BACE2_MOUSE
ID BACE2_MOUSE Reviewed; 514 AA.
AC Q9JL18; Q3TNS7; Q8C5E9; Q8C793; Q9R1P7;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Beta-secretase 2;
DE EC=3.4.23.45 {ECO:0000269|PubMed:21907142};
DE AltName: Full=Aspartyl protease 1;
DE Short=ASP1;
DE Short=Asp 1;
DE AltName: Full=Beta-site amyloid precursor protein cleaving enzyme 2;
DE Short=Beta-site APP cleaving enzyme 2;
DE AltName: Full=Memapsin-1;
DE AltName: Full=Membrane-associated aspartic protease 1;
DE AltName: Full=Theta-secretase;
DE Flags: Precursor;
GN Name=Bace2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Choi D.K., Sugano S., Sakaki Y.;
RT "Molecular characterization of the mouse Asp1 gene, a homolog of the human
RT ASP1 (Down Syndrome region aspartyl protease).";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye, Heart, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 260-514.
RX PubMed=10683441; DOI=10.1016/s0014-5793(00)01192-3;
RA Acquati F., Accarino M.P., Nucci C., Fumagalli P., Jovine L.,
RA Ottolenghi S., Taramelli R.;
RT "The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of
RT the aspartic protease family, maps to the down critical region.";
RL FEBS Lett. 468:59-64(2000).
RN [6]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=21907142; DOI=10.1016/j.cmet.2011.06.018;
RA Esterhazy D., Stuetzer I., Wang H., Rechsteiner M.P., Beauchamp J.,
RA Doebeli H., Hilpert H., Matile H., Prummer M., Schmidt A., Lieske N.,
RA Boehm B., Marselli L., Bosco D., Kerr-Conte J., Aebersold R., Spinas G.A.,
RA Moch H., Migliorini C., Stoffel M.;
RT "Bace2 is a beta cell-enriched protease that regulates pancreatic beta cell
RT function and mass.";
RL Cell Metab. 14:365-377(2011).
CC -!- FUNCTION: Responsible for the proteolytic processing of the amyloid
CC precursor protein (APP). Cleaves APP, between residues 690 and 691,
CC leading to the generation and extracellular release of beta-cleaved
CC soluble APP, and a corresponding cell-associated C-terminal fragment
CC which is later released by gamma-secretase. It has also been shown that
CC it can cleave APP between residues 671 and 672 (By similarity).
CC Responsible also for the proteolytic processing of CLTRN in pancreatic
CC beta cells (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9Y5Z0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-
CC Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid
CC precursor protein.; EC=3.4.23.45;
CC Evidence={ECO:0000250|UniProtKB:Q9Y5Z0, ECO:0000269|PubMed:21907142};
CC -!- SUBUNIT: Monomer. Interacts ith RTN3 and RTN4.
CC {ECO:0000250|UniProtKB:Q9Y5Z0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142};
CC Single-pass type I membrane protein {ECO:0000250}. Golgi apparatus
CC {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Endosome
CC {ECO:0000250}. Cell surface {ECO:0000250}. Note=Colocalized with CLTRN.
CC {ECO:0000269|PubMed:21907142}.
CC -!- TISSUE SPECIFICITY: High expression in pancreatic islets. Expressed at
CC much lower levels in the pituitary, colon, and ovaries and is nearly
CC absent from all the other tissues. {ECO:0000269|PubMed:21907142}.
CC -!- PTM: Undergoes autoproteolytic cleavage.
CC {ECO:0000250|UniProtKB:Q9Y5Z0}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q9Y5Z0}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; AF216310; AAF36599.1; -; mRNA.
DR EMBL; AK052309; BAC34931.1; -; mRNA.
DR EMBL; AK078770; BAC37384.1; -; mRNA.
DR EMBL; AK165036; BAE38011.1; -; mRNA.
DR EMBL; CH466602; EDL03663.1; -; Genomic_DNA.
DR EMBL; BC120773; AAI20774.1; -; mRNA.
DR EMBL; BC131947; AAI31948.1; -; mRNA.
DR EMBL; AF051150; AAD45964.1; -; mRNA.
DR CCDS; CCDS28359.1; -.
DR RefSeq; NP_062390.3; NM_019517.5.
DR AlphaFoldDB; Q9JL18; -.
