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Information on EC 3.4.11.22 - aminopeptidase I and Organism(s) Homo sapiens

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.11 Aminopeptidases
                3.4.11.22 aminopeptidase I
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This record set is specific for:
Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Release of an N-terminal amino acid, preferably a neutral or hydrophobic one, from a polypeptide. Aminoacyl-arylamides are poor substrates
Synonyms
erap1, aminopeptidase i, endoplasmic reticulum aminopeptidase 1, leucine-aminopeptidase, eraap, endoplasmic reticulum aminopeptidase, a-lap, arts-1, aminopeptidase 1, lapase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Actinase AS
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alpha-Aminoacyl-peptide hydrolase
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-
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Aminooligopeptidase
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Aminopeptidase
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aminopeptidase ERAP1
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Aminopeptidase III
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-
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Aminopeptidase yscI
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-
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Aminopeptidase yscII
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-
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Aminopeptidase yscXVI
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-
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Aminopolypeptidase
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Amylorhizin aminopeptidase
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Amylorizin
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API
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endoplasmic reticulum aminopeptidase
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endoplasmic reticulum aminopeptidase 1
endoplasmic reticulum aminopeptidase associated with antigen presentation
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ERAAP
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ERAP1
L-aminopeptidase
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LAPIV
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Leu.AP
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-
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Leucin aminopeptidase V
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-
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Leucine aminopeptidase IV
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-
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Leucineaminopeptidase I
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-
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Metallo aminopeptidase
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-
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Polypeptidase
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-
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Yeast aminopeptidase I
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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-
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CAS REGISTRY NUMBER
COMMENTARY hide
9031-94-1
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-(2-[(4-methylbenzene-1-sulfonyl)amino]ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl 2-[(leucylamino)methyl]piperidine-1-carboxylate + H2O
N-[2-(6-hydroxy-1,3-dioxo-6,6a-dihydro-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl]-4-methylbenzene-1-sulfonamide + hexahydroimidazo[1,5-a]pyridin-3(2H)-one + 2-amino-4-methylpentanoic acid
show the reaction diagram
two-photon fluorescent probe SNCL, can be applied for monitoring of the activity in living cells and tissues
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-
?
L-leucine-7-amido-4-methylcoumarin + H2O
L-leucine + 7-amino-4-methylcoumarin
show the reaction diagram
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-
-
?
LGGGGGGGGGGL + H2O
L-leucine + GGGGGGGGGGL
show the reaction diagram
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-
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?
LGGGGGGGGGL + H2O
L-leucine + GGGGGGGGGL
show the reaction diagram
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-
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?
LGGGL + H2O
L-leucine + GGGL
show the reaction diagram
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-
-
?
QITANRELIQQEL + H2O
? + TANRELIQQEL
show the reaction diagram
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intermediate product TANRELIQQEL is further processed
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?
WEVYEKCALK + H2O
L-Trp + EVYEKCALK
show the reaction diagram
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-
-
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?
WRVYEKCALK + H2O
L-Trp + RVYEKCALK
show the reaction diagram
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?
WRVYEKMALKC + H2O
L-Trp + RVYEKMALKC
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
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ERAP1 trims a large variety of long peptide sequences efficiently, and its activity drops dramatically for peptides shorter than eight or nine amino acids, the enzyme efficiently excises virtually any amino acid in the context of a larger peptide, ERAP1 has broad N-terminal specificity due to strong preferences for residues downstream in the peptide-substrate sequence
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
amastatin
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about 50% inhibition at 0.1 mM
leucinethiol
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about 80% inhibition at 0.1 mM
Nalpha-(2-[[(1-amino-3-phenylpropyl)(hydroxy)phosphoryl]methyl]pent-4-ynoyl)-D-phenylalaninamide
potent phosphinic pseudopeptide inhibitor
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
interferon gamma
treating HeLa cells with interferon-gamma increases the amount of ERAP1
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.328
WEVYEKCALK
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at 37°C
0.075
WRVYEKCALK
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at 37°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
CD8+
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ERAP1_HUMAN
941
0
107235
Swiss-Prot
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulation of mutants K228R, Q730E, R528R/Q730E. The K528R polymorphism has strong effects on the conformational distribution of ERAP1
sitting drop vapor diffusion method
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to 1.6 A resolution, structure of the closed-conformation of ERAP1 with inhibitor Nalpha-(2-[[(1-amino-3-phenylpropyl)(hydroxy)phosphoryl]methyl]pent-4-ynoyl)-D-phenylalaninamide bound in its active site. Inhibitor Nalpha-(2-[[(1-amino-3-phenylpropyl)(hydroxy)phosphoryl]methyl]pent-4-ynoyl)-D-phenylalaninamide is coordinated to the zinc ion via its phosphinic group with a geometry that imitates a transition state analogue
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K528R
K528R/Q730E
combination of single nucleotide polymorphisms, activity similar to wild-type. The effects of mutations K528R and Q730E are independent and additive
Q730E
single nucelotide polymorphism, about 2000% of wild-type activtiy with fluorogenic substrate L-leucine-7-amido-4-methylcoumarin. Mutation at position 730 leads to an increased preference for smaller peptides
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
from culture medium, immobilized metal ion affinity chromatography (Ni2+), gel filtration
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immobilized metal ion affinity chromatography (Ni2+)
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Ni-NTA column chromatography, MonoQ column chromatography, and Superdex S200 gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in insect cells driven by a baculoviral vector
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His-tagged protein expressed in insect cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
human cytomegalovirus downregulates expression during viral infection
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
two-photon fluorescent probe SNCL exhibits high sensitivity toward ERAP1, with about a 95-fold fluorescence enhancement at 550 nm. SNCL can be applied for monitoring ERAP1 in tumor tissue with an imaging depth of 50-120 microm
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Evnouchidou, I.; Berardi, M.J.; Stratikos, E.
