BACE1_HUMAN
ID BACE1_HUMAN Reviewed; 501 AA.
AC P56817; A0M8W7; B0YIU9; E9PE65; H7BXJ9; Q9BYB9; Q9BYC0; Q9BYC1; Q9UJT5;
AC Q9ULS1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 3.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=Beta-secretase 1 {ECO:0000305};
DE EC=3.4.23.46 {ECO:0000269|PubMed:10677483};
DE AltName: Full=Aspartyl protease 2 {ECO:0000303|PubMed:10656250};
DE Short=ASP2 {ECO:0000303|PubMed:10656250};
DE Short=Asp 2 {ECO:0000303|PubMed:10656250};
DE AltName: Full=Beta-site amyloid precursor protein cleaving enzyme 1;
DE Short=Beta-site APP cleaving enzyme 1;
DE AltName: Full=Memapsin-2 {ECO:0000303|PubMed:10677483, ECO:0000303|PubMed:14567678};
DE AltName: Full=Membrane-associated aspartic protease 2;
DE Flags: Precursor;
GN Name=BACE1 {ECO:0000312|HGNC:HGNC:933}; Synonyms=BACE, KIAA1149;
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 A).
RC TISSUE=Brain;
RX PubMed=10531052; DOI=10.1126/science.286.5440.735;
RA Vassar R., Bennett B.D., Babu-Khan S., Kahn S., Mendiaz E.A., Denis P.,
RA Teplow D.B., Ross S., Amarante P., Loeloff R., Luo Y., Fisher S.,
RA Fuller J., Edenson S., Lile J., Jarosinski M.A., Biere A.L., Curran E.,
RA Burgess T., Louis J.-C., Collins F., Treanor J., Rogers G., Citron M.;
RT "Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the
RT transmembrane aspartic protease BACE.";
RL Science 286:735-741(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), PROTEIN SEQUENCE OF 46-68, AND
RP CHARACTERIZATION.
RC TISSUE=Brain;
RX PubMed=10591214; DOI=10.1038/990114;
RA Sinha S., Anderson J.P., Barbour R., Basi G.S., Caccavello R., Davis D.,
RA Doan M., Dovey H.F., Frigon N., Hong J., Jacobson-Croak K., Jewett N.,
RA Keim P., Knops J., Lieberburg I., Power M., Tan H., Tatsuno G., Tung J.,
RA Schenk D., Seubert P., Suomensaari S.M., Wang S., Walker D., Zhao J.,
RA McConlogue L., Varghese J.;
RT "Purification and cloning of amyloid precursor protein beta-secretase from
RT human brain.";
RL Nature 402:537-540(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND MUTAGENESIS OF ASP-93
RP AND ASP-284.
RX PubMed=10656250; DOI=10.1006/mcne.1999.0811;
RA Hussain I., Powell D.J., Howlett D.R., Tew D.G., Meek T.D., Chapman C.,
RA Gloger I.S., Murphy K.E., Southan C.D., Ryan D.M., Smith T.S.,
RA Simmons D.L., Walsh F.S., Dingwall C., Christie G.;
RT "Identification of a novel aspartic proteinase (Asp 2) as beta-secretase.";
RL Mol. Cell. Neurosci. 14:419-427(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
RC TISSUE=Brain, and Pancreas;
RA Michel B., De Pietri Tonelli D., Zacchetti D., Keller P.;
RT "New beta-site APP cleaving enzyme isoform (BACE-1B) obtained from human
RT brain and pancreas.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
RC TISSUE=Pancreas;
RA Zacchetti D., De Pietri Tonelli D., Schnurbus R.;
RT "New beta-site APP cleaving enzyme isoform (BACE-1C) obtained from human
RT pancreas.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B; C AND D).
RC TISSUE=Brain;
RX PubMed=11516562; DOI=10.1016/s0304-3940(01)01912-7;
RA Tanahashi H., Tabira T.;
RT "Three novel alternatively spliced isoforms of the human beta-site amyloid
RT precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-
RT peptide production.";
RL Neurosci. Lett. 307:9-12(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [9]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-265.
RG NIEHS SNPs program;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [13]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Lung;
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 [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-501 (ISOFORM A), FUNCTION, TISSUE
RP SPECIFICITY, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [16]
RP TISSUE SPECIFICITY, AND GLYCOSYLATION.
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 [17]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=11466313; DOI=10.1074/jbc.m104350200;
RA Yan R., Han P., Miao H., Greengard P., Xu H.;
RT "The transmembrane domain of the Alzheimer's beta-secretase (BACE1)
RT determines its late Golgi localization and access to beta -amyloid
RT precursor protein (APP) substrate.";
RL J. Biol. Chem. 276:36788-36796(2001).
RN [18]
RP DISULFIDE BONDS.
RX PubMed=11953458; DOI=10.1046/j.0022-3042.2002.00806.x;
RA Fischer F., Molinari M., Bodendorf U., Paganetti P.;
RT "The disulphide bonds in the catalytic domain of BACE are critical but not
RT essential for amyloid precursor protein processing activity.";
RL J. Neurochem. 80:1079-1088(2002).
RN [19]
RP INTERACTION WITH GGA1; GGA2 AND GGA3.
RX PubMed=14567678; DOI=10.1021/bi035199h;
RA He X., Zhu G., Koelsch G., Rodgers K.K., Zhang X.C., Tang J.;
RT "Biochemical and structural characterization of the interaction of memapsin
RT 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins.";
RL Biochemistry 42:12174-12180(2003).
RN [20]
RP INTERACTION WITH RTN1; RTN2; RTN3 AND RTN4, AND ACTIVITY REGULATION.
RX PubMed=15286784; DOI=10.1038/nm1088;
RA He W., Lu Y., Qahwash I., Hu X.-Y., Chang A., Yan R.;
RT "Reticulon family members modulate BACE1 activity and amyloid-beta peptide
RT generation.";
RL Nat. Med. 10:959-965(2004).
RN [21]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF 499-LEU-LEU-500, AND LYSOSOMAL
RP DEGRADATION.
RX PubMed=16033761; DOI=10.1074/jbc.m506199200;
RA Koh Y.H., von Arnim C.A., Hyman B.T., Tanzi R.E., Tesco G.;
RT "BACE is degraded via the lysosomal pathway.";
RL J. Biol. Chem. 280:32499-32504(2005).
RN [22]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-498 AND 499-LEU-LEU-500.
RX PubMed=15615712; DOI=10.1074/jbc.m411296200;
RA He X., Li F., Chang W.P., Tang J.;
RT "GGA proteins mediate the recycling pathway of memapsin 2 (BACE).";
RL J. Biol. Chem. 280:11696-11703(2005).
RN [23]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF SER-498, AND PHOSPHORYLATION AT
RP SER-498.
RX PubMed=15886016; DOI=10.1016/j.mcn.2005.03.014;
RA Wahle T., Prager K., Raffler N., Haass C., Famulok M., Walter J.;
RT "GGA proteins regulate retrograde transport of BACE1 from endosomes to the
RT trans-Golgi network.";
RL Mol. Cell. Neurosci. 29:453-461(2005).
RN [24]
RP INTERACTION WITH RTN3 AND RTN4, AND ACTIVITY REGULATION.
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 [25]
RP INTERACTION WITH RTN3.
RX PubMed=16979658; DOI=10.1016/j.jmb.2006.07.094;
RA He W., Hu X., Shi Q., Zhou X., Lu Y., Fisher C., Yan R.;
RT "Mapping of interaction domains mediating binding between BACE1 and
RT RTN/Nogo proteins.";
RL J. Mol. Biol. 363:625-634(2006).
RN [26]
RP INTERACTION WITH SORL1.
RX PubMed=16407538; DOI=10.1523/jneurosci.3882-05.2006;
RA Spoelgen R., von Arnim C.A., Thomas A.V., Peltan I.D., Koker M., Deng A.,
RA Irizarry M.C., Andersen O.M., Willnow T.E., Hyman B.T.;
RT "Interaction of the cytosolic domains of sorLA/LR11 with the amyloid
RT precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme.";
RL J. Neurosci. 26:418-428(2006).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, ACETYLATION AT
RP LYS-126; LYS-275; LYS-279; LYS-285; LYS-299; LYS-300 AND LYS-307, AND
RP GLYCOSYLATION.
RX PubMed=17425515; DOI=10.1042/bj20070040;
RA Costantini C., Ko M.H., Jonas M.C., Puglielli L.;
RT "A reversible form of lysine acetylation in the ER and Golgi lumen controls
RT the molecular stabilization of BACE1.";
RL Biochem. J. 407:383-395(2007).
RN [28]
RP INTERACTION WITH PCSK9.
RX PubMed=18660751; DOI=10.1038/embor.2008.132;
RA Jonas M.C., Costantini C., Puglielli L.;
RT "PCSK9 is required for the disposal of non-acetylated intermediates of the
RT nascent membrane protein BACE1.";
RL EMBO Rep. 9:916-922(2008).
RN [29]
RP ACETYLATION AT LYS-126; LYS-275; LYS-279; LYS-285; LYS-299; LYS-300 AND
RP LYS-307 BY NAT8 AND NAT8B, DEACETYLATION, AND INTERACTION WITH NAT8 AND
RP NAT8B.
RX PubMed=19011241; DOI=10.1074/jbc.m804901200;
RA Ko M.H., Puglielli L.;
RT "Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based
RT lysine acetyltransferases post-translationally regulate BACE1 levels.";
RL J. Biol. Chem. 284:2482-2492(2009).
RN [30]
RP FUNCTION, INTERACTION WITH SNX6, AND SUBCELLULAR LOCATION.
RX PubMed=20354142; DOI=10.1096/fj.09-146357;
RA Okada H., Zhang W., Peterhoff C., Hwang J.C., Nixon R.A., Ryu S.H.,
RA Kim T.W.;
RT "Proteomic identification of sorting nexin 6 as a negative regulator of
RT BACE1-mediated APP processing.";
RL FASEB J. 24:2783-2794(2010).
RN [31]
RP UBIQUITINATION AT LYS-501, AND MUTAGENESIS OF 499-LEU-LEU-500 AND LYS-501.
RX PubMed=20484053; DOI=10.1074/jbc.m109.092742;
RA Kang E.L., Cameron A.N., Piazza F., Walker K.R., Tesco G.;
RT "Ubiquitin regulates GGA3-mediated degradation of BACE1.";
RL J. Biol. Chem. 285:24108-24119(2010).
RN [32]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF 499-LEU-LEU-500 AND LYS-501, AND
RP DOMAIN.
RX PubMed=23109336; DOI=10.1074/jbc.m112.407072;
RA Kang E.L., Biscaro B., Piazza F., Tesco G.;
RT "BACE1 protein endocytosis and trafficking are differentially regulated by
RT ubiquitination at lysine 501 and the Di-leucine motif in the carboxyl
RT terminus.";
RL J. Biol. Chem. 287:42867-42880(2012).
RN [33]
RP INDUCTION BY NFATC4.
RX PubMed=25663301; DOI=10.1007/s11064-015-1533-1;
RA Mei Z., Yan P., Tan X., Zheng S., Situ B.;
RT "Transcriptional regulation of BACE1 by NFAT3 leads to enhanced
RT amyloidogenic processing.";
RL Neurochem. Res. 40:829-836(2015).
RN [34]
RP INTERACTION WITH BIN1.
RX PubMed=27179792; DOI=10.1093/hmg/ddw146;
RA Miyagawa T., Ebinuma I., Morohashi Y., Hori Y., Young Chang M., Hattori H.,
RA Maehara T., Yokoshima S., Fukuyama T., Tsuji S., Iwatsubo T.,
RA Prendergast G.C., Tomita T.;
RT "BIN1 regulates BACE1 intracellular trafficking and amyloid-beta
RT production.";
RL Hum. Mol. Genet. 25:2948-2958(2016).
RN [35]
RP DEUBIQUITINATION AT LYS-501, MUTAGENESIS OF LYS-501, AND SUBCELLULAR
RP LOCATION.
