Protein:BACE2 |
Protein Summary |
 Gene summary |
| Gene name: BACE2 | ASpdb.0 ID: 25825 | Gene | Gene symbol | BACE2 | Gene ID | 25825 |
| Gene name | beta-secretase 2 |
| Synonyms | AEPLC|ALP56|ASP1|ASP21|BAE2|CDA13|CEAP1|DRAP |
| Cytomap | 21q22.2-q22.3 |
| Type of gene | protein-coding |
| Description | beta-secretase 256 kDa aspartic-like proteaseDown syndrome region aspartic proteaseSLCO3A1/BACE2 fusionaspartyl protease 1beta-site APP-cleaving enzyme 2beta-site amyloid beta A4 precursor protein-cleaving enzyme 2memapsin-1membrane-associated asp |
| Modification date | 20240403 |
| UniProtAcc | Q9Y5Z0 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | BACE2 | GO:0004190 | aspartic-type endopeptidase activity | 10591213 |
| Gene | BACE2 | GO:0005794 | Golgi apparatus | 11423558 |
| Gene | BACE2 | GO:0005886 | plasma membrane | 21907142 |
| Gene | BACE2 | GO:0006509 | membrane protein ectodomain proteolysis | 10591213 |
| Gene | BACE2 | GO:0016485 | protein processing | 23754390 |
| Gene | BACE2 | GO:0033162 | melanosome membrane | 23754390 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q9Y5Z0-1 | Q9Y5Z0-1_6jsz_A.pdb | 6JSZ | X-ray | 1.53 | A | 75 | 460 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q9Y5Z0 | BACE2 | Q9Y5Z0-1 | Q9Y5Z0-2 | 518 | 468 | 329 | 378 | Deletion | none | none | 328 | 328 |
| Q9Y5Z0 | BACE2 | Q9Y5Z0-1 | Q9Y5Z0-3 | 518 | 396 | 379 | 396 | Substitution | LYIQPMMGAGLNYECYRF | KLQVLQCLKFPGLSQQRM | 379 | 396 |
| Q9Y5Z0 | BACE2 | Q9Y5Z0-1 | Q9Y5Z0-3 | 518 | 396 | 397 | 518 | Deletion | none | none | 396 | 396 |
| Q9Y5Z0 | BACE2 | Q9Y5Z0-1 | Q9Y5Z0-4 | 518 | 439 | 1 | 79 | Deletion | none | none | 0 | 0 |
| Q9Y5Z0 | BACE2 | Q9Y5Z0-1 | Q9Y5Z0-5 | 518 | 423 | 1 | 95 | Deletion | none | none | 0 | 0 |
| Multiple sequence alignment of our canonical and alternatively spliced BACE2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of BACE2 |
| UniProt-id | ENSG | ENST | ENSP |
| Q9Y5Z0-1 | ENSG00000182240.16 | ENST00000330333.11 | ENSP00000332979.6 |
| Q9Y5Z0-2 | ENSG00000182240.16 | ENST00000347667.5 | ENSP00000327528.4 |
| Q9Y5Z0-3 | ENSG00000182240.16 | ENST00000328735.10 | ENSP00000333854.6 |
| UniProt-id | NM ID | NP ID |
| Q9Y5Z0-1 | NM_012105.4 | NP_036237.2 |
| Q9Y5Z0-2 | NM_138991.2 | NP_620476.1 |
| Q9Y5Z0-3 | NM_138992.2 | NP_620477.1 |
| Amino acid sequences of our canonical and alternatively spliced BACE2 |
| accession_id | Protein sequence |
| Q9Y5Z0-1 | MGALARALLLPLLAQWLLRAAPELAPAPFTLPLRVAAATNRVVAPTPGPGTPAERHADGLALALEPALASPAGAANFLAMVDNLQGDSGR GYYLEMLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKGFNTSFLVNIATI FESENFFLPGIKWNGILGLAYATLAKPSSSLETFFDSLVTQANIPNVFSMQMCGAGLPVAGSGTNGGSLVLGGIEPSLYKGDIWYTPIKE EWYYQIEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFDAVVEAVARASLIPEFSDGFWTGSQLACWTNSETPWSYFPKISI YLRDENSSRSFRITILPQLYIQPMMGAGLNYECYRFGISPSTNALVIGATVMEGFYVIFDRAQKRVGFAASPCAEIAGAAVSEISGPFST |
| Q9Y5Z0-2 | MGALARALLLPLLAQWLLRAAPELAPAPFTLPLRVAAATNRVVAPTPGPGTPAERHADGLALALEPALASPAGAANFLAMVDNLQGDSGR GYYLEMLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKGFNTSFLVNIATI FESENFFLPGIKWNGILGLAYATLAKPSSSLETFFDSLVTQANIPNVFSMQMCGAGLPVAGSGTNGGSLVLGGIEPSLYKGDIWYTPIKE EWYYQIEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFDAVVEAVARASLLYIQPMMGAGLNYECYRFGISPSTNALVIGAT VMEGFYVIFDRAQKRVGFAASPCAEIAGAAVSEISGPFSTEDVASNCVPAQSLSEPILWIVSYALMSVCGAILLVLIVLLLLPFRCQRRP |
| Q9Y5Z0-3 | MGALARALLLPLLAQWLLRAAPELAPAPFTLPLRVAAATNRVVAPTPGPGTPAERHADGLALALEPALASPAGAANFLAMVDNLQGDSGR GYYLEMLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKGFNTSFLVNIATI FESENFFLPGIKWNGILGLAYATLAKPSSSLETFFDSLVTQANIPNVFSMQMCGAGLPVAGSGTNGGSLVLGGIEPSLYKGDIWYTPIKE EWYYQIEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFDAVVEAVARASLIPEFSDGFWTGSQLACWTNSETPWSYFPKISI |
