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0BACE1_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameBACE1
DescriptionBeta-secretase 1 precursor (ec 3.4.23.46) (beta-site app cleaving enzyme 1) (beta-site amyloid precursor protein cleaving enzyme 1) (aspartyl protease 2) (asp 2) (asp2) (membrane-associated aspartic protease 2) (memapsin-2).
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0005768 endosome (IDA)
0005794 Golgi apparatus (IDA)
0005887 integral to plasma membrane (TAS)
0004190 aspartic-type endopeptidase activity (IDA)
0008798 beta-aspartyl-peptidase activity (TAS)
0050435 beta-amyloid metabolism (IDA)
0006509 membrane protein ectodomain proteolysis (TAS)

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schematic display of those terms with internal associations, click the node and browse the corresponding GO term
Domain Architecture (Details)
InterPro domains unassigned to SynO:
Peptidases are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry. Families are grouped by their catalytic type.he first character representing the catalytic type: A.spartic; C.ysteine; G.lutamic acid; M.etallo; S.erine; T.hreonine; and U.nknown. A clan that contains families of more than one type is described as being of type P. The serine.hreonine and cysteine peptidases utilise the catalytic part of an amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic.lutamic and metallopeptidases.he nucleophile is an activated water molecule. Aspartic endopeptidases () of vertebrate.ungal and retroviral origin have been characterised .Aspartate peptidases are so named because Asp residues are the ligands of the activated water molecule in all examples where the catalytic residues have been identified.lthough at least one viral enzyme is believed to have an Asp and an Asn as its catalytic dyad. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related).nd further sub-divided into families.argely on the basis of their tertiary structure.This group of aspartic peptidases belong to MEROPS peptidase family A1 (pepsin family.lan AA). The type example is pepsin A from Homo sapiens. Aspartic endopeptidases include pepsins.athepsins.nd renins. Most members of the pepsin family specifically cleave bonds in peptides that are at least six residues in length.ith hydrophobic residues in both the P1 and P1 positions . Crystallography has shown the active site to form a groove across the junction of the two lobes.ith an extended loop projecting over the cleft to form an 11-residue flap.hich encloses substrates and inhibitors within the active site . Specificity is determined by several hydrophobic residues surrounding the catalytic aspartates.nd by three residues in the flap.Cysteine residues are well conserved within the pepsin family.epsin itself containing three disulphide loops. The first loop is found in all but the fungal enzymes.nd is usually around five residues in length.ut is longer in barrierpepsin and candidapepsin; the second loop is also small and found only in the animal enzymes; and the third loop is the largest.ound in all members of the family.xcept for the cysteine-free polyporopepsin. The loops are spread unequally throughout the two lobes.uggesting that they formed after the initial gene duplication and fusion event .This family does not include the retroviral nor retrotransposon aspartic proteases which are much smaller and appear to be homologous to the single domain aspartic proteases.
  IPR001461:Peptidase A1, pepsin
Peptidases are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry. Families are grouped by their catalytic type.he first character representing the catalytic type: A.spartic; C.ysteine; G.lutamic acid; M.etallo; S.erine; T.hreonine; and U.nknown. A clan that contains families of more than one type is described as being of type P. The serine.hreonine and cysteine peptidases utilise the catalytic part of an amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic.lutamic and metallopeptidases.he nucleophile is an activated water molecule. Aspartic endopeptidases () of vertebrate.ungal and retroviral origin have been characterised .Aspartate peptidases are so named because Asp residues are the ligands of the activated water molecule in all examples where the catalytic residues have been identified.lthough at least one viral enzyme is believed to have an Asp and an Asn as its catalytic dyad. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related).nd further sub-divided into families.argely on the basis of their tertiary structure.These aspartate proteases all contain a common closed beta barrel structure.hich includes pepsin.athepsin.hymosin.eta-secretase.lasmepsin.lant acid proteases and retroviral proteases .
  IPR009007:Peptidase aspartic, catalytic
Peptidases are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry. Families are grouped by their catalytic type.he first character representing the catalytic type: A.spartic; C.ysteine; G.lutamic acid; M.etallo; S.erine; T.hreonine; and U.nknown. A clan that contains families of more than one type is described as being of type P. The serine.hreonine and cysteine peptidases utilise the catalytic part of an amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic.lutamic and metallopeptidases.he nucleophile is an activated water molecule. Aspartic endopeptidases () of vertebrate.ungal and retroviral origin have been characterised .Aspartate peptidases are so named because Asp residues are the ligands of the activated water molecule in all examples where the catalytic residues have been identified.lthough at least one viral enzyme is believed to have an Asp and an Asn as its catalytic dyad. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related).nd further sub-divided into families.argely on the basis of their tertiary structure.One of the major neuropathological hallmarks of Alzheimers disease (AD)is the progressive formation in the brain of insoluble amyloid plaques and vascular deposits consisting of beta-amyloid protein (beta-APP) .Production of beta-APP requires proteolytic cleavage of the large type-1 transmembrane (TM) protein amyloid precursor protein (APP) . This processis performed by a variety of enzymes known as secretases. To initiate beta-APP formation.eta-secretase cleaves APP to release a soluble N-terminal fragment (APPsBeta) and a C-terminal fragment that remains membrane bound. This fragment is subsequently cleaved by gamma-secretase to liberate beta-APP.Several independent studies identified a novel TM aspartic protease as themajor beta-secretase . This protein.ermed beta-site APP cleavingenzyme 1 (BACE1).hares 64% amino acid sequence similarity with a secondenzyme.ermed BACE2. Together.ACE1 and BACE2 define a novel family of aspartyl proteases . Both enzymes share significant sequence similaritywith other members of the pepsin family of aspartyl proteases and contain the two characteristic D(T/S)G(T/S) motifs that form the catalytic site.However.y contrast with other aspartyl proteases.ACE1 and BACE2 aretype I TM proteins. Each protein comprises a large lumenal domain containingthe active centre. single TM domain and a small cytoplasmic tail.
  IPR009119:Peptidase A1, beta-site APP cleaving enzyme, BACE
Peptidases are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry. Families are grouped by their catalytic type.he first character representing the catalytic type: A.spartic; C.ysteine; G.lutamic acid; M.etallo; S.erine; T.hreonine; and U.nknown. A clan that contains families of more than one type is described as being of type P. The serine.hreonine and cysteine peptidases utilise the catalytic part of an amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic.lutamic and metallopeptidases.he nucleophile is an activated water molecule. Aspartic endopeptidases () of vertebrate.ungal and retroviral origin have been characterised .Aspartate peptidases are so named because Asp residues are the ligands of the activated water molecule in all examples where the catalytic residues have been identified.lthough at least one viral enzyme is believed to have an Asp and an Asn as its catalytic dyad. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related).nd further sub-divided into families.argely on the basis of their tertiary structure.This group of aspartic peptidases belong to MEROPS peptidase family A1 (clan AA.epsin family). They are transmembrane aspartic endopeptidases which in human is a candidate beta-secretase in Alzheimers disease (together with memapsin 1..One of the major neuropathological hallmarks of Alzheimers disease (AD)is the progressive formation in the brain of insoluble amyloid plaques and vascular deposits consisting of beta-amyloid protein (beta-APP) .Production of beta-APP requires proteolytic cleavage of the large type-1 transmembrane (TM) protein amyloid precursor protein (APP) . This processis performed by a variety of enzymes known as secretases. To initiate beta-APP formation.eta-secretase cleaves APP to release a soluble N-terminal fragment (APPsBeta) and a C-terminal fragment that remains membrane bound. This fragment is subsequently cleaved by gamma-secretase to liberate beta-APP.Several independent studies identified a novel TM aspartic protease as themajor beta-secretase . This protein.ermed Memapsin-2 or beta-site APP cleaving enzyme 1 (BACE1).hares 64% amino acid sequence similarity with a second enzyme.ermed BACE2. Together.ACE1 and BACE2 define a novel family of aspartyl proteases . Both enzymes share significant sequence similarity with other members of the pepsin family of aspartyl proteases and contain the two characteristic D(T/S)G(T/S) motifs that form the catalytic site. However.y contrast with other aspartyl proteases.ACE1 and BACE2 are type I TM proteins. Each protein comprises a large lumenal domain containing the active centre. single TM domain and a small cytoplasmic tail. Memapsin-2.as a broad tissue distribution.ith brain expression levels moderately higher than those of peripheral tissues. Mice deficient in BACE1 are healthy.ertile.nd appear normal in gross anatomy.issue histology and clinical chemistry. BACE1 -/- mice that are also hemizygous for an amyloid precursor protein transgene lack brain beta-amyloid and beta-secretase-cleaved APP C-terminal fragments . These findings substantiate the theory that BACE1 acts as the major beta-secretase in vivo.nd suggest that therapeutic inhibition of BACE1 as a potential treatment for Alzheimers disease may be free of mechanism- based toxicity.
  IPR009120:Peptidase A1, beta-site APP cleaving enzyme 1, BACE 1
IPR001461:Asp 
Evalue:-15.8538722991943 
Location:74-418IPR009119:BACEFAMILY 
Evalue:0 
Location:27-46IPR009120:BACE1 
Evalue:0 
Location:14-26IPR009120:BACE1 
Evalue:0 
Location:421-432
SequencesProtein: BACE1_HUMAN (501 aa)
mRNA: NM_012104
Local Annotation
Synapse Ontology
endosome of the presynaptic compartment. A cellular structure that is involved in the transport of proteins in the neuron after the proteins are endocytosed from the outside to the inside of the cell.
sdb:0088 endosome  (Evidence:keywords)
Microglias, one kind of glias in CNS, are responsible for removing most of the waste and cellular debris from the CNS
sdb:0267 removing metabolic mass  (Evidence:keywords)
KO assignmentK04521
  Level 3 annotation:
    beta-site APP-cleaving enzyme 1
  Level 2 annotation:
    Alzheimer's disease
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 1370 residues, 116661626-116665733Exon2: 59 residues, 116666413-116666585Exon3: 52 residues, 116666825-116666975Exon4: 36 residues, 116667637-116667739Exon5: 47 residues, 116668979-116669114Exon6: 48 residues, 116669796-116669934Exon7: 74 residues, 116671056-116671273Exon8: 31 residues, 116672798-116672887Exon9: 242 residues, 116691460-116692182Exon10: 2 residues, -Jump to BACE1_HUMAN  
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Loci Cluster (Details)Loci: 3995 116661626-116692182 ~-31K 7822(BACE1)(-)Loci: 3994 116211678-116213548 ~-2K 7809(APOA1)(-)Link out to UCSC