Beta-secretase 2 precursor - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q9Y5Z0 (BACE2_HUMAN)

Last modified June 16, 2009. Version 87. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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

Gene names

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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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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.

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General annotation (Comments)

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	Interacts ith RTN3 and RTN4. Ref.11
Subcellular location	Membrane; Single-pass type I membrane protein.
Sequence similarities	Belongs to the peptidase A1 family.

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Ontologies

Keywords
Cellular component	Membrane
Domain	Signal Transmembrane
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Glycoprotein Zymogen
Technical term	3D-structure
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 Non-traceable author statement. Source: UniProtKB protein modification process Ref.4 Traceable author statement. Source: ProtInc protein secretion Ref.4 Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Non-traceable author statement. Source: UniProtKB membrane fraction Ref.4 Traceable author statement. Source: ProtInc
Molecular function	aspartic-type endopeptidase activity Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

Potential

Propeptide

21 – ?

Potential

PRO_0000025945

Chain

? – 518

Beta-secretase 2

PRO_0000025946

Regions

Topological domain

21 – 473

453

Extracellular Potential

Transmembrane

474 – 494

Potential

Topological domain

495 – 518

Cytoplasmic Potential

Sites

Active site

110

By similarity

Active site

303

By similarity

Amino acid modifications

Glycosylation

170

N-linked (GlcNAc...) Potential

Glycosylation

366

N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict

A → T in AAF13714. Ref.4

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9Y5Z0-1 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 2E903150823760D3
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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

« Hide

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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].
[2]	"Identification of a novel aspartic proteinase (Asp 2) as beta-secretase." Hussain I., Powell D.J., Howlett D.R., Tew D.G., Meek T.D., Chapman C., Gloger I.S., Murphy K.E., Southan C.D., Ryan D.M., Smith T.S., Simmons D.L., Walsh F.S., Dingwall C., Christie G. Mol. Cell. Neurosci. 14:419-427(1999) [PubMed: 10656250] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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]. Tissue: Bone marrow.
[4]	"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].
[5]	"Cloning of a gene from chromosome 21 Down region encoding a potential transmembrane aspartyl protease." Accarino M.P., Fumagalli P., Ottolenghi S., Taramelli R. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Cloning of a novel mammalian aspartyl protease." Solans A., Estivill X., de la Luna S. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"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. Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"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. Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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]. Tissue: Skin.
[10]	"Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity." Turner R.T. III, Loy J.A., Nguyen C., Devasamudram T., Ghosh A.K., Koelsch G., Tang J. Biochemistry 41:8742-8746(2002) [PubMed: 12093293] [Abstract] Cited for: CHARACTERIZATION.
[11]	"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.

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Cross-references

Sequence databases

AF200342 mRNA. Translation: AAF17078.1.
AF204944 mRNA. Translation: AAF26368.1.
AF117892 mRNA. Translation: AAD45240.1.
AF200192 mRNA. Translation: AAF13714.1.
AF050171 mRNA. Translation: AAD45963.1.
AF178532 mRNA. Translation: AAF29494.1.
AY358927 mRNA. Translation: AAQ89286.1.
AL163284 Genomic DNA. Translation: CAB90458.1.
AL163285 Genomic DNA. Translation: CAB90554.1.
BC014453 mRNA. Translation: AAH14453.1.

IPI

IPI00001954.

RefSeq

NP_036237.2.

UniGene

Hs.529408

3D structure databases

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

SMR

Q9Y5Z0. Positions 78-460.

ModBase

Search...

Protein family/group databases

MEROPS

A01.041.

Proteomic databases

PRIDE

Q9Y5Z0.

Genome annotation databases

Ensembl

ENSG00000182240. Homo sapiens. [Contig view]

GeneID

25825.

KEGG

hsa:25825.

Organism-specific databases

GeneCards

GC21P041461.

H-InvDB

HIX0016123.

HGNC

HGNC:934. BACE2.

HPA

CAB008975.

MIM

605668. gene.

PharmGKB

PA25233.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9Y5Z0.

HOVERGEN

Q9Y5Z0.

OMA

Q9Y5Z0. EPILWIV.

Enzyme and pathway databases

BRENDA

3.4.23.45. 247.

Gene expression databases

ArrayExpress

Q9Y5Z0.

Bgee

Q9Y5Z0.

CleanEx

HS_BACE2.

GermOnline

ENSG00000182240. Homo sapiens.

Family and domain databases

InterPro

IPR009119. Pept_A1_BACE.
IPR009121. Pept_A1_BACE2.
IPR001461. Peptidase_A1.
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...

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Entry information

Entry name

BACE2_HUMAN

Accession

Primary (citable) accession number: Q9Y5Z0
Secondary accession number(s): Q9UJT6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1999
Last modified:	June 16, 2009
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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