RX PubMed=27302062; DOI=10.1074/jbc.m116.718023;
RA Yeates E.F., Tesco G.;
RT "The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1
RT Enzyme Ubiquitination and Degradation.";
RL J. Biol. Chem. 291:15753-15766(2016).
RN [36]
RP SUBCELLULAR LOCATION.
RX PubMed=27084579; DOI=10.1242/jcs.185215;
RA Kurkinen K.M., Marttinen M., Turner L., Natunen T., Maekinen P.,
RA Haapalinna F., Sarajaervi T., Gabbouj S., Kurki M., Paananen J.,
RA Koivisto A.M., Rauramaa T., Leinonen V., Tanila H., Soininen H.,
RA Lucas F.R., Haapasalo A., Hiltunen M.;
RT "SEPT8 modulates beta-amyloidogenic processing of APP by affecting the
RT sorting and accumulation of BACE1.";
RL J. Cell Sci. 129:2224-2238(2016).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 56-446 IN COMPLEX WITH SUBSTRATE
RP ANALOG.
RX PubMed=11021803; DOI=10.1126/science.290.5489.150;
RA Hong L., Koelsch G., Lin X., Wu S., Terzyan S., Ghosh A.K., Zhang X.C.,
RA Tang J.;
RT "Structure of the protease domain of memapsin 2 (beta-secretase) complexed
RT with inhibitor.";
RL Science 290:150-153(2000).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 56-446 IN COMPLEX WITH SUBSTRATE
RP ANALOG.
RX PubMed=12206667; DOI=10.1021/bi026232n;
RA Hong L., Turner R.T. III, Koelsch G., Shin D., Ghosh A.K., Tang J.;
RT "Crystal structure of memapsin 2 (beta-secretase) in complex with an
RT inhibitor OM00-3.";
RL Biochemistry 41:10963-10967(2002).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 58-446.
RX PubMed=15096037; DOI=10.1021/bi0498252;
RA Hong L., Tang J.;
RT "Flap position of free memapsin 2 (beta-secretase), a model for flap
RT opening in aspartic protease catalysis.";
RL Biochemistry 43:4689-4695(2004).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 43-453 IN COMPLEX WITH SUBSTRATE
RP ANALOG.
RX PubMed=15451669; DOI=10.1016/j.jmb.2004.08.018;
RA Patel S., Vuillard L., Cleasby A., Murray C.W., Yon J.;
RT "Apo and inhibitor complex structures of BACE (beta-secretase).";
RL J. Mol. Biol. 343:407-416(2004).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 58-446.
RX PubMed=15628850; DOI=10.1021/bi048106k;
RA Turner R.T. III, Hong L., Koelsch G., Ghosh A.K., Tang J.;
RT "Structural locations and functional roles of new subsites S5, S6, and S7
RT in memapsin 2 (beta-secretase).";
RL Biochemistry 44:105-112(2005).
CC -!- FUNCTION: Responsible for the proteolytic processing of the amyloid
CC precursor protein (APP). Cleaves at the N-terminus of the A-beta
CC peptide sequence, between residues 671 and 672 of APP, leads to the
CC generation and extracellular release of beta-cleaved soluble APP, and a
CC corresponding cell-associated C-terminal fragment which is later
CC released by gamma-secretase (PubMed:10656250, PubMed:10677483,
CC PubMed:20354142). Cleaves CHL1 (By similarity).
CC {ECO:0000250|UniProtKB:P56818, ECO:0000269|PubMed:10656250,
CC ECO:0000269|PubMed:10677483, ECO:0000269|PubMed:20354142}.
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=3.4.23.46;
CC Evidence={ECO:0000269|PubMed:10677483};
CC -!- ACTIVITY REGULATION: Inhibited by RTN3 and RTN4.
CC {ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:16965550}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15.2 mM for APP cleaved by PSEN1 (at pH4)
CC {ECO:0000269|PubMed:10677483};
CC KM=1 mM for APP Swedish variant (at pH4)
CC {ECO:0000269|PubMed:10677483};
CC Note=kcat is 0.67 sec(-1) and 2.45 sec(-1) for APP cleaved by PSEN1
CC and APP Swedish variant, respectively (PubMed:10677483).
CC {ECO:0000269|PubMed:10677483};
CC -!- SUBUNIT: Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3
CC (via their VHS domain); the interaction highly increases when BACE1 is
CC phosphorylated at Ser-498 (PubMed:14567678, PubMed:15886016). Interacts
CC with RTN1; RTN2; RTN3 and RTN4; the interaction leads to inhibition of
CC amyloid precursor protein processing (PubMed:15286784, PubMed:16965550,
CC PubMed:16979658). Interacts with SNX6 (PubMed:20354142). Interacts with
CC PCSK9 (PubMed:18660751). Interacts with NAT8 and NAT8B
CC (PubMed:19011241). Interacts with BIN1 (PubMed:27179792). Interacts
CC (via extracellular domain) with ADAM10 (via extracellular domain) (By
CC similarity). Interacts with SORL1; this interaction may affect binding
CC with APP and hence reduce APP cleavage (PubMed:16407538).
CC {ECO:0000250|UniProtKB:P56818, ECO:0000269|PubMed:14567678,
CC ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:15886016,
CC ECO:0000269|PubMed:16407538, ECO:0000269|PubMed:16965550,
CC ECO:0000269|PubMed:16979658, ECO:0000269|PubMed:18660751,
CC ECO:0000269|PubMed:19011241, ECO:0000269|PubMed:20354142,
CC ECO:0000269|PubMed:27179792}.
CC -!- INTERACTION:
CC P56817; O14672: ADAM10; NbExp=3; IntAct=EBI-2433139, EBI-1536151;
CC P56817; P05067: APP; NbExp=11; IntAct=EBI-2433139, EBI-77613;
CC P56817; Q9UJY5: GGA1; NbExp=4; IntAct=EBI-2433139, EBI-447141;
CC P56817; Q9UJY4: GGA2; NbExp=2; IntAct=EBI-2433139, EBI-447646;
CC P56817; Q9NZ52: GGA3; NbExp=2; IntAct=EBI-2433139, EBI-447404;
CC P56817; P10997: IAPP; NbExp=2; IntAct=EBI-2433139, EBI-8526679;
CC P56817; Q9Y287: ITM2B; NbExp=4; IntAct=EBI-2433139, EBI-2866431;
CC P56817; Q03721: KCNC4; NbExp=3; IntAct=EBI-2433139, EBI-11334865;
CC P56817; P49768: PSEN1; NbExp=6; IntAct=EBI-2433139, EBI-297277;
CC P56817; Q9UNH7: SNX6; NbExp=2; IntAct=EBI-2433139, EBI-949294;
CC P56817; Q8BNX1: Clec4g; Xeno; NbExp=2; IntAct=EBI-2433139, EBI-11176364;
CC P56817-1; O95197-3: RTN3; NbExp=2; IntAct=EBI-2433297, EBI-11525735;
CC P56817-1; Q9NQC3-2: RTN4; NbExp=3; IntAct=EBI-2433297, EBI-10296096;
CC P56817-1; Q9NQC3-3: RTN4; NbExp=2; IntAct=EBI-2433297, EBI-11526335;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11466313};
CC Single-pass type I membrane protein {ECO:0000305|PubMed:11466313}.
CC Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:11466313,
CC ECO:0000269|PubMed:15615712, ECO:0000269|PubMed:15886016,
CC ECO:0000269|PubMed:17425515, ECO:0000269|PubMed:20354142,
CC ECO:0000269|PubMed:23109336}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:17425515}. Endosome
CC {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15886016}. Cell
CC surface {ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15886016,
CC ECO:0000269|PubMed:17425515, ECO:0000269|PubMed:23109336}. Cytoplasmic
CC vesicle membrane {ECO:0000269|PubMed:11466313,
CC ECO:0000269|PubMed:15886016}; Single-pass type I membrane protein
CC {ECO:0000305|PubMed:11466313}. Membrane raft
CC {ECO:0000250|UniProtKB:P56818}. Lysosome {ECO:0000269|PubMed:16033761,
CC ECO:0000269|PubMed:23109336, ECO:0000269|PubMed:27084579,
CC ECO:0000269|PubMed:27302062}. Late endosome
CC {ECO:0000269|PubMed:16033761, ECO:0000269|PubMed:23109336,
CC ECO:0000269|PubMed:27084579, ECO:0000269|PubMed:27302062}. Early
CC endosome {ECO:0000269|PubMed:15615712, ECO:0000269|PubMed:15886016,
CC ECO:0000269|PubMed:23109336, ECO:0000269|PubMed:27084579,
CC ECO:0000269|PubMed:27302062}. Recycling endosome
CC {ECO:0000269|PubMed:15886016, ECO:0000269|PubMed:27084579,
CC ECO:0000269|PubMed:27302062}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P56818}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P56818}. Note=Predominantly localized to the
CC later Golgi/trans-Golgi network (TGN) and minimally detectable in the
CC early Golgi compartments. A small portion is also found in the
CC endoplasmic reticulum, endosomes and on the cell surface
CC (PubMed:17425515, PubMed:11466313). Colocalization with APP in early
CC endosomes is due to addition of bisecting N-acetylglucosamine wich
CC blocks targeting to late endosomes and lysosomes (By similarity).
CC Retrogradly transported from endosomal compartments to the trans-Golgi
CC network in a phosphorylation- and GGA1- dependent manner
CC (PubMed:15886016). {ECO:0000250|UniProtKB:P56818,
CC ECO:0000269|PubMed:11466313, ECO:0000269|PubMed:15886016,
CC ECO:0000269|PubMed:17425515}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=A; Synonyms=BACE-1A, BAC-501;
CC IsoId=P56817-1; Sequence=Displayed;
CC Name=B; Synonyms=BACE-1B, BACE-I-476;
CC IsoId=P56817-2; Sequence=VSP_005223;
CC Name=C; Synonyms=BACE-1C, BACE-I-457;
CC IsoId=P56817-3; Sequence=VSP_005222;
CC Name=D; Synonyms=BACE-1D, BACE-I-432;
CC IsoId=P56817-4; Sequence=VSP_005222, VSP_005223;
CC Name=5;
CC IsoId=P56817-5; Sequence=VSP_047092, VSP_047093;
CC Name=6;
CC IsoId=P56817-6; Sequence=VSP_047092, VSP_047093, VSP_005223;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the brain and pancreas.
CC In the brain, expression is highest in the substantia nigra, locus
CC coruleus and medulla oblongata. {ECO:0000269|PubMed:10677483,
CC ECO:0000269|PubMed:11083922}.
CC -!- INDUCTION: Up-regulated by the Ca(2+)-regulated transcription factor
CC NFATC4. {ECO:0000269|PubMed:25663301}.
CC -!- DOMAIN: DXXLL motif is required for a proper endocytosis and retrograde
CC transport to the trans-Golgi network, as well as for regulation of
CC lysosomal degradation. {ECO:0000269|PubMed:23109336}.
CC -!- DOMAIN: The transmembrane domain is necessary for its activity. It
CC determines its late Golgi localization and access to its substrate,
CC APP. {ECO:0000269|PubMed:11466313}.
CC -!- PTM: N-Glycosylated (PubMed:11083922, PubMed:17425515). Addition of a
CC bisecting N-acetylglucosamine by MGAT3 blocks lysosomal targeting,
CC further degradation and is required for maintaining stability under
CC stress conditions (By similarity). {ECO:0000250|UniProtKB:P56818,
CC ECO:0000269|PubMed:11083922, ECO:0000269|PubMed:17425515}.
CC -!- PTM: Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-
CC 279, Lys-285, Lys-299, Lys-300 and Lys-307. Acetylation by NAT8 and
CC NAT8B is transient and deacetylation probably occurs in the Golgi.
CC Acetylation regulates the maturation, the transport to the plasma
CC membrane, the stability and the expression of the protein.
CC {ECO:0000269|PubMed:17425515, ECO:0000269|PubMed:19011241}.
