UniProtKB - Q9Y5Z0 (BACE2_HUMAN)
Beta-secretase 2
BACE2
Functioni
Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading 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. It has also been shown that it can cleave APP between residues 671 and 672. Responsible also for the proteolytic processing of CLTRN in pancreatic beta cells (PubMed:21907142).
6 PublicationsCatalytic activityi
- Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein.2 Publications EC:3.4.23.45
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 110 | 1 | ||
Active sitei | 303 | 1 |
GO - Molecular functioni
- aspartic-type endopeptidase activity Source: UniProtKB
GO - Biological processi
- amyloid-beta metabolic process Source: GO_Central
- glucose homeostasis Source: UniProtKB
- membrane protein ectodomain proteolysis Source: UniProtKB
- negative regulation of amyloid precursor protein biosynthetic process Source: UniProtKB
- peptide hormone processing Source: UniProtKB
- proteolysis Source: UniProtKB
Keywordsi
Molecular function | Aspartyl protease, Hydrolase, Protease |
Enzyme and pathway databases
BRENDAi | 3.4.23.45, 2681 3.4.24.56, 2681 |
PathwayCommonsi | Q9Y5Z0 |
SignaLinki | Q9Y5Z0 |
SIGNORi | Q9Y5Z0 |
Protein family/group databases
MEROPSi | A01.041 |
TCDBi | 8.A.32.1.2, the Beta-amyloid cleaving enzyme (bace1) family 8.A.32.1.3, the Beta-amyloid cleaving enzyme (bace1) family |
Names & Taxonomyi
Protein namesi | Recommended name: Beta-secretase 2 (EC:3.4.23.451 Publication)Alternative name(s): Aspartic-like protease 56 kDa Aspartyl protease 1 Short name: ASP1 Short name: Asp 1 Beta-site amyloid precursor protein cleaving enzyme 2 Short name: Beta-site APP cleaving enzyme 2 Down region aspartic protease Short name: DRAP Memapsin-1 Membrane-associated aspartic protease 1 Theta-secretase |
Gene namesi | Name:BACE2 Synonyms:AEPLC, ALP56, ASP21 ORF Names:CDA13, UNQ418/PRO852 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:934, BACE2 |
MIMi | 605668, gene |
neXtProti | NX_Q9Y5Z0 |
VEuPathDBi | HostDB:ENSG00000182240 |
Subcellular locationi
Endoplasmic reticulum
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein Sequence analysis
Golgi apparatus
- Golgi apparatus 1 Publication
Endosome
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Endosome
- endosome Source: GO_Central
Golgi apparatus
- Golgi apparatus Source: UniProtKB
- trans-Golgi network Source: GO_Central
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB
- membrane Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 21 – 473 | ExtracellularSequence analysisAdd BLAST | 453 | |
Transmembranei | 474 – 494 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 495 – 518 | CytoplasmicSequence analysisAdd BLAST | 24 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 110 | D → A or N: Loss of autoproteolytic cleavage. 2 Publications | 1 | |
Mutagenesisi | 303 | D → A: Loss of autoproteolytic cleavage. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 25825 |
OpenTargetsi | ENSG00000182240 |
PharmGKBi | PA25233 |
Miscellaneous databases
Pharosi | Q9Y5Z0, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2525 |
GuidetoPHARMACOLOGYi | 2331 |
Genetic variation databases
BioMutai | BACE2 |
DMDMi | 6685260 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
PropeptideiPRO_0000025945 | 21 – 62 | 5 PublicationsAdd BLAST | 42 | |
ChainiPRO_0000025946 | 63 – 518 | Beta-secretase 2Add BLAST | 456 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 170 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 233 ↔ 433 | 1 Publication | ||
Disulfide bondi | 292 ↔ 457 | 1 Publication | ||
Disulfide bondi | 344 ↔ 393 | 1 Publication | ||
Glycosylationi | 366 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
Autocatalytic cleavage, Disulfide bond, Glycoprotein, ZymogenProteomic databases
jPOSTi | Q9Y5Z0 |
MassIVEi | Q9Y5Z0 |
MaxQBi | Q9Y5Z0 |
PaxDbi | Q9Y5Z0 |
PeptideAtlasi | Q9Y5Z0 |
PRIDEi | Q9Y5Z0 |
ProteomicsDBi | 86546 [Q9Y5Z0-1] 86547 [Q9Y5Z0-2] 86548 [Q9Y5Z0-3] 86549 [Q9Y5Z0-4] 86550 [Q9Y5Z0-5] |
PTM databases
GlyGeni | Q9Y5Z0, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | Q9Y5Z0 |
PhosphoSitePlusi | Q9Y5Z0 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000182240, Expressed in parotid gland and 223 other tissues |
Genevisiblei | Q9Y5Z0, HS |
Organism-specific databases
HPAi | ENSG00000182240, Tissue enhanced (salivary) |
Interactioni
Subunit structurei
Monomer. Interacts ith RTN3 and RTN4.