| Q9Y5Z0-4 | MVDNLQGDSGRGYYLEMLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKGF NTSFLVNIATIFESENFFLPGIKWNGILGLAYATLAKPSSSLETFFDSLVTQANIPNVFSMQMCGAGLPVAGSGTNGGSLVLGGIEPSLY KGDIWYTPIKEEWYYQIEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFDAVVEAVARASLIPEFSDGFWTGSQLACWTNSE TPWSYFPKISIYLRDENSSRSFRITILPQLYIQPMMGAGLNYECYRFGISPSTNALVIGATVMEGFYVIFDRAQKRVGFAASPCAEIAGA |
| Q9Y5Z0-5 | MLIGTPPQKLQILVDTGSSNFAVAGTPHSYIDTYFDTERSSTYRSKGFDVTVKYTQGSWTGFVGEDLVTIPKGFNTSFLVNIATIFESEN FFLPGIKWNGILGLAYATLAKPSSSLETFFDSLVTQANIPNVFSMQMCGAGLPVAGSGTNGGSLVLGGIEPSLYKGDIWYTPIKEEWYYQ IEILKLEIGGQSLNLDCREYNADKAIVDSGTTLLRLPQKVFDAVVEAVARASLIPEFSDGFWTGSQLACWTNSETPWSYFPKISIYLRDE NSSRSFRITILPQLYIQPMMGAGLNYECYRFGISPSTNALVIGATVMEGFYVIFDRAQKRVGFAASPCAEIAGAAVSEISGPFSTEDVAS |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| BACE2 (go to UniProt):Q9Y5Z0 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q9Y5Z0 | Topological domain | 21 | 473 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=329;End=378 |
| Q9Y5Z0 | Topological domain | 21 | 473 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=379;End=396 |
| Q9Y5Z0 | Topological domain | 21 | 473 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=397;End=518 |
| Q9Y5Z0 | Topological domain | 21 | 473 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=79 |
| Q9Y5Z0 | Topological domain | 21 | 473 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=95 |
| Q9Y5Z0 | Transmembrane | 474 | 494 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=397;End=518 |
| Q9Y5Z0 | Topological domain | 495 | 518 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=397;End=518 |
| Q9Y5Z0 | Domain | 92 | 429 | Note=Peptidase A1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01103 | Type=Deletion;Start=329;End=378 |
| Q9Y5Z0 | Domain | 92 | 429 | Note=Peptidase A1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01103 | Type=Substitution;Start=379;End=396 |
| Q9Y5Z0 | Domain | 92 | 429 | Note=Peptidase A1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01103 | Type=Deletion;Start=397;End=518 |
| Q9Y5Z0 | Domain | 92 | 429 | Note=Peptidase A1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01103 | Type=Deletion;Start=1;End=95 |
Gene Isoform Structures and Expression Levels for BACE2 |
| Gene structures of our canonical and alternative spliced genes of BACE2 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of Q9Y5Z0-1 |
| 3D view using mol* of Q9Y5Z0-2 |
| 3D view using mol* of Q9Y5Z0-3 |
| 3D view using mol* of Q9Y5Z0-4 |
| 3D view using mol* of Q9Y5Z0-5 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of Q9Y5Z0-1 |
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| pLDDT distribution across the protein length of Q9Y5Z0-2 |
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| pLDDT distribution across the protein length of Q9Y5Z0-3 |
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| pLDDT distribution across the protein length of Q9Y5Z0-4 |
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| pLDDT distribution across the protein length of Q9Y5Z0-5 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q9Y5Z0-1 |
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| Ramachandran plot of Q9Y5Z0-2 |
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| Ramachandran plot of Q9Y5Z0-5 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q9Y5Z0-1 | 1.052 | 199 | 1.052 | 574.525 | 0.456 | 0.775 | 1.007 | 0.76 | 1.084 | 0.701 | 0.732 | 89,90,91,108,110,112,113,114,115,147,148,149,150,1 51,185,186,188,191,193,196,204,205,206,239,240,273 ,299,301,303,305,306,307,308,310,395,399,401,402,4 03,404,406 |
| Q9Y5Z0-2 | 1.091 | 287 | 1.164 | 654.444 | 0.547 | 0.717 | 0.869 | 1.308 | 0.632 | 2.071 | 1.594 | 25,26,27,28,29,30,31,32,33,35,235,264,265,266,281, 283,284,285,309,311,319,323,326,327,329,330,346,34 7,348,357,360,361,363,364,365,378,391,392,393,394, 395,396,397,398 |
| Q9Y5Z0-3 | 1.087 | 144 | 1.128 | 579.327 | 0.596 | 0.769 | 0.888 | 0.759 | 0.837 | 0.907 | 1.451 | 31,88,91,92,150,232,276,278,281,295,297,298,299,30 0,301,302,303,304,306,307,308,309,310,311,312,315, 360,362,373,379,380,381 |
