Q9Y5Z0 (BACE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-secretase 2
EC=3.4.23.45

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

Gene names

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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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 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.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7
Induction	Up-regulated in primary breast and colon tumors and liver metastasis. Ref.2
Post-translational modification	Undergoes autoproteolytic cleavage. Glycosylated. Ref.4 Ref.6
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 Transmembrane helix
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Autocatalytic cleavage Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	membrane protein ectodomain proteolysis Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of amyloid precursor protein biosynthetic process Inferred from mutant phenotype PubMed 12801932. Source: UniProtKB peptide hormone processing Non-traceable author statement Ref.5. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay Ref.15. 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 Non-traceable author statement Ref.5. Source: UniProtKB
Molecular_function	aspartic-type endopeptidase activity Inferred from direct assay Ref.1. 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 C;

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

Isoform 3 (identifier: Q9Y5Z0-3)

Also known as: Isoform B;

The sequence of this isoform differs from the canonical sequence as follows:
     379-396: LYIQPMMGAGLNYECYRF → KLQVLQCLKFPGLSQQRM
     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

Helical; 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 → KLQVLQCLKFPGLSQQRM 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

Isoform 3:

Sequence conflict

381

1

Q → R in AAF35836. Ref.3

Sequence conflict

396

1

M → F in AAF35836. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

518

Helix Strand Turn

Details...

Beta strand

84 – 87

4

Turn

88 – 90

3

Beta strand

91 – 98

8

Turn

99 – 102

4

Beta strand

103 – 110

8

Beta strand

116 – 119

4

Helix

132 – 134

3

Beta strand

139 – 148

10

Beta strand

153 – 165

13

Turn

166 – 168

3

Beta strand

169 – 185

17

Beta strand

195 – 198

4

Helix

202 – 204

3

Helix

214 – 222

9

Beta strand

228 – 232

5

Beta strand

247 – 253

7

Helix

256 – 258

3

Beta strand

263 – 267

5

Turn

271 – 274

4

Beta strand

278 – 283

6

Turn

292 – 296

5

Beta strand

300 – 302

3

Beta strand

307 – 312

6

Helix

313 – 325

13

Helix

334 – 338

5

Beta strand

340 – 345

6

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 – 403

13

Beta strand

405 – 407

3

Helix

409 – 412

4

Beta strand

415 – 420

6

Turn

421 – 424

4

Beta strand

425 – 430

6

Beta strand

435 – 438

4

Beta strand

442 – 449

8

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 C) [UniParc]. 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 B) [UniParc]. Checksum: EDB3A7AF391CEACA	FASTA	396	42,985
	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 QVLQCLKFPG LSQQRM
	Isoform 4 [UniParc]. 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 [UniParc]. 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. NM_012105.3.
NP_620476.1. NM_138991.1.
NP_620477.1. NM_138992.1.

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	[»]

ProteinModelPortal

Q9Y5Z0.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000332979.

Protein family/group databases

MEROPS

A01.041.

PTM databases

PhosphoSite

Q9Y5Z0.

Polymorphism databases

DMDM

6685260.

Proteomic databases

PaxDb

Q9Y5Z0.

PRIDE

Q9Y5Z0.

Protocols and materials databases

DNASU

25825.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000328735; ENSP00000333854; ENSG00000182240.
ENST00000330333; ENSP00000332979; ENSG00000182240.
ENST00000347667; ENSP00000327528; ENSG00000182240.

GeneID

25825.

KEGG

hsa:25825.

UCSC

uc002yyw.3. human.
uc002yyx.3. human.
uc002yyy.3. human.

Organism-specific databases

CTD

25825.

GeneCards

GC21P042539.

HGNC

HGNC:934. BACE2.

HPA

CAB008975.

MIM

605668. gene.

neXtProt

NX_Q9Y5Z0.

PharmGKB

PA25233.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG267436.

HOVERGEN

HBG059578.

InParanoid

Q9Y5Z0.

KO

K07747.

OMA

IASNCVP.

OrthoDB

EOG4THVSX.

PhylomeDB

Q9Y5Z0.

Enzyme and pathway databases

BioCyc

MetaCyc:G66-33964-MONOMER.

BRENDA

3.4.23.45. 2681.

Gene expression databases

Bgee

Q9Y5Z0.

CleanEx

HS_BACE2.

Genevestigator

Q9Y5Z0.

GermOnline

ENSG00000182240. Homo sapiens.

Family and domain databases

Gene3D

2.40.70.10. 2 hits.

InterPro

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

PANTHER

PTHR13683. PTHR13683. 1 hit.

Pfam

PF00026. Asp. 1 hit.
[Graphical view]

PRINTS

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

SUPFAM

SSF50630. Pept_Aspartic. 1 hit.

PROSITE

PS00141. ASP_PROTEASE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9Y5Z0.

ChEMBL

CHEMBL2525.

ChiTaRS

BACE2. human.

EvolutionaryTrace

Q9Y5Z0.

GenomeRNAi

25825.

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:	May 1, 2013
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.