BACE2_HUMAN
ID BACE2_HUMAN Reviewed; 518 AA.
AC Q9Y5Z0; A8K7P1; Q5DIH8; Q8N2D4; Q9H2V8; Q9NZL1; Q9NZL2; Q9UJT6;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Beta-secretase 2;
DE EC=3.4.23.45 {ECO:0000269|PubMed:21907142};
DE AltName: Full=Aspartic-like protease 56 kDa;
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=Down region aspartic protease;
DE Short=DRAP;
DE AltName: Full=Memapsin-1;
DE AltName: Full=Membrane-associated aspartic protease 1;
DE AltName: Full=Theta-secretase;
DE Flags: Precursor;
GN Name=BACE2; Synonyms=AEPLC, ALP56, ASP21; ORFNames=CDA13, UNQ418/PRO852;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF N-TERMINUS,
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10591213; DOI=10.1038/990107;
RA Yan R., Bienkowski M.J., Shuck M.E., Miao H., Tory M.C., Pauley A.M.,
RA Brashier J.R., Stratman N.C., Mathews W.R., Buhl A.E., Carter D.B.,
RA Tomasselli A.G., Parodi L.A., Heinrikson R.L., Gurney M.E.;
RT "Membrane-anchored aspartyl protease with Alzheimer's disease beta-
RT secretase activity.";
RL Nature 402:533-537(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AUTOCATALYTIC CLEAVAGE, INDUCTION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF ASP-110 AND ASP-303.
RC TISSUE=Bone marrow;
RX PubMed=10838186; DOI=10.1016/s0925-4439(00)00014-4;
RA Xin H., Stephans J.C., Duan X., Harrowe G., Kim E., Grieshammer U.,
RA Kingsley C., Giese K.;
RT "Identification of a novel aspartic-like protease differentially expressed
RT in human breast cancer cell lines.";
RL Biochim. Biophys. Acta 1501:125-137(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
RX PubMed=10965118; DOI=10.1159/000015608;
RA Solans A., Estivill X., de La Luna S.;
RT "A new aspartyl protease on 21q22.3, BACE2, is highly similar to
RT Alzheimer's amyloid precursor protein beta-secretase.";
RL Cytogenet. Cell Genet. 89:177-184(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP GLYCOSYLATION.
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10749877; DOI=10.1074/jbc.m002688200;
RA Bennett B.D., Babu-Khan S., Loeloff R., Louis J.-C., Curran E., Citron M.,
RA Vassar R.;
RT "Expression analysis of BACE2 in brain and peripheral tissues.";
RL J. Biol. Chem. 275:20647-20651(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF N-TERMINUS,
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=11083922; DOI=10.1006/mcne.2000.0884;
RA Hussain I., Powell D.J., Howlett D.R., Chapman G.A., Gilmour L.,
RA Murdock P.R., Tew D.G., Meek T.D., Chapman C., Schneider K.,
RA Ratcliffe S.J., Tattersall D., Testa T.T., Southan C., Ryan D.M.,
RA Simmons D.L., Walsh F.S., Dingwall C., Christie G.;
RT "ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase
RT site.";
RL Mol. Cell. Neurosci. 16:609-619(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10677483; DOI=10.1073/pnas.97.4.1456;
RA Lin X., Koelsch G., Wu S., Downs D., Dashti A., Tang J.;
RT "Human aspartic protease memapsin 2 cleaves the beta-secretase site of
RT beta-amyloid precursor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:1456-1460(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Pheochromocytoma;
RA Li Y., Huang Q., Peng Y., Song H., Yu Y., Xu S., Ren S., Chen Z., Han Z.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Ovary, and Stomach;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-47, AND FUNCTION.
RX PubMed=15857888; DOI=10.1096/fj.04-3426com;
RA Sun X., Wang Y., Qing H., Christensen M.A., Liu Y., Zhou W., Tong Y.,
RA Xiao C., Huang Y., Zhang S., Liu X., Song W.;
RT "Distinct transcriptional regulation and function of the human BACE2 and
RT BACE1 genes.";
RL FASEB J. 19:739-749(2005).
RN [15]
RP PROTEIN SEQUENCE OF N-TERMINUS, AUTOCATALYTIC CLEAVAGE, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11423558; DOI=10.1074/jbc.m105583200;
RA Yan R., Munzner J.B., Shuck M.E., Bienkowski M.J.;
RT "BACE2 functions as an alternative alpha-secretase in cells.";
RL J. Biol. Chem. 276:34019-34027(2001).
RN [16]
RP PROTEIN SEQUENCE OF N-TERMINUS, AND FUNCTION.
RX PubMed=16816112; DOI=10.1096/fj.05-5632com;
RA Sun X., He G., Song W.;
RT "BACE2, as a novel APP theta-secretase, is not responsible for the
RT pathogenesis of Alzheimer's disease in Down syndrome.";
RL FASEB J. 20:1369-1376(2006).
RN [17]
RP PROTEIN SEQUENCE OF N-TERMINUS, X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF
RP 78-460, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=16305800; DOI=10.1016/j.jmb.2005.10.027;
RA Ostermann N., Eder J., Eidhoff U., Zink F., Hassiepen U., Worpenberg S.,
RA Maibaum J., Simic O., Hommel U., Gerhartz B.;
RT "Crystal structure of human BACE2 in complex with a hydroxyethylamine
RT transition-state inhibitor.";
RL J. Mol. Biol. 355:249-261(2006).
RN [18]
RP AUTOCATALYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-110.
RX PubMed=11316808; DOI=10.1074/jbc.m101069200;
RA Hussain I., Christie G., Schneider K., Moore S., Dingwall C.;
RT "Prodomain processing of Asp1 (BACE2) is autocatalytic.";
RL J. Biol. Chem. 276:23322-23328(2001).
RN [19]
RP INTERACTION WITH RTN3 AND RTN4.
RX PubMed=16965550; DOI=10.1111/j.1460-9568.2006.05005.x;
RA Murayama K.S., Kametani F., Saito S., Kume H., Akiyama H., Araki W.;
RT "Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability
RT to produce amyloid beta-protein.";
RL Eur. J. Neurosci. 24:1237-1244(2006).
RN [20]
RP SUBCELLULAR LOCATION, FUNCTION, 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. Responsible also for
CC the proteolytic processing of CLTRN in pancreatic beta cells
CC (PubMed:21907142). {ECO:0000269|PubMed:10591213,
CC ECO:0000269|PubMed:11083922, ECO:0000269|PubMed:11423558,
CC ECO:0000269|PubMed:15857888, ECO:0000269|PubMed:16816112,
CC ECO:0000269|PubMed:21907142}.
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:0000269|PubMed:11083922, ECO:0000269|PubMed:21907142};
CC -!- SUBUNIT: Monomer. Interacts ith RTN3 and RTN4.
CC {ECO:0000269|PubMed:16305800, ECO:0000269|PubMed:16965550}.
CC -!- INTERACTION:
CC Q9Y5Z0; P05067: APP; NbExp=3; IntAct=EBI-11282723, EBI-77613;
CC Q9Y5Z0; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-11282723, EBI-2875816;
CC Q9Y5Z0; Q13510-3: ASAH1; NbExp=3; IntAct=EBI-11282723, EBI-25917771;
CC Q9Y5Z0; Q86XM0: CATSPERD; NbExp=3; IntAct=EBI-11282723, EBI-10260328;
CC Q9Y5Z0; Q9Y6W6: DUSP10; NbExp=3; IntAct=EBI-11282723, EBI-3443946;
CC Q9Y5Z0; P10997: IAPP; NbExp=3; IntAct=EBI-11282723, EBI-8526679;
CC Q9Y5Z0; P57682: KLF3; NbExp=3; IntAct=EBI-11282723, EBI-8472267;
CC Q9Y5Z0; P08727: KRT19; NbExp=3; IntAct=EBI-11282723, EBI-742756;
CC Q9Y5Z0; Q92615: LARP4B; NbExp=3; IntAct=EBI-11282723, EBI-1052558;
CC Q9Y5Z0; Q14847-2: LASP1; NbExp=3; IntAct=EBI-11282723, EBI-9088686;
CC Q9Y5Z0; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-11282723, EBI-9088829;
CC Q9Y5Z0; P42679: MATK; NbExp=3; IntAct=EBI-11282723, EBI-751664;
CC Q9Y5Z0; Q8WZ73-3: RFFL; NbExp=3; IntAct=EBI-11282723, EBI-25839575;
CC Q9Y5Z0; Q9BSD3: RHNO1; NbExp=3; IntAct=EBI-11282723, EBI-9658624;
CC Q9Y5Z0; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-11282723, EBI-25837959;
CC Q9Y5Z0; O75558: STX11; NbExp=3; IntAct=EBI-11282723, EBI-714135;
CC Q9Y5Z0; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-11282723, EBI-3923210;
CC Q9Y5Z0; Q9BXU0: TEX12; NbExp=3; IntAct=EBI-11282723, EBI-12090309;
CC Q9Y5Z0; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-11282723, EBI-9089156;
CC Q9Y5Z0; P06753-2: TPM3; NbExp=3; IntAct=EBI-11282723, EBI-10977875;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21907142};
CC Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus
CC {ECO:0000269|PubMed:11423558}. Endoplasmic reticulum. Endosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Isoform A;
CC IsoId=Q9Y5Z0-1; Sequence=Displayed;
CC Name=2; Synonyms=Isoform C;
CC IsoId=Q9Y5Z0-2; Sequence=VSP_038025;
CC Name=3; Synonyms=Isoform B;
CC IsoId=Q9Y5Z0-3; Sequence=VSP_038026, VSP_038027;
CC Name=4;
CC IsoId=Q9Y5Z0-4; Sequence=VSP_038024;
CC Name=5;
CC IsoId=Q9Y5Z0-5; Sequence=VSP_038023;
CC -!- TISSUE SPECIFICITY: Brain. Present in neurons within the hippocampus,
CC frontal cortex and temporal cortex (at protein level). Expressed at low
CC levels in most peripheral tissues and at higher levels in colon,
CC kidney, pancreas, placenta, prostate, stomach and trachea. Expressed at
CC low levels in the brain. Found in spinal cord, medulla oblongata,
CC substantia nigra and locus coruleus. Expressed in the ductal epithelium
CC of both normal and malignant prostate. {ECO:0000269|PubMed:10591213,
CC ECO:0000269|PubMed:10677483, ECO:0000269|PubMed:10683441,
CC ECO:0000269|PubMed:10749877, ECO:0000269|PubMed:10838186,
CC ECO:0000269|PubMed:10965118, ECO:0000269|PubMed:11083922}.
CC -!- INDUCTION: Up-regulated in primary breast and colon tumors and liver
CC metastasis. {ECO:0000269|PubMed:10838186}.
CC -!- PTM: Undergoes autoproteolytic cleavage. {ECO:0000269|PubMed:11316808,
CC ECO:0000269|PubMed:11423558}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:10683441,
CC ECO:0000269|PubMed:11083922}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; AF200342; AAF17078.1; -; mRNA.
DR EMBL; AF117892; AAD45240.1; -; mRNA.
DR EMBL; AF178532; AAF29494.1; -; mRNA.
DR EMBL; AF188276; AAF35835.1; -; mRNA.
DR EMBL; AF188277; AAF35836.1; -; mRNA.
DR EMBL; AF050171; AAD45963.1; -; mRNA.
DR EMBL; AF204944; AAF26368.1; -; mRNA.
DR EMBL; AF200192; AAF13714.1; -; mRNA.
DR EMBL; AF212252; AAG41783.1; -; mRNA.
DR EMBL; AY358927; AAQ89286.1; -; mRNA.
DR EMBL; AK075539; BAC11682.1; -; mRNA.
DR EMBL; AK292056; BAF84745.1; -; mRNA.
DR EMBL; AL163284; CAB90458.1; -; Genomic_DNA.
DR EMBL; AL163285; CAB90554.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09611.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09613.1; -; Genomic_DNA.
DR EMBL; BC014453; AAH14453.1; -; mRNA.
