BACE2 (beta-site APP-cleaving enzyme 2, memapsin-1) is a type I transmembrane aspartic protease of the pepsin family, the paralog of the Alzheimer beta-secretase BACE1. It traffics through the Golgi and endosomes to the plasma membrane and early melanosomes. In melanocytes it cleaves PMEL in its juxtamembrane domain, releasing the luminal fragment that forms the amyloid matrix of melanosomes; Bace2-null mice have coat-color defects. In pancreatic beta cells it is the sheddase of TMEM27/CLTRN, and loss of Bace2 activity increases beta-cell mass and improves glucose control. In cells it cleaves APP mainly within the amyloid-beta region near the alpha site, which limits amyloid-beta production, and in vitro it degrades amyloid-beta efficiently. In lymphatic endothelial cells it sheds VEGFR3, modulating lymphangiogenic signalling. It matures by autocatalytic removal of its prodomain, and it can also cleave IAPP in vitro.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004190 aspartic-type endopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Aspartic-type endopeptidase activity (IBA). BACE2 is a membrane-anchored aspartic protease (pepsin family, EC 3.4.23.45) with two catalytic aspartates. Purified BACE2 autoactivates and cleaves APP peptides in vitro. In cells it sheds TMEM27/CLTRN, PMEL and APP. Core function. Reason: [PMID:11423558 "Herein we show that purified BACE2 can be autoactivated in vitro."] [PMID:11423558 "Purified BACE2 cleaves human amyloid precursor protein (APP) sequences at the beta-secretase site, and near the alpha-secretase site, mainly at A beta-Phe(20)--Ala(21) and also at A beta-Phe(19)--Phe(20)."] [file:human/BACE2/BACE2-uniprot.txt "CC precursor protein.; EC=3.4.23.45;"] [file:human/BACE2/BACE2-uniprot.txt "FT ACT_SITE 110"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002492112 SUPPORTS TRANSFER BACE/pepsin-family node with BACE1 (P56817) and rodent orthologs. Membrane-anchored aspartic protease activity, secretory-pathway localization and ectodomain shedding are conserved in BACE2. Supporting Evidence: PMID:11423558 Herein we show that purified BACE2 can be autoactivated in vitro. PMID:11423558 Purified BACE2 cleaves human amyloid precursor protein (APP) sequences at the beta-secretase site, and near the alpha-secretase site, mainly at A beta-Phe(20)--Ala(21) and also at A beta-Phe(19)--Phe(20). file:human/BACE2/BACE2-uniprot.txt CC precursor protein.; EC=3.4.23.45; file:human/BACE2/BACE2-uniprot.txt FT ACT_SITE 110 |
| GO:0004190 aspartic-type endopeptidase activity | IDA PMID:10591213 Membrane-anchored aspartyl protease with Alzheimer's disease... | ACCEPT | Summary: Aspartic-type endopeptidase activity (IDA). BACE2 is a membrane-anchored aspartic protease (pepsin family, EC 3.4.23.45) with two catalytic aspartates. Purified BACE2 autoactivates and cleaves APP peptides in vitro. In cells it sheds TMEM27/CLTRN, PMEL and APP. Core function. The cached abstract foregrounds Asp2 (BACE1). The curator's full-text reading, which UniProt also cites for BACE2 function, is relied on; the activity is independently established for purified BACE2. Reason: [PMID:11423558 "Herein we show that purified BACE2 can be autoactivated in vitro."] [PMID:11423558 "Purified BACE2 cleaves human amyloid precursor protein (APP) sequences at the beta-secretase site, and near the alpha-secretase site, mainly at A beta-Phe(20)--Ala(21) and also at A beta-Phe(19)--Phe(20)."] [file:human/BACE2/BACE2-uniprot.txt "CC precursor protein.; EC=3.4.23.45;"] [file:human/BACE2/BACE2-uniprot.txt "FT ACT_SITE 110"] Supporting Evidence: PMID:11423558 Herein we show that purified BACE2 can be autoactivated in vitro. PMID:11423558 Purified BACE2 cleaves human amyloid precursor protein (APP) sequences at the beta-secretase site, and near the alpha-secretase site, mainly at A beta-Phe(20)--Ala(21) and also at A beta-Phe(19)--Phe(20). file:human/BACE2/BACE2-uniprot.txt CC precursor protein.; EC=3.4.23.45; file:human/BACE2/BACE2-uniprot.txt FT ACT_SITE 110 |
| GO:0004190 aspartic-type endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Aspartic-type endopeptidase activity (IEA). BACE2 is a membrane-anchored aspartic protease (pepsin family, EC 3.4.23.45) with two catalytic aspartates. Purified BACE2 autoactivates and cleaves APP peptides in vitro. In cells it sheds TMEM27/CLTRN, PMEL and APP. Core function. Reason: [PMID:11423558 "Herein we show that purified BACE2 can be autoactivated in vitro."] [PMID:11423558 "Purified BACE2 cleaves human amyloid precursor protein (APP) sequences at the beta-secretase site, and near the alpha-secretase site, mainly at A beta-Phe(20)--Ala(21) and also at A beta-Phe(19)--Phe(20)."] [file:human/BACE2/BACE2-uniprot.txt "CC precursor protein.; EC=3.4.23.45;"] [file:human/BACE2/BACE2-uniprot.txt "FT ACT_SITE 110"] Supporting Evidence: PMID:11423558 Herein we show that purified BACE2 can be autoactivated in vitro. PMID:11423558 Purified BACE2 cleaves human amyloid precursor protein (APP) sequences at the beta-secretase site, and near the alpha-secretase site, mainly at A beta-Phe(20)--Ala(21) and also at A beta-Phe(19)--Phe(20). file:human/BACE2/BACE2-uniprot.txt CC precursor protein.; EC=3.4.23.45; file:human/BACE2/BACE2-uniprot.txt FT ACT_SITE 110 |
