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Protein

Beta-secretase 1

Gene

Bace1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer amyloid precursor protein.

Enzyme regulationi

Inhibited by RTN3 and RTN4.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei93 – 931PROSITE-ProRule annotation
Active sitei289 – 2891PROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Aspartyl protease, Hydrolase, Protease

Enzyme and pathway databases

BRENDAi3.4.23.46. 3474.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Bace1
Synonyms:Bace
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1346542. Bace1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 457436ExtracellularSequence AnalysisAdd
BLAST
Transmembranei458 – 47821HelicalSequence AnalysisAdd
BLAST
Topological domaini479 – 50123CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • axon Source: MGI
  • cell surface Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: MGI
  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • endosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • integral component of plasma membrane Source: MGI
  • late endosome Source: MGI
  • membrane Source: MGI
  • multivesicular body Source: MGI
  • plasma membrane Source: MGI
  • trans-Golgi network Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show a higher mortality rate early in life.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Propeptidei22 – 4524Sequence AnalysisPRO_0000025941Add
BLAST
Chaini46 – 501456Beta-secretase 1PRO_0000025942Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei126 – 1261N6-acetyllysineBy similarity
Glycosylationi153 – 1531N-linked (GlcNAc...)Sequence Analysis
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi216 ↔ 420By similarity
Glycosylationi223 – 2231N-linked (GlcNAc...)Sequence Analysis
Modified residuei275 – 2751N6-acetyllysineBy similarity
Disulfide bondi278 ↔ 443By similarity
Modified residuei279 – 2791N6-acetyllysineBy similarity
Modified residuei285 – 2851N6-acetyllysineBy similarity
Modified residuei299 – 2991N6-acetyllysineBy similarity
Modified residuei300 – 3001N6-acetyllysineBy similarity
Modified residuei307 – 3071N6-acetyllysineBy similarity
Disulfide bondi330 ↔ 380By similarity
Glycosylationi354 – 3541N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-Glycosylated.By similarity
Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307. Acetylation by NAT8 and NAT8B is transient and deacetylation probably occurs in the Golgi. Acetylation regulates the maturation, the transport to the plasma membrane, the stability and the expression of the protein (By similarity).By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiP56818.
PRIDEiP56818.

PTM databases

PhosphoSiteiP56818.

Expressioni

Tissue specificityi

Brain.

Gene expression databases

BgeeiP56818.
CleanExiMM_BACE1.
ExpressionAtlasiP56818. baseline and differential.
GenevisibleiP56818. MM.

Interactioni

Subunit structurei

Monomer. Interacts with GGA1, GGA2 and GGA3. Interacts with RTN3 and RTN4. Interacts with SNX6 (By similarity). Interacts with PCSK9 (By similarity). Interacts with NAT8 and NAT8B (By similarity).By similarity

Protein-protein interaction databases

BioGridi204741. 9 interactions.
STRINGi10090.ENSMUSP00000034591.

Structurei

3D structure databases

ProteinModelPortaliP56818.
SMRiP56818. Positions 58-453.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni479 – 50123Interaction with RTN3By similarityAdd
BLAST

Domaini

The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP (By similarity).By similarity

Sequence similaritiesi

Belongs to the peptidase A1 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG71700.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000036572.
HOVERGENiHBG059578.
InParanoidiP56818.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG7DNNVW.
PhylomeDBiP56818.
TreeFamiTF329595.

