Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Beta-secretase 2

Gene

BACE2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 672.5 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1101
Active sitei3031

GO - Molecular functioni

  • amyloid-beta binding Source: GO_Central
  • aspartic-type endopeptidase activity Source: UniProtKB

GO - Biological processi

  • amyloid-beta metabolic process Source: GO_Central
  • membrane protein ectodomain proteolysis Source: UniProtKB
  • negative regulation of amyloid precursor protein biosynthetic process Source: UniProtKB
  • peptide hormone processing Source: UniProtKB
  • protein catabolic process Source: GO_Central
  • proteolysis Source: UniProtKB

Keywordsi

Molecular functionAspartyl protease, Hydrolase, Protease

Enzyme and pathway databases

BioCyciMetaCyc:G66-33964-MONOMER
BRENDAi3.4.23.45 2681

Protein family/group databases

MEROPSiA01.041
TCDBi8.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:3.4.23.45)
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

EuPathDBiHostDB:ENSG00000182240.15
HGNCiHGNC:934 BACE2
MIMi605668 gene
neXtProtiNX_Q9Y5Z0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 473ExtracellularSequence analysisAdd BLAST453
Transmembranei474 – 494HelicalSequence analysisAdd BLAST21
Topological domaini495 – 518CytoplasmicSequence analysisAdd BLAST24

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi110D → A or N: Loss of autoproteolytic cleavage. 2 Publications1
Mutagenesisi303D → A: Loss of autoproteolytic cleavage. 1 Publication1

Organism-specific databases

DisGeNETi25825
OpenTargetsiENSG00000182240
PharmGKBiPA25233

Chemistry databases

ChEMBLiCHEMBL2525
GuidetoPHARMACOLOGYi2331

Polymorphism and mutation databases

BioMutaiBACE2
DMDMi6685260

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002594521 – 625 PublicationsAdd BLAST42
ChainiPRO_000002594663 – 518Beta-secretase 2Add BLAST456

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi170N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi233 ↔ 4331 Publication
Disulfide bondi292 ↔ 4571 Publication
Disulfide bondi344 ↔ 3931 Publication
Glycosylationi366N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Undergoes autoproteolytic cleavage.
Glycosylated.2 Publications

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ9Y5Z0
PeptideAtlasiQ9Y5Z0
PRIDEiQ9Y5Z0
ProteomicsDBi86546
86547 [Q9Y5Z0-2]
86548 [Q9Y5Z0-3]
86549 [Q9Y5Z0-4]
86550 [Q9Y5Z0-5]

PTM databases

iPTMnetiQ9Y5Z0
PhosphoSitePlusiQ9Y5Z0

Miscellaneous databases

PMAP-CutDBiQ9Y5Z0

Expressioni

Tissue specificityi

Brain. Present in neurons within the hippocampus, frontal cortex and temporal cortex (at protein level). Expressed at low levels in most peripheral tissues and at higher levels in colon, kidney, pancreas, placenta, prostate, stomach and trachea. Expressed at low levels in the brain. Found in spinal cord, medulla oblongata, substantia nigra and locus coruleus. Expressed in the ductal epithelium of both normal and malignant prostate.7 Publications

Inductioni

Up-regulated in primary breast and colon tumors and liver metastasis.1 Publication

Gene expression databases

BgeeiENSG00000182240
CleanExiHS_BACE2
GenevisibleiQ9Y5Z0 HS

Organism-specific databases

HPAiHPA035416

Interactioni

Subunit structurei

Monomer. Interacts ith RTN3 and RTN4.2 Publications

Protein-protein interaction databases

BioGridi117353, 18 interactors
IntActiQ9Y5Z0, 2 interactors
MINTiQ9Y5Z0
STRINGi9606.ENSP00000332979

Chemistry databases

BindingDBiQ9Y5Z0

Structurei

Secondary structure

1518
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi78 – 80Combined sources3
Beta strandi84 – 87Combined sources4
Helixi88 – 90Combined sources3
Beta strandi91 – 98Combined sources8
Turni99 – 102Combined sources4
Beta strandi103 – 110Combined sources8
Beta strandi116 – 119Combined sources4
Helixi132 – 134Combined sources3
Beta strandi139 – 149Combined sources11
Beta strandi152 – 164Combined sources13
Turni166 – 168Combined sources3
Beta strandi173 – 185Combined sources13
Beta strandi194 – 198Combined sources5
Helixi202 – 204Combined sources3
Beta strandi205 – 207Combined sources3
Helixi214 – 222Combined sources9
Beta strandi228 – 232Combined sources5
Beta strandi247 – 253Combined sources7
Helixi256 – 258Combined sources3
Beta strandi264 – 267Combined sources4
Turni271 – 274Combined sources4
Beta strandi278 – 283Combined sources6
Helixi292 – 295Combined sources4
Beta strandi300 – 302Combined sources3
Beta strandi308 – 312Combined sources5
Helixi313 – 326Combined sources14
Beta strandi327 – 329Combined sources3
Helixi334 – 337Combined sources4
Helixi339 – 342Combined sources4
Beta strandi343 – 346Combined sources4
Helixi347 – 349Combined sources3
Helixi352 – 354Combined sources3
Beta strandi358 – 363Combined sources6
Beta strandi369 – 375Combined sources7
Helixi377 – 380Combined sources4
Beta strandi381 – 384Combined sources4
Beta strandi391 – 403Combined sources13
Beta strandi405 – 407Combined sources3
Helixi409 – 412Combined sources4
Beta strandi415 – 420Combined sources6
Turni421 – 424Combined sources4
Beta strandi425 – 430Combined sources6
Beta strandi435 – 438Combined sources4
Beta strandi439 – 449Combined sources11
Beta strandi451 – 453Combined sources3