| GO:0005515 protein binding | IPI PMID:26840340 Identification of Human Islet Amyloid Polypeptide as a BACE2... | REMOVE | Summary: Protein binding (IPI) with IAPP, from the IAPP substrate study. IAPP is a BACE2 substrate in vitro. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:26840340 Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with STX11, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with APP, from a neurodegenerative-disease interactome screen. APP is a BACE2 substrate; this is captured by the endopeptidase and amyloid-beta rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with TPM3, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with KRT19, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with MATK, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with KLF3, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with ASAH1, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with LASP1, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with LGALS9C, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with CATSPERD, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with TMTC1, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with TCP10L, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with RFFL, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with LARP4B, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with RHNO1, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with TEX12, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with SCAPER, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with ARFGAP3, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) with DUSP10, from a neurodegenerative-disease interactome screen. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005768 endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Endosome (IBA). BACE2 localizes to endosomes and acts in endosomal precursors of melanosomes, where it processes PMEL. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC {ECO:0000269|PubMed:11423558}. Endoplasmic reticulum. Endosome."] [PMID:11423558 "BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain."] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002299446 SUPPORTS TRANSFER BACE/pepsin-family node with BACE1 (P56817) and rodent orthologs. Membrane-anchored aspartic protease activity, secretory-pathway localization and ectodomain shedding are conserved in BACE2. Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC {ECO:0000269|PubMed:11423558}. Endoplasmic reticulum. Endosome. PMID:11423558 BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain. PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0005768 endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Endosome (IEA). BACE2 localizes to endosomes and acts in endosomal precursors of melanosomes, where it processes PMEL. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC {ECO:0000269|PubMed:11423558}. Endoplasmic reticulum. Endosome."] [PMID:11423558 "BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain."] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC {ECO:0000269|PubMed:11423558}. Endoplasmic reticulum. Endosome. PMID:11423558 BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain. PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Endoplasmic reticulum (IEA). A biosynthetic transit compartment. Kept as non-core. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC {ECO:0000269|PubMed:11423558}. Endoplasmic reticulum. Endosome."] [PMID:11423558 "BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain."] ORGANELLES check (2026-11-04, ER batch 1). The row maps UniProt SL-0095; in the UniProt line the PubMed:11423558 tag belongs to the preceding Golgi item and the "Endoplasmic reticulum" item carries no evidence tag of its own, but the same paper's abstract reports an ER pool directly. BACE2 is a type I membrane protease (signal peptide 1-20, propeptide 21-62, lumenal domain 21-473, TM 474-494) with no ER-retention motif and no ER-resident function; its substrates are cleaved in endosomes/melanosomes and at the cell surface. The ER pool is the real but transient biosynthetic (pro-enzyme) pool seen in a multi-compartment imaging study, so the organelle claim holds as a minor location and the row stays KEEP_AS_NON_CORE rather than MARK_AS_OVER_ANNOTATED. No NEW ER membrane row: topology says any ER pool is membrane-inserted, but the only ER-specific line is transit, which this policy does not treat as residence, so the annotation stays at the root. Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC {ECO:0000269|PubMed:11423558}. Endoplasmic reticulum. Endosome. file:human/BACE2/BACE2-uniprot.txt FT TRANSMEM 474..494 PMID:11423558 BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain. |
