Beta-secretase 2

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.

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
Gene location (Human)
Chr.Chromosome 21 (human)[1]
Band21q22.2-q22.3Start41,167,801 bp[1]
End41,282,530 bp[1]
RNA expression pattern
More reference expression data
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: 97.36 – 97.44 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Interactions

BACE2 has been shown to interact with GGA1[10] and GGA2.[10]

References
  1. GRCh38: Ensembl release 89: ENSG00000182240 - Ensembl, May 2017
  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.
  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.
  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.
  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. 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.

Further reading


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