2 PublicationsBinary interactionsi
Q9Y5Z0
Protein-protein interaction databases
BioGRIDi | 117353, 80 interactors |
IntActi | Q9Y5Z0, 38 interactors |
MINTi | Q9Y5Z0 |
STRINGi | 9606.ENSP00000332979 |
Chemistry databases
BindingDBi | Q9Y5Z0 |
Miscellaneous databases
RNActi | Q9Y5Z0, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9Y5Z0 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9Y5Z0 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 92 – 429 | Peptidase A1PROSITE-ProRule annotationAdd BLAST | 338 |
Sequence similaritiesi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1339, Eukaryota |
GeneTreei | ENSGT00940000159548 |
HOGENOMi | CLU_039009_0_0_1 |
InParanoidi | Q9Y5Z0 |
OMAi | CWMKGET |
OrthoDBi | 753343at2759 |
PhylomeDBi | Q9Y5Z0 |
TreeFami | TF329595 |
Family and domain databases
CDDi | cd05473, beta_secretase_like, 1 hit |
Gene3Di | 2.40.70.10, 2 hits |
InterProi | View protein in InterPro IPR001461, Aspartic_peptidase_A1 IPR001969, Aspartic_peptidase_AS IPR009119, BACE IPR009121, BACE2 IPR033874, Memapsin-like IPR033121, PEPTIDASE_A1 IPR021109, Peptidase_aspartic_dom_sf |
PANTHERi | PTHR47965, PTHR47965, 1 hit PTHR47965:SF40, PTHR47965:SF40, 1 hit |
Pfami | View protein in Pfam PF00026, Asp, 1 hit |
PRINTSi | PR01817, BACE2 PR01815, BACEFAMILY PR00792, PEPSIN |
SUPFAMi | SSF50630, SSF50630, 1 hit |
PROSITEi | View protein in PROSITE PS00141, ASP_PROTEASE, 2 hits PS51767, PEPTIDASE_A1, 1 hit |
s (5)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGALARALLL PLLAQWLLRA APELAPAPFT LPLRVAAATN RVVAPTPGPG
60 70 80 90 100
TPAERHADGL ALALEPALAS PAGAANFLAM VDNLQGDSGR GYYLEMLIGT
110 120 130 140 150
PPQKLQILVD TGSSNFAVAG TPHSYIDTYF DTERSSTYRS KGFDVTVKYT
160 170 180 190 200
QGSWTGFVGE DLVTIPKGFN TSFLVNIATI FESENFFLPG IKWNGILGLA
210 220 230 240 250
YATLAKPSSS LETFFDSLVT QANIPNVFSM QMCGAGLPVA GSGTNGGSLV
260 270 280 290 300
LGGIEPSLYK GDIWYTPIKE EWYYQIEILK LEIGGQSLNL DCREYNADKA
310 320 330 340 350
IVDSGTTLLR LPQKVFDAVV EAVARASLIP EFSDGFWTGS QLACWTNSET
360 370 380 390 400
PWSYFPKISI YLRDENSSRS FRITILPQLY IQPMMGAGLN YECYRFGISP
410 420 430 440 450
STNALVIGAT VMEGFYVIFD RAQKRVGFAA SPCAEIAGAA VSEISGPFST
460 470 480 490 500
EDVASNCVPA QSLSEPILWI VSYALMSVCG AILLVLIVLL LLPFRCQRRP
510
RDPEVVNDES SLVRHRWK
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
Sequence conflicti | 36 | A → T in AAF13714 (PubMed:10677483).Curated | 1 | ||
Sequence conflicti | 184 | E → G in BAC11682 (PubMed:14702039).Curated | 1 | ||
Sequence conflicti | 192 | K → Q in BAC11682 (PubMed:14702039).Curated | 1 | ||
