fuller J., Edenson S., Lile J., Jarosinski M.A., Biere A.L., Curran E. , Burgess T., Louis J.-C., Collins F., Treanor J., Rogers G., Citron M. Science 286:735-741(1999) [PubMed: 10531052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF190727 mRNA. Translation: AAF04144.1.
RefSeq	NP_062077.1.
UniGene	Rn.207201
3D structure databases
HSSP	HSSP built from PDB template 1M4H based on UniProtKB P56817.
SMR	P56819. Positions 56-446.
ModBase	Search...
Protein family/group databases
MEROPS	A01.004.
Genome annotation databases
Ensembl	ENSRNOG00000016847. Rattus norvegicus. [Contig view]
GeneID	29392.
KEGG	rno:29392.
Organism-specific databases
RGD	2191. Bace1.
Phylogenomic databases
HOVERGEN	P56819.
Gene expression databases
ArrayExpress	P56819.
GermOnline	ENSRNOG00000016847. Rattus norvegicus.
Family and domain databases
InterPro	IPR009119. Pept_A1_BACE. IPR009120. Pept_A1_BACE1. IPR001969. Pept_Asp_AS. IPR009007. Pept_Aspartc_cat. IPR001461. Peptidase_A1. [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]
ProDom	P56819. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
ProtoNet	Search...

Entry information

Entry name

BACE1_RAT

Accession

Primary (citable) accession number: P56819

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 30, 2000
Last modified:	July 22, 2008
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)