| Q9Y5Z0-4 | 1.054 | 255 | 1.026 | 632.835 | 0.416 | 0.779 | 1.033 | 0.593 | 1.17 | 0.507 | 0.79 | 8,9,10,11,12,29,31,33,34,35,36,68,69,70,71,72,106, 107,109,110,111,112,114,117,125,126,127,155,157,15 8,159,194,220,222,224,225,226,227,228,229,231,300, 303,304,305,306,316,322,323,324,325,327,330,331,33 4 |
| Q9Y5Z0-5 | 1.008 | 348 | 1.021 | 1329.125 | 0.6 | 0.71 | 0.892 | 0.465 | 1.059 | 0.439 | 1.095 | 1,11,12,13,14,15,17,18,19,20,52,53,54,55,56,70,71, 72,73,91,93,98,101,102,109,110,111,135,136,137,138 ,139,140,141,142,143,144,145,146,147,148,149,150,1 51,152,153,154,155,156,178,203,204,206,208,209,210 ,211,212,213,215,257,283,284,287,288,289,290,291,2 92,293,296,297,298,300,306,307,308,309,311,314,315 ,318,341,342 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q9Y5Z0-1_Q9Y5Z0-1_6jsz_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q9Y5Z0-1_6jsz_A_Q9Y5Z0-2.pdb |
| 3D view using mol* of Q9Y5Z0-1_6jsz_A_Q9Y5Z0-3.pdb |
| 3D view using mol* of Q9Y5Z0-1_6jsz_A_Q9Y5Z0-4.pdb |
| 3D view using mol* of Q9Y5Z0-1_6jsz_A_Q9Y5Z0-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q9Y5Z0-1_Q9Y5Z0-2.pdb |
| 3D view using mol* of Q9Y5Z0-1_Q9Y5Z0-3.pdb |
| 3D view using mol* of Q9Y5Z0-1_Q9Y5Z0-4.pdb |
| 3D view using mol* of Q9Y5Z0-1_Q9Y5Z0-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q9Y5Z0-1_vs_Q9Y5Z0-2.png |
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| ./stats/secondary_structure/figure/Q9Y5Z0-1_vs_Q9Y5Z0-3.png |
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| ./stats/secondary_structure/figure/Q9Y5Z0-1_vs_Q9Y5Z0-4.png |
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| ./stats/secondary_structure/figure/Q9Y5Z0-1_vs_Q9Y5Z0-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q9Y5Z0-1_vs_Q9Y5Z0-2.png |
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| ./stats/relative_asa/Q9Y5Z0-1_vs_Q9Y5Z0-3.png |
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| ./stats/relative_asa/Q9Y5Z0-1_vs_Q9Y5Z0-4.png |
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| ./stats/relative_asa/Q9Y5Z0-1_vs_Q9Y5Z0-5.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to BACE2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to BACE2 |
| Previous studies relating to the alternative splicing of BACE2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| BACE2 | 10965118 | A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase. | Down syndrome individuals develop abnormalities of most organs, including all the pathological and neurochemical features of Alzheimer's disease, by the early age of 30 yr. Here, we report the isolation and characterization of BACE2, a gene mapping on human chromosome 21q22.3, which is highly similar to a transmembrane aspartyl protease, BACE (for beta-site APP-cleaving enzyme), which is able to catalyze the beta-secretase cleavage of Alzheimer's amyloid precursor protein (APP). BACE2 is expressed in a wide variety of organs and tissues, with several transcripts due to alternative splicing and the use of two polyadenylation signals. The BACE2 gene product is a 518 amino acid protein with the signature of an aspartic protease, a 20-residue signal peptide, and two putative N-glycosylation sites. In addition, and similarly to BACE, BACE2 differs from the other members of the human aspartic protease family in the number and distribution of putative disulfide bonds and in the presence of an extended C-terminal region which contains a predicted transmembrane segment. BACE2 could be involved in the Alzheimer-like neuropathology of Down syndrome, as well as in Alzheimer's disease linked to chromosome 21 but not showing mutations in APP. | D000544 | Alzheimer Disease |
Clinically important variants in BACE2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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