Sequence conflicti | 233 | C → R in BAC11682 (PubMed:14702039).Curated | 1 | ||
Isoform 3 (identifier: Q9Y5Z0-3) | |||||
Sequence conflicti | 381 | Q → R in AAF35836 (PubMed:10965118).Curated | 1 | ||
Sequence conflicti | 396 | M → F in AAF35836 (PubMed:10965118).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_038023 | 1 – 95 | Missing in isoform 5. 1 PublicationAdd BLAST | 95 | |
Alternative sequenceiVSP_038024 | 1 – 79 | Missing in isoform 4. 1 PublicationAdd BLAST | 79 | |
Alternative sequenceiVSP_038025 | 329 – 378 | Missing in isoform 2. 1 PublicationAdd BLAST | 50 | |
Alternative sequenceiVSP_038026 | 379 – 396 | LYIQP…ECYRF → KLQVLQCLKFPGLSQQRM in isoform 3. 1 PublicationAdd BLAST | 18 | |
Alternative sequenceiVSP_038027 | 397 – 518 | Missing in isoform 3. 1 PublicationAdd BLAST | 122 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF200342 mRNA Translation: AAF17078.1 AF117892 mRNA Translation: AAD45240.1 AF178532 mRNA Translation: AAF29494.1 AF188276 mRNA Translation: AAF35835.1 AF188277 mRNA Translation: AAF35836.1 AF050171 mRNA Translation: AAD45963.1 AF204944 mRNA Translation: AAF26368.1 AF200192 mRNA Translation: AAF13714.1 AF212252 mRNA Translation: AAG41783.1 AY358927 mRNA Translation: AAQ89286.1 AK075539 mRNA Translation: BAC11682.1 AK292056 mRNA Translation: BAF84745.1 AL163284 Genomic DNA Translation: CAB90458.1 AL163285 Genomic DNA Translation: CAB90554.1 CH471079 Genomic DNA Translation: EAX09611.1 CH471079 Genomic DNA Translation: EAX09613.1 BC014453 mRNA Translation: AAH14453.1 AY769996 Genomic DNA Translation: AAX14808.1 |
CCDSi | CCDS13668.1 [Q9Y5Z0-1] CCDS13669.1 [Q9Y5Z0-2] CCDS13670.1 [Q9Y5Z0-3] |
RefSeqi | NP_036237.2, NM_012105.4 [Q9Y5Z0-1] NP_620476.1, NM_138991.2 [Q9Y5Z0-2] NP_620477.1, NM_138992.2 [Q9Y5Z0-3] |
Genome annotation databases
Ensembli | ENST00000328735; ENSP00000333854; ENSG00000182240 [Q9Y5Z0-3] ENST00000330333; ENSP00000332979; ENSG00000182240 ENST00000347667; ENSP00000327528; ENSG00000182240 [Q9Y5Z0-2] |
GeneIDi | 25825 |
KEGGi | hsa:25825 |
MANE-Selecti | ENST00000330333.11; ENSP00000332979.6; NM_012105.5; NP_036237.2 |
UCSCi | uc002yyw.5, human [Q9Y5Z0-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF200342 mRNA Translation: AAF17078.1 AF117892 mRNA Translation: AAD45240.1 AF178532 mRNA Translation: AAF29494.1 AF188276 mRNA Translation: AAF35835.1 AF188277 mRNA Translation: AAF35836.1 AF050171 mRNA Translation: AAD45963.1 AF204944 mRNA Translation: AAF26368.1 AF200192 mRNA Translation: