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P56818 (BACE1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beta-secretase 1

EC=3.4.23.46
Alternative name(s):
Aspartyl protease 2
Short name=ASP2
Short name=Asp 2
Beta-site amyloid precursor protein cleaving enzyme 1
Short name=Beta-site APP cleaving enzyme 1
Memapsin-2
Membrane-associated aspartic protease 2
Gene names
Name:Bace1
Synonyms:Bace
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length501 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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 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. Interacts with SNX6 By similarity. Interacts with PCSK9 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein. Golgi apparatustrans-Golgi network By similarity. Endoplasmic reticulum By similarity. Endosome By similarity. Cell surface By similarity. Cytoplasmic vesicle membrane 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.

Tissue specificity

Brain.

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.

Disruption phenotype

Mice show a higher mortality rate early in life. Ref.7

Sequence similarities

Belongs to the peptidase A1 family.

Ontologies

Keywords
   Cellular componentCytoplasmic vesicle
Endoplasmic reticulum
Endosome
Golgi apparatus
Membrane
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionAspartyl protease
Hydrolase
Protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbeta-amyloid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from sequence or structural similarity. Source: UniProtKB

axon

Inferred from direct assay PubMed 11740561. Source: MGI

cell surface

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasmic vesicle

Inferred from direct assay PubMed 11740561. Source: MGI

cytoplasmic vesicle membrane

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 component of plasma membrane

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from direct assay PubMed 15886206. Source: MGI

trans-Golgi network

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionaspartic-type endopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

endopeptidase activity

Inferred from direct assay PubMed 15123597. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Propeptide22 – 4524 Potential
PRO_0000025941
Chain46 – 501456Beta-secretase 1
PRO_0000025942

Regions

Topological domain22 – 457436Extracellular Potential
Transmembrane458 – 47821Helical; Potential
Topological domain479 – 50123Cytoplasmic Potential
Region479 – 50123Interaction with RTN3 By similarity

Sites

Active site931 By similarity
Active site2891 By similarity

Amino acid modifications

Glycosylation1531N-linked (GlcNAc...) Potential
Glycosylation1721N-linked (GlcNAc...) Potential
Glycosylation2231N-linked (GlcNAc...) Potential
Glycosylation3541N-linked (GlcNAc...) Potential
Disulfide bond216 ↔ 420 By similarity
Disulfide bond278 ↔ 443 By similarity
Disulfide bond330 ↔ 380 By similarity

Sequences

Sequence LengthMass (Da)Tools
P56818 [UniParc].

Last modified August 14, 2001. Version 2.
Checksum: C085A013145E474E

FASTA50155,748
        10         20         30         40         50         60 
MAPALHWLLL WVGSGMLPAQ GTHLGIRLPL RSGLAGPPLG LRLPRETDEE SEEPGRRGSF 

        70         80         90        100        110        120 
VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA VGAAPHPFLH RYYQRQLSST 

       130        140        150        160        170        180 
YRDLRKGVYV 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 

« Hide

References

« Hide 'large scale' 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. expand/collapse author list , Burgess T., Louis J.-C., Collins F., Treanor J., Rogers G., Citron M.
Science 286:735-741(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Bennett B.D., Vassar R., Citron M.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO 6 AND 81-87.
[3]"Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity."
Yan R., Bienkowski M.J., Shuck M.E., Miao H., Tory M.C., Pauley A.M., Brashier J.R., Stratman N.C., Mathews W.R., Buhl A.E., Carter D.B., Tomasselli A.G., Parodi L.A., Heinrikson R.L., Gurney M.E.
Nature 402:533-537(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Aorta, Head and Testis.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[6]Lubec G., Sunyer B., Chen W.-Q.
Submitted (JAN-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 301-307, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[7]"Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice."
Dominguez D., Tournoy J., Hartmann D., Huth T., Cryns K., Deforce S., Serneels L., Camacho I.E., Marjaux E., Craessaerts K., Roebroek A.J.M., Schwake M., D'Hooge R., Bach P., Kalinke U., Moechars D., Alzheimer C., Reiss K., Saftig P., De Strooper B.
J. Biol. Chem. 280:30797-30806(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF190726 mRNA. Translation: AAF04143.2.
AF200346 mRNA. Translation: AAF17082.1.
AK014464 mRNA. Translation: BAB29370.1.
AK033112 mRNA. Translation: BAC28156.1.
AK041285 mRNA. Translation: BAC30889.1.
BC048189 mRNA. Translation: AAH48189.1.
RefSeqNP_001139419.1. NM_001145947.1.
NP_035922.4. NM_011792.5.
UniGeneMm.24044.

3D structure databases

ProteinModelPortalP56818.
SMRP56818. Positions 58-453.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204741. 4 interactions.

Chemistry

ChEMBLCHEMBL4593.

Protein family/group databases

MEROPSA01.004.

PTM databases

PhosphoSiteP56818.

Proteomic databases

PRIDEP56818.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034591; ENSMUSP00000034591; ENSMUSG00000032086.
GeneID23821.
KEGGmmu:23821.
UCSCuc009pgh.2. mouse.

Organism-specific databases

CTD23621.
MGIMGI:1346542. Bace1.

Phylogenomic databases

eggNOGNOG71700.
GeneTreeENSGT00710000106265.
HOGENOMHOG000036572.
HOVERGENHBG059578.
InParanoidP56818.
KOK04521.
OMAPDMEDCG.
OrthoDBEOG7DNNVW.
PhylomeDBP56818.
TreeFamTF329595.

Enzyme and pathway databases

BRENDA3.4.23.46. 3474.

Gene expression databases

ArrayExpressP56818.
BgeeP56818.
CleanExMM_BACE1.
GenevestigatorP56818.

Family and domain databases

Gene3D2.40.70.10. 2 hits.
InterProIPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR009119. Pept_A1_BACE.
IPR009120. Pept_A1_BACE1.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERPTHR13683. PTHR13683. 1 hit.
PfamPF00026. Asp. 1 hit.
[Graphical view]
PRINTSPR01816. BACE1.
PR01815. BACEFAMILY.
PR00792. PEPSIN.
SUPFAMSSF50630. SSF50630. 1 hit.
PROSITEPS00141. ASP_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSBACE1. mouse.
NextBio303471.
PROP56818.
SOURCESearch...

Entry information

Entry nameBACE1_MOUSE
AccessionPrimary (citable) accession number: P56818
Secondary accession number(s): Q544D0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 14, 2001
Last modified: April 16, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot