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Information on EC 3.4.11.22 - aminopeptidase I and Organism(s) Mus musculus and UniProt Accession Q9EQH2
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3.4.11.22 aminopeptidase ISpecify your search results
Word Map
- 3.4.11.22
- spondylitis
-
ankylosing
-
trim
- aminopeptidases
-
histocompatibility
- vacuole
-
hla-b27
- autoimmune
- psoriasis
-
eraps
-
cargo
-
cytoplasm-to-vacuole
-
peptidome
-
macroautophagy
- spondyloarthritis
- allotypes
- oxytocinase
- bestatin
-
double-membrane
- maltase
-
exopeptidase
-
immunopeptidome
-
tnfaip3
-
as-associated
-
antigen-processing
-
birdshot
- medicine
-
traf3ip2
-
autoinflammatory
- analysis
- nutrition
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
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
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
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 III
-
-
-
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Aminopeptidase yscI
-
-
-
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Aminopeptidase yscII
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-
-
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Aminopeptidase yscXVI
-
-
-
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Aminopolypeptidase
-
-
-
-
Amylorhizin aminopeptidase
-
-
-
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Amylorizin
-
-
-
-
API
-
-
-
-
L-aminopeptidase
-
-
-
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LAPIV
-
-
-
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Leu.AP
-
-
-
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Leucin aminopeptidase V
-
-
-
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Leucine aminopeptidase IV
-
-
-
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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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Yeast aminopeptidase I
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9031-94-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-Leu-7-amido-4-methylcoumarin + H2O
L-Leu + 7-amino-4-methylcoumarin
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efficient cleavage
-
-
?
L-leucine-4-methylcoumaryl-7-amide + H2O
L-leucine + 7-amino-4-methylcoumarin
-
-
-
-
?
L-Met-7-amido-4-methylcoumarin + H2O
L-Met + 7-amino-4-methylcoumarin
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slower cleavage compared to L-Leu-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
-
ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules, overview, loss of enzyme results in disruption of generation of naturally processed peptides in the endoplasmic reticulum, decreased stability of peptide-MHC class I complexes, and diminished CD8+ T cell responses
-
-
?
additional information
?
-
-
ERAP1 trims MHC class I-presented peptides in vivo and plays an important role in immunodominance, overview
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-
?
additional information
?
-
-
ERAP1 does not degrade other substrates of the X-7-amido-4-methylcoumarin form except L-Leu-7-amido-4-methylcoumarin and L-Met-7-amido-4-methylcoumarin
-
-
?
additional information
?
-
-
ERAP1 trims peptides with length of 10-14 residues very efficiently down to 8-9 residues long while further trimming is practically absent
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules, overview, loss of enzyme results in disruption of generation of naturally processed peptides in the endoplasmic reticulum, decreased stability of peptide-MHC class I complexes, and diminished CD8+ T cell responses
-
-
?
additional information
?
-
-
ERAP1 trims MHC class I-presented peptides in vivo and plays an important role in immunodominance, overview
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
physiological function
in the presence of aminopeptidase inhibitor amastatin, nitric oxide synthesis in activated RAW264.7 cells is significantly decreased. Subsequently, significant reduction of nitric oxide synthesis is observed in aminopeptidase ERAP1 knockdown cells compared with wild-type cells. This reduction is rescued by exogenously added ERAP1. When peritoneal macrophages prepared from ERAP1 knockout mouse are employed, reduction of nitric oxide synthesis in knockout mouse macrophages is also attributable to ERAP1. In the presence of amastatin, further reduction is observed in knockout mouse-derived macrophages
physiological function
mice lacking isoform ERAP1 exhibit exaggerated innate immune responses early during pathogen recognition, as characterized by increased activation of splenic and hepatic natural killer and natural killer T-cells and enhanced production of proinflammatory cytokines such as IL12 and MCP1. ERAP1 is playing a critical role in natural killer cell development and function. ERAP1-KO mice show higher frequencies of terminally matured natural killer cells, as well as higher frequencies of licensed natural killer cells expressing the Ly49C and Ly49I receptors which positively correlates with an enhanced natural killer cell activation and IFNc production by ERAP1-KO mice challenged with pro-inflammatory stimuli. During pathogen recognition, ERAP1 regulates IL12 production by CD11c+ dendritic cells specifically
physiological function
-
intracellular ERAP1 induces angiogenesis through endothelial integrin activation, while the secreted form of the enzyme suppresses angiogenesis through angiotensin II inactivation. ERAP1 participates in the innate immune response by increasing the production of cytokine receptors. ERAP1 is associated with the MHC class I antigen processing and presentation pathway
physiological function
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secreted from RAW-264.7 cells after costimulation with lipopolysaccharide and interferon-gamma
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Q181E
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different substrate specificity, cleaves basic amino acid residues preferentially
additional information
additional information
-
generation of ERAAP-deficient mutant mice of strain 129/J by gene excision, the mutants show reduced and altered MHC class I molecules
additional information
-
generation of ERAP1-knockout mice, which show a shift in the hierarchy of immunodominance in viral infections, even when the responding T-cells have the same T-cell receptor repertoire, mutant immunodominance hierarchy: GP276, NP396, GP33, GP34, GP118, NP205, CD8+ T-cell responses to viral epitopes are altered in transgenic mice, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
from culture medium, hydroxyapatite chromatography, immobilized metal ion affinity chromatography (Co2+)
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hammer, G.E.; Gonzalez, F.; Champsaur, M.; Cado, D.; Shastri, N.
The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules
Nat. Immunol.
7
103-112
2006
Mus musculus
York, I.A.; Brehm, M.A.; Zendzian, S.; Towne, C.F.; Rock, K.L.
Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance
Proc. Natl. Acad. Sci. USA
103
9202-9207
2006
Mus musculus
Evnouchidou, I.; Papakyriakou, A.; Stratikos, E.
A new role for Zn(II) aminopeptidases: antigenic peptide generation and destruction
Curr. Pharm. Des.
15
3656-3670
2009
Mus musculus
Goto, Y.; Ogawa, K.; Hattori, A.; Tsujimoto, M.
Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the activation of macrophages induced by lipopolysaccharide and interferon-gamma
J. Biol. Chem.
286
21906-21914
2011
Mus musculus
Goto, Y.; Ogawa, K.; Nakamura, T.J.; Hattori, A.; Tsujimoto, M.
Substrate-dependent nitric oxide synthesis by secreted endoplasmic reticulum aminopeptidase 1 in macrophages
J. Biochem.
157
439-449
2015
Mus musculus (Q9EQH2), Mus musculus
Aldhamen, Y.A.; Seregin, S.S.; Rastall, D.P.; Aylsworth, C.F.; Pepelyayeva, Y.; Busuito, C.J.; Godbehere-Roosa, S.; Kim, S.; Amalfitano, A.
Endoplasmic reticulum aminopeptidase-1 functions regulate key aspects of the innate immune response
PLoS ONE
8
e69539
2013
Mus musculus (Q9EQH2)
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