A continuous fluorigenic assay for the measurement of the activity of endoplasmic reticulum aminopeptidase 1: competition kinetics as a tool for enzyme specificity investigation
Anal. Biochem.
395
33-40
2009
Homo sapiens
Manually annotated by BRENDA team
Tsui, F.W.; Haroon, N.; Reveille, J.D.; Rahman, P.; Chiu, B.; Tsui, H.W.; Inman, R.D.
Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis
Ann. Rheum. Dis.
69
733-736
2010
Homo sapiens
Manually annotated by BRENDA team
Maksymowych, W.P.; Inman, R.D.; Gladman, D.D.; Reeve, J.P.; Pope, A.; Rahman, P.
Association of a specific ERAP1/ARTS1 haplotype with disease susceptibility in ankylosing spondylitis
Arthritis Rheum.
60
1317-1323
2009
Homo sapiens
Manually annotated by BRENDA team
Johnson, M.P.; Roten, L.T.; Dyer, T.D.; East, C.E.; Forsmo, S.; Blangero, J.; Brennecke, S.P.; Austgulen, R.; Moses, E.K.
The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations
Hum. Genet.
126
655-666
2009
Homo sapiens
Manually annotated by BRENDA team
Kim, S.; Lee, S.; Shin, J.; Kim, Y.; Evnouchidou, I.; Kim, D.; Kim, Y.K.; Kim, Y.E.; Ahn, J.H.; Riddell, S.R.; Stratikos, E.; Kim, V.N.; Ahn, K.
Human cytomegalovirus microRNA miR-US4-1 inhibits CD8(+) T cell responses by targeting the aminopeptidase ERAP1
Nat. Immunol.
12
984-991
2011
Homo sapiens
Manually annotated by BRENDA team
Kochan, G.; Krojer, T.; Harvey, D.; Fischer, R.; Chen, L.; Vollmar, M.; von Delft, F.; Kavanagh, K.L.; Brown, M.A.; Bowness, P.; Wordsworth, P.; Kessler, B.M.; Oppermann, U.
Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming
Proc. Natl. Acad. Sci. USA
108
7745-7750
2011
Homo sapiens
Manually annotated by BRENDA team
Chen, L.; Fischer, R.; Peng, Y.; Reeves, E.; McHugh, K.; Ternette, N.; Hanke, T.; Dong, T.; Elliott, T.; Shastri, N.; Kollnberger, S.; James, E.; Kessler, B.; Bowness, P.
Critical role of endoplasmic reticulum aminopeptidase 1 in determining the length and sequence of peptides bound and presented by HLA-B27
Arthritis Rheum.
66
284-294
2014
Homo sapiens (Q9NZ08)
Manually annotated by BRENDA team
Aldhamen, Y.; Pepelyayeva, Y.; Rastall, D.; Seregin, S.; Zervoudi, E.; Koumantou, D.; Aylsworth, C.; Quiroga, D.; Godbehere, S.; Georgiadis, D.; Stratikos, E.; Amalfitano, A.
Autoimmune disease-associated variants of extracellular endoplasmic reticulum aminopeptidase 1 induce altered innate immune responses by human immune cells
J. Innate Immun.
7
275-289
2015
Homo sapiens (Q9NZ08), Homo sapiens
Manually annotated by BRENDA team
Giastas, P.; Neu, M.; Rowland, P.; Stratikos, E.
High-resolution crystal structure of endoplasmic reticulum aminopeptidase 1 with bound phosphinic transition-state analogue inhibitor
ACS Med. Chem. Lett.
10
708-713
2019
Homo sapiens (Q9NZ08)
Manually annotated by BRENDA team
Xu, S.; Liu, H.W.; Hu, X.X.; Huan, S.Y.; Zhang, J.; Liu, Y.C.; Yuan, L.; Qu, F.L.; Zhang, X.B.; Tan, W.
Visualization of endoplasmic reticulum aminopeptidase 1 under different redox conditions with a two-photon fluorescent probe
Anal. Chem.
89
7641-7648
2017
Homo sapiens (Q9NZ08)
Manually annotated by BRENDA team
Aoki, K.; Furuya, A.; Matsumoto, K.; Tsujimoto, M.
The gene expression of two endoplasmic reticulum aminopeptidase 1 isoforms is regulated by distinct posttranscriptional mechanisms
Biochem. Biophys. Res. Commun.
503
3180-3185
2018
Homo sapiens (Q9NZ08), Homo sapiens
Manually annotated by BRENDA team
Yousaf, N.; Low, W.; Onipinla, A.; Mein, C.; Caulfield, M.; Munroe, P.; Chernajovsky, Y.
Differences between disease-associated endoplasmic reticulum aminopeptidase 1 (ERAP1) isoforms in cellular expression, interactions with tumour necrosis factor receptor 1 (TNF-R1) and regulation by cytokines
Clin. Exp. Immunol.
180
289-304
2015
Homo sapiens (Q9NZ08)
Manually annotated by BRENDA team
Stamogiannos, A.; Koumantou, D.; Papakyriakou, A.; Stratikos, E.
Effects of polymorphic variation on the mechanism of Endoplasmic Reticulum Aminopeptidase 1
Mol. Immunol.
67
426-435
2015
Homo sapiens (Q9NZ08), Homo sapiens
Manually annotated by BRENDA team