3D structure databases

ProteinModelPortaliQ9Y5Z0
SMRiQ9Y5Z0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y5Z0

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 429Peptidase A1PROSITE-ProRule annotationAdd BLAST338

Sequence similaritiesi

Belongs to the peptidase A1 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1339 Eukaryota
ENOG410XNV7 LUCA
GeneTreeiENSGT00910000144168
HOVERGENiHBG059578
InParanoidiQ9Y5Z0
KOiK07747
OMAiCYRFGIS
OrthoDBiEOG091G0CNK
PhylomeDBiQ9Y5Z0
TreeFamiTF329595

Family and domain databases

CDDicd05473 beta_secretase_like, 1 hit
Gene3Di2.40.70.10, 2 hits
InterProiView 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
PANTHERiPTHR13683 PTHR13683, 1 hit
PTHR13683:SF262 PTHR13683:SF262, 1 hit
PfamiView protein in Pfam
PF00026 Asp, 1 hit
PRINTSiPR01817 BACE2
PR01815 BACEFAMILY
PR00792 PEPSIN
SUPFAMiSSF50630 SSF50630, 1 hit
PROSITEiView protein in PROSITE
PS00141 ASP_PROTEASE, 2 hits
PS51767 PEPTIDASE_A1, 1 hit

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y5Z0-1) [UniParc]FASTAAdd to basket
Also known as: Isoform A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:518
Mass (Da):56,180
Last modified:November 1, 1999 - v1
Checksum:i2E903150823760D3
GO
Isoform 2 (identifier: Q9Y5Z0-2) [UniParc]FASTAAdd to basket
Also known as: Isoform C

The sequence of this isoform differs from the canonical sequence as follows:
     329-378: Missing.

Show »
Length:468
Mass (Da):50,325
Checksum:i717E0920126A0142
GO
Isoform 3 (identifier: Q9Y5Z0-3) [UniParc]FASTAAdd to basket
Also known as: Isoform B

The sequence of this isoform differs from the canonical sequence as follows:
     379-396: LYIQPMMGAGLNYECYRF → KLQVLQCLKFPGLSQQRM
     397-518: Missing.

Show »
Length:396
Mass (Da):42,985
Checksum:iEDB3A7AF391CEACA
GO
Isoform 4 (identifier: Q9Y5Z0-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.

Show »
Length:439
Mass (Da):48,275
Checksum:i02EC0E0E50F11602
GO
Isoform 5 (identifier: Q9Y5Z0-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-95: Missing.

Show »
Length:423
Mass (Da):46,476
Checksum:i675FBF380B57CE7D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti36A → T in AAF13714 (PubMed:10677483).Curated1
Sequence conflicti184E → G in BAC11682 (PubMed:14702039).Curated1
Sequence conflicti192K → Q in BAC11682 (PubMed:14702039).Curated1
Sequence conflicti233C → R in BAC11682 (PubMed:14702039).Curated1
Isoform 3 (identifier: Q9Y5Z0-3)
Sequence conflicti381Q → R in AAF35836 (PubMed:10965118).Curated1
Sequence conflicti396M → F in AAF35836 (PubMed:10965118).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0380231 – 95Missing in isoform 5. 1 PublicationAdd BLAST95
Alternative sequenceiVSP_0380241 – 79Missing in isoform 4. 1 PublicationAdd BLAST79
Alternative sequenceiVSP_038025329 – 378Missing in isoform 2. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_038026379 – 396LYIQP…ECYRF → KLQVLQCLKFPGLSQQRM in isoform 3. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_038027397 – 518Missing in isoform 3. 1 PublicationAdd BLAST122

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
CCDSiCCDS13668.1 [Q9Y5Z0-1]
CCDS13669.1 [Q9Y5Z0-2]
CCDS13670.1 [Q9Y5Z0-3]
RefSeqiNP_036237.2, NM_012105.4 [Q9Y5Z0-1]
NP_620476.1, NM_138991.2 [Q9Y5Z0-2]
NP_620477.1, NM_138992.2 [Q9Y5Z0-3]
UniGeneiHs.43047
Hs.529408

Genome annotation databases

EnsembliENST00000328735; ENSP00000333854; ENSG00000182240 [Q9Y5Z0-3]
ENST00000330333; ENSP00000332979; ENSG00000182240 [Q9Y5Z0-1]
ENST00000347667; ENSP00000327528; ENSG00000182240 [Q9Y5Z0-2]
GeneIDi25825
KEGGihsa:25825
UCSCiuc002yyw.5 human [Q9Y5Z0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiBACE2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5Z0
Secondary accession number(s): A8K7P1
, Q5DIH8, Q8N2D4, Q9H2V8, Q9NZL1, Q9NZL2, Q9UJT6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1999
Last modified: June 20, 2018
This is version 173 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health