CC -!- PTM: Palmitoylation mediates lipid raft localization.
CC {ECO:0000250|UniProtKB:P56818}.
CC -!- PTM: Ubiquitinated at Lys-501, ubiquitination leads to lysosomal
CC degradation (PubMed:27302062, PubMed:16033761, PubMed:20484053,
CC PubMed:23109336). Monoubiquitinated and 'Lys-63'-linked polyubitinated
CC (PubMed:20484053). Deubiquitnated by USP8; inhibits lysosomal
CC degradation (PubMed:27302062). {ECO:0000269|PubMed:16033761,
CC ECO:0000269|PubMed:20484053, ECO:0000269|PubMed:23109336,
CC ECO:0000269|PubMed:27302062}.
CC -!- PTM: Phosphorylation at Ser-498 is required for interaction with GGA1
CC and retrograded transport from endosomal compartments to the trans-
CC Golgi network. Non-phosphorylated BACE1 enters a direct recycling route
CC to the cell surface. {ECO:0000269|PubMed:15886016}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86463.2; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/bace1/";
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DR EMBL; AF190725; AAF04142.1; -; mRNA.
DR EMBL; AF201468; AAF18982.1; -; mRNA.
DR EMBL; AF200343; AAF17079.1; -; mRNA.
DR EMBL; AF204943; AAF26367.1; -; mRNA.
DR EMBL; AF338816; AAK38374.1; -; mRNA.
DR EMBL; AF338817; AAK38375.1; -; mRNA.
DR EMBL; AB050436; BAB40931.1; -; mRNA.
DR EMBL; AB050437; BAB40932.1; -; mRNA.
DR EMBL; AB050438; BAB40933.1; -; mRNA.
DR EMBL; AB032975; BAA86463.2; ALT_FRAME; mRNA.
DR EMBL; DQ007053; AAY16982.1; -; Genomic_DNA.
DR EMBL; EF444940; ACA05927.1; -; Genomic_DNA.
DR EMBL; AP000892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67313.1; -; Genomic_DNA.
DR EMBL; BC065492; AAH65492.1; -; mRNA.
DR EMBL; AF200193; AAF13715.1; -; mRNA.
DR CCDS; CCDS44739.1; -. [P56817-2]
DR CCDS; CCDS44740.1; -. [P56817-3]
DR CCDS; CCDS44741.1; -. [P56817-4]
DR CCDS; CCDS55786.1; -. [P56817-6]
DR CCDS; CCDS55787.1; -. [P56817-5]
DR CCDS; CCDS8383.1; -. [P56817-1]
DR PIR; A59090; A59090.
DR RefSeq; NP_001193978.1; NM_001207049.1. [P56817-6]
DR RefSeq; NP_036236.1; NM_012104.4. [P56817-1]
DR RefSeq; NP_620427.1; NM_138971.3. [P56817-3]
DR RefSeq; NP_620428.1; NM_138972.3. [P56817-2]
DR RefSeq; NP_620429.1; NM_138973.3. [P56817-4]
DR PDB; 1FKN; X-ray; 1.90 A; A/B=56-446.
DR PDB; 1M4H; X-ray; 2.10 A; A/B=56-446.
DR PDB; 1PY1; X-ray; 2.60 A; E/F/G/H=494-501.
DR PDB; 1SGZ; X-ray; 2.00 A; A/B/C/D=58-446.
DR PDB; 1TQF; X-ray; 1.80 A; A=43-446.
DR PDB; 1UJJ; X-ray; 2.60 A; C=490-501.
DR PDB; 1UJK; X-ray; 1.90 A; C/D=490-501.
DR PDB; 1W50; X-ray; 1.75 A; A=43-453.
DR PDB; 1W51; X-ray; 2.55 A; A=43-453.
DR PDB; 1XN2; X-ray; 1.90 A; A/B/C/D=58-446.
DR PDB; 1XN3; X-ray; 2.00 A; A/B/C/D=58-446.
DR PDB; 1XS7; X-ray; 2.80 A; D=58-446.
DR PDB; 1YM2; X-ray; 2.05 A; A/B/C=48-447.
DR PDB; 1YM4; X-ray; 2.25 A; A/B/C=48-453.
DR PDB; 2B8L; X-ray; 1.70 A; A=43-446.
DR PDB; 2B8V; X-ray; 1.80 A; A=43-446.
DR PDB; 2F3E; X-ray; 2.11 A; A/B/C=48-447.
DR PDB; 2F3F; X-ray; 2.30 A; A/B/C=48-447.
DR PDB; 2FDP; X-ray; 2.50 A; A/B/C=59-446.
DR PDB; 2G94; X-ray; 1.86 A; A/B/C/D=58-446.
DR PDB; 2HIZ; X-ray; 2.50 A; A/B/C=14-453.
DR PDB; 2HM1; X-ray; 2.20 A; A=57-453.
DR PDB; 2IQG; X-ray; 1.70 A; A=57-453.
DR PDB; 2IRZ; X-ray; 1.80 A; A=43-446.
DR PDB; 2IS0; X-ray; 2.20 A; A=43-446.
DR PDB; 2NTR; X-ray; 1.80 A; A=43-446.
DR PDB; 2OAH; X-ray; 1.80 A; A=43-446.
DR PDB; 2OF0; X-ray; 2.25 A; A=45-446.
DR PDB; 2OHK; X-ray; 2.20 A; A=45-446.
DR PDB; 2OHL; X-ray; 2.65 A; A=45-446.
DR PDB; 2OHM; X-ray; 2.70 A; A=45-446.
DR PDB; 2OHN; X-ray; 2.15 A; A=45-446.
DR PDB; 2OHP; X-ray; 2.25 A; A=45-446.
DR PDB; 2OHQ; X-ray; 2.10 A; A=45-446.
DR PDB; 2OHR; X-ray; 2.25 A; A=45-446.
DR PDB; 2OHS; X-ray; 2.45 A; A=45-446.
DR PDB; 2OHT; X-ray; 2.30 A; A=45-446.
DR PDB; 2OHU; X-ray; 2.35 A; A=45-446.
DR PDB; 2P4J; X-ray; 2.50 A; A/B/C/D=58-446.
DR PDB; 2P83; X-ray; 2.50 A; A/B/C=14-446.
DR PDB; 2P8H; X-ray; 1.80 A; A=43-446.
DR PDB; 2PH6; X-ray; 2.00 A; A=43-446.
DR PDB; 2PH8; X-ray; 1.70 A; A=43-446.
DR PDB; 2Q11; X-ray; 2.40 A; A/B/C=59-446.
DR PDB; 2Q15; X-ray; 2.40 A; A=62-446.
DR PDB; 2QK5; X-ray; 2.20 A; A/B=55-447.
DR PDB; 2QMD; X-ray; 1.65 A; A/B=55-447.
DR PDB; 2QMF; X-ray; 1.75 A; A/B=55-447.
DR PDB; 2QMG; X-ray; 1.89 A; A/B=55-447.
DR PDB; 2QP8; X-ray; 1.50 A; A/B=55-447.
DR PDB; 2QU2; X-ray; 2.60 A; A=46-454.
DR PDB; 2QU3; X-ray; 2.00 A; A=46-454.
DR PDB; 2QZK; X-ray; 1.80 A; A=43-446.
DR PDB; 2QZL; X-ray; 1.80 A; A=43-446.
DR PDB; 2VA5; X-ray; 2.75 A; A=14-453.
DR PDB; 2VA6; X-ray; 2.50 A; A=14-453.
DR PDB; 2VA7; X-ray; 2.20 A; A=14-453.
DR PDB; 2VIE; X-ray; 1.90 A; A=61-452.
DR PDB; 2VIJ; X-ray; 1.60 A; A=61-452.
DR PDB; 2VIY; X-ray; 1.82 A; A=61-452.
DR PDB; 2VIZ; X-ray; 1.60 A; A=61-452.
DR PDB; 2VJ6; X-ray; 1.80 A; A=61-452.
DR PDB; 2VJ7; X-ray; 1.60 A; A=61-452.
DR PDB; 2VJ9; X-ray; 1.60 A; A=61-452.
DR PDB; 2VKM; X-ray; 2.05 A; A/B/C/D=58-446.
DR PDB; 2VNM; X-ray; 1.79 A; A=61-452.
DR PDB; 2VNN; X-ray; 1.87 A; A=61-452.
DR PDB; 2WEZ; X-ray; 1.70 A; A=61-452.
DR PDB; 2WF0; X-ray; 1.60 A; A=61-452.
DR PDB; 2WF1; X-ray; 1.60 A; A=61-452.
DR PDB; 2WF2; X-ray; 1.80 A; A=61-452.
DR PDB; 2WF3; X-ray; 2.08 A; A=61-452.
DR PDB; 2WF4; X-ray; 1.80 A; A=61-452.
DR PDB; 2WJO; X-ray; 2.50 A; A=58-460.
DR PDB; 2XFI; X-ray; 1.73 A; A=61-452.
DR PDB; 2XFJ; X-ray; 1.80 A; A=61-452.
DR PDB; 2XFK; X-ray; 1.80 A; A=61-452.
DR PDB; 2ZDZ; X-ray; 2.00 A; A=46-454.
DR PDB; 2ZE1; X-ray; 2.20 A; A=46-454.
DR PDB; 2ZHR; X-ray; 2.50 A; A/B=45-454.
DR PDB; 2ZHS; X-ray; 2.70 A; A=45-454.
DR PDB; 2ZHT; X-ray; 2.35 A; A=45-454.
DR PDB; 2ZHU; X-ray; 2.40 A; A=45-454.
DR PDB; 2ZHV; X-ray; 1.85 A; A=45-454.
DR PDB; 2ZJH; X-ray; 2.60 A; A=43-446.
DR PDB; 2ZJI; X-ray; 2.30 A; A=43-446.
DR PDB; 2ZJJ; X-ray; 2.20 A; A=43-446.
DR PDB; 2ZJK; X-ray; 3.00 A; A/B/C=43-446.
DR PDB; 2ZJL; X-ray; 2.10 A; A=43-446.
DR PDB; 2ZJM; X-ray; 1.90 A; A=43-446.
DR PDB; 2ZJN; X-ray; 2.70 A; A=43-446.
DR PDB; 3BRA; X-ray; 2.30 A; A=46-454.
DR PDB; 3BUF; X-ray; 2.30 A; A=46-454.
DR PDB; 3BUG; X-ray; 2.50 A; A=46-454.
DR PDB; 3BUH; X-ray; 2.30 A; A=46-454.
DR PDB; 3CIB; X-ray; 1.72 A; A/B=58-447.
DR PDB; 3CIC; X-ray; 1.75 A; A/B=58-447.
DR PDB; 3CID; X-ray; 1.80 A; A/B=58-447.
DR PDB; 3CKP; X-ray; 2.30 A; A/B/C=43-454.
DR PDB; 3CKR; X-ray; 2.70 A; A/B/C=43-454.
DR PDB; 3DM6; X-ray; 2.60 A; A/B/C=42-446.
DR PDB; 3DUY; X-ray; 1.97 A; A/B/C=48-447.
DR PDB; 3DV1; X-ray; 2.10 A; A/B/C=48-447.
DR PDB; 3DV5; X-ray; 2.10 A; A/B/C=48-447.
DR PDB; 3EXO; X-ray; 2.10 A; A=43-454.
DR PDB; 3FKT; X-ray; 1.90 A; A=43-446.
DR PDB; 3H0B; X-ray; 2.70 A; A/B/C=43-446.
DR PDB; 3HVG; X-ray; 2.26 A; A/B/C=46-453.
DR PDB; 3HW1; X-ray; 2.48 A; A/B/C=46-453.
DR PDB; 3I25; X-ray; 2.10 A; A/B/C=42-446.
DR PDB; 3IGB; X-ray; 2.24 A; A=46-454.
DR PDB; 3IN3; X-ray; 2.00 A; A=46-454.
