Table 1.

Cleavage sites, proteolytic fragments, and molecular function of known BACE1 substrates.

Substrate	Gene	Basic function	BACE1 cleavage product and function	γ-Secretase cleavage product and function	Cleavage site	Reference
Amyloid precursor protein	APP	Neurite growth, neuronal migration, neuroprotection	C99, APPsβ, further processed to N-APP: proapoptotic signal, induces neuronal death	Aβ: forms toxic oligomers, leads to AD	SEVKM-DAEFR	Haass and Selkoe (2007), Kim and Tsai (2009)
APPSWE	APP	Rare genetic mutant of FAD, enhances cleavage by BACE1	As for APP	As for APP	SEVNL-DAEFR	Citron et al. (1992)
Amyloid precursor-like protein 1	APLP1	Embryonic development; double KO with ALPL2, but not APP, leads to postnatal lethality	APLP1-CTF, soluble ectodomain	APLP1-ICD	ERKVN-ASVPR	von Koch et al. (1997), Heber et al. (2000), Eggert et al. (2004), Li and Sudhof (2004)
Amyloid precursor-like protein 2	APLP2	Embryonic development; double KO with APP, or APLP1 leads to postnatal lethality	APLP2-CTF, soluble ectodomain	APLP2-ICD	DVKEM-IFNAE	As for APLP1
Neuregulin 1	NRG1	ErbB2–ErbB4 ligand, myelination, axon guidance, synapse formation, schizophrenia risk factor	NRG1-CTF, NRG1-NTF: ErbB2–ErbB4 ligand, possibly further processed to yield soluble EGF-like domain	NRG1-ICD: transcriptional activity	LGIEF-MEAEE	Hu et al. (2006), Willem et al. (2006), Hu et al. (2008), Mei and Xiong (2008)
Neuregulin 3	NRG3	ErbB4 ligand, oligodendrocyte survival, cortical development; risk factor for schizophrenia, cognitive impairment, and autism	NRG3-CTF, soluble ectodomain: ErbB4 ligand		LGIEF-MMESEE	Zhang et al. (1997), Carteron et al. (2006), Hu et al. (2008), Kao et al. (2010)
Sodium channel NaV1.1 β1 subunit	SCN1B	Regulates cell surface expression and kinetics of VGSCs	β1-CTF	β1-ICD		Wong et al. (2005)
Sodium channel NaV1.1 β2 subunit	SCN2B	As for SCN1B	β2-CTF	β2-ICD: transcriptional activity, regulates expression of VGSC α-subunit	GKIYL-QVLLE	Wong et al. (2005), Kim et al. (2007), Kovacs et al. (2010)
Sodium channel NaV1.1 β3 subunit	SCN3B	As for SCN1B	β3-CTF	β3-ICD		As for β1 subunit
Sodium channel NaV1.1 β4 subunit	SCN4B	As for SCN1B	β4-CTF	β4-ICD	ATIFL-QVVDK	As for β2 subunit
β-Galactoside α2,6-sialyltransferase 1	ST6GAL1	Glycosyltransferase	ST6GAL1-NTF, soluble ectodomain: released into serum		EALTI-QAKEF	Kaplan et al. (1983), Kitazume et al. (2005), Sugimoto et al. (2007)
P-selectin glycoprotein ligand 1	SELPLG	Cell adhesion, leukocyte recruitment by binding to P-selectin	PSGL-1-CTF, soluble ectodomain		AASNL-SVNYP	Lichtenthaler et al. (2003), Carlow et al. (2009)
Interleukin-1 receptor type 2	IL1R2	Decoy receptor for interleukin-1	IL1R2-CTF, soluble ectodomain	IL1R2-ICD	NTLSF-QTLRT	Kuhn et al. (2007)
Low density lipoprotein receptor-related protein	LRP1	Multifunctional endocytic receptor (incl. APP), regulation of signaling pathways, lipid metabolism, Aβ degradation	LRP-CTF, soluble ectodomain	LRP-ICD: transcriptional activity in vitro	Unknown	von Arnim et al. (2005), Lillis et al. (2008), Wagner and Pietrzik (2011)