AAF13714.1 AF212252 mRNA Translation: AAG41783.1 AY358927 mRNA Translation: AAQ89286.1 AK075539 mRNA Translation: BAC11682.1 AK292056 mRNA Translation: BAF84745.1 AL163284 Genomic DNA Translation: CAB90458.1 AL163285 Genomic DNA Translation: CAB90554.1 CH471079 Genomic DNA Translation: EAX09611.1 CH471079 Genomic DNA Translation: EAX09613.1 BC014453 mRNA Translation: AAH14453.1 AY769996 Genomic DNA Translation: AAX14808.1 |
CCDSi | CCDS13668.1 [Q9Y5Z0-1] CCDS13669.1 [Q9Y5Z0-2] CCDS13670.1 [Q9Y5Z0-3] |
RefSeqi | NP_036237.2, NM_012105.4 [Q9Y5Z0-1] NP_620476.1, NM_138991.2 [Q9Y5Z0-2] NP_620477.1, NM_138992.2 [Q9Y5Z0-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2EWY | X-ray | 3.10 | A/B/C/D | 78-460 | [»] | |
3ZKG | X-ray | 1.90 | A/B | 75-460 | [»] | |
3ZKI | X-ray | 2.40 | A/B | 75-460 | [»] | |
3ZKM | X-ray | 1.85 | A/B | 75-460 | [»] | |
3ZKN | X-ray | 2.00 | A/B | 75-460 | [»] | |
3ZKQ | X-ray | 1.51 | A | 75-460 | [»] | |
3ZKS | X-ray | 2.11 | A | 75-460 | [»] | |
3ZKX | X-ray | 2.37 | A | 75-460 | [»] | |
3ZL7 | X-ray | 3.20 | A | 75-460 | [»] | |
3ZLQ | X-ray | 2.10 | A/B | 75-460 | [»] | |
4BEL | X-ray | 1.85 | A/B | 75-460 | [»] | |
4BFB | X-ray | 2.21 | A/B | 75-460 | [»] | |
6JSZ | X-ray | 1.53 | A | 75-460 | [»] | |
6UJ0 | X-ray | 2.15 | A/B | 1-460 | [»] | |
6UJ1 | X-ray | 3.03 | A/B | 1-460 | [»] | |
7D5B | X-ray | 1.31 | A | 75-460 | [»] | |
7D5U | X-ray | 2.04 | A | 75-460 | [»] | |
7N4N | X-ray | 1.41 | A | 75-460 | [»] | |
SMRi | Q9Y5Z0 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 117353, 80 interactors |
IntActi | Q9Y5Z0, 38 interactors |
MINTi | Q9Y5Z0 |
STRINGi | 9606.ENSP00000332979 |
Chemistry databases
BindingDBi | Q9Y5Z0 |
ChEMBLi | CHEMBL2525 |
GuidetoPHARMACOLOGYi | 2331 |
Protein family/group databases
MEROPSi | A01.041 |
TCDBi | 8.A.32.1.2, the Beta-amyloid cleaving enzyme (bace1) family 8.A.32.1.3, the Beta-amyloid cleaving enzyme (bace1) family |
PTM databases
GlyGeni | Q9Y5Z0, 3 sites, 1 O-linked glycan (1 site) |
iPTMneti | Q9Y5Z0 |
PhosphoSitePlusi | Q9Y5Z0 |
Genetic variation databases
BioMutai | BACE2 |
DMDMi | 6685260 |
Proteomic databases
jPOSTi | Q9Y5Z0 |
MassIVEi | Q9Y5Z0 |
MaxQBi | Q9Y5Z0 |
PaxDbi | Q9Y5Z0 |
PeptideAtlasi | Q9Y5Z0 |
PRIDEi | Q9Y5Z0 |
ProteomicsDBi | 86546 [Q9Y5Z0-1] 86547 [Q9Y5Z0-2] 86548 [Q9Y5Z0-3] 86549 [Q9Y5Z0-4] 86550 [Q9Y5Z0-5] |
Protocols and materials databases
ABCDi | Q9Y5Z0, 3 sequenced antibodies |
Antibodypediai | 4410, 534 antibodies from 37 providers |
DNASUi | 25825 |
Genome annotation databases