DR PDB; 3IN4; X-ray; 2.30 A; A=46-454.
DR PDB; 3IND; X-ray; 2.25 A; A=46-454.
DR PDB; 3INE; X-ray; 2.00 A; A=46-454.
DR PDB; 3INF; X-ray; 1.85 A; A=46-454.
DR PDB; 3INH; X-ray; 1.80 A; A=46-454.
DR PDB; 3IVH; X-ray; 1.80 A; A=57-453.
DR PDB; 3IVI; X-ray; 2.20 A; A/B/C=57-453.
DR PDB; 3IXJ; X-ray; 2.20 A; A/B/C=59-446.
DR PDB; 3IXK; X-ray; 2.50 A; A/B/C=42-446.
DR PDB; 3K5C; X-ray; 2.12 A; A/B/C=48-447.
DR PDB; 3K5D; X-ray; 2.90 A; A/B/C=48-453.
DR PDB; 3K5F; X-ray; 2.25 A; A/B/C=48-447.
DR PDB; 3K5G; X-ray; 2.00 A; A/B/C=48-447.
DR PDB; 3KMX; X-ray; 1.70 A; A/B=53-447.
DR PDB; 3KMY; X-ray; 1.90 A; A/B=53-447.
DR PDB; 3KN0; X-ray; 1.90 A; A/B=53-447.
DR PDB; 3KYR; X-ray; 2.60 A; A/B/C=42-446.
DR PDB; 3L38; X-ray; 2.10 A; A=46-454.
DR PDB; 3L3A; X-ray; 2.36 A; A=46-454.
DR PDB; 3L58; X-ray; 1.80 A; A/B=41-454.
DR PDB; 3L59; X-ray; 2.00 A; A/B=41-454.
DR PDB; 3L5B; X-ray; 1.80 A; A/B=41-454.
DR PDB; 3L5C; X-ray; 1.80 A; A/B=41-454.
DR PDB; 3L5D; X-ray; 1.75 A; A/B=41-454.
DR PDB; 3L5E; X-ray; 1.53 A; A/B=41-454.
DR PDB; 3L5F; X-ray; 1.70 A; A/B=41-454.
DR PDB; 3LHG; X-ray; 2.10 A; A=46-454.
DR PDB; 3LNK; X-ray; 1.80 A; A/B=53-447.
DR PDB; 3LPI; X-ray; 2.05 A; A/B=14-454.
DR PDB; 3LPJ; X-ray; 1.79 A; A/B=14-454.
DR PDB; 3LPK; X-ray; 1.93 A; A/B=14-454.
DR PDB; 3MSJ; X-ray; 1.80 A; A/B/C=43-453.
DR PDB; 3MSK; X-ray; 2.00 A; A=48-453.
DR PDB; 3MSL; X-ray; 2.40 A; A=48-453.
DR PDB; 3N4L; X-ray; 2.70 A; A/B/C=57-453.
DR PDB; 3NSH; X-ray; 2.20 A; A/B/C=57-453.
DR PDB; 3OHF; X-ray; 2.10 A; A/B=14-454.
DR PDB; 3OHH; X-ray; 2.01 A; A/B=14-454.
DR PDB; 3OOZ; X-ray; 1.80 A; A=46-454.
DR PDB; 3PI5; X-ray; 2.40 A; A/B/C=48-447.
DR PDB; 3QBH; X-ray; 2.24 A; A/B/C=48-447.
DR PDB; 3QI1; X-ray; 2.30 A; A=57-453.
DR PDB; 3R1G; X-ray; 2.80 A; B=57-453.
DR PDB; 3R2F; X-ray; 2.53 A; A/B/D/E=14-454.
DR PDB; 3RSV; X-ray; 2.50 A; A=43-453.
DR PDB; 3RSX; X-ray; 2.48 A; A=43-453.
DR PDB; 3RTH; X-ray; 2.70 A; A=43-453.
DR PDB; 3RTM; X-ray; 2.76 A; A=43-453.
DR PDB; 3RTN; X-ray; 2.70 A; A=43-453.
DR PDB; 3RU1; X-ray; 2.30 A; A=43-453.
DR PDB; 3RVI; X-ray; 2.65 A; A=43-453.
DR PDB; 3S2O; X-ray; 2.60 A; A=48-453.
DR PDB; 3S7L; X-ray; 2.16 A; A=46-454.
DR PDB; 3S7M; X-ray; 2.20 A; A=46-454.
DR PDB; 3SKF; X-ray; 3.00 A; A/B=14-454.
DR PDB; 3SKG; X-ray; 2.88 A; A/B/D/E=14-454.
DR PDB; 3TPJ; X-ray; 1.61 A; A=43-454.
DR PDB; 3TPL; X-ray; 2.50 A; A/B/C=43-454.
DR PDB; 3TPP; X-ray; 1.60 A; A=43-454.
DR PDB; 3TPR; X-ray; 2.55 A; A=43-454.
DR PDB; 3U6A; X-ray; 2.20 A; A/B/C=58-446.
DR PDB; 3UDH; X-ray; 1.70 A; A=58-453.
DR PDB; 3UDJ; X-ray; 1.80 A; A=58-453.
DR PDB; 3UDK; X-ray; 2.51 A; A=58-453.
DR PDB; 3UDM; X-ray; 1.94 A; A=58-453.
DR PDB; 3UDN; X-ray; 2.19 A; A=58-453.
DR PDB; 3UDP; X-ray; 1.95 A; A=58-453.
DR PDB; 3UDQ; X-ray; 2.73 A; A=58-453.
DR PDB; 3UDR; X-ray; 1.95 A; A=58-453.
DR PDB; 3UDY; X-ray; 2.00 A; A=58-453.
DR PDB; 3UFL; X-ray; 1.90 A; A=58-446.
DR PDB; 3UQP; X-ray; 1.77 A; A=43-454.
DR PDB; 3UQR; X-ray; 3.06 A; A/B/C=43-454.
DR PDB; 3UQU; X-ray; 1.70 A; A=43-454.
DR PDB; 3UQW; X-ray; 2.20 A; A=43-454.
DR PDB; 3UQX; X-ray; 1.70 A; A=43-454.
DR PDB; 3VEU; X-ray; 1.52 A; A=48-447.
DR PDB; 3VF3; X-ray; 1.48 A; A=48-447.
DR PDB; 3VG1; X-ray; 1.77 A; A=48-447.
DR PDB; 3VV6; X-ray; 2.05 A; A=43-454.
DR PDB; 3VV7; X-ray; 2.10 A; A=43-454.
DR PDB; 3VV8; X-ray; 2.50 A; A=43-454.
DR PDB; 3WB4; X-ray; 2.25 A; A=43-454.
DR PDB; 3WB5; X-ray; 2.50 A; A=43-454.
DR PDB; 3ZMG; X-ray; 1.74 A; A=46-454.
DR PDB; 3ZOV; X-ray; 2.10 A; A=46-454.
DR PDB; 4ACU; X-ray; 1.75 A; A=43-453.
DR PDB; 4ACX; X-ray; 2.00 A; A=43-453.
DR PDB; 4AZY; X-ray; 1.79 A; A=43-453.
DR PDB; 4B00; X-ray; 1.83 A; A=43-453.
DR PDB; 4B05; X-ray; 1.80 A; A=43-453.
DR PDB; 4B0Q; X-ray; 1.87 A; A=62-445.
DR PDB; 4B1C; X-ray; 1.95 A; A=58-445.
DR PDB; 4B1D; X-ray; 1.95 A; A=58-445.
DR PDB; 4B1E; X-ray; 1.95 A; A=58-445.
DR PDB; 4B70; X-ray; 1.60 A; A=61-445.
DR PDB; 4B72; X-ray; 1.60 A; A=58-445.
DR PDB; 4B77; X-ray; 1.80 A; A=58-445.
DR PDB; 4B78; X-ray; 1.50 A; A=62-445.
DR PDB; 4BEK; X-ray; 2.39 A; A=46-454.
DR PDB; 4BFD; X-ray; 2.30 A; A=46-454.
DR PDB; 4D83; X-ray; 2.40 A; A/B/C=48-447.
DR PDB; 4D85; X-ray; 2.65 A; A=48-453.
DR PDB; 4D88; X-ray; 1.70 A; A=48-447.
DR PDB; 4D89; X-ray; 1.65 A; A=48-447.
DR PDB; 4D8C; X-ray; 2.07 A; A/B/C=48-447.
DR PDB; 4DH6; X-ray; 2.50 A; A=43-453.
DR PDB; 4DI2; X-ray; 2.00 A; A/B/C=43-453.
DR PDB; 4DJU; X-ray; 1.80 A; A/B=41-454.
DR PDB; 4DJV; X-ray; 1.73 A; A/B=41-454.
DR PDB; 4DJW; X-ray; 1.90 A; A/B=41-454.
DR PDB; 4DJX; X-ray; 1.50 A; A/B=41-454.
DR PDB; 4DJY; X-ray; 1.86 A; A/B=41-454.
DR PDB; 4DPF; X-ray; 1.80 A; A=57-446.
DR PDB; 4DPI; X-ray; 1.90 A; A=57-446.
DR PDB; 4DUS; X-ray; 2.50 A; A=43-453.
DR PDB; 4DV9; X-ray; 2.08 A; A=43-454.
DR PDB; 4DVF; X-ray; 1.80 A; A/B=43-454.
DR PDB; 4EWO; X-ray; 1.80 A; A=61-446.
DR PDB; 4EXG; X-ray; 1.80 A; A=61-446.
DR PDB; 4FCO; X-ray; 1.76 A; A=43-454.
DR PDB; 4FGX; X-ray; 1.59 A; A=43-454.
DR PDB; 4FM7; X-ray; 1.56 A; A=58-453.
DR PDB; 4FM8; X-ray; 1.90 A; A=58-453.
DR PDB; 4FRI; X-ray; 2.30 A; A=43-453.
DR PDB; 4FRJ; X-ray; 1.95 A; A=43-453.
DR PDB; 4FRK; X-ray; 2.10 A; A=43-453.
DR PDB; 4FRS; X-ray; 1.70 A; A/B=53-447.
DR PDB; 4FS4; X-ray; 1.74 A; A/B=58-447.
DR PDB; 4FSE; X-ray; 2.65 A; A/B/D/E=14-454.
DR PDB; 4FSL; X-ray; 2.50 A; A/B/D/E=43-453.
DR PDB; 4GID; X-ray; 2.00 A; A/B/C/D=59-446.
DR PDB; 4GMI; X-ray; 1.80 A; A=57-446.
DR PDB; 4H1E; X-ray; 1.90 A; A/B=41-454.
DR PDB; 4H3F; X-ray; 1.70 A; A/B=41-454.
DR PDB; 4H3G; X-ray; 1.85 A; A/B=41-454.
DR PDB; 4H3I; X-ray; 1.96 A; A/B=41-454.
DR PDB; 4H3J; X-ray; 1.60 A; A/B=41-454.
DR PDB; 4HA5; X-ray; 1.83 A; A/B=41-454.
DR PDB; 4HZT; X-ray; 1.80 A; A=57-453.
DR PDB; 4I0D; X-ray; 1.91 A; A=57-453.
DR PDB; 4I0E; X-ray; 1.70 A; A=57-453.
DR PDB; 4I0F; X-ray; 1.80 A; A=57-453.
DR PDB; 4I0G; X-ray; 1.78 A; A=57-453.
DR PDB; 4I0H; X-ray; 2.20 A; A/B/C=57-453.
DR PDB; 4I0I; X-ray; 2.20 A; A/B/C=57-453.
DR PDB; 4I0J; X-ray; 1.99 A; A=57-453.
DR PDB; 4I0Z; X-ray; 1.80 A; A=57-453.
DR PDB; 4I10; X-ray; 2.07 A; A=57-453.
DR PDB; 4I11; X-ray; 1.89 A; A=57-453.
DR PDB; 4I12; X-ray; 1.78 A; A=57-453.
