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#######################
# Document Properties #
#######################
SET DOCUMENT Copyright = "Copyright © 2018 Fraunhofer Institute SCAI, All rights reserved."
SET DOCUMENT Licenses = "CC BY 4.0"
SET DOCUMENT ContactInfo = "charles.hoyt@scai.fraunhofer.de"
SET DOCUMENT Name = "Effects of peptides derived from BACE1 catalytic domain on APP processing"
SET DOCUMENT Version = "1.0.0"
SET DOCUMENT Authors = "Rana Aldisi"
SET DOCUMENT Description = ""
##############
# Namespaces #
##############
# Namespaces hosted on https://github.com/pharmacome/terminology
# --------------------------------------------------------------
DEFINE NAMESPACE CHEBI AS URL "https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns"
DEFINE NAMESPACE DRUGBANK AS URL "https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/drugbank-names.belns"
DEFINE NAMESPACE ECCODE AS URL "https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/ec-code.belns"
# DEFINE NAMESPACE FB AS URL "https://raw.githubusercontent.com/pharmacome/terminology/80171ae62cf43aa1fc8a6c326b94537ab342458c/external/fb-names.belns"
DEFINE NAMESPACE HBP AS URL "https://raw.githubusercontent.com/pharmacome/terminology/3074b85b858455d8eeb76cfcdef685ced19bbe11/export/hbp-names.belns"
DEFINE NAMESPACE HGNC AS URL "https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns"
DEFINE NAMESPACE HGNCGENEFAMILY AS URL "https://raw.githubusercontent.com/pharmacome/terminology/3074b85b858455d8eeb76cfcdef685ced19bbe11/external/hgnc.genefamily-names.belns"
DEFINE NAMESPACE GO AS URL "https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/go-names.belns"
DEFINE NAMESPACE INTERPRO AS URL "https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/interpro-names.belns"
DEFINE NAMESPACE MESH AS URL "https://raw.githubusercontent.com/pharmacome/terminology/8ccfed235e418e4c8aa576f9a5ef0f838e794c7f/external/mesh-names.belns"
DEFINE NAMESPACE MGI AS URL "https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/mgi-names.belns"
DEFINE NAMESPACE NCBIGENE AS URL "https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/entrez.belns"
DEFINE NAMESPACE PFAM AS URL "https://raw.githubusercontent.com/pharmacome/terminology/8ccfed235e418e4c8aa576f9a5ef0f838e794c7f/external/pfam-names.belns"
DEFINE NAMESPACE RGD AS URL "https://raw.githubusercontent.com/pharmacome/terminology/f2f993e599694ab5ce989cc39d789a499f75db99/external/rgd-names.belns"
# Namespaces hosted on https://github.com/sorgerlab/famplex
# ---------------------------------------------------------
DEFINE NAMESPACE FPLX AS URL "https://raw.githubusercontent.com/sorgerlab/famplex/e8ae9926ff95266032cb74f77973c84939bffbeb/export/famplex.belns"
# Namespaces hosted on https://arty.scai.fraunhofer.de/artifactory/bel/namespace
# ------------------------------------------------------------------------------
DEFINE NAMESPACE HP AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/namespace/hp/hp-20171108.belns"
# Namespaces defined with regular expressions
# -------------------------------------------
DEFINE NAMESPACE DBSNP AS PATTERN "rs[0-9]+"
DEFINE NAMESPACE TAXONOMY AS PATTERN "^\d+$"
###############
# Annotations #
###############
# Annotations defined with regular expressions
# --------------------------------------------
DEFINE ANNOTATION Species AS PATTERN "^\d+$"
# Annotations hosted on https://arty.scai.fraunhofer.de/artifactory/bel/annotation
# --------------------------------------------------------------------------------
DEFINE ANNOTATION Anatomy AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/anatomy/anatomy-20170511.belanno"
DEFINE ANNOTATION CellLine AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/cell-line/cell-line-20170511.belanno"
DEFINE ANNOTATION CellStructure AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/cell-structure/cell-structure-20170511.belanno"
DEFINE ANNOTATION Cell AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/cell/cell-20170511.belanno"
DEFINE ANNOTATION Confidence AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/confidence/confidence-1.0.0.belanno"
DEFINE ANNOTATION Disease AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/disease/disease-20170511.belanno"
DEFINE ANNOTATION MeSHAnatomy AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/mesh-anatomy/mesh-anatomy-20170511.belanno"
DEFINE ANNOTATION MeSHDisease AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/mesh-diseases/mesh-diseases-20170511.belanno"
DEFINE ANNOTATION Subgraph AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/neurommsig/neurommsig-1.0.3.belanno"
DEFINE ANNOTATION TextLocation AS URL "https://arty.scai.fraunhofer.de/artifactory/bel/annotation/text-location/text-location-1.0.1.belanno"
##############
# Statements #
##############
SET Citation={"PubMed", "17293005"}
#BI-1 = p(HGNC:BACE1, frag("67_78"))
#BI-2 = p(HGNC:BACE1, frag("69_75"))
#BI-3 = p(HGNC:BACE1, frag("228_236"))
#BI-4 = p(HGNC:BACE1, frag("230_235"))
SET Evidence="BI-1 treatment dose-dependently inhibited
the release of both sAPPa and sAPPb in the conditioned
medium (Figs. 2A and 3A). The 50% inhibitory concentrations
(IC50) of BI-1 were about 1.5 mM for sAPPa and 0.9 mM for APPb,
respectively. But BI-2, which is mainly composed of the core
region BACE1 69–73, did not show the inhibitory effects"
#BI - 2 is 69 - 73
SET Confidence = "Medium"
p(HGNC:BACE1, frag("67_78")) -| sec(a(HBP:"sAPP-beta"))
p(HGNC:BACE1, frag("67_78")) -| sec(a(HBP:"sAPP-alpha"))
p(HGNC:BACE1, frag("69_73")) causesNoChange sec(a(HBP:"sAPP-beta"))
p(HGNC:BACE1, frag("69_73")) causesNoChange sec(a(HBP:"sAPP-alpha"))
UNSET Confidence
SET Evidence="BI-3 also potentially inhibited the release of sAPPb
(IC50 = 0.5 mM) and sAPPa (IC50 = 3.4 mM, Figs. 2B and 3B). BI-
4, which is short peptide of BI-3, showed no effects on sAPP
secretion."