| GO:0005794 Golgi apparatus | IDA PMID:11423558 BACE2 functions as an alternative alpha-secretase in cells. | ACCEPT | Summary: Golgi apparatus (IDA). BACE2 is detected in the Golgi apparatus. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus"] [PMID:11423558 "BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus PMID:11423558 BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | ACCEPT | Summary: Golgi apparatus (IEA). BACE2 is detected in the Golgi apparatus. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus"] [PMID:11423558 "BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus PMID:11423558 BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain. |
| GO:0005802 trans-Golgi network | IBA GO_REF:0000033 | ACCEPT | Summary: Trans-Golgi network (IBA). BACE2 localizes to the ER, Golgi, trans-Golgi network, endosomes and plasma membrane. The TGN is on the sorting route of BACE-family proteases. Accepted. Reason: [PMID:11423558 "BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002299446 SUPPORTS TRANSFER BACE/pepsin-family node with BACE1 (P56817) and rodent orthologs. Membrane-anchored aspartic protease activity, secretory-pathway localization and ectodomain shedding are conserved in BACE2. Supporting Evidence: PMID:11423558 BACE2 localizes in the endoplasmic reticulum, Golgi, trans-Golgi network, endosomes, and plasma membrane, and its cellular localization patterns depend on the presence of its transmembrane domain. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane (IBA). BACE2 is a single-pass type I membrane protein at the plasma membrane, where it sheds TMEM27 in beta cells. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142};"] [file:human/BACE2/BACE2-uniprot.txt "FT TRANSMEM 474..494"] [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002299446 SUPPORTS TRANSFER BACE/pepsin-family node with BACE1 (P56817) and rodent orthologs. Membrane-anchored aspartic protease activity, secretory-pathway localization and ectodomain shedding are conserved in BACE2. Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142}; file:human/BACE2/BACE2-uniprot.txt FT TRANSMEM 474..494 PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. |
| GO:0005886 plasma membrane | IDA PMID:21907142 Bace2 is a Ξ² cell-enriched protease that regulates pancreati... | ACCEPT | Summary: Plasma membrane (IDA). BACE2 is a single-pass type I membrane protein at the plasma membrane, where it sheds TMEM27 in beta cells. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142};"] [file:human/BACE2/BACE2-uniprot.txt "FT TRANSMEM 474..494"] [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142}; file:human/BACE2/BACE2-uniprot.txt FT TRANSMEM 474..494 PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane (IEA). BACE2 is a single-pass type I membrane protein at the plasma membrane, where it sheds TMEM27 in beta cells. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142};"] [file:human/BACE2/BACE2-uniprot.txt "FT TRANSMEM 474..494"] [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142}; file:human/BACE2/BACE2-uniprot.txt FT TRANSMEM 474..494 PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: Proteolysis (IEA). Proteolysis; a correct but broad parent of the shedding and processing rows. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC -!- FUNCTION: Responsible for the proteolytic processing of the amyloid"] [PMID:10749877 "BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC -!- FUNCTION: Responsible for the proteolytic processing of the amyloid PMID:10749877 BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family. |
| GO:0006508 proteolysis | NAS PMID:10749877 Expression analysis of BACE2 in brain and peripheral tissues... | ACCEPT | Summary: Proteolysis (NAS). Proteolysis; a correct but broad parent of the shedding and processing rows. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC -!- FUNCTION: Responsible for the proteolytic processing of the amyloid"] [PMID:10749877 "BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC -!- FUNCTION: Responsible for the proteolytic processing of the amyloid PMID:10749877 BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family. |