DR PDB; 4I1C; X-ray; 2.00 A; A=57-453.
DR PDB; 4IVS; X-ray; 2.64 A; A=43-454.
DR PDB; 4IVT; X-ray; 1.60 A; A=43-454.
DR PDB; 4J0P; X-ray; 1.97 A; A=46-454.
DR PDB; 4J0T; X-ray; 2.05 A; A=46-454.
DR PDB; 4J0V; X-ray; 1.94 A; A=46-454.
DR PDB; 4J0Y; X-ray; 1.77 A; A=46-454.
DR PDB; 4J0Z; X-ray; 2.13 A; A=46-454.
DR PDB; 4J17; X-ray; 1.81 A; A=46-454.
DR PDB; 4J1C; X-ray; 2.01 A; A=46-454.
DR PDB; 4J1E; X-ray; 1.78 A; A=46-454.
DR PDB; 4J1F; X-ray; 2.25 A; A=46-454.
DR PDB; 4J1H; X-ray; 2.20 A; A=46-454.
DR PDB; 4J1I; X-ray; 2.05 A; A=46-454.
DR PDB; 4J1K; X-ray; 2.18 A; A=46-454.
DR PDB; 4JOO; X-ray; 1.80 A; A=57-453.
DR PDB; 4JP9; X-ray; 1.80 A; A=57-453.
DR PDB; 4JPC; X-ray; 1.80 A; A=57-453.
DR PDB; 4JPE; X-ray; 1.80 A; A=57-453.
DR PDB; 4K8S; X-ray; 2.39 A; A/B/C=59-446.
DR PDB; 4K9H; X-ray; 2.29 A; A/B/C=59-446.
DR PDB; 4KE0; X-ray; 2.30 A; A/B/C=43-453.
DR PDB; 4KE1; X-ray; 1.91 A; A=43-453.
DR PDB; 4L7G; X-ray; 1.38 A; A=57-453.
DR PDB; 4L7H; X-ray; 1.85 A; A=57-453.
DR PDB; 4L7J; X-ray; 1.65 A; A=57-453.
DR PDB; 4LC7; X-ray; 1.70 A; A=57-453.
DR PDB; 4LXA; X-ray; 1.95 A; A/B/C=48-447.
DR PDB; 4LXK; X-ray; 2.05 A; A/B/C=48-447.
DR PDB; 4LXM; X-ray; 2.30 A; A/B/C=48-447.
DR PDB; 4N00; X-ray; 1.80 A; A=57-453.
DR PDB; 4PZW; X-ray; 1.80 A; A=57-453.
DR PDB; 4PZX; X-ray; 1.80 A; A=57-453.
DR PDB; 4R5N; X-ray; 1.80 A; A=57-453.
DR PDB; 4R8Y; X-ray; 1.90 A; A/B=41-454.
DR PDB; 4R91; X-ray; 1.58 A; A/B=41-454.
DR PDB; 4R92; X-ray; 1.71 A; A/B=41-454.
DR PDB; 4R93; X-ray; 1.71 A; A/B=41-454.
DR PDB; 4R95; X-ray; 1.99 A; A/B=41-454.
DR PDB; 4RCD; X-ray; 1.90 A; A=43-453.
DR PDB; 4RCE; X-ray; 2.40 A; A=43-453.
DR PDB; 4RCF; X-ray; 1.78 A; A=43-453.
DR PDB; 4RRN; X-ray; 1.80 A; A=57-453.
DR PDB; 4RRO; X-ray; 1.80 A; A=57-453.
DR PDB; 4RRS; X-ray; 1.80 A; A=57-453.
DR PDB; 4TRW; X-ray; 2.85 A; A/B/C=58-447.
DR PDB; 4TRY; X-ray; 2.75 A; A/B/C=60-447.
DR PDB; 4TRZ; X-ray; 3.25 A; A/B/C=60-447.
DR PDB; 4WTU; X-ray; 1.85 A; A=43-453.
DR PDB; 4WY1; X-ray; 1.98 A; A=58-453.
DR PDB; 4WY6; X-ray; 2.10 A; A=46-454.
DR PDB; 4X2L; X-ray; 2.55 A; A=46-454.
DR PDB; 4X7I; X-ray; 1.77 A; A/B=14-454.
DR PDB; 4XKX; X-ray; 1.80 A; A=43-453.
DR PDB; 4XXS; X-ray; 1.86 A; A=46-454.
DR PDB; 4YBI; X-ray; 1.84 A; A/B=14-454.
DR PDB; 4ZPE; X-ray; 1.70 A; A=43-446.
DR PDB; 4ZPF; X-ray; 1.80 A; A=43-446.
DR PDB; 4ZPG; X-ray; 2.00 A; A=43-446.
DR PDB; 4ZSM; X-ray; 1.96 A; A/B=14-454.
DR PDB; 4ZSP; X-ray; 1.91 A; A/B=14-454.
DR PDB; 4ZSQ; X-ray; 2.30 A; A/B=14-454.
DR PDB; 4ZSR; X-ray; 1.65 A; A/B=14-454.
DR PDB; 5CLM; X-ray; 2.61 A; A=46-446.
DR PDB; 5DQC; X-ray; 2.47 A; A/B/C=58-447.
DR PDB; 5ENK; X-ray; 2.11 A; A=14-454.
DR PDB; 5ENM; X-ray; 1.98 A; A=14-454.
DR PDB; 5EZX; X-ray; 1.90 A; A=57-446.
DR PDB; 5EZZ; X-ray; 2.10 A; A=57-446.
DR PDB; 5F00; X-ray; 1.95 A; A=57-446.
DR PDB; 5F01; X-ray; 1.52 A; A=57-446.
DR PDB; 5HD0; X-ray; 1.65 A; A/B=41-454.
DR PDB; 5HDU; X-ray; 1.58 A; A/B=41-454.
DR PDB; 5HDV; X-ray; 1.71 A; A/B=41-454.
DR PDB; 5HDX; X-ray; 1.60 A; A/B=41-454.
DR PDB; 5HDZ; X-ray; 1.49 A; A/B=41-454.
DR PDB; 5HE4; X-ray; 1.53 A; A/B=41-454.
DR PDB; 5HE5; X-ray; 1.55 A; A/B=41-454.
DR PDB; 5HE7; X-ray; 1.71 A; A/B=41-454.
DR PDB; 5HTZ; X-ray; 1.95 A; A/B=43-454.
DR PDB; 5HU0; X-ray; 1.83 A; A/B=43-454.
DR PDB; 5HU1; X-ray; 1.50 A; A/B=43-454.
DR PDB; 5I3V; X-ray; 1.62 A; A=43-453.
DR PDB; 5I3W; X-ray; 2.15 A; A=43-453.
DR PDB; 5I3X; X-ray; 1.85 A; A=43-453.
DR PDB; 5I3Y; X-ray; 2.15 A; A=43-453.
DR PDB; 5IE1; X-ray; 2.30 A; A=43-453.
DR PDB; 5KQF; X-ray; 1.98 A; A=14-454.
DR PDB; 5KR8; X-ray; 2.12 A; A=14-454.
DR PDB; 5MBW; X-ray; 2.95 A; A=46-454.
DR PDB; 5MCO; X-ray; 2.49 A; A=46-454.
DR PDB; 5MCQ; X-ray; 1.82 A; A=46-454.
DR PDB; 5MXD; X-ray; 2.52 A; A/B/C=22-446.
DR PDB; 5QCO; X-ray; 2.70 A; A/B/C=48-447.
DR PDB; 5QCP; X-ray; 2.45 A; A/B/C=48-447.
DR PDB; 5QCQ; X-ray; 1.97 A; A/B/C=48-447.
DR PDB; 5QCR; X-ray; 2.20 A; A/B/C=48-447.
DR PDB; 5QCS; X-ray; 2.31 A; A/B/C=48-447.
DR PDB; 5QCT; X-ray; 2.05 A; A/B/C=48-447.
DR PDB; 5QCU; X-ray; 1.95 A; A/B/C=48-447.
DR PDB; 5QCV; X-ray; 2.25 A; A/B/C=48-447.
DR PDB; 5QCW; X-ray; 2.10 A; A/B/C=48-447.
DR PDB; 5QCX; X-ray; 2.20 A; A/B/C=48-447.
DR PDB; 5QCY; X-ray; 2.15 A; A/B/C=48-447.
DR PDB; 5QCZ; X-ray; 2.30 A; A/B/C=48-447.
DR PDB; 5QD0; X-ray; 2.60 A; A/B/C=48-447.
DR PDB; 5QD1; X-ray; 2.40 A; A/B/C=48-447.
DR PDB; 5QD2; X-ray; 2.50 A; A/B/C=48-447.
DR PDB; 5QD3; X-ray; 2.46 A; A/B/C=48-447.
DR PDB; 5QD4; X-ray; 2.11 A; A/B/C=48-447.
DR PDB; 5QD5; X-ray; 2.30 A; A/B/C=48-447.
DR PDB; 5QD6; X-ray; 2.51 A; A/B/C=48-447.
DR PDB; 5QD7; X-ray; 2.12 A; A/B/C=48-447.
DR PDB; 5QD8; X-ray; 2.45 A; A/B/C=48-447.
DR PDB; 5QD9; X-ray; 2.60 A; A/B/C=48-447.
DR PDB; 5QDA; X-ray; 2.10 A; A/B/C=48-447.
DR PDB; 5QDB; X-ray; 2.10 A; A/B/C=48-447.
DR PDB; 5QDC; X-ray; 2.10 A; A/B/C=48-447.
DR PDB; 5QDD; X-ray; 2.00 A; A/B/C=48-447.
DR PDB; 5T1U; X-ray; 1.78 A; A=46-454.
DR PDB; 5T1W; X-ray; 2.96 A; A=46-454.
DR PDB; 5TOL; X-ray; 2.51 A; A=43-454.
DR PDB; 5UYU; X-ray; 1.90 A; A=43-453.
DR PDB; 5V0N; X-ray; 2.15 A; A/B/C=14-454.
DR PDB; 5YGX; X-ray; 2.20 A; A=43-454.
DR PDB; 5YGY; X-ray; 2.30 A; A=43-454.
DR PDB; 6BFD; X-ray; 1.62 A; A/B=14-454.
DR PDB; 6BFE; X-ray; 1.51 A; A/B=14-454.
DR PDB; 6BFW; X-ray; 1.84 A; A/B=14-454.
DR PDB; 6BFX; X-ray; 1.99 A; A/B=14-454.
DR PDB; 6C2I; X-ray; 1.95 A; A=43-453.
DR PDB; 6DHC; X-ray; 2.85 A; A/B/C=14-454.
DR PDB; 6DMI; X-ray; 1.90 A; A=57-446.
DR PDB; 6E3Z; X-ray; 1.94 A; A/B/C=22-446.
DR PDB; 6EJ2; X-ray; 1.46 A; A=1-501.
DR PDB; 6EJ3; X-ray; 1.94 A; A=1-501.
DR PDB; 6EQM; X-ray; 1.35 A; A=48-447.
DR PDB; 6FGY; X-ray; 1.54 A; A=60-453.
DR PDB; 6JSE; X-ray; 2.00 A; A=43-454.
DR PDB; 6JSF; X-ray; 2.30 A; A=43-454.
DR PDB; 6JSG; X-ray; 2.30 A; A=43-454.
DR PDB; 6JSN; X-ray; 2.60 A; A=43-454.
DR PDB; 6JT3; X-ray; 2.40 A; A=43-454.
DR PDB; 6JT4; X-ray; 2.20 A; A=43-454.
DR PDB; 6NV7; X-ray; 2.13 A; A/B/C=58-447.
DR PDB; 6NV9; X-ray; 2.13 A; A/B/C=58-447.
DR PDB; 6NW3; X-ray; 2.35 A; A/B/C=58-447.
DR PDB; 6OD6; X-ray; 2.00 A; A/B/C=22-446.
DR PDB; 6PZ4; X-ray; 1.85 A; A=43-453.
