Reviewed, UniProtKB/Swiss-Prot Q9Y5Z0 (BACE2_HUMAN)

Names and origin

Protein names

Recommended name:
    Beta-secretase 2
    EC=3.4.23.45
Alternative name(s):
    Beta-site APP-cleaving enzyme 2
    Aspartyl protease 1
      Short name=Asp 1
      Short name=ASP1
    Membrane-associated aspartic protease 1
    Memapsin-1
    Aspartic-like protease 56 kDa
    Down region aspartic protease
      Short name=DRAP
    Theta-secretase

Gene names

Name:	BACE2
Synonyms:	AEPLC, ALP56, ASP21
ORF Names:	CDA13, UNQ418/PRO852

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	518 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672. Ref.1 Ref.6 Ref.14 Ref.15 Ref.16
Catalytic activity	Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein.
Subunit structure	Monomer. Interacts ith RTN3 and RTN4. Ref.17 Ref.19
Subcellular location	Membrane; Single-pass type I membrane protein. Golgi apparatus. Endoplasmic reticulum. Endosome. Cell surface Ref.6 Ref.15.
Tissue specificity	Brain. Present in neurons within the hippocampus, frontal cortex and temporal cortex (at protein level). Expressed at low levels in most peripheral tissues and at higher levels in colon, kidney, pancreas, placenta, prostate, stomach and trachea. Expressed at low levels in the brain. Found in spinal cord, medulla oblongata, substantia nigra and locus coruleus. Expressed in the ductal epithelium of both normal and malignant prostate. Ref.1 Ref.6 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7
Induction	Up-regulated in primary breast and colon tumors and liver metastasis. Ref.2
Post-translational modification	Undergoes autoproteolytic cleavage. Glycosylated. Ref.6 Ref.4
Sequence similarities	Belongs to the peptidase A1 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Endosome Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Autocatalytic cleavage Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	membrane protein ectodomain proteolysis Ref.1 Inferred from direct assay. Source: UniProtKB negative regulation of amyloid precursor protein biosynthetic process Inferred from mutant phenotype. Source: UniProtKB peptide hormone processing Ref.5 Non-traceable author statement. Source: UniProtKB
Cellular component	Golgi apparatus Ref.15 Inferred from direct assay. Source: UniProtKB cell surface Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell endosome Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Ref.5 Non-traceable author statement. Source: UniProtKB
Molecular function	aspartic-type endopeptidase activity Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y5Z0-1)

Also known as: Isoform A;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y5Z0-2)

Also known as: Isoform B;

The sequence of this isoform differs from the canonical sequence as follows:
     329-378: Missing.

Isoform 3 (identifier: Q9Y5Z0-3)

Also known as: Isoform C;

The sequence of this isoform differs from the canonical sequence as follows:
     379-396: LYIQPMMGAGLNYECYRF → KLRVLQCLKFPGLSQQRF
     397-518: Missing.

Isoform 4 (identifier: Q9Y5Z0-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.

Isoform 5 (identifier: Q9Y5Z0-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-95: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Potential

Propeptide

21 – 62

42

PRO_0000025945

Chain

63 – 518

456

Beta-secretase 2

PRO_0000025946

Regions

Topological domain

21 – 473

453

Extracellular Potential

Transmembrane

474 – 494

21

Potential

Topological domain

495 – 518

24

Cytoplasmic Potential

Sites

Active site

110

1

Active site

303

1

Amino acid modifications

Glycosylation

170

1

N-linked (GlcNAc...) Potential

Glycosylation

366

1

N-linked (GlcNAc...) Potential

Disulfide bond

233 ↔ 433

Ref.17

Disulfide bond

292 ↔ 457

Ref.17

Disulfide bond

344 ↔ 393

Ref.17

Natural variations

Alternative sequence

1 – 95

95

Missing in isoform 5.

VSP_038023

Alternative sequence

1 – 79

79

Missing in isoform 4.

VSP_038024

Alternative sequence

329 – 378

50

Missing in isoform 2.

VSP_038025

Alternative sequence

379 – 396

18

LYIQP…ECYRF → KLRVLQCLKFPGLSQQRF in isoform 3.

VSP_038026

Alternative sequence

397 – 518

122

Missing in isoform 3.