DR EMBL; AY769996; AAX14808.1; -; Genomic_DNA.
DR CCDS; CCDS13668.1; -. [Q9Y5Z0-1]
DR CCDS; CCDS13669.1; -. [Q9Y5Z0-2]
DR CCDS; CCDS13670.1; -. [Q9Y5Z0-3]
DR RefSeq; NP_036237.2; NM_012105.4. [Q9Y5Z0-1]
DR RefSeq; NP_620476.1; NM_138991.2. [Q9Y5Z0-2]
DR RefSeq; NP_620477.1; NM_138992.2. [Q9Y5Z0-3]
DR PDB; 2EWY; X-ray; 3.10 A; A/B/C/D=78-460.
DR PDB; 3ZKG; X-ray; 1.90 A; A/B=75-460.
DR PDB; 3ZKI; X-ray; 2.40 A; A/B=75-460.
DR PDB; 3ZKM; X-ray; 1.85 A; A/B=75-460.
DR PDB; 3ZKN; X-ray; 2.00 A; A/B=75-460.
DR PDB; 3ZKQ; X-ray; 1.51 A; A=75-460.
DR PDB; 3ZKS; X-ray; 2.11 A; A=75-460.
DR PDB; 3ZKX; X-ray; 2.37 A; A=75-460.
DR PDB; 3ZL7; X-ray; 3.20 A; A=75-460.
DR PDB; 3ZLQ; X-ray; 2.10 A; A/B=75-460.
DR PDB; 4BEL; X-ray; 1.85 A; A/B=75-460.
DR PDB; 4BFB; X-ray; 2.21 A; A/B=75-460.
DR PDB; 6JSZ; X-ray; 1.53 A; A=75-460.
DR PDB; 6UJ0; X-ray; 2.15 A; A/B=1-460.
DR PDB; 6UJ1; X-ray; 3.03 A; A/B=1-460.
DR PDB; 7D5B; X-ray; 1.31 A; A=75-460.
DR PDB; 7D5U; X-ray; 2.04 A; A=75-460.
DR PDB; 7F1G; X-ray; 1.50 A; A=75-460.
DR PDB; 7N4N; X-ray; 1.41 A; A=75-460.
DR PDBsum; 2EWY; -.
DR PDBsum; 3ZKG; -.
DR PDBsum; 3ZKI; -.
DR PDBsum; 3ZKM; -.
DR PDBsum; 3ZKN; -.
DR PDBsum; 3ZKQ; -.
DR PDBsum; 3ZKS; -.
DR PDBsum; 3ZKX; -.
DR PDBsum; 3ZL7; -.
DR PDBsum; 3ZLQ; -.
DR PDBsum; 4BEL; -.
DR PDBsum; 4BFB; -.
DR PDBsum; 6JSZ; -.
DR PDBsum; 6UJ0; -.
DR PDBsum; 6UJ1; -.
DR PDBsum; 7D5B; -.
DR PDBsum; 7D5U; -.
DR PDBsum; 7F1G; -.
DR PDBsum; 7N4N; -.
DR AlphaFoldDB; Q9Y5Z0; -.
DR SMR; Q9Y5Z0; -.
DR BioGRID; 117353; 98.
DR IntAct; Q9Y5Z0; 38.
DR MINT; Q9Y5Z0; -.
DR STRING; 9606.ENSP00000332979; -.
DR BindingDB; Q9Y5Z0; -.
DR ChEMBL; CHEMBL2525; -.
DR GuidetoPHARMACOLOGY; 2331; -.
DR MEROPS; A01.041; -.
DR TCDB; 8.A.32.1.2; the Beta-amyloid cleaving enzyme (bace1) family.
DR TCDB; 8.A.32.1.3; the Beta-amyloid cleaving enzyme (bace1) family.
DR GlyGen; Q9Y5Z0; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y5Z0; -.
DR PhosphoSitePlus; Q9Y5Z0; -.
DR BioMuta; BACE2; -.
DR DMDM; 6685260; -.
DR EPD; Q9Y5Z0; -.