DR SMR; Q9JL18; -.
DR STRING; 10090.ENSMUSP00000043918; -.
DR BindingDB; Q9JL18; -.
DR ChEMBL; CHEMBL3638357; -.
DR MEROPS; A01.041; -.
DR GlyGen; Q9JL18; 2 sites.
DR iPTMnet; Q9JL18; -.
DR PhosphoSitePlus; Q9JL18; -.
DR MaxQB; Q9JL18; -.
DR PaxDb; Q9JL18; -.
DR PRIDE; Q9JL18; -.
DR ProteomicsDB; 277174; -.
DR DNASU; 56175; -.
DR GeneID; 56175; -.
DR KEGG; mmu:56175; -.
DR UCSC; uc008ade.2; mouse.
DR CTD; 25825; -.
DR MGI; MGI:1860440; Bace2.
DR eggNOG; KOG1339; Eukaryota.
DR InParanoid; Q9JL18; -.
DR OrthoDB; 753343at2759; -.
DR PhylomeDB; Q9JL18; -.
DR TreeFam; TF329595; -.
DR BRENDA; 3.4.23.45; 3474.
DR BioGRID-ORCS; 56175; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Bace2; mouse.
DR PRO; PR:Q9JL18; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9JL18; protein.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031045; C:dense core granule; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IBA:GO_Central.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IMP:MGI.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IBA:GO_Central.
DR GO; GO:0042593; P:glucose homeostasis; ISO:MGI.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:UniProtKB.
DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0140448; P:signaling receptor ligand precursor processing; IMP:MGI.
DR CDD; cd05473; beta_secretase_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR009119; BACE.
DR InterPro; IPR009121; BACE2.
DR InterPro; IPR033874; Memapsin-like.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47965; PTHR47965; 1.
DR PANTHER; PTHR47965:SF40; PTHR47965:SF40; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR01817; BACE2.
DR PRINTS; PR01815; BACEFAMILY.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW Aspartyl protease; Autocatalytic cleavage; Cell membrane; Disulfide bond;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Golgi apparatus; Hydrolase;
KW Membrane; Protease; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..62
FT /evidence="ECO:0000250"
FT /id="PRO_0000383646"
FT CHAIN 63..514
FT /note="Beta-secretase 2"
FT /id="PRO_0000383647"
FT TOPO_DOM 20..469
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 470..490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 491..514
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 88..425
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 106
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 229..429
FT /evidence="ECO:0000250"
FT DISULFID 288..453
FT /evidence="ECO:0000250"
FT DISULFID 340..389
FT /evidence="ECO:0000250"
FT CONFLICT 11
FT /note="L -> P (in Ref. 2; BAC34931/BAE38011/BAC37384)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="G -> R (in Ref. 2; BAC34931/BAE38011/BAC37384)"
FT /evidence="ECO:0000305"
FT CONFLICT 53
FT /note="E -> G (in Ref. 2; BAC37384)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="I -> T (in Ref. 2; BAC34931)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="L -> V (in Ref. 5; AAD45964)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 55800 MW; A70725F2C1DF5B47 CRC64;
MGALLRALLL LVLAQWLLSA VPALAPAPFT LPLQVAGATN HRASAVPGLG TPELPRADGL
ALALEPVRAT ANFLAMVDNL QGDSGRGYYL EMLIGTPPQK VQILVDTGSS NFAVAGAPHS
YIDTYFDSES SSTYHSKGFD VTVKYTQGSW TGFVGEDLVT IPKGFNSSFL VNIATIFESE
NFFLPGIKWN GILGLAYAAL AKPSSSLETF FDSLVAQAKI PDIFSMQMCG AGLPVAGSGT
NGGSLVLGGI EPSLYKGDIW YTPIKEEWYY QIEILKLEIG GQNLNLDCRE YNADKAIVDS
GTTLLRLPQK VFDAVVEAVA RTSLIPEFSD GFWTGAQLAC WTNSETPWAY FPKISIYLRD
ENASRSFRIT ILPQLYIQPM MGAGFNYECY RFGISSSTNA LVIGATVMEG FYVVFDRAQR
RVGFAVSPCA EIEGTTVSEI SGPFSTEDIA SNCVPAQALN EPILWIVSYA LMSVCGAILL
VLILLLLLPL HCRHAPRDPE VVNDESSLVR HRWK