DR PDB; 6UVP; X-ray; 1.56 A; A/B=14-454.
DR PDB; 6UVV; X-ray; 1.63 A; A/B=14-454.
DR PDB; 6UVY; X-ray; 1.71 A; A/B=14-454.
DR PDB; 6UWP; X-ray; 1.29 A; A/B=14-454.
DR PDB; 6UWV; X-ray; 1.47 A; A/B=14-454.
DR PDB; 6WNY; X-ray; 1.86 A; A=43-453.
DR PDB; 7B1E; X-ray; 1.62 A; A=48-447.
DR PDB; 7B1P; X-ray; 1.77 A; A=48-447.
DR PDB; 7B1Q; X-ray; 1.94 A; A=48-447.
DR PDB; 7D2V; X-ray; 2.10 A; A=43-454.
DR PDB; 7D2X; X-ray; 2.45 A; A=43-454.
DR PDB; 7D36; X-ray; 2.30 A; A=43-454.
DR PDB; 7D5A; X-ray; 2.20 A; A=43-454.
DR PDB; 7DCZ; X-ray; 2.30 A; A=43-454.
DR PDB; 7F1D; X-ray; 2.05 A; A=43-454.
DR PDB; 7MYI; X-ray; 1.25 A; A/B=14-454.
DR PDB; 7MYR; X-ray; 1.72 A; A/B=14-454.
DR PDB; 7MYU; X-ray; 1.94 A; A/B=14-454.
DR PDB; 7N66; X-ray; 2.10 A; A=43-454.
DR PDBsum; 1FKN; -.
DR PDBsum; 1M4H; -.
DR PDBsum; 1PY1; -.
DR PDBsum; 1SGZ; -.
DR PDBsum; 1TQF; -.
DR PDBsum; 1UJJ; -.
DR PDBsum; 1UJK; -.
DR PDBsum; 1W50; -.
DR PDBsum; 1W51; -.
DR PDBsum; 1XN2; -.
DR PDBsum; 1XN3; -.
DR PDBsum; 1XS7; -.
DR PDBsum; 1YM2; -.
DR PDBsum; 1YM4; -.
DR PDBsum; 2B8L; -.
DR PDBsum; 2B8V; -.
DR PDBsum; 2F3E; -.
DR PDBsum; 2F3F; -.
DR PDBsum; 2FDP; -.
DR PDBsum; 2G94; -.
DR PDBsum; 2HIZ; -.
DR PDBsum; 2HM1; -.
DR PDBsum; 2IQG; -.
DR PDBsum; 2IRZ; -.
DR PDBsum; 2IS0; -.
DR PDBsum; 2NTR; -.
DR PDBsum; 2OAH; -.
DR PDBsum; 2OF0; -.
DR PDBsum; 2OHK; -.
DR PDBsum; 2OHL; -.
DR PDBsum; 2OHM; -.
DR PDBsum; 2OHN; -.
DR PDBsum; 2OHP; -.
DR PDBsum; 2OHQ; -.
DR PDBsum; 2OHR; -.
DR PDBsum; 2OHS; -.
DR PDBsum; 2OHT; -.
DR PDBsum; 2OHU; -.
DR PDBsum; 2P4J; -.
DR PDBsum; 2P83; -.
DR PDBsum; 2P8H; -.
DR PDBsum; 2PH6; -.
DR PDBsum; 2PH8; -.
DR PDBsum; 2Q11; -.
DR PDBsum; 2Q15; -.
DR PDBsum; 2QK5; -.
DR PDBsum; 2QMD; -.
DR PDBsum; 2QMF; -.
DR PDBsum; 2QMG; -.
DR PDBsum; 2QP8; -.
DR PDBsum; 2QU2; -.
DR PDBsum; 2QU3; -.
DR PDBsum; 2QZK; -.
DR PDBsum; 2QZL; -.
DR PDBsum; 2VA5; -.
DR PDBsum; 2VA6; -.
DR PDBsum; 2VA7; -.
DR PDBsum; 2VIE; -.
DR PDBsum; 2VIJ; -.
DR PDBsum; 2VIY; -.
DR PDBsum; 2VIZ; -.
DR PDBsum; 2VJ6; -.
DR PDBsum; 2VJ7; -.
DR PDBsum; 2VJ9; -.
DR PDBsum; 2VKM; -.
DR PDBsum; 2VNM; -.
DR PDBsum; 2VNN; -.
DR PDBsum; 2WEZ; -.
DR PDBsum; 2WF0; -.
DR PDBsum; 2WF1; -.
DR PDBsum; 2WF2; -.
DR PDBsum; 2WF3; -.
DR PDBsum; 2WF4; -.
DR PDBsum; 2WJO; -.
DR PDBsum; 2XFI; -.
DR PDBsum; 2XFJ; -.
DR PDBsum; 2XFK; -.
DR PDBsum; 2ZDZ; -.
DR PDBsum; 2ZE1; -.
DR PDBsum; 2ZHR; -.
DR PDBsum; 2ZHS; -.
DR PDBsum; 2ZHT; -.
DR PDBsum; 2ZHU; -.
DR PDBsum; 2ZHV; -.
DR PDBsum; 2ZJH; -.
DR PDBsum; 2ZJI; -.
DR PDBsum; 2ZJJ; -.
DR PDBsum; 2ZJK; -.
DR PDBsum; 2ZJL; -.
DR PDBsum; 2ZJM; -.
DR PDBsum; 2ZJN; -.
DR PDBsum; 3BRA; -.
DR PDBsum; 3BUF; -.
DR PDBsum; 3BUG; -.
DR PDBsum; 3BUH; -.
DR PDBsum; 3CIB; -.
DR PDBsum; 3CIC; -.
DR PDBsum; 3CID; -.
DR PDBsum; 3CKP; -.
DR PDBsum; 3CKR; -.
DR PDBsum; 3DM6; -.
DR PDBsum; 3DUY; -.
DR PDBsum; 3DV1; -.
DR PDBsum; 3DV5; -.
DR PDBsum; 3EXO; -.
DR PDBsum; 3FKT; -.
DR PDBsum; 3H0B; -.
DR PDBsum; 3HVG; -.
DR PDBsum; 3HW1; -.
DR PDBsum; 3I25; -.
DR PDBsum; 3IGB; -.
DR PDBsum; 3IN3; -.
DR PDBsum; 3IN4; -.
DR PDBsum; 3IND; -.
DR PDBsum; 3INE; -.
DR PDBsum; 3INF; -.
DR PDBsum; 3INH; -.
DR PDBsum; 3IVH; -.
DR PDBsum; 3IVI; -.
DR PDBsum; 3IXJ; -.
DR PDBsum; 3IXK; -.
DR PDBsum; 3K5C; -.
DR PDBsum; 3K5D; -.
DR PDBsum; 3K5F; -.
DR PDBsum; 3K5G; -.
DR PDBsum; 3KMX; -.
DR PDBsum; 3KMY; -.
DR PDBsum; 3KN0; -.
DR PDBsum; 3KYR; -.
DR PDBsum; 3L38; -.
DR PDBsum; 3L3A; -.
DR PDBsum; 3L58; -.
DR PDBsum; 3L59; -.
DR PDBsum; 3L5B; -.
DR PDBsum; 3L5C; -.
DR PDBsum; 3L5D; -.
DR PDBsum; 3L5E; -.
DR PDBsum; 3L5F; -.
DR PDBsum; 3LHG; -.
DR PDBsum; 3LNK; -.
DR PDBsum; 3LPI; -.
DR PDBsum; 3LPJ; -.
DR PDBsum; 3LPK; -.
DR PDBsum; 3MSJ; -.
DR PDBsum; 3MSK; -.
DR PDBsum; 3MSL; -.
DR PDBsum; 3N4L; -.
DR PDBsum; 3NSH; -.
DR PDBsum; 3OHF; -.
DR PDBsum; 3OHH; -.
DR PDBsum; 3OOZ; -.
DR PDBsum; 3PI5; -.
DR PDBsum; 3QBH; -.
DR PDBsum; 3QI1; -.
DR PDBsum; 3R1G; -.
DR PDBsum; 3R2F; -.
DR PDBsum; 3RSV; -.
DR PDBsum; 3RSX; -.
DR PDBsum; 3RTH; -.
DR PDBsum; 3RTM; -.
DR PDBsum; 3RTN; -.
DR PDBsum; 3RU1; -.
DR PDBsum; 3RVI; -.
DR PDBsum; 3S2O; -.
DR PDBsum; 3S7L; -.
DR PDBsum; 3S7M; -.
DR PDBsum; 3SKF; -.
DR PDBsum; 3SKG; -.
DR PDBsum; 3TPJ; -.
DR PDBsum; 3TPL; -.
DR PDBsum; 3TPP; -.
DR PDBsum; 3TPR; -.
DR PDBsum; 3U6A; -.
DR PDBsum; 3UDH; -.
DR PDBsum; 3UDJ; -.
DR PDBsum; 3UDK; -.
DR PDBsum; 3UDM; -.
DR PDBsum; 3UDN; -.
DR PDBsum; 3UDP; -.
DR PDBsum; 3UDQ; -.
DR PDBsum; 3UDR; -.
DR PDBsum; 3UDY; -.
DR PDBsum; 3UFL; -.
DR PDBsum; 3UQP; -.
DR PDBsum; 3UQR; -.
DR PDBsum; 3UQU; -.
DR PDBsum; 3UQW; -.
DR PDBsum; 3UQX; -.
DR PDBsum; 3VEU; -.
DR PDBsum; 3VF3; -.
DR PDBsum; 3VG1; -.
DR PDBsum; 3VV6; -.
DR PDBsum; 3VV7; -.
DR PDBsum; 3VV8; -.
DR PDBsum; 3WB4; -.
DR PDBsum; 3WB5; -.
DR PDBsum; 3ZMG; -.
DR PDBsum; 3ZOV; -.
DR PDBsum; 4ACU; -.
DR PDBsum; 4ACX; -.
DR PDBsum; 4AZY; -.
DR PDBsum; 4B00; -.
DR PDBsum; 4B05; -.
DR PDBsum; 4B0Q; -.
DR PDBsum; 4B1C; -.
DR PDBsum; 4B1D; -.
DR PDBsum; 4B1E; -.
DR PDBsum; 4B70; -.
DR PDBsum; 4B72; -.
DR PDBsum; 4B77; -.
DR PDBsum; 4B78; -.
DR PDBsum; 4BEK; -.
DR PDBsum; 4BFD; -.
DR PDBsum; 4D83; -.
DR PDBsum; 4D85; -.
DR PDBsum; 4D88; -.
DR PDBsum; 4D89; -.
DR PDBsum; 4D8C; -.
DR PDBsum; 4DH6; -.
DR PDBsum; 4DI2; -.
DR PDBsum; 4DJU; -.
DR PDBsum; 4DJV; -.
DR PDBsum; 4DJW; -.
DR PDBsum; 4DJX; -.
DR PDBsum; 4DJY; -.
DR PDBsum; 4DPF; -.
DR PDBsum; 4DPI; -.
DR PDBsum; 4DUS; -.
DR PDBsum; 4DV9; -.
DR PDBsum; 4DVF; -.
DR PDBsum; 4EWO; -.
DR PDBsum; 4EXG; -.
DR PDBsum; 4FCO; -.
DR PDBsum; 4FGX; -.
DR PDBsum; 4FM7; -.
DR PDBsum; 4FM8; -.
DR PDBsum; 4FRI; -.
DR PDBsum; 4FRJ; -.
DR PDBsum; 4FRK; -.
DR PDBsum; 4FRS; -.
DR PDBsum; 4FS4; -.
DR PDBsum; 4FSE; -.
DR PDBsum; 4FSL; -.
DR PDBsum; 4GID; -.
DR PDBsum; 4GMI; -.
DR PDBsum; 4H1E; -.
DR PDBsum; 4H3F; -.
DR PDBsum; 4H3G; -.
DR PDBsum; 4H3I; -.