VSP_038027

Experimental info

Mutagenesis

110

1

D → A or N: Loss of autoproteolytic cleavage. Ref.2 Ref.18

Mutagenesis

303

1

D → A: Loss of autoproteolytic cleavage. Ref.2

Sequence conflict

36

1

A → T in AAF13714. Ref.7

Sequence conflict

184

1

E → G in BAC11682. Ref.10

Sequence conflict

192

1

K → Q in BAC11682. Ref.10

Sequence conflict

233

1

C → R in BAC11682. Ref.10

Secondary structure

1

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518

Helix Strand Turn

Details...

Beta strand

93 – 98

6

Beta strand

103 – 109

7

Helix

132 – 134

3

Beta strand

161 – 164

4

Beta strand

173 – 175

3

Beta strand

181 – 185

5

Helix

202 – 204

3

Helix

214 – 222

9

Beta strand

228 – 231

4

Helix

256 – 258

3

Beta strand

263 – 267

5

Turn

271 – 274

4

Beta strand

278 – 282

5

Turn

292 – 296

5

Beta strand

310 – 312

3

Helix

313 – 325

13

Beta strand

341 – 345

5

Beta strand

347 – 349

3

Helix

351 – 354

4

Beta strand

358 – 363

6

Beta strand

369 – 375

7

Helix

377 – 380

4

Beta strand

381 – 384

4

Beta strand

391 – 395

5

Beta strand

399 – 403

5

Beta strand

405 – 407

3

Turn

410 – 412

3

Beta strand

416 – 420

5

Turn

421 – 424

4

Beta strand

442 – 445

4

Beta strand

447 – 449

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Isoform A) [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 2E903150823760D3	FASTA	518	56,180
	10 20 30 40 50 60 MGALARALLL PLLAQWLLRA APELAPAPFT LPLRVAAATN RVVAPTPGPG TPAERHADGL 70 80 90 100 110 120 ALALEPALAS PAGAANFLAM VDNLQGDSGR GYYLEMLIGT PPQKLQILVD TGSSNFAVAG 130 140 150 160 170 180 TPHSYIDTYF DTERSSTYRS KGFDVTVKYT QGSWTGFVGE DLVTIPKGFN TSFLVNIATI 190 200 210 220 230 240 FESENFFLPG IKWNGILGLA YATLAKPSSS LETFFDSLVT QANIPNVFSM QMCGAGLPVA 250 260 270 280 290 300 GSGTNGGSLV LGGIEPSLYK GDIWYTPIKE EWYYQIEILK LEIGGQSLNL DCREYNADKA 310 320 330 340 350 360 IVDSGTTLLR LPQKVFDAVV EAVARASLIP EFSDGFWTGS QLACWTNSET PWSYFPKISI 370 380 390 400 410 420 YLRDENSSRS FRITILPQLY IQPMMGAGLN YECYRFGISP STNALVIGAT VMEGFYVIFD 430 440 450 460 470 480 RAQKRVGFAA SPCAEIAGAA VSEISGPFST EDVASNCVPA QSLSEPILWI VSYALMSVCG 490 500 510 AILLVLIVLL LLPFRCQRRP RDPEVVNDES SLVRHRWK
	Isoform 2 (Isoform B). Checksum: 717E0920126A0142	FASTA	468	50,325
	10 20 30 40 50 60 MGALARALLL PLLAQWLLRA APELAPAPFT LPLRVAAATN RVVAPTPGPG TPAERHADGL 70 80 90 100 110 120 ALALEPALAS PAGAANFLAM VDNLQGDSGR GYYLEMLIGT PPQKLQILVD TGSSNFAVAG 130 140 150 160 170 180 TPHSYIDTYF DTERSSTYRS KGFDVTVKYT QGSWTGFVGE DLVTIPKGFN TSFLVNIATI 190 200 210 220 230 240 FESENFFLPG IKWNGILGLA YATLAKPSSS LETFFDSLVT QANIPNVFSM QMCGAGLPVA 250 260 270 280 290 300 GSGTNGGSLV LGGIEPSLYK GDIWYTPIKE EWYYQIEILK LEIGGQSLNL DCREYNADKA 310 320 330 340 350 360 IVDSGTTLLR LPQKVFDAVV EAVARASLLY IQPMMGAGLN YECYRFGISP STNALVIGAT 370 380 390 400 410 420 VMEGFYVIFD RAQKRVGFAA SPCAEIAGAA VSEISGPFST EDVASNCVPA QSLSEPILWI 430 440 450 460 VSYALMSVCG AILLVLIVLL LLPFRCQRRP RDPEVVNDES SLVRHRWK
	Isoform 3 (Isoform C). Checksum: 5F73A7AF391CEAC9	FASTA	396	43,029
	10 20 30 40 50 60 MGALARALLL PLLAQWLLRA APELAPAPFT LPLRVAAATN RVVAPTPGPG TPAERHADGL 70 80 90 100 110 120 ALALEPALAS PAGAANFLAM VDNLQGDSGR GYYLEMLIGT PPQKLQILVD TGSSNFAVAG 130 140 150 160 170 180 TPHSYIDTYF DTERSSTYRS KGFDVTVKYT QGSWTGFVGE DLVTIPKGFN TSFLVNIATI 190 200 210 220 230 240 FESENFFLPG IKWNGILGLA YATLAKPSSS LETFFDSLVT QANIPNVFSM QMCGAGLPVA 250 260 270 280 290 300 GSGTNGGSLV LGGIEPSLYK GDIWYTPIKE EWYYQIEILK LEIGGQSLNL DCREYNADKA 310 320 330 340 350 360 IVDSGTTLLR LPQKVFDAVV EAVARASLIP EFSDGFWTGS QLACWTNSET PWSYFPKISI 370 380 390 YLRDENSSRS FRITILPQKL RVLQCLKFPG LSQQRF