Ensembli | ENST00000328735; ENSP00000333854; ENSG00000182240 [Q9Y5Z0-3] ENST00000330333; ENSP00000332979; ENSG00000182240 ENST00000347667; ENSP00000327528; ENSG00000182240 [Q9Y5Z0-2] |
GeneIDi | 25825 |
KEGGi | hsa:25825 |
MANE-Selecti | ENST00000330333.11; ENSP00000332979.6; NM_012105.5; NP_036237.2 |
UCSCi | uc002yyw.5, human [Q9Y5Z0-1] |
Organism-specific databases
CTDi | 25825 |
DisGeNETi | 25825 |
GeneCardsi | BACE2 |
HGNCi | HGNC:934, BACE2 |
HPAi | ENSG00000182240, Tissue enhanced (salivary) |
MIMi | 605668, gene |
neXtProti | NX_Q9Y5Z0 |
OpenTargetsi | ENSG00000182240 |
PharmGKBi | PA25233 |
VEuPathDBi | HostDB:ENSG00000182240 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1339, Eukaryota |
GeneTreei | ENSGT00940000159548 |
HOGENOMi | CLU_039009_0_0_1 |
InParanoidi | Q9Y5Z0 |
OMAi | CWMKGET |
OrthoDBi | 753343at2759 |
PhylomeDBi | Q9Y5Z0 |
TreeFami | TF329595 |
Enzyme and pathway databases
BRENDAi | 3.4.23.45, 2681 3.4.24.56, 2681 |
PathwayCommonsi | Q9Y5Z0 |
SignaLinki | Q9Y5Z0 |
SIGNORi | Q9Y5Z0 |
Miscellaneous databases
BioGRID-ORCSi | 25825, 3 hits in 1041 CRISPR screens |
ChiTaRSi | BACE2, human |
EvolutionaryTracei | Q9Y5Z0 |
GeneWikii | Beta-secretase_2 |
GenomeRNAii | 25825 |
Pharosi | Q9Y5Z0, Tchem |
PROi | PR:Q9Y5Z0 |
RNActi | Q9Y5Z0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000182240, Expressed in parotid gland and 223 other tissues |
Genevisiblei | Q9Y5Z0, HS |
Family and domain databases
CDDi | cd05473, beta_secretase_like, 1 hit |
Gene3Di | 2.40.70.10, 2 hits |
InterProi | View protein in InterPro IPR001461, Aspartic_peptidase_A1 IPR001969, Aspartic_peptidase_AS IPR009119, BACE IPR009121, BACE2 IPR033874, Memapsin-like IPR033121, PEPTIDASE_A1 IPR021109, Peptidase_aspartic_dom_sf |
PANTHERi | PTHR47965, PTHR47965, 1 hit PTHR47965:SF40, PTHR47965:SF40, 1 hit |
Pfami | View protein in Pfam PF00026, Asp, 1 hit |
PRINTSi | PR01817, BACE2 PR01815, BACEFAMILY PR00792, PEPSIN |
SUPFAMi | SSF50630, SSF50630, 1 hit |
PROSITEi | View protein in PROSITE PS00141, ASP_PROTEASE, 2 hits PS51767, PEPTIDASE_A1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | BACE2_HUMAN | |
Accessioni | Q9Y5Z0Primary (citable) accession number: Q9Y5Z0 Secondary accession number(s): A8K7P1 Q9UJT6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | November 1, 1999 | |
Last modified: | February 23, 2022 | |
This is version 196 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 21
Human chromosome 21: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families