DR jPOST; Q9Y5Z0; -.
DR MassIVE; Q9Y5Z0; -.
DR MaxQB; Q9Y5Z0; -.
DR PaxDb; Q9Y5Z0; -.
DR PeptideAtlas; Q9Y5Z0; -.
DR PRIDE; Q9Y5Z0; -.
DR ProteomicsDB; 86546; -. [Q9Y5Z0-1]
DR ProteomicsDB; 86547; -. [Q9Y5Z0-2]
DR ProteomicsDB; 86548; -. [Q9Y5Z0-3]
DR ProteomicsDB; 86549; -. [Q9Y5Z0-4]
DR ProteomicsDB; 86550; -. [Q9Y5Z0-5]
DR ABCD; Q9Y5Z0; 3 sequenced antibodies.
DR Antibodypedia; 4410; 532 antibodies from 38 providers.
DR DNASU; 25825; -.
DR Ensembl; ENST00000328735.10; ENSP00000333854.6; ENSG00000182240.16. [Q9Y5Z0-3]
DR Ensembl; ENST00000330333.11; ENSP00000332979.6; ENSG00000182240.16. [Q9Y5Z0-1]
DR Ensembl; ENST00000347667.5; ENSP00000327528.4; ENSG00000182240.16. [Q9Y5Z0-2]
DR GeneID; 25825; -.
DR KEGG; hsa:25825; -.
DR MANE-Select; ENST00000330333.11; ENSP00000332979.6; NM_012105.5; NP_036237.2.
DR UCSC; uc002yyw.5; human. [Q9Y5Z0-1]
DR CTD; 25825; -.
DR DisGeNET; 25825; -.
DR GeneCards; BACE2; -.
DR HGNC; HGNC:934; BACE2.
DR HPA; ENSG00000182240; Tissue enhanced (salivary).
DR MIM; 605668; gene.
DR neXtProt; NX_Q9Y5Z0; -.
DR OpenTargets; ENSG00000182240; -.
DR PharmGKB; PA25233; -.
DR VEuPathDB; HostDB:ENSG00000182240; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000159548; -.
DR HOGENOM; CLU_039009_0_0_1; -.
DR InParanoid; Q9Y5Z0; -.
DR OMA; PLRIYPG; -.
DR OrthoDB; 753343at2759; -.
DR PhylomeDB; Q9Y5Z0; -.
DR TreeFam; TF329595; -.
DR BioCyc; MetaCyc:G66-33964-MON; -.
DR BRENDA; 3.4.23.45; 2681.
DR BRENDA; 3.4.24.56; 2681.
DR PathwayCommons; Q9Y5Z0; -.
DR SignaLink; Q9Y5Z0; -.
DR SIGNOR; Q9Y5Z0; -.
DR BioGRID-ORCS; 25825; 8 hits in 1074 CRISPR screens.
DR ChiTaRS; BACE2; human.
DR EvolutionaryTrace; Q9Y5Z0; -.
DR GeneWiki; Beta-secretase_2; -.
DR GenomeRNAi; 25825; -.
DR Pharos; Q9Y5Z0; Tchem.
DR PRO; PR:Q9Y5Z0; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; Q9Y5Z0; protein.
DR Bgee; ENSG00000182240; Expressed in parotid gland and 180 other tissues.
DR Genevisible; Q9Y5Z0; HS.
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; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IBA:GO_Central.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; IMP:UniProtKB.