	Isoform 4. Checksum: 02EC0E0E50F11602	FASTA	439	48,275
	10 20 30 40 50 60 MVDNLQGDSG RGYYLEMLIG TPPQKLQILV DTGSSNFAVA GTPHSYIDTY FDTERSSTYR 70 80 90 100 110 120 SKGFDVTVKY TQGSWTGFVG EDLVTIPKGF NTSFLVNIAT IFESENFFLP GIKWNGILGL 130 140 150 160 170 180 AYATLAKPSS SLETFFDSLV TQANIPNVFS MQMCGAGLPV AGSGTNGGSL VLGGIEPSLY 190 200 210 220 230 240 KGDIWYTPIK EEWYYQIEIL KLEIGGQSLN LDCREYNADK AIVDSGTTLL RLPQKVFDAV 250 260 270 280 290 300 VEAVARASLI PEFSDGFWTG SQLACWTNSE TPWSYFPKIS IYLRDENSSR SFRITILPQL 310 320 330 340 350 360 YIQPMMGAGL NYECYRFGIS PSTNALVIGA TVMEGFYVIF DRAQKRVGFA ASPCAEIAGA 370 380 390 400 410 420 AVSEISGPFS TEDVASNCVP AQSLSEPILW IVSYALMSVC GAILLVLIVL LLLPFRCQRR 430 PRDPEVVNDE SSLVRHRWK
	Isoform 5. Checksum: 675FBF380B57CE7D	FASTA	423	46,476
	10 20 30 40 50 60 MLIGTPPQKL QILVDTGSSN FAVAGTPHSY IDTYFDTERS STYRSKGFDV TVKYTQGSWT 70 80 90 100 110 120 GFVGEDLVTI PKGFNTSFLV NIATIFESEN FFLPGIKWNG ILGLAYATLA KPSSSLETFF 130 140 150 160 170 180 DSLVTQANIP NVFSMQMCGA GLPVAGSGTN GGSLVLGGIE PSLYKGDIWY TPIKEEWYYQ 190 200 210 220 230 240 IEILKLEIGG QSLNLDCREY NADKAIVDSG TTLLRLPQKV FDAVVEAVAR ASLIPEFSDG 250 260 270 280 290 300 FWTGSQLACW TNSETPWSYF PKISIYLRDE NSSRSFRITI LPQLYIQPMM GAGLNYECYR 310 320 330 340 350 360 FGISPSTNAL VIGATVMEGF YVIFDRAQKR VGFAASPCAE IAGAAVSEIS GPFSTEDVAS 370 380 390 400 410 420 NCVPAQSLSE PILWIVSYAL MSVCGAILLV LIVLLLLPFR CQRRPRDPEV VNDESSLVRH RWK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity." Yan R., Bienkowski M.J., Shuck M.E., Miao H., Tory M.C., Pauley A.M., Brashier J.R., Stratman N.C., Mathews W.R., Buhl A.E., Carter D.B., Tomasselli A.G., Parodi L.A., Heinrikson R.L., Gurney M.E. Nature 402:533-537(1999) [PubMed: 10591213] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, TISSUE SPECIFICITY.
[2]	"Identification of a novel aspartic-like protease differentially expressed in human breast cancer cell lines." Xin H., Stephans J.C., Duan X., Harrowe G., Kim E., Grieshammer U., Kingsley C., Giese K. Biochim. Biophys. Acta 1501:125-137(2000) [PubMed: 10838186] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AUTOCATALYTIC CLEAVAGE, INDUCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-110 AND ASP-303. Tissue: Bone marrow.
[3]	"A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase." Solans A., Estivill X., de La Luna S. Cytogenet. Cell Genet. 89:177-184(2000) [PubMed: 10965118] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
[4]	"The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region." Acquati F., Accarino M.P., Nucci C., Fumagalli P., Jovine L., Ottolenghi S., Taramelli R. FEBS Lett. 468:59-64(2000) [PubMed: 10683441] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, GLYCOSYLATION.
[5]	"Expression analysis of BACE2 in brain and peripheral tissues." Bennett B.D., Babu-Khan S., Loeloff R., Louis J.-C., Curran E., Citron M., Vassar R. J. Biol. Chem. 275:20647-20651(2000) [PubMed: 10749877] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[6]	"ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site." Hussain I., Powell D.J., Howlett D.R., Chapman G.A., Gilmour L., Murdock P.R., Tew D.G., Meek T.D., Chapman C., Schneider K., Ratcliffe S.J., Tattersall D., Testa T.T., Southan C., Ryan D.M., Simmons D.L., Walsh F.S., Dingwall C., Christie G. Mol. Cell. Neurosci. 16:609-619(2000) [PubMed: 11083922] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION.