DR PDBsum; 4H3J; -.
DR PDBsum; 4HA5; -.
DR PDBsum; 4HZT; -.
DR PDBsum; 4I0D; -.
DR PDBsum; 4I0E; -.
DR PDBsum; 4I0F; -.
DR PDBsum; 4I0G; -.
DR PDBsum; 4I0H; -.
DR PDBsum; 4I0I; -.
DR PDBsum; 4I0J; -.
DR PDBsum; 4I0Z; -.
DR PDBsum; 4I10; -.
DR PDBsum; 4I11; -.
DR PDBsum; 4I12; -.
DR PDBsum; 4I1C; -.
DR PDBsum; 4IVS; -.
DR PDBsum; 4IVT; -.
DR PDBsum; 4J0P; -.
DR PDBsum; 4J0T; -.
DR PDBsum; 4J0V; -.
DR PDBsum; 4J0Y; -.
DR PDBsum; 4J0Z; -.
DR PDBsum; 4J17; -.
DR PDBsum; 4J1C; -.
DR PDBsum; 4J1E; -.
DR PDBsum; 4J1F; -.
DR PDBsum; 4J1H; -.
DR PDBsum; 4J1I; -.
DR PDBsum; 4J1K; -.
DR PDBsum; 4JOO; -.
DR PDBsum; 4JP9; -.
DR PDBsum; 4JPC; -.
DR PDBsum; 4JPE; -.
DR PDBsum; 4K8S; -.
DR PDBsum; 4K9H; -.
DR PDBsum; 4KE0; -.
DR PDBsum; 4KE1; -.
DR PDBsum; 4L7G; -.
DR PDBsum; 4L7H; -.
DR PDBsum; 4L7J; -.
DR PDBsum; 4LC7; -.
DR PDBsum; 4LXA; -.
DR PDBsum; 4LXK; -.
DR PDBsum; 4LXM; -.
DR PDBsum; 4N00; -.
DR PDBsum; 4PZW; -.
DR PDBsum; 4PZX; -.
DR PDBsum; 4R5N; -.
DR PDBsum; 4R8Y; -.
DR PDBsum; 4R91; -.
DR PDBsum; 4R92; -.
DR PDBsum; 4R93; -.
DR PDBsum; 4R95; -.
DR PDBsum; 4RCD; -.
DR PDBsum; 4RCE; -.
DR PDBsum; 4RCF; -.
DR PDBsum; 4RRN; -.
DR PDBsum; 4RRO; -.
DR PDBsum; 4RRS; -.
DR PDBsum; 4TRW; -.
DR PDBsum; 4TRY; -.
DR PDBsum; 4TRZ; -.
DR PDBsum; 4WTU; -.
DR PDBsum; 4WY1; -.
DR PDBsum; 4WY6; -.
DR PDBsum; 4X2L; -.
DR PDBsum; 4X7I; -.
DR PDBsum; 4XKX; -.
DR PDBsum; 4XXS; -.
DR PDBsum; 4YBI; -.
DR PDBsum; 4ZPE; -.
DR PDBsum; 4ZPF; -.
DR PDBsum; 4ZPG; -.
DR PDBsum; 4ZSM; -.
DR PDBsum; 4ZSP; -.
DR PDBsum; 4ZSQ; -.
DR PDBsum; 4ZSR; -.
DR PDBsum; 5CLM; -.
DR PDBsum; 5DQC; -.
DR PDBsum; 5ENK; -.
DR PDBsum; 5ENM; -.
DR PDBsum; 5EZX; -.
DR PDBsum; 5EZZ; -.
DR PDBsum; 5F00; -.
DR PDBsum; 5F01; -.
DR PDBsum; 5HD0; -.
DR PDBsum; 5HDU; -.
DR PDBsum; 5HDV; -.
DR PDBsum; 5HDX; -.
DR PDBsum; 5HDZ; -.
DR PDBsum; 5HE4; -.
DR PDBsum; 5HE5; -.
DR PDBsum; 5HE7; -.
DR PDBsum; 5HTZ; -.
DR PDBsum; 5HU0; -.
DR PDBsum; 5HU1; -.
DR PDBsum; 5I3V; -.
DR PDBsum; 5I3W; -.
DR PDBsum; 5I3X; -.
DR PDBsum; 5I3Y; -.
DR PDBsum; 5IE1; -.
DR PDBsum; 5KQF; -.
DR PDBsum; 5KR8; -.
DR PDBsum; 5MBW; -.
DR PDBsum; 5MCO; -.
DR PDBsum; 5MCQ; -.
DR PDBsum; 5MXD; -.
DR PDBsum; 5QCO; -.
DR PDBsum; 5QCP; -.
DR PDBsum; 5QCQ; -.
DR PDBsum; 5QCR; -.
DR PDBsum; 5QCS; -.
DR PDBsum; 5QCT; -.
DR PDBsum; 5QCU; -.
DR PDBsum; 5QCV; -.
DR PDBsum; 5QCW; -.
DR PDBsum; 5QCX; -.
DR PDBsum; 5QCY; -.
DR PDBsum; 5QCZ; -.
DR PDBsum; 5QD0; -.
DR PDBsum; 5QD1; -.
DR PDBsum; 5QD2; -.
DR PDBsum; 5QD3; -.
DR PDBsum; 5QD4; -.
DR PDBsum; 5QD5; -.
DR PDBsum; 5QD6; -.
DR PDBsum; 5QD7; -.
DR PDBsum; 5QD8; -.
DR PDBsum; 5QD9; -.
DR PDBsum; 5QDA; -.
DR PDBsum; 5QDB; -.
DR PDBsum; 5QDC; -.
DR PDBsum; 5QDD; -.
DR PDBsum; 5T1U; -.
DR PDBsum; 5T1W; -.
DR PDBsum; 5TOL; -.
DR PDBsum; 5UYU; -.
DR PDBsum; 5V0N; -.
DR PDBsum; 5YGX; -.
DR PDBsum; 5YGY; -.
DR PDBsum; 6BFD; -.
DR PDBsum; 6BFE; -.
DR PDBsum; 6BFW; -.
DR PDBsum; 6BFX; -.
DR PDBsum; 6C2I; -.
DR PDBsum; 6DHC; -.
DR PDBsum; 6DMI; -.
DR PDBsum; 6E3Z; -.
DR PDBsum; 6EJ2; -.
DR PDBsum; 6EJ3; -.
DR PDBsum; 6EQM; -.
DR PDBsum; 6FGY; -.
DR PDBsum; 6JSE; -.
DR PDBsum; 6JSF; -.
DR PDBsum; 6JSG; -.
DR PDBsum; 6JSN; -.
DR PDBsum; 6JT3; -.
DR PDBsum; 6JT4; -.
DR PDBsum; 6NV7; -.
DR PDBsum; 6NV9; -.
DR PDBsum; 6NW3; -.
DR PDBsum; 6OD6; -.
DR PDBsum; 6PZ4; -.
DR PDBsum; 6UVP; -.
DR PDBsum; 6UVV; -.
DR PDBsum; 6UVY; -.
DR PDBsum; 6UWP; -.
DR PDBsum; 6UWV; -.
DR PDBsum; 6WNY; -.
DR PDBsum; 7B1E; -.
DR PDBsum; 7B1P; -.
DR PDBsum; 7B1Q; -.
DR PDBsum; 7D2V; -.
DR PDBsum; 7D2X; -.
DR PDBsum; 7D36; -.
DR PDBsum; 7D5A; -.
DR PDBsum; 7DCZ; -.
DR PDBsum; 7F1D; -.
DR PDBsum; 7MYI; -.
DR PDBsum; 7MYR; -.
DR PDBsum; 7MYU; -.
DR PDBsum; 7N66; -.
DR AlphaFoldDB; P56817; -.
DR BMRB; P56817; -.
DR SMR; P56817; -.
DR BioGRID; 117154; 31.
DR CORUM; P56817; -.
DR DIP; DIP-41388N; -.
DR IntAct; P56817; 40.
DR MINT; P56817; -.
DR STRING; 9606.ENSP00000318585; -.
DR BindingDB; P56817; -.
DR ChEMBL; CHEMBL4822; -.
DR DrugBank; DB07573; (2S)-1-(2,5-dimethylphenoxy)-3-morpholin-4-ylpropan-2-ol.
DR DrugBank; DB07736; (2S)-4-(4-fluorobenzyl)-N-(2-sulfanylethyl)piperazine-2-carboxamide.
DR DrugBank; DB07737; (2S)-4-(4-fluorobenzyl)-N-(3-sulfanylpropyl)piperazine-2-carboxamide.
DR DrugBank; DB07519; (6R)-2-amino-6-[2-(3'-methoxybiphenyl-3-yl)ethyl]-3,6-dimethyl-5,6-dihydropyrimidin-4(3H)-one.
DR DrugBank; DB07874; (6S)-2-amino-6-(3'-methoxybiphenyl-3-yl)-3,6-dimethyl-5,6-dihydropyrimidin-4(3H)-one.
DR DrugBank; DB07535; 2-amino-6-[2-(1H-indol-6-yl)ethyl]pyrimidin-4(3H)-one.
DR DrugBank; DB08749; 3-(2-AMINO-6-BENZOYLQUINAZOLIN-3(4H)-YL)-N-CYCLOHEXYL-N-METHYLPROPANAMIDE.
DR DrugBank; DB07345; 4-(2-aminoethyl)-2-cyclohexylphenol.
DR DrugBank; DB07346; 4-(2-aminoethyl)-2-ethylphenol.
DR DrugBank; DB07110; 4-(4-FLUOROBENZYL)PIPERIDINE.
DR DrugBank; DB07415; 4-[(1S)-1-(3-fluoro-4-methoxyphenyl)-2-(2-methoxy-5-nitrophenyl)ethyl]-1H-imidazol-2-amine.
DR DrugBank; DB07206; 6-[2-(1H-INDOL-6-YL)ETHYL]PYRIDIN-2-AMINE.
DR DrugBank; DB07245; 6-[2-(3'-METHOXYBIPHENYL-3-YL)ETHYL]PYRIDIN-2-AMINE.
DR DrugBank; DB06073; CTS-21166.
DR DrugBank; DB02378; MMI-175.
DR DrugBank; DB07734; N-(1-benzylpiperidin-4-yl)-4-sulfanylbutanamide.
DR DrugBank; DB07019; N-[(5R,14R)-5-AMINO-5,14-DIMETHYL-4-OXO-3-OXA-18-AZATRICYCLO[15.3.1.1~7,11~]DOCOSA-1(21),7(22),8,10,17,19-HEXAEN-19-YL]-N-METHYLMETHANESULFONAMIDE.
DR DrugBank; DB07735; N-[1-(2,6-dimethoxybenzyl)piperidin-4-yl]-4-sulfanylbutanamide.
DR DrugBank; DB07738; N-[1-(5-bromo-2,3-dimethoxybenzyl)piperidin-4-yl]-4-sulfanylbutanamide.
DR DrugBank; DB06930; N-[amino(imino)methyl]-2-(2,5-diphenyl-1H-pyrrol-1-yl)acetamide.
DR DrugBank; DB07089; N-[amino(imino)methyl]-2-[2-(2-chlorophenyl)-4-(4-propoxyphenyl)-3-thienyl]acetamide.
DR DrugBank; DB07175; N-{2-methyl-5-[(6-phenylpyrimidin-4-yl)amino]phenyl}methanesulfonamide.
DR DrugBank; DB07284; N~3~-(3-PYRIDIN-3-YLBENZYL)PYRIDINE-2,3-DIAMINE.
DR DrugBank; DB07993; N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2,3-DIAMINE.
DR DrugBank; DB07303; N~3~-[3-(5-METHOXYPYRIDIN-3-YL)BENZYL]PYRIDINE-2,3-DIAMINE.
DR DrugBank; DB07994; N~3~-[5-(1H-INDOL-6-YL)-2-(PYRIDIN-2-YLMETHOXY)BENZYL]PYRIDINE-2,3-DIAMINE.