DR GO; GO:0016486; P:peptide hormone processing; NAS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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 3D-structure; Alternative splicing; Aspartyl protease;
KW Autocatalytic cleavage; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Golgi apparatus; Hydrolase; Membrane; Protease; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..62
FT /evidence="ECO:0000269|PubMed:10591213,
FT ECO:0000269|PubMed:11083922, ECO:0000269|PubMed:11423558,
FT ECO:0000269|PubMed:16305800, ECO:0000269|PubMed:16816112"
FT /id="PRO_0000025945"
FT CHAIN 63..518
FT /note="Beta-secretase 2"
FT /id="PRO_0000025946"
FT TOPO_DOM 21..473
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 474..494
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 495..518
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 92..429
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 110
FT ACT_SITE 303
FT CARBOHYD 170
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 233..433
FT /evidence="ECO:0000269|PubMed:16305800"
FT DISULFID 292..457
FT /evidence="ECO:0000269|PubMed:16305800"
FT DISULFID 344..393
FT /evidence="ECO:0000269|PubMed:16305800"
FT VAR_SEQ 1..95
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038023"
FT VAR_SEQ 1..79
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.8"
FT /id="VSP_038024"
FT VAR_SEQ 329..378
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10965118"
FT /id="VSP_038025"
FT VAR_SEQ 379..396
FT /note="LYIQPMMGAGLNYECYRF -> KLQVLQCLKFPGLSQQRM (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:10965118"
FT /id="VSP_038026"
FT VAR_SEQ 397..518
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10965118"
FT /id="VSP_038027"
FT MUTAGEN 110
FT /note="D->A,N: Loss of autoproteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:10838186,
FT ECO:0000269|PubMed:11316808"
FT MUTAGEN 303
FT /note="D->A: Loss of autoproteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:10838186"
FT CONFLICT 36
FT /note="A -> T (in Ref. 7; AAF13714)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="E -> G (in Ref. 10; BAC11682)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="K -> Q (in Ref. 10; BAC11682)"
FT /evidence="ECO:0000305"
FT CONFLICT 233
FT /note="C -> R (in Ref. 10; BAC11682)"
FT /evidence="ECO:0000305"
FT HELIX 78..80
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:7D5B"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 91..98
FT /evidence="ECO:0007829|PDB:7D5B"
FT TURN 99..102
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 103..110
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 139..149
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 152..164
FT /evidence="ECO:0007829|PDB:7D5B"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 173..185
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:6UJ1"
FT HELIX 214..222
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 228..232
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 247..253
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 264..270
FT /evidence="ECO:0007829|PDB:7D5B"
FT TURN 271..274
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:6JSZ"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 308..312
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 313..326
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 339..342
FT /evidence="ECO:0007829|PDB:3ZKN"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:7N4N"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:4BFB"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 358..363
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 369..375
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 377..379
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 393..403
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 405..407
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 409..412
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 415..420
FT /evidence="ECO:0007829|PDB:7D5B"
FT TURN 421..424
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 425..430
FT /evidence="ECO:0007829|PDB:7D5B"
FT HELIX 432..434
FT /evidence="ECO:0007829|PDB:6UJ0"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:6UJ1"
FT STRAND 439..449
FT /evidence="ECO:0007829|PDB:7D5B"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:6JSZ"
FT CONFLICT Q9Y5Z0-3:381
FT /note="Q -> R (in Ref. 3; AAF35836)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9Y5Z0-3:396
FT /note="M -> F (in Ref. 3; AAF35836)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 518 AA; 56180 MW; 2E903150823760D3 CRC64;
MGALARALLL PLLAQWLLRA APELAPAPFT LPLRVAAATN RVVAPTPGPG TPAERHADGL
ALALEPALAS PAGAANFLAM VDNLQGDSGR GYYLEMLIGT PPQKLQILVD TGSSNFAVAG
TPHSYIDTYF DTERSSTYRS KGFDVTVKYT QGSWTGFVGE DLVTIPKGFN TSFLVNIATI
FESENFFLPG IKWNGILGLA YATLAKPSSS LETFFDSLVT QANIPNVFSM QMCGAGLPVA
GSGTNGGSLV LGGIEPSLYK GDIWYTPIKE EWYYQIEILK LEIGGQSLNL DCREYNADKA
IVDSGTTLLR LPQKVFDAVV EAVARASLIP EFSDGFWTGS QLACWTNSET PWSYFPKISI
YLRDENSSRS FRITILPQLY IQPMMGAGLN YECYRFGISP STNALVIGAT VMEGFYVIFD
RAQKRVGFAA SPCAEIAGAA VSEISGPFST EDVASNCVPA QSLSEPILWI VSYALMSVCG
AILLVLIVLL LLPFRCQRRP RDPEVVNDES SLVRHRWK
