General Information of the Protein
Protein ID
PT06790
Protein Name
Signal peptide peptidase-like 2A
Secondarily
Protein Name
Intramembrane protease 3
Presenilin-like protein 2
Gene Name
SPPL2A
Secondarily
Gene Name
IMP3
PSL2
PSEC0147
Sequence
MGPQRRLSPAGAALLWGFLLQLTAAQEAILHASGNGTTKDYCMLYNPYWTALPSTLENATSISLMNLTSTPLCNLSDIPPVGIKSKAVVVPWGSCHFLEKARIAQKGGAEAMLVVNNSVLFPPSGNRSEFPDVKILIAFISYKDFRDMNQTLGDNITVKMYSPSWPNFDYTMVVIFVIAVFTVALGGYWSGLVELENLKAVTTEDREMRKKKEEYLTFSPLTVVIFVVICCVMMVLLYFFYKWLVYVMIAIFCIASAMSLYNCLAALIHKIPYGQCTIACRGKNMEVRLIFLSGLCIAVAVVWAVFRNEDRWAWILQDILGIAFCLNLIKTLKLPNFKSCVILLGLLLLYDVFFVFITPFITKNGESIMVELAAGPFGNNEKLPVVIRVPKLIYFSVMSVCLMPVSILGFGDIIVPGLLIAYCRRFDVQTGSSYIYYVSSTVAYAIGMILTFVVLVLMKKGQPALLYLVPCTLITASVVAWRRKEMKKFWKGNSYQMMDHLDCATNEENPVISGEQIVQQ
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Hydrolase
Function
Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane. Functions in FASLG, ITM2B and TNF processing (PubMed:16829952, PubMed:16829951, PubMed:17557115, PubMed:17965014). Catalyzes the intramembrane cleavage of the anchored fragment of shed TNF-alpha (TNF), which promotes the release of the intracellular domain (ICD) for signaling to the nucleus (PubMed:16829952). Also responsible for the intramembrane cleavage of Fas antigen ligand FASLG, which promotes the release of the intracellular FasL domain (FasL ICD) (PubMed:17557115). Essential for degradation of the invariant chain CD74 that plays a central role in the function of antigen-presenting cells in the immune system (By similarity). Plays a role in the regulation of innate and adaptive immunity (PubMed:16829952). Catalyzes the intramembrane cleavage of the simian foamy virus envelope glycoprotein gp130 independently of prior ectodomain shedding by furin or furin-like proprotein convertase (PC)-mediated cleavage proteolysis (PubMed:23132852).
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Uniprot ID
Primary ID:
Q8TCT8

Secondarily ID:
B2RDS0
Q8TAW1
Q96SZ8
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Ensembl ID
ENSG00000138600
HGNC ID
HGNC:30227
Subcellular Location
Late endosome membrane
Lysosome membrane
Membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000006 , HEK293
Compound ID Compound Name Compound Formula
CP0463365
(2R)-N'-(3,5-difluorophenyl)-2-methyl-N-[(6S)-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]butanediamide
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C23H24F2N4O3
 1
1
IC50 = 5 nM
   TI
   LI
   LO
   TS
CP0001342
benzyl N-[(2S)-4-methyl-1-[[(2S)-4-methyl-1-[[3-[[(2S)-4-methyl-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]-2-oxopropyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]carbamate
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C43H64N6O9
 1
1
IC50 = 6 nM
   TI
   LI
   LO
   TS
CP0013350
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3-tert-butyl-N-cyclobutylbenzenesulfonamide
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C23H32N2O3S
 1
1
IC50 = 7 nM
   TI
   LI
   LO
   TS
CP0013376
N-[(2S,3S)-3-amino-2-hydroxy-3-[4-(trifluoromethoxy)phenyl]propyl]-4-tert-butyl-N-cyclobutylbenzenesulfonamide
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C24H31F3N2O4S
 1
1
IC50 = 9 nM
   TI
   LI
   LO
   TS
CP0000571
(2S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl)propanamide
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C26H23F2N3O4
 1
1
IC50 = 10 nM
   TI
   LI
   LO
   TS
CP0014645
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-N-cyclobutyl-5,5,8,8-tetramethyl-6,7-dihydronaphthalene-2-sulfonamide
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C27H38N2O3S
 1
1
IC50 = 13 nM
   TI
   LI
   LO
   TS
CP0007975
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3,4-dichloro-N-cycloheptylbenzenesulfonamide
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C22H28Cl2N2O3S
 1
1
IC50 = 15 nM
   TI
   LI
   LO
   TS
CP0013293
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-4-tert-butyl-N-cyclobutylbenzenesulfonamide
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C23H32N2O3S
 1
1
IC50 = 25 nM
   TI
   LI
   LO
   TS
CP0430084
(2R)-2-methyl-N'-(2-methylphenyl)-N-[(6S)-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]butanediamide
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C24H28N4O3
 1
1
IC50 = 35 nM
   TI
   LI
   LO
   TS
CP0328884