SET Confidence = "High"
p(HGNC:BACE1, frag("228_236")) -| sec(a(HBP:"sAPP-beta"))
p(HGNC:BACE1, frag("228_236")) -| sec(a(HBP:"sAPP-alpha"))
p(HGNC:BACE1, frag("230_235")) causesNoChange sec(a(HBP:"sAPP-beta"))
p(HGNC:BACE1, frag("230_235")) causesNoChange sec(a(HBP:"sAPP-alpha"))
UNSET Confidence
SET Evidence="Surprisingly, BI-1 treatment
resulted in a drastic, dose-dependent increase in the level
of intracellular APPa (Figs. 2A and 3A). BI-3 also induced the
accumulation of intracellular APPa until the concentration
of BI-3 was raised to 12.5 mM; however, treatment of BI-3
with 25 mM decreased the level of intracellular APPa."
SET Confidence = "High"
p(HGNC:BACE1, frag("67_78")) -> a(HBP:"sAPP-alpha", loc(GO:intracellular))
p(HGNC:BACE1, frag("228_236")) -> a(HBP:"sAPP-alpha", loc(GO:intracellular))
UNSET Confidence
SET Evidence="Neither, BI-1 nor,
BI-3, nor any of the other peptides used in this study,
induced any changes of full-length APP levels. They also did
not affect the level of b-actin."
#b-actin : ACTB
SET Confidence = "High"
p(HGNC:BACE1, frag("67_78")) causesNoChange a(CHEBI:"amyloid-beta")
p(HGNC:BACE1, frag("69_75")) causesNoChange a(CHEBI:"amyloid-beta")
p(HGNC:BACE1, frag("228_236")) causesNoChange a(CHEBI:"amyloid-beta")
p(HGNC:BACE1, frag("230_235")) causesNoChange a(CHEBI:"amyloid-beta")
p(HGNC:BACE1, frag("67_78")) causesNoChange p(HGNC:ACTB)
p(HGNC:BACE1, frag("69_75")) causesNoChange p(HGNC:ACTB)
p(HGNC:BACE1, frag("228_236")) causesNoChange p(HGNC:ACTB)
p(HGNC:BACE1, frag("230_235")) causesNoChange p(HGNC:ACTB)
UNSET Confidence
SET Evidence="Taken together, these results show that BI-1 and BI-3 not
only selectively reduce the level of APPbeta but also lead to the
accumulation of APPalpha in cells with no change of full-length
APP level."
SET Confidence = "High"
p(HGNC:BACE1, frag("67_78")) -| a(HBP:"sAPP-beta")
p(HGNC:BACE1, frag("228_236")) -| a(HBP:"sAPP-beta")
p(HGNC:BACE1, frag("67_78")) -> a(HBP:"sAPP-alpha")
p(HGNC:BACE1, frag("228_236")) -> a(HBP:"sAPP-alpha")
UNSET Confidence
SET Evidence="These results
suggest that BACE1 derived peptides do not directly inhibit
BACE activities in vitro when the fluorogenic peptides are used
as a substrate."
SET Confidence = "Medium"
p(HGNC:BACE1, frag("69_75")) causesNoChange act(p(HGNC:BACE1))
p(HGNC:BACE1, frag("230_235")) causesNoChange act(p(HGNC:BACE1))
p(HGNC:BACE1, frag("228_236")) causesNoChange act(p(HGNC:BACE1))
p(HGNC:BACE1, frag("67_78")) causesNoChange act(p(HGNC:BACE1))
UNSET Confidence
SET Evidence="BI-1 treatment
effectively reduced Ab 40 levels (IC50 = 0.06 mM) in the
conditioned medium. BI-3 also inhibited Ab 40 production
(IC50 = 0.2 mM), although the effective concentrations were
relatively high compared to those of BI-1."
#AB 40 : Amyloid- beta polypeptide 40
SET Confidence = "High"
p(HGNC:BACE1, frag("67_78")) -| a(CHEBI:"amyloid-beta polypeptide 40")
p(HGNC:BACE1, frag("228_236")) -| a(CHEBI:"amyloid-beta polypeptide 40")
UNSET Confidence