[7]	"Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein." Lin X., Koelsch G., Wu S., Downs D., Dashti A., Tang J. Proc. Natl. Acad. Sci. U.S.A. 97:1456-1460(2000) [PubMed: 10677483] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[8]	Li Y., Huang Q., Peng Y., Song H., Yu Y., Xu S., Ren S., Chen Z., Han Z. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). Tissue: Pheochromocytoma.
[9]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[10]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5). Tissue: Ovary and Stomach.
[11]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skin.
[14]	"Distinct transcriptional regulation and function of the human BACE2 and BACE1 genes." Sun X., Wang Y., Qing H., Christensen M.A., Liu Y., Zhou W., Tong Y., Xiao C., Huang Y., Zhang S., Liu X., Song W. FASEB J. 19:739-749(2005) [PubMed: 15857888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-47, FUNCTION.
[15]	"BACE2 functions as an alternative alpha-secretase in cells." Yan R., Munzner J.B., Shuck M.E., Bienkowski M.J. J. Biol. Chem. 276:34019-34027(2001) [PubMed: 11423558] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, AUTOCATALYTIC CLEAVAGE, FUNCTION, SUBCELLULAR LOCATION.
[16]	"BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome." Sun X., He G., Song W. FASEB J. 20:1369-1376(2006) [PubMed: 16816112] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION.
[17]	"Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor." Ostermann N., Eder J., Eidhoff U., Zink F., Hassiepen U., Worpenberg S., Maibaum J., Simic O., Hommel U., Gerhartz B. J. Mol. Biol. 355:249-261(2006) [PubMed: 16305800] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 78-460, SUBUNIT, DISULFIDE BONDS.
[18]	"Prodomain processing of Asp1 (BACE2) is autocatalytic." Hussain I., Christie G., Schneider K., Moore S., Dingwall C. J. Biol. Chem. 276:23322-23328(2001) [PubMed: 11316808] [Abstract] Cited for: AUTOCATALYTIC CLEAVAGE, MUTAGENESIS OF ASP-110.
[19]	"Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein." Murayama K.S., Kametani F., Saito S., Kume H., Akiyama H., Araki W. Eur. J. Neurosci. 24:1237-1244(2006) [PubMed: 16965550] [Abstract] Cited for: INTERACTION WITH RTN3 AND RTN4.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF200342 mRNA. Translation: AAF17078.1.
AF117892 mRNA. Translation: AAD45240.1.
AF178532 mRNA. Translation: AAF29494.1.
AF188276 mRNA. Translation: AAF35835.1.
AF188277 mRNA. Translation: AAF35836.1.
AF050171 mRNA. Translation: AAD45963.1.
AF204944 mRNA. Translation: AAF26368.1.
AF200192 mRNA. Translation: AAF13714.1.
AF212252 mRNA. Translation: AAG41783.1.
AY358927 mRNA. Translation: AAQ89286.1.
AK075539 mRNA. Translation: BAC11682.1.
AK292056 mRNA. Translation: BAF84745.1.
AL163284 Genomic DNA. Translation: CAB90458.1.
AL163285 Genomic DNA. Translation: CAB90554.1.
CH471079 Genomic DNA. Translation: EAX09611.1.
CH471079 Genomic DNA. Translation: EAX09613.1.
BC014453 mRNA. Translation: AAH14453.1.
AY769996 Genomic DNA. Translation: AAX14808.1.