(2R)-N'-(5-fluoro-2-methylpyridin-3-yl)-2-methyl-N-[(6S)-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]butanediamide
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C23H26FN5O3
 1
1
IC50 = 44 nM
   TI
   LI
   LO
   TS
CP0495110
(2R)-2-methyl-N'-(3-methylphenyl)-N-[(6S)-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]butanediamide
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C24H28N4O3
 1
1
IC50 = 70 nM
   TI
   LI
   LO
   TS
CP0408802
(2R)-N'-(5-fluoro-2-methylpyridin-3-yl)-N-[(6S)-10-fluoro-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]-2-methylbutanediamide
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C23H25F2N5O3
 1
1
IC50 = 76 nM
   TI
   LI
   LO
   TS
CP0460550
(2S)-2-cyclopropyl-N-[(6S)-5,11-dioxospiro[3,6-dihydro-1H-pyrazolo[1,2-b][2,3]benzodiazepine-2,1'-cyclopropane]-6-yl]-N'-(5-fluoro-2-methylpyridin-3-yl)butanediamide
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C27H28FN5O4
 1
1
IC50 = 77 nM
   TI
   LI
   LO
   TS
CP0013292
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3,4-dichloro-N-cyclobutylbenzenesulfonamide
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C19H22Cl2N2O3S
 1
1
IC50 = 88 nM
   TI
   LI
   LO
   TS
CP0011744
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3,4-dichloro-N-(2-methylpropyl)benzenesulfonamide
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C19H24Cl2N2O3S
 1
1
IC50 = 200 nM
   TI
   LI
   LO
   TS
CP0481546
(2S)-2-cyclopropyl-N-[(6S)-5,11-dioxo-1,2,3,6-tetrahydropyrazolo[1,2-b][2,3]benzodiazepin-6-yl]-N'-(5-fluoro-2-methylpyridin-3-yl)butanediamide
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C25H26FN5O4
 1
1
IC50 = 225 nM
   TI
   LI
   LO
   TS
CP0013349
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3,4-dichloro-N-propan-2-yloxybenzenesulfonamide
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C18H22Cl2N2O4S
 1
1
IC50 = 350 nM
   TI
   LI
   LO
   TS
CP0013291
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-N-benzyl-3,4-dichlorobenzenesulfonamide
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C22H22Cl2N2O3S
 1
1
IC50 = 620 nM
   TI
   LI
   LO
   TS
CP0007976
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-N-cyclobutyl-1,3-benzothiazole-5-sulfonamide
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C20H23N3O3S2
 1
1
IC50 = 840 nM
   TI
   LI
   LO
   TS
CP0512502
N-[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]-3,4-dichloro-N-(2-methylpropyl)benzenesulfonamide
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C20H26Cl2N2O3S
 1
1
IC50 = 860 nM
   TI
   LI
   LO
   TS
CP0481547
(2R)-N-[(6S)-5,11-dioxo-1,2,3,6-tetrahydropyrazolo[1,2-b][2,3]benzodiazepin-6-yl]-N'-(5-fluoro-2-methylpyridin-3-yl)-2-methylbutanediamide
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C23H24FN5O4
 1
1
IC50 = 870 nM
   TI
   LI
   LO
   TS
CP0014400
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3,4-dichloro-N-(1-methylcyclobutyl)benzenesulfonamide
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C20H24Cl2N2O3S
 1
1
IC50 = 900 nM
   TI
   LI
   LO
   TS
CP0014314
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3,4-dichloro-N-(2-hydroxy-2-methylpropyl)benzenesulfonamide
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C19H24Cl2N2O4S
 1
1
IC50 = 910 nM
   TI
   LI
   LO
   TS
CP0478246
(2R)-2-methyl-N'-(2-methylpyridin-3-yl)-N-[(6S)-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]butanediamide
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C23H27N5O3
 1
1
IC50 = 1020 nM
   TI
   LI
   LO
   TS
CP0481545
(2R)-2-methyl-N'-(4-methylphenyl)-N-[(6S)-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]butanediamide
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C24H28N4O3
 1
1
IC50 = 1390 nM
   TI
   LI
   LO
   TS
CP0013374
N-[(2S,3S)-3-amino-2-hydroxy-3-phenylpropyl]-3,4-dichloro-N-(oxetan-3-yl)benzenesulfonamide
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C18H20Cl2N2O4S
 1
1
IC50 = 1500 nM
   TI
   LI
   LO
   TS
CP0463364
(2R)-2-methyl-N-[(6S)-5-oxo-2,3,6,11-tetrahydro-1H-pyrazolo[1,2-b][2,3]benzodiazepin-6-yl]-N'-[2-(trifluoromethyl)phenyl]butanediamide
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C24H25F3N4O3
 1
1
IC50 = 2850 nM
   TI
   LI
   LO
   TS
CP0512501
benzyl N-[(2S,3S)-4-[(3,4-dichlorophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
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C28H32Cl2N2O5S
 1
1
IC50 = 4300 nM
   TI
   LI
   LO
   TS