BACE2_RAT
ID BACE2_RAT Reviewed; 514 AA.
AC Q6IE75; B2GVB0;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Beta-secretase 2;
DE EC=3.4.23.45 {ECO:0000250|UniProtKB:Q9Y5Z0};
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [2]
RP IDENTIFICATION.
RC STRAIN=Sprague-Dawley;
RX PubMed=15060002; DOI=10.1101/gr.1946304;
RA Puente X.S., Lopez-Otin C.;
RT "A genomic analysis of rat proteases and protease inhibitors.";
RL Genome Res. 14:609-622(2004).
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|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};
CC -!- SUBUNIT: Monomer. Interacts ith RTN3 and RTN4.
CC {ECO:0000250|UniProtKB:Q9Y5Z0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9Y5Z0};
CC Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q9Y5Z0}. Endoplasmic reticulum {ECO:0000250}.
CC Endosome {ECO:0000250}.
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; BC166597; AAI66597.1; -; mRNA.
DR EMBL; BN000318; CAE48373.1; -; mRNA.
DR RefSeq; NP_001002802.1; NM_001002802.1.
DR AlphaFoldDB; Q6IE75; -.
DR SMR; Q6IE75; -.
DR STRING; 10116.ENSRNOP00000002679; -.
DR BindingDB; Q6IE75; -.
DR ChEMBL; CHEMBL2331066; -.
DR MEROPS; A01.041; -.
DR GlyGen; Q6IE75; 2 sites.
DR PhosphoSitePlus; Q6IE75; -.
DR PaxDb; Q6IE75; -.
DR PRIDE; Q6IE75; -.
DR Ensembl; ENSRNOT00000002679; ENSRNOP00000002679; ENSRNOG00000001953.
DR GeneID; 288227; -.
DR KEGG; rno:288227; -.
DR UCSC; RGD:1303241; rat.
DR CTD; 25825; -.
DR RGD; 1303241; Bace2.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000159548; -.
DR HOGENOM; CLU_039009_0_0_1; -.
DR InParanoid; Q6IE75; -.
DR OMA; PLRIYPG; -.
DR OrthoDB; 753343at2759; -.
DR PhylomeDB; Q6IE75; -.
DR TreeFam; TF329595; -.
DR PRO; PR:Q6IE75; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001953; Expressed in stomach and 19 other tissues.
DR Genevisible; Q6IE75; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031045; C:dense core granule; IDA:RGD.
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; ISS: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; ISO:RGD.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IBA:GO_Central.
DR GO; GO:0048143; P:astrocyte activation; IEP:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
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; ISO:RGD.
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 2: Evidence at transcript 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..20
FT /evidence="ECO:0000255"
FT PROPEP 21..62
FT /evidence="ECO:0000250"
FT /id="PRO_0000383648"
FT CHAIN 63..514
FT /note="Beta-secretase 2"
FT /id="PRO_0000383649"
FT TOPO_DOM 21..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 188
FT /note="K -> R (in Ref. 1; AAI66597)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 55858 MW; 70D31A970E2A0CDD CRC64;
MGALLRALLL PLLAQWLLRA VPVLAPAPFT LPLQVAGAAN HRASTVPGLG TPELPRADGL
ALALEPARAT ANFLAMVDNL QGDSGRGYYL EMLIGTPPQK VRILVDTGSS NFAVAGAPHS
YIDTYFDSES SSTYHSKGFE VTVKYTQGSW TGFVGEDLVT IPKGFNSSFL VNIATIFESE
NFFLPGIKWN GILGLAYAAL AKPSSSLETF FDSLVAQAKI PDIFSMQMCG AGLPVAGSGT
NGGSLVLGGI EPSLYKGDIW YTPIKEEWYY QIEILKLEIG GQSLNLDCRE YNADKAIVDS
GTTLLRLPQK VFDAVVEAVA RTSLIPEFSD GFWTGAQLAC WTNSETPWAY FPKISIYLRD
ENASRSFRIT ILPQLYIQPM MGAGFNYECY RFGISSSTNA LVIGATVMEG FYVVFDRAQR
RVGFAVSPCA EIAGTTVSEI SGPFSTEDIA SNCVPAQALN EPILWIVSYA LMSVCGAILL
VLILLLLFPL HCRHAPRDPE VVNDESSLVR HRWK