DR DrugBank; DB07281; N~3~-BENZYLPYRIDINE-2,3-DIAMINE.
DR DrugBank; DB12285; Verubecestat.
DR DrugCentral; P56817; -.
DR GuidetoPHARMACOLOGY; 2330; -.
DR MEROPS; A01.004; -.
DR TCDB; 8.A.32.1.1; the Beta-amyloid cleaving enzyme (bace1) family.
DR GlyConnect; 71; 7 N-Linked glycans.
DR GlyConnect; 72; 10 N-Linked glycans.
DR GlyGen; P56817; 5 sites, 34 N-linked glycans (1 site).
DR iPTMnet; P56817; -.
DR PhosphoSitePlus; P56817; -.
DR SwissPalm; P56817; -.
DR BioMuta; BACE1; -.
DR DMDM; 296434407; -.
DR jPOST; P56817; -.
DR MassIVE; P56817; -.
DR PaxDb; P56817; -.
DR PeptideAtlas; P56817; -.
DR PRIDE; P56817; -.
DR ProteomicsDB; 19820; -.
DR ProteomicsDB; 43307; -.
DR ProteomicsDB; 56947; -. [P56817-1]
DR ProteomicsDB; 56948; -. [P56817-2]
DR ProteomicsDB; 56949; -. [P56817-3]
DR ProteomicsDB; 56950; -. [P56817-4]
DR ABCD; P56817; 4 sequenced antibodies.
DR Antibodypedia; 4285; 912 antibodies from 46 providers.
DR DNASU; 23621; -.
DR Ensembl; ENST00000313005.11; ENSP00000318585.6; ENSG00000186318.18. [P56817-1]
DR Ensembl; ENST00000392937.10; ENSP00000475405.1; ENSG00000186318.18. [P56817-5]
DR Ensembl; ENST00000428381.6; ENSP00000402228.2; ENSG00000186318.18. [P56817-4]
DR Ensembl; ENST00000445823.6; ENSP00000403685.2; ENSG00000186318.18. [P56817-3]
DR Ensembl; ENST00000510630.5; ENSP00000422461.1; ENSG00000186318.18. [P56817-6]
DR Ensembl; ENST00000513780.5; ENSP00000424536.1; ENSG00000186318.18. [P56817-2]
DR GeneID; 23621; -.
DR KEGG; hsa:23621; -.
DR MANE-Select; ENST00000313005.11; ENSP00000318585.6; NM_012104.6; NP_036236.1.
DR UCSC; uc001pqw.4; human. [P56817-1]
DR CTD; 23621; -.
DR DisGeNET; 23621; -.
DR GeneCards; BACE1; -.
DR HGNC; HGNC:933; BACE1.
DR HPA; ENSG00000186318; Group enriched (brain, pancreas).
DR MIM; 604252; gene.
DR neXtProt; NX_P56817; -.
DR OpenTargets; ENSG00000186318; -.
DR PharmGKB; PA25232; -.
DR VEuPathDB; HostDB:ENSG00000186318; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000157786; -.
DR HOGENOM; CLU_039009_0_0_1; -.
DR InParanoid; P56817; -.
DR OMA; ELEDCGY; -.
DR OrthoDB; 429758at2759; -.
DR PhylomeDB; P56817; -.
DR TreeFam; TF329595; -.
DR BioCyc; MetaCyc:ENSG00000160610-MON; -.
DR BRENDA; 3.4.23.46; 2681.
DR PathwayCommons; P56817; -.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SABIO-RK; P56817; -.
DR SignaLink; P56817; -.
DR SIGNOR; P56817; -.
DR BioGRID-ORCS; 23621; 9 hits in 1080 CRISPR screens.
DR ChiTaRS; BACE1; human.
DR EvolutionaryTrace; P56817; -.
DR GeneWiki; Beta-secretase_1; -.
DR GenomeRNAi; 23621; -.
DR Pharos; P56817; Tchem.
DR PRO; PR:P56817; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P56817; protein.
DR Bgee; ENSG00000186318; Expressed in inferior vagus X ganglion and 203 other tissues.
DR ExpressionAtlas; P56817; baseline and differential.
DR Genevisible; P56817; HS.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0070931; C:Golgi-associated vesicle lumen; TAS:Reactome.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005771; C:multivesicular body; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IPI:Alzheimers_University_of_Toronto.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008798; F:beta-aspartyl-peptidase activity; TAS:Reactome.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:CACAO.
DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISS:ARUK-UCL.
DR GO; GO:0034205; P:amyloid-beta formation; IDA:ARUK-UCL.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IDA:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0071287; P:cellular response to manganese ion; IEA:Ensembl.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IGI:ARUK-UCL.
DR GO; GO:0060134; P:prepulse inhibition; IEA:Ensembl.
DR GO; GO:0016485; P:protein processing; IDA:ARUK-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0010288; P:response to lead ion; IEA:Ensembl.
DR GO; GO:0009314; P:response to radiation; IEA:Ensembl.
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; IPR009120; BACE1.
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:SF69; PTHR47965:SF69; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR01815; BACEFAMILY.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Aspartyl protease;
KW Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Endosome;
KW Glycoprotein; Golgi apparatus; Hydrolase; Isopeptide bond; Lipoprotein;
KW Lysosome; Membrane; Palmitate; Phosphoprotein; Protease;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..45
FT /evidence="ECO:0000269|PubMed:10591214"
FT /id="PRO_0000025939"
FT CHAIN 46..501
FT /note="Beta-secretase 1"
FT /id="PRO_0000025940"
FT TOPO_DOM 22..457
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 479..501
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 75..416
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 39..58
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 479..501
FT /note="Interaction with RTN3"
FT MOTIF 496..500
FT /note="DXXLL"
FT /evidence="ECO:0000269|PubMed:15886016"
FT COMPBIAS 43..58
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 289
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT MOD_RES 126
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17425515,
FT ECO:0000269|PubMed:19011241"
FT MOD_RES 275
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17425515,
FT ECO:0000269|PubMed:19011241"
FT MOD_RES 279
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17425515,
FT ECO:0000269|PubMed:19011241"
FT MOD_RES 285
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17425515,
FT ECO:0000269|PubMed:19011241"
FT MOD_RES 299
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17425515,
FT ECO:0000269|PubMed:19011241"
FT MOD_RES 300
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17425515,
FT ECO:0000269|PubMed:19011241"
FT MOD_RES 307
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:17425515,
FT ECO:0000269|PubMed:19011241"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15886016"
FT LIPID 474
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P56818"
FT LIPID 478
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P56818"
FT LIPID 482
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P56818"
FT LIPID 485
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P56818"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 216..420
FT /evidence="ECO:0000269|PubMed:11953458"
FT DISULFID 278..443
FT /evidence="ECO:0000269|PubMed:11953458"
FT DISULFID 330..380
FT /evidence="ECO:0000269|PubMed:11953458"
FT CROSSLNK 501
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20484053,
FT ECO:0000269|PubMed:27302062"
FT VAR_SEQ 1..20
FT /note="MAQALPWLLLWMGAGVLPAH -> MVPFIYLQAHFTLCSGWSST (in
FT isoform 5 and isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_047092"
FT VAR_SEQ 21..120
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_047093"
FT VAR_SEQ 146..189
FT /note="Missing (in isoform C and isoform D)"
FT /evidence="ECO:0000303|PubMed:11516562, ECO:0000303|Ref.6"
FT /id="VSP_005222"
FT VAR_SEQ 190..214
FT /note="Missing (in isoform B, isoform D and isoform 6)"
FT /evidence="ECO:0000303|PubMed:11516562, ECO:0000303|Ref.5"
FT /id="VSP_005223"
FT VARIANT 265
FT /note="V -> A (in dbSNP:rs28989503)"
FT /evidence="ECO:0000269|Ref.10"
FT /id="VAR_060692"
FT VARIANT 481
FT /note="R -> C (in dbSNP:rs539765)"
FT /id="VAR_051509"
FT MUTAGEN 93
FT /note="D->N: Decreases beta-cleaved soluble APP
FT production."
FT /evidence="ECO:0000269|PubMed:10656250"
FT MUTAGEN 284
FT /note="D->N: Almost abolishes beta-cleaved soluble APP
FT production."
FT /evidence="ECO:0000269|PubMed:10656250"
FT MUTAGEN 498
FT /note="S->A: No effect on endocytosis from the cell
FT surface. Increases recycling from endosomes to the cell
FT surface."
FT /evidence="ECO:0000269|PubMed:15615712,
FT ECO:0000269|PubMed:15886016"
FT MUTAGEN 498
FT /note="S->D: No effect on endocytosis form the cell
FT surface. Decreases recycling from endosomes to the cell
FT surface."
FT /evidence="ECO:0000269|PubMed:15886016"
FT MUTAGEN 499..500
FT /note="LL->AA: Impairs endocytosis and produces a delayed
FT retrograde transport to the trans-Golgi network and
FT delivery to the lysosmes, decreasinf its degradation.
FT Disrupts location to late endosomes and lysosomes. Locates
FT mainly at the cell surface. No effect on degradation
FT regulated by GGA3. Effects on protein stability and
FT defective internalization increases; when associated with
FT R-501."
FT /evidence="ECO:0000269|PubMed:15615712,
FT ECO:0000269|PubMed:16033761, ECO:0000269|PubMed:20484053,
FT ECO:0000269|PubMed:23109336"
FT MUTAGEN 501
FT /note="K->R: Inhibits ubiquitination. No effect on
FT endocytosis rate. Induced protein stability and
FT acculmulation in early and late endosomes, lysosomes and
FT cell membrane. Effects on protein stability and defective
FT internalization increases; when associated with A-499-500-
FT A."
FT /evidence="ECO:0000269|PubMed:20484053,
FT ECO:0000269|PubMed:23109336, ECO:0000269|PubMed:27302062"
FT TURN 61..65
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 74..81
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 82..85
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:3S7L"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 122..132
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 135..147
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 149..152
FT /evidence="ECO:0007829|PDB:6E3Z"
FT STRAND 155..168
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:1SGZ"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:4FSL"
FT HELIX 197..204
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 224..229
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 233..239
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 245..253
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 257..260
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 264..269
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 278..282
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 299..312
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 313..315
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:2VA7"
FT HELIX 338..340
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 344..349
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 355..361
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 363..366
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 367..370
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 379..383
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 385..390
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 396..399
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 402..407
FT /evidence="ECO:0007829|PDB:7MYI"
FT TURN 408..411
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 412..418
FT /evidence="ECO:0007829|PDB:7MYI"
FT STRAND 430..436
FT /evidence="ECO:0007829|PDB:7MYI"
FT HELIX 440..443
FT /evidence="ECO:0007829|PDB:7MYI"
SQ SEQUENCE 501 AA; 55764 MW; 377CE4C824ACEF05 CRC64;
MAQALPWLLL WMGAGVLPAH GTQHGIRLPL RSGLGGAPLG LRLPRETDEE PEEPGRRGSF
VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA VGAAPHPFLH RYYQRQLSST
YRDLRKGVYV PYTQGKWEGE LGTDLVSIPH GPNVTVRANI AAITESDKFF INGSNWEGIL
GLAYAEIARP DDSLEPFFDS LVKQTHVPNL FSLQLCGAGF PLNQSEVLAS VGGSMIIGGI
DHSLYTGSLW YTPIRREWYY EVIIVRVEIN GQDLKMDCKE YNYDKSIVDS GTTNLRLPKK
VFEAAVKSIK AASSTEKFPD GFWLGEQLVC WQAGTTPWNI FPVISLYLMG EVTNQSFRIT
ILPQQYLRPV EDVATSQDDC YKFAISQSST GTVMGAVIME GFYVVFDRAR KRIGFAVSAC
HVHDEFRTAA VEGPFVTLDM EDCGYNIPQT DESTLMTIAY VMAAICALFM LPLCLMVCQW
RCLRCLRQQH DDFADDISLL K
