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Beta-secretase 2

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BACE2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBACE2, AEPLC, ALP56, ASP1, ASP21, BAE2, CDA13, CEAP1, DRAP, beta-site APP-cleaving enzyme 2, beta-secretase 2
External IDsOMIM: 605668; MGI: 1860440; HomoloGene: 22696; GeneCards: BACE2; OMA:BACE2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

25825

56175

Ensembl

ENSG00000182240

ENSMUSG00000040605

UniProt

Q9Y5Z0

Q9JL18

RefSeq (mRNA)

NM_138992
NM_012105
NM_138991

NM_019517

RefSeq (protein)

NP_036237
NP_620476
NP_620477

NP_062390

Location (UCSC)Chr 21: 41.17 – 41.28 MbChr 16: 97.16 – 97.24 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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.

Gene

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This gene is located in the "Down critical region" of chromosome 21, which has been implicated in the pathogenesis of Down syndrome. Three transcript variants encoding different isoforms have been described for this gene.[8]

Function

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See also: integral membrane protein and glycoprotein

The protein encoded by this gene is a member of the peptidase A1 family, and functions as a type I integral membrane glycoprotein and aspartic protease. It is involved in the proteolytic cleavage of amyloid precursor protein (APP), a key step in the production of amyloid beta peptide. Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease and a common complication in Down syndrome.

BACE2 has also been identified as the primary protease responsible for the release of the amyloidogenic ectodomain of Pmel17 in melanocytes, a process essential for the formation of the melanosome amyloid matrix.[9]

Clinical significance

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BACE2 has been implicated in the maintenance of pancreatic β cells and regulation of glucose homeostasis. In mouse models, higher BACE2 activity has been associated with improved pancreatic function, suggesting potential therapeutic relevance for Type 2 Diabetes research.[10] In a separate context, a homozygous 25-base pair deletion in the BACE2 gene has been linked to the unique brown-and-white coat coloration in some giant pandas, as opposed to the typical black-and-white phenotype observed in the wild type.[11]

Interactions

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BACE2 has been shown to interact with GGA1[12] and GGA2.[12]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000182240 – Ensembl, May 2017
  2. ^ a b c 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 RT, Loy JA, Nguyen C, Devasamudram T, Ghosh AK, Koelsch G, et al. (July 2002). "Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity". Biochemistry. 41 (27): 8742–8746. doi:10.1021/bi025926t. PMID 12093293.
  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): 177–184. doi:10.1159/000015608. PMID 10965118. S2CID 39880508.
  7. ^ Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, et al. (May 2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–319. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID 10830953.
  8. ^ a b "Entrez Gene: BACE2 beta-site APP-cleaving enzyme 2".
  9. ^ Rochin L, Hurbain I, Serneels L, Fort C, Watt B, Leblanc P, et al. (Jun 2013). "BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells". Proceedings of the National Academy of Sciences of the United States of America. 110 (26): 10658–10663. Bibcode:2013PNAS..11010658R. doi:10.1073/pnas.1220748110. PMC 3696817. PMID 23754390.
  10. ^ Esterházy D, Stützer I, Wang H, Rechsteiner MP, Beauchamp J, Döbeli H, et al. (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.
  11. ^ *Guan D, Sun S, Song L, Zhao P, Nie Y, Huang X, et al. (Mar 2024). "Taking a color photo: A homozygous 25-bp deletion in Bace2 may cause brown-and-white coat color in giant pandas". Proceedings of the National Academy of Sciences of the United States of America. 121 (11): e2317430121. Bibcode:2024PNAS..12117430G. doi:10.1073/pnas.2317430121. PMC 10945837. PMID 38437540.
  12. ^ 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): 183–187. Bibcode:2002FEBSL.524..183H. doi:10.1016/S0014-5793(02)03052-1. PMID 12135764. S2CID 42042430.

Further reading

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