Family and domain databases

Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR009119. BACE.
IPR009120. BACE1.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERiPTHR13683. PTHR13683. 1 hit.
PfamiPF00026. Asp. 1 hit.
[Graphical view]
PRINTSiPR01816. BACE1.
PR01815. BACEFAMILY.
PR00792. PEPSIN.
SUPFAMiSSF50630. SSF50630. 1 hit.
PROSITEiPS00141. ASP_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P56818-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPALHWLLL WVGSGMLPAQ GTHLGIRLPL RSGLAGPPLG LRLPRETDEE
60 70 80 90 100
SEEPGRRGSF VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA
110 120 130 140 150
VGAAPHPFLH RYYQRQLSST YRDLRKGVYV PYTQGKWEGE LGTDLVSIPH
160 170 180 190 200
GPNVTVRANI AAITESDKFF INGSNWEGIL GLAYAEIARP DDSLEPFFDS
210 220 230 240 250
LVKQTHIPNI FSLQLCGAGF PLNQTEALAS VGGSMIIGGI DHSLYTGSLW
260 270 280 290 300
YTPIRREWYY EVIIVRVEIN GQDLKMDCKE YNYDKSIVDS GTTNLRLPKK
310 320 330 340 350
VFEAAVKSIK AASSTEKFPD GFWLGEQLVC WQAGTTPWNI FPVISLYLMG
360 370 380 390 400
EVTNQSFRIT ILPQQYLRPV EDVATSQDDC YKFAVSQSST GTVMGAVIME
410 420 430 440 450
GFYVVFDRAR KRIGFAVSAC HVHDEFRTAA VEGPFVTADM EDCGYNIPQT
460 470 480 490 500
DESTLMTIAY VMAAICALFM LPLCLMVCQW RCLRCLRHQH DDFADDISLL

K
Length:501
Mass (Da):55,748
Last modified:August 14, 2001 - v2
Checksum:iC085A013145E474E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS23135.1.
RefSeqiNP_001139419.1. NM_001145947.1.
NP_035922.4. NM_011792.5.
UniGeneiMm.24044.

Genome annotation databases

EnsembliENSMUST00000034591; ENSMUSP00000034591; ENSMUSG00000032086.
GeneIDi23821.
KEGGimmu:23821.
UCSCiuc009pgh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS23135.1.
RefSeqiNP_001139419.1. NM_001145947.1.
NP_035922.4. NM_011792.5.
UniGeneiMm.24044.

3D structure databases

ProteinModelPortaliP56818.
SMRiP56818. Positions 58-453.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204741. 9 interactions.
STRINGi10090.ENSMUSP00000034591.

Chemistry

BindingDBiP56818.
ChEMBLiCHEMBL4593.

PTM databases

PhosphoSiteiP56818.

Proteomic databases

MaxQBiP56818.
PRIDEiP56818.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034591; ENSMUSP00000034591; ENSMUSG00000032086.
GeneIDi23821.
KEGGimmu:23821.
UCSCiuc009pgh.2. mouse.

Organism-specific databases

CTDi23621.
MGIiMGI:1346542. Bace1.

Phylogenomic databases

eggNOGiNOG71700.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000036572.
HOVERGENiHBG059578.
InParanoidiP56818.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG7DNNVW.
PhylomeDBiP56818.
TreeFamiTF329595.

Enzyme and pathway databases

BRENDAi3.4.23.46. 3474.

Miscellaneous databases

ChiTaRSiBace1. mouse.
NextBioi303471.
PROiP56818.
SOURCEiSearch...

Gene expression databases

BgeeiP56818.
CleanExiMM_BACE1.
ExpressionAtlasiP56818. baseline and differential.
GenevisibleiP56818. MM.

Family and domain databases

Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR009119. BACE.
IPR009120. BACE1.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERiPTHR13683. PTHR13683. 1 hit.
PfamiPF00026. Asp. 1 hit.
[Graphical view]
PRINTSiPR01816. BACE1.
PR01815. BACEFAMILY.
PR00792. PEPSIN.
SUPFAMiSSF50630. SSF50630. 1 hit.
PROSITEiPS00141. ASP_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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. 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.
    , 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. Cited for: DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiBACE1_MOUSE
AccessioniPrimary (citable) accession number: P56818
Secondary accession number(s): Q544D0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 14, 2001
Last modified: June 24, 2015
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.