Beta-secretase 2

BACE2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2EWY, 3ZKG, 3ZKI, 3ZKM, 3ZKN, 3ZKQ, 3ZKS, 3ZKX, 3ZL7, 3ZLQ, 4BEL, 4BFB
Identifiers
Aliases	BACE2, AEPLC, ALP56, ASP1, ASP21, BAE2, CDA13, CEAP1, DRAP, beta-site APP-cleaving enzyme 2, beta-secretase 2
External IDs	OMIM: 605668 MGI: 1860440 HomoloGene: 22696 GeneCards: BACE2
Gene location (Human)
Chr.	Chromosome 21 (human)
End	41,282,530 bp
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	97,244,136 bp
RNA expression pattern
	Top expressed in
	parotid gland; ; minor salivary gland; ; stomach; ; salivary gland; ; left coronary artery; ; gallbladder; ; hair follicle; ; islet of Langerhans; ; thoracic aorta;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	peptidase activity; amyloid-beta binding; hydrolase activity; aspartic-type endopeptidase activity;
Cellular component	integral component of membrane; cell surface; endosome; Golgi apparatus; endoplasmic reticulum; membrane; plasma membrane; cytoplasm; trans-Golgi network; dense core granule;
Biological process	peptide hormone processing; protein catabolic process; amyloid-beta metabolic process; negative regulation of amyloid precursor protein biosynthetic process; proteolysis; membrane protein ectodomain proteolysis; astrocyte activation; glucose homeostasis;
	Sources:Amigo / QuickGO
Orthologs
	25825
	56175
	ENSG00000182240
	ENSMUSG00000040605
	Q9Y5Z0
	Q9JL18
	NM_138992; NM_012105; NM_138991
	NM_019517
	NP_036237; NP_620476; NP_620477
	NP_062390
	Wikidata
View/Edit Human	View/Edit Mouse

Beta-secretase 2 (EC 3.4.23.45, also known as Memapsin-1) is an enzyme^[5]^[6]^[7]^[8] that cleaves Glu-Val-Asn-Leu!Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein. BACE2 is a close homolog of BACE1.

Function[]

Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease and a frequent complication of Down syndrome. Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein by 2 proteases, one of which is the protein encoded by this gene. This gene localizes to the 'Down critical region' of chromosome 21. The encoded protein, a member of the peptidase A1 protein family, is a type I integral membrane glycoprotein and aspartic protease. Three transcript variants encoding different isoforms have been described for this gene.^[8] It has been reported that BACE2 is the main protease that mediates the release of the amyloidogenic ectodomain of Pmel17 in melanocytes. ^[9] BACE2 has also been observed in mice to be correlated with maintaining the pancreatic β cells and improving control of glucose homeostasis, which may prove to be useful for research on Type 2 Diabetes.^[10]

Interactions[]

BACE2 has been shown to interact with GGA1^[11] and GGA2.^[11]

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000182240 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000040605 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Turner, R.T.; Loy, J.A.; Nguyen, C.; Devasamudram, T.; Ghosh, A.K.; Koelsch, G.; Tang, J. (2002). "Specificity of memapsin 1 and its implications on the design of memapsin 2 (β-secretase) inhibitor selectivity". Biochemistry. 41 (27): 8742–8746. doi:10.1021/bi025926t. PMID 12093293.
^ Solans A, Estivill X, de La Luna S (Sep 2000). "A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase". Cytogenetics and Cell Genetics. 89 (3–4): 177–84. doi:10.1159/000015608. PMID 10965118. S2CID 39880508.
^ Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML (May 2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID 10830953.
^ ^a ^b "Entrez Gene: BACE2 beta-site APP-cleaving enzyme 2".
^ BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells Pubmed
^ Esterházy, Daria; Stützer, Ina; Wang, Haiyan; Rechsteiner, Markus P.; Beauchamp, Jeremy; Döbeli, Heinz; Hilpert, Hans; Matile, Hugues; Prummer, Michael; Schmidt, Alexander; Lieske, Nora (2011-09-07). "Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass". Cell Metabolism. 14 (3): 365–377. doi:10.1016/j.cmet.2011.06.018. ISSN 1932-7420. PMID 21907142.
^ ^a ^b He X, Chang WP, Koelsch G, Tang J (Jul 2002). "Memapsin 2 (beta-secretase) cytosolic domain binds to the VHS domains of GGA1 and GGA2: implications on the endocytosis mechanism of memapsin 2". FEBS Letters. 524 (1–3): 183–7. doi:10.1016/S0014-5793(02)03052-1. PMID 12135764. S2CID 42042430.

External links[]

https://web.archive.org/web/20070318110931/http://www.ihop-net.org/UniPub/iHOP/gs/129262.html
Online Mendelian Inheritance in Man (OMIM): 605668
Human BACE2 genome location and BACE2 gene details page in the UCSC Genome Browser.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000182240 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000040605 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Turner, R.T.; Loy, J.A.; Nguyen, C.; Devasamudram, T.; Ghosh, A.K.; Koelsch, G.; Tang, J. (2002). "Specificity of memapsin 1 and its implications on the design of memapsin 2 (β-secretase) inhibitor selectivity". Biochemistry. 41 (27): 8742–8746. doi:10.1021/bi025926t. PMID 12093293.

[pmid10965118-6] Solans A, Estivill X, de La Luna S (Sep 2000). "A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase". Cytogenetics and Cell Genetics. 89 (3–4): 177–84. doi:10.1159/000015608. PMID 10965118. S2CID 39880508.

[pmid10830953-7] Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML (May 2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID 10830953.

[entrez-8] "Entrez Gene: BACE2 beta-site APP-cleaving enzyme 2".

[9] BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells Pubmed

[10] Esterházy, Daria; Stützer, Ina; Wang, Haiyan; Rechsteiner, Markus P.; Beauchamp, Jeremy; Döbeli, Heinz; Hilpert, Hans; Matile, Hugues; Prummer, Michael; Schmidt, Alexander; Lieske, Nora (2011-09-07). "Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass". Cell Metabolism. 14 (3): 365–377. doi:10.1016/j.cmet.2011.06.018. ISSN 1932-7420. PMID 21907142.

[pmid12135764-11] He X, Chang WP, Koelsch G, Tang J (Jul 2002). "Memapsin 2 (beta-secretase) cytosolic domain binds to the VHS domains of GGA1 and GGA2: implications on the endocytosis mechanism of memapsin 2". FEBS Letters. 524 (1–3): 183–7. doi:10.1016/S0014-5793(02)03052-1. PMID 12135764. S2CID 42042430.

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v t Proteases: aspartate proteases (EC 3.4.23)
Vertebrate	Pepsin Chymosin Renin Signal peptide peptidase Beta secretase 1 2
Pathogenic	Plasmepsin HIV-1 protease
Plant	Nepenthesin
Cathepsin	D E

v t Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Beta-secretase 2

Contents

Function[]

Interactions[]

References[]

Further reading[]

External links[]