| GO:0006509 membrane protein ectodomain proteolysis | IBA GO_REF:0000033 | ACCEPT | Summary: Membrane protein ectodomain proteolysis (IBA). BACE2 sheds the ectodomains of type I membrane proteins. It releases the TMEM27/CLTRN ectodomain in murine and human beta cells, and it cleaves PMEL in the juxtamembrane domain to release the amyloidogenic luminal fragment. Core process. Reason: [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002299446 SUPPORTS TRANSFER BACE/pepsin-family node with BACE1 (P56817) and rodent orthologs. Membrane-anchored aspartic protease activity, secretory-pathway localization and ectodomain shedding are conserved in BACE2. Supporting Evidence: PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:10591213 Membrane-anchored aspartyl protease with Alzheimer's disease... | ACCEPT | Summary: Membrane protein ectodomain proteolysis (IDA). BACE2 sheds the ectodomains of type I membrane proteins. It releases the TMEM27/CLTRN ectodomain in murine and human beta cells, and it cleaves PMEL in the juxtamembrane domain to release the amyloidogenic luminal fragment. Core process. The cached abstract foregrounds Asp2 (BACE1). The curator's full-text reading, which UniProt also cites for BACE2 function, is relied on; the activity is independently established for purified BACE2. Reason: [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Supporting Evidence: PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0006509 membrane protein ectodomain proteolysis | IEA GO_REF:0000117 | ACCEPT | Summary: Membrane protein ectodomain proteolysis (IEA). BACE2 sheds the ectodomains of type I membrane proteins. It releases the TMEM27/CLTRN ectodomain in murine and human beta cells, and it cleaves PMEL in the juxtamembrane domain to release the amyloidogenic luminal fragment. Core process. Reason: [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Supporting Evidence: PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:21907142 Bace2 is a Ξ² cell-enriched protease that regulates pancreati... | ACCEPT | Summary: Membrane protein ectodomain proteolysis (IMP). BACE2 sheds the ectodomains of type I membrane proteins. It releases the TMEM27/CLTRN ectodomain in murine and human beta cells, and it cleaves PMEL in the juxtamembrane domain to release the amyloidogenic luminal fragment. Core process. Reason: [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Supporting Evidence: PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane (IEA). A C-terminal transmembrane anchor; membrane-bound. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "FT TRANSMEM 474..494"] [PMID:10749877 "BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt FT TRANSMEM 474..494 PMID:10749877 BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family. |
| GO:0016020 membrane | NAS PMID:10749877 Expression analysis of BACE2 in brain and peripheral tissues... | ACCEPT | Summary: Membrane (NAS). A C-terminal transmembrane anchor; membrane-bound. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "FT TRANSMEM 474..494"] [PMID:10749877 "BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt FT TRANSMEM 474..494 PMID:10749877 BACE and BACE2 are unique among aspartic proteases in that they possess a carboxyl-terminal extension with a predicted transmembrane region and together they define a new family. |
| GO:0016485 protein processing | IBA GO_REF:0000033 | ACCEPT | Summary: Protein processing (IBA). BACE2 processes PMEL in melanocytes and APP/IAPP peptides. Accepted. Reason: [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] [file:human/BACE2/BACE2-uniprot.txt "CC Involved in the proteolytic shedding of PMEL at early stages of"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002492112 SUPPORTS TRANSFER BACE/pepsin-family node with BACE1 (P56817) and rodent orthologs. Membrane-anchored aspartic protease activity, secretory-pathway localization and ectodomain shedding are conserved in BACE2. Supporting Evidence: PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. file:human/BACE2/BACE2-uniprot.txt CC Involved in the proteolytic shedding of PMEL at early stages of |
| GO:0016485 protein processing | IDA PMID:23754390 BACE2 processes PMEL to form the melanosome amyloid matrix i... | ACCEPT | Summary: Protein processing (IDA). BACE2 processes PMEL in melanocytes and APP/IAPP peptides. Accepted. Reason: [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] [file:human/BACE2/BACE2-uniprot.txt "CC Involved in the proteolytic shedding of PMEL at early stages of"] Supporting Evidence: PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. file:human/BACE2/BACE2-uniprot.txt CC Involved in the proteolytic shedding of PMEL at early stages of |
