Endoplasmic reticulum aminopeptidase 2

Function

Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Preferentially hydrolyzes the basic residues Arg and Lys.

Classification

Family (Pfam)

PF11838 ERAP1_C, PF01433 Peptidase_M1, PF17900 Peptidase_M1_N

InterPro

Aminopeptidase_N-like_N, Aminopeptidase_N-like_N_sf, ERAP1-like_C_dom, M1_APN-typ, Peptidase_M1, Peptidase_M1_aminopeptidases, Peptidase_M1_dom, Peptidase_M4/M1_CTD_sf

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 14

• 3SE6 X-ray 3.08A
• 4E36 X-ray 3.22A
• 4JBS X-ray 2.79A
• 5AB0 X-ray 2.50A
• 5AB2 X-ray 2.73A
• 5CU5 X-ray 3.02A
• 5J6S X-ray 2.80A
• 5K1V X-ray 2.90A
• 6EA4 X-ray 2.45A
• 7NSK X-ray 3.10A
• 7NUP X-ray 3.10A
• 7P7P X-ray 3.00A
• … and 2 more

A predicted model is available from AlphaFold.

Gene Ontology · 14

• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005789 endoplasmic reticulum membrane
• GO:0004177 aminopeptidase activity
• GO:0004175 endopeptidase activity
• GO:0070006 metalloaminopeptidase activity
• GO:0008237 metallopeptidase activity
• GO:0008270 zinc ion binding
• GO:0002250 adaptive immune response
• GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I
• GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
• GO:0043171 peptide catabolic process
• GO:0006508 proteolysis
• GO:0008217 regulation of blood pressure

Drugs targeting this protein · 1

• TOSEDOSTAT inhibitor

Related proteins · sequence + function similarity

• Endoplasmic reticulum aminopeptidase 2 1.00
• Endoplasmic reticulum aminopeptidase 2 0.97
• Endoplasmic reticulum aminopeptidase 1 0.96
• Endoplasmic reticulum aminopeptidase 1 0.95
• Endoplasmic reticulum aminopeptidase 1 0.95
• Leucyl-cystinyl aminopeptidase 0.94
• Leucyl-cystinyl aminopeptidase 0.94
• Leucyl-cystinyl aminopeptidase 0.93
• Glutamyl aminopeptidase 0.88
• Glutamyl aminopeptidase 0.87
• Aminopeptidase Q 0.86
• Glutamyl aminopeptidase 0.85

Co-cited proteins · studied together in the literature

• Endoplasmic reticulum aminopeptidase 1 2 shared papers

Literature · 10 cited papers

• The crystal structure of human endoplasmic reticulum aminopeptidase 2 reveals the atomic basis for distinct roles in antigen processing. Biochemistry · 2012
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Inactivation of RB1 in mantle-cell lymphoma detected by nonsense-mediated mRNA decay pathway inhibition and microarray analysis. Blood · 2007
• Expression of endoplasmic reticulum aminopeptidases in EBV-B cell lines from healthy donors and in leukemia/lymphoma, carcinoma, and melanoma cell lines. J. Immunol. · 2006
• Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J. Proteome Res. · 2005
• The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a 'molecular ruler' mechanism. Proc. Natl. Acad. Sci. U.S.A. · 2005
• Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat. Immunol. · 2005
• Regulation of the human leukocyte-derived arginine aminopeptidase/endoplasmic reticulum-aminopeptidase 2 gene by interferon-gamma. FEBS J. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases. J. Biol. Chem. · 2003