IPI

IPI00001954.
IPI00024561.
IPI00254431.
IPI00944447.
IPI00944495.

RefSeq

NP_036237.2.
NP_620476.1.
NP_620477.1.

UniGene

Hs.529408

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EWY	X-ray	3.10	A/B/C/D	78-460	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q9Y5Z0.

Protein family/group databases

MEROPS

A01.041.

Proteomic databases

PRIDE

Q9Y5Z0.

Genome annotation databases

Ensembl

ENST00000328735; ENSP00000333854; ENSG00000182240; Homo sapiens. [Genome view]
ENST00000330333; ENSP00000332979; ENSG00000182240; Homo sapiens. [Genome view]
ENST00000347667; ENSP00000327528; ENSG00000182240; Homo sapiens. [Genome view]

GeneID

25825.

KEGG

hsa:25825.

UCSC

uc002yyw.1. human.

Organism-specific databases

CTD

25825.

GeneCards

GC21P041461.

H-InvDB

HIX0016123.

HGNC

HGNC:934. BACE2.

HPA

CAB008975.

MIM

605668. gene.

PharmGKB

PA25233.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG714116.

HOVERGEN

Q9Y5Z0.

InParanoid

Q9Y5Z0.

OMA

IASNCVP.

OrthoDB

EOG9RFPBZ.

PhylomeDB

Q9Y5Z0.

Enzyme and pathway databases

BRENDA

3.4.23.45. 247.

Gene expression databases

ArrayExpress

Q9Y5Z0.

Bgee

Q9Y5Z0.

CleanEx

HS_BACE2.

Genevestigator

Q9Y5Z0.

GermOnline

ENSG00000182240. Homo sapiens.

Family and domain databases

InterPro

IPR009119. Pept_A1_BACE.
IPR009121. Pept_A1_BACE2.
IPR001461. Peptidase_A1.
IPR021109. Peptidase_aspartic.
IPR001969. Peptidase_aspartic_AS.
IPR009007. Peptidase_aspartic_catalytic.
[Graphical view]

Gene3D

G3DSA:2.40.70.10. Pept_Aspartc_cat. 2 hits.

PANTHER

PTHR13683. Peptidase_A1. 1 hit.

Pfam

PF00026. Asp. 1 hit.
[Graphical view]

PRINTS

PR01817. BACE2.
PR01815. BACEFAMILY.
PR00792. PEPSIN.

PROSITE

PS00141. ASP_PROTEASE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

47099.

PMAP-CutDB

Q9Y5Z0.

SOURCE

Search...

Entry information

Entry name

BACE2_HUMAN

Accession

Primary (citable) accession number: Q9Y5Z0
Secondary accession number(s): A8K7P1 , Q5DIH8, Q8N2D4, Q9H2V8, Q9NZL1, Q9NZL2, Q9UJT6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1999
Last modified:	February 9, 2010
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.