| GO:0016486 peptide hormone processing | NAS PMID:10749877 Expression analysis of BACE2 in brain and peripheral tissues... | MARK AS OVER ANNOTATED | Summary: Peptide hormone processing (NAS). The cited expression study reports BACE2 mRNA in pancreas and other peripheral tissues. Its abstract makes no peptide-hormone-processing claim. BACE2 can cleave the amyloidogenic hormone IAPP in vitro, but it is not established as a prohormone convertase. Over-annotation. Reason: [PMID:10749877 "Northern analysis reveals that BACE2 mRNA is expressed at low levels in most human peripheral tissues and at higher levels in colon, kidney, pancreas, placenta, prostate, stomach, and trachea."] [PMID:26840340 "Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity."] Supporting Evidence: PMID:10749877 Northern analysis reveals that BACE2 mRNA is expressed at low levels in most human peripheral tissues and at higher levels in colon, kidney, pancreas, placenta, prostate, stomach, and trachea. PMID:26840340 Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. |
| GO:0032438 melanosome organization | IMP PMID:23754390 BACE2 processes PMEL to form the melanosome amyloid matrix i... | ACCEPT | Summary: Melanosome organization (IMP). Through PMEL processing, BACE2 is needed to form the amyloid matrix that drives melanosome morphogenesis. Bace2-null mice have coat-color defects. Accepted. Reason: [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] [PMID:23754390 "BACE2 is highly expressed in pigment cells and Bace2(-/-) but not Bace1(-/-) mice display coat color defects, implying a specific role for BACE2 during melanogenesis."] Supporting Evidence: PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. PMID:23754390 BACE2 is highly expressed in pigment cells and Bace2(-/-) but not Bace1(-/-) mice display coat color defects, implying a specific role for BACE2 during melanogenesis. |
| GO:0033162 melanosome membrane | IDA PMID:23754390 BACE2 processes PMEL to form the melanosome amyloid matrix i... | ACCEPT | Summary: Melanosome membrane (IDA). BACE2 colocalizes with PMEL in stage I and II melanosomes. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC Melanosome {ECO:0000269|PubMed:23754390}. Note=Colocalizes with PMEL in"] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC Melanosome {ECO:0000269|PubMed:23754390}. Note=Colocalizes with PMEL in PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0042470 melanosome | EXP PMID:23754390 BACE2 processes PMEL to form the melanosome amyloid matrix i... | ACCEPT | Summary: Melanosome (EXP). BACE2 localizes to early (stage I/II) melanosomes with PMEL. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC Melanosome {ECO:0000269|PubMed:23754390}. Note=Colocalizes with PMEL in"] [PMID:23754390 "By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis."] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC Melanosome {ECO:0000269|PubMed:23754390}. Note=Colocalizes with PMEL in PMID:23754390 By using biochemical and morphological analyses, combined with RNA silencing, pharmacologic inhibition, and BACE2 overexpression in a human melanocytic cell line, we show that BACE2 cleaves the integral membrane form of PMEL within the juxtamembrane domain, releasing the PMEL luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis. |
| GO:0042470 melanosome | IEA GO_REF:0000044 | ACCEPT | Summary: Melanosome (IEA). BACE2 localizes to early (stage I/II) melanosomes with PMEL. Accepted. Reason: [file:human/BACE2/BACE2-uniprot.txt "CC Melanosome {ECO:0000269|PubMed:23754390}. Note=Colocalizes with PMEL in"] Supporting Evidence: file:human/BACE2/BACE2-uniprot.txt CC Melanosome {ECO:0000269|PubMed:23754390}. Note=Colocalizes with PMEL in |
| GO:0042593 glucose homeostasis | IMP PMID:21907142 Bace2 is a Ξ² cell-enriched protease that regulates pancreati... | KEEP AS NON CORE | Summary: Glucose homeostasis (IMP). Mice lacking Bace2 activity, or treated with an inhibitor, have more beta-cell mass and better glucose control, because TMEM27 shedding is lost. A physiological consequence of the shedding activity; kept as non-core. Reason: [PMID:21907142 "Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented Ξ² cell mass and improved control of glucose homeostasis due to increased insulin levels."] [PMID:21907142 "Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells."] Supporting Evidence: PMID:21907142 Mice with functionally inactive Bace2 and insulin-resistant mice treated with a newly identified Bace2 inhibitor both display augmented Ξ² cell mass and improved control of glucose homeostasis due to increased insulin levels. PMID:21907142 Here we identified, through a siRNA screen, beta site amyloid precursor protein cleaving enzyme 2 (Bace2) as the sheddase of the proproliferative plasma membrane protein Tmem27 in murine and human Ξ² cells. |
| GO:0042985 negative regulation of amyloid precursor protein biosynthetic process | IMP PMID:12801932 Antagonistic effects of beta-site amyloid precursor protein-... | MODIFY | Summary: Negative regulation of amyloid precursor protein biosynthetic process (IMP). BACE2 knockdown increases beta-cleaved sAPP and Abeta secretion, because BACE2 cleaves within the Abeta domain near the alpha site. Purified BACE2 also degrades Abeta efficiently. That reduces Abeta formation; it does not regulate APP synthesis. The appropriate term is negative regulation of amyloid-beta formation. Reason: [PMID:12801932 "Selective inactivation of BACE2 by RNAi results in increased beta-cleaved secreted APP and A beta peptide secretion from cells."] [PMID:12801932 "Our observations of changes in APP metabolism and A beta are consistent with a role of BACE2 in suppressing A beta production in cells that co-express both enzymes."] [PMID:11423558 "Alternatively, in cells BACE2 has a limited effect on the beta-secretase site but efficiently cleaves the sequences near the alpha-secretase site."] [PMID:22986058 "However, in vitro, BACE2 was also found to be a particularly avid AΓDP, with a catalytic efficiency exceeding all known AΓDPs except insulin-degrading enzyme (IDE)."] Proposed replacements: negative regulation of amyloid-beta formation Supporting Evidence: PMID:12801932 Selective inactivation of BACE2 by RNAi results in increased beta-cleaved secreted APP and A beta peptide secretion from cells. PMID:12801932 Our observations of changes in APP metabolism and A beta are consistent with a role of BACE2 in suppressing A beta production in cells that co-express both enzymes. PMID:11423558 Alternatively, in cells BACE2 has a limited effect on the beta-secretase site but efficiently cleaves the sequences near the alpha-secretase site. PMID:22986058 However, in vitro, BACE2 was also found to be a particularly avid AΓDP, with a catalytic efficiency exceeding all known AΓDPs except insulin-degrading enzyme (IDE). |
| GO:0050435 amyloid-beta metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Amyloid-beta metabolic process (IBA). BACE2 cleaves APP within the Abeta region, reducing Abeta production. In vitro it is also an avid Abeta-degrading protease, second in catalytic efficiency only to IDE. BACE2 is expressed at low levels in brain, so this is kept as non-core relative to its PMEL, TMEM27 and VEGFR3 shedding roles. Reason: [PMID:11423558 "Alternatively, in cells BACE2 has a limited effect on the beta-secretase site but efficiently cleaves the sequences near the alpha-secretase site."] [PMID:12801932 "Our observations of changes in APP metabolism and A beta are consistent with a role of BACE2 in suppressing A beta production in cells that co-express both enzymes."] [PMID:22986058 "However, in vitro, BACE2 was also found to be a particularly avid AΓDP, with a catalytic efficiency exceeding all known AΓDPs except insulin-degrading enzyme (IDE)."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002299446 SUPPORTS TRANSFER BACE/pepsin-family node with BACE1 (P56817) and rodent orthologs. Membrane-anchored aspartic protease activity, secretory-pathway localization and ectodomain shedding are conserved in BACE2. Supporting Evidence: PMID:11423558 Alternatively, in cells BACE2 has a limited effect on the beta-secretase site but efficiently cleaves the sequences near the alpha-secretase site. PMID:12801932 Our observations of changes in APP metabolism and A beta are consistent with a role of BACE2 in suppressing A beta production in cells that co-express both enzymes. PMID:22986058 However, in vitro, BACE2 was also found to be a particularly avid AΓDP, with a catalytic efficiency exceeding all known AΓDPs except insulin-degrading enzyme (IDE). |
| GO:0016540 protein autoprocessing | IDA PMID:11316808 Prodomain processing of Asp1 (BACE2) is autocatalytic. | NEW | Summary: Protein autoprocessing (NEW, IDA). BACE2 removes its own prodomain by autocatalytic cleavage between Leu62 and Ala63. Mutating the catalytic Asp110 to Asn abolishes the cleavage, and purified BACE2 also autoactivates in vitro. BACE2 is the catalyst acting on itself, so it does the work of the process. ASPRV1 is a comparator protease reviewed with this term. Reason: [PMID:11316808 "Here we show that prodomain processing of Asp1 occurs between Leu(62) and Ala(63) and is autocatalytic."] [PMID:11316808 "Mutation of one of the conserved catalytic aspartic acid residues in the active site of Asp1 to asparagine (D110N) abolished this cleavage."] [PMID:11423558 "Herein we show that purified BACE2 can be autoactivated in vitro."] Supporting Evidence: PMID:11316808 Here we show that prodomain processing of Asp1 occurs between Leu(62) and Ala(63) and is autocatalytic. PMID:11316808 Mutation of one of the conserved catalytic aspartic acid residues in the active site of Asp1 to asparagine (D110N) abolished this cleavage. PMID:11423558 Herein we show that purified BACE2 can be autoactivated in vitro. |
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Experiment: Map the BACE2 substrate repertoire in beta cells and melanocytes by secretome/sheddome proteomics in BACE2-knockout versus inhibitor-treated cells.
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