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    ERAP2 endoplasmic reticulum aminopeptidase 2 [ Homo sapiens (human) ]

    Gene ID: 64167, updated on 27-Nov-2024

    Summary

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    Official Symbol
    ERAP2provided by HGNC
    Official Full Name
    endoplasmic reticulum aminopeptidase 2provided by HGNC
    Primary source
    HGNC:HGNC:29499
    See related
    Ensembl:ENSG00000164308 MIM:609497; AllianceGenome:HGNC:29499
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LRAP; L-RAP
    Summary
    This gene encodes a zinc metalloaminopeptidase of the M1 protease family that resides in the endoplasmic reticulum and functions in N-terminal trimming antigenic epitopes for presentation by major histocompatibility complex (MHC) class I molecules. Certain mutations in this gene are associated with the inflammatory arthritis syndrome ankylosing spondylitis and pre-eclampsia. This gene is located adjacent to a closely related aminopeptidase gene on chromosome 5. [provided by RefSeq, Jul 2016]
    Expression
    Broad expression in lymph node (RPKM 22.9), spleen (RPKM 19.0) and 23 other tissues See more
    Orthologs
    all
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    Genomic context

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    See ERAP2 in Genome Data Viewer
    Location:
    5q15
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (96875939..96919716)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (97376720..97420596)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (96211643..96255420)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124901031 Neighboring gene endoplasmic reticulum aminopeptidase 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:96143101-96143602 Neighboring gene uncharacterized LOC124901033 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:96143603-96144102 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22816 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22817 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16196 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:96172729-96173230 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:96173231-96173730 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22818 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22819 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22820 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22821 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:96220180-96220354 Neighboring gene Sharpr-MPRA regulatory region 14932 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22822 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22824 Neighboring gene uncharacterized LOC124901030 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22825 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22826 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16197 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22827 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16198 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22828 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16199 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16200 Neighboring gene ribosomal protein S20 pseudogene 16 Neighboring gene leucyl and cystinyl aminopeptidase

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Functional Interaction of the Ankylosing Spondylitis-Associated Endoplasmic Reticulum Aminopeptidase 2 With the HLA-B*27 Peptidome in Human Cells. Martín-Esteban A, et al. Arthritis Rheumatol, 2016 Oct. PMID 27110896
    2. Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility. Ebrazeh M, et al. Int J Rheum Dis, 2021 Apr. PMID 33550689
    3. A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection? Saulle I, et al. Cells, 2020 Aug 24. PMID 32847031, Free PMC Article
    4. Endoplasmic reticulum aminopeptidase 2 gene single nucleotide polymorphisms in association with susceptibility to ankylosing spondylitis in an Iranian population. Ebrazeh M, et al. Immunol Lett, 2020 Jul. PMID 32360304
    5. Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2). Lorente E, et al. Mol Cell Proteomics, 2020 Jun. PMID 32265295, Free PMC Article

    See all (102) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The effect of rs2910686 on ERAP2 expression in IBD and epithelial inflammatory response.
      Title: The effect of rs2910686 on ERAP2 expression in IBD and epithelial inflammatory response.
    2. A study of the association between single nucleotide polymorphisms of the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene and the risk of ankylosing spondylitis in Egyptians.
      Title: A study of the association between single nucleotide polymorphisms of the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene and the risk of ankylosing spondylitis in Egyptians.
    3. A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.
      Title: A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.
    4. ERAP1 and ERAP2 Haplotypes Influence Suboptimal HLA-B*27:05-Restricted Anti-Viral CD8+ T Cell Responses Cross-Reactive to Self-Epitopes.
      Title: ERAP1 and ERAP2 Haplotypes Influence Suboptimal HLA-B*27:05-Restricted Anti-Viral CD8+ T Cell Responses Cross-Reactive to Self-Epitopes.
    5. Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
      Title: Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.
    6. A Comparative Review of Pregnancy and Cancer and Their Association with Endoplasmic Reticulum Aminopeptidase 1 and 2.
      Title: A Comparative Review of Pregnancy and Cancer and Their Association with Endoplasmic Reticulum Aminopeptidase 1 and 2.
    7. ERAP2 supports TCR recognition of three immunotherapy targeted tumor epitopes.
      Title: ERAP2 supports TCR recognition of three immunotherapy targeted tumor epitopes.
    8. The ER Aminopeptidases, ERAP1 and ERAP2, synergize to self-modulate their respective activities.
      Title: The ER Aminopeptidases, ERAP1 and ERAP2, synergize to self-modulate their respective activities.
    9. ERAP2 as a potential biomarker for predicting gemcitabine response in patients with pancreatic cancer.
      Title: ERAP2 as a potential biomarker for predicting gemcitabine response in patients with pancreatic cancer.
    10. ERAP2 is a novel target involved in autophagy and activation of pancreatic stellate cells via UPR signaling pathway.
      Title: ERAP2 is a novel target involved in autophagy and activation of pancreatic stellate cells via UPR signaling pathway.
    Submit: New GeneRIF Correction See all GeneRIFs (74)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.
    EBI GWAS Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with ERAP2; predicted interaction to be involved in antigenicity/immunity PubMed
    capsid gag HIV-1 p24 levels in PBMC cultures are significantly lower in ERAP2 homoA compared with both homoB and heteroAB samples, suggesting homoA is correlated with resistance to HIV-1 infection PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ23633, FLJ23701, FLJ23807

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables aminopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables endopeptidase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables metalloaminopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metallopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables peptide binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables zinc ion binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in antigen processing and presentation of endogenous peptide antigen via MHC class I TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in antigen processing and presentation of peptide antigen via MHC class I TAS
    Traceable Author Statement
    more info
    		  
    involved_in peptide catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of blood pressure TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum lumen IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in endoplasmic reticulum membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    endoplasmic reticulum aminopeptidase 2
    Names
    leukocyte-derived arginine aminopeptidase
    NP_001123612.1
    NP_001316158.1
    NP_001316162.1
    NP_071745.1
    XP_011541846.1
    XP_047273446.1
    XP_054209052.1
    XP_054209053.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_051092.1 RefSeqGene

      Range
      5562..48765
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001130140.2 → NP_001123612.1  endoplasmic reticulum aminopeptidase 2 isoform 1

      See identical proteins and their annotated locations for NP_001123612.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same protein (isoform 1).
      Source sequence(s)
      AC008850, AF191545, AK312864, AV688559, CA311579, DA990479, DB159802
      Consensus CDS
      CCDS4086.1
      UniProtKB/Swiss-Prot
      Q6P179, Q7Z5K1, Q8TD32, Q8WVJ4, Q9HBX2
      UniProtKB/TrEMBL
      B2R769
      Related
      ENSP00000421175.2, ENST00000510373.6
      Conserved Domains (3) summary
      cd09601
      Location:76 → 548
      M1_APN_2; Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)
      pfam01433
      Location:68 → 458
      Peptidase_M1; Peptidase family M1
      pfam11838
      Location:621 → 938
      ERAP1_C; ERAP1-like C-terminal domain

    2. NM_001329229.1 → NP_001316158.1  endoplasmic reticulum aminopeptidase 2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 2 which is shorter than isoform 1.
      Source sequence(s)
      AC008850, AV688559, BC065240, BU430967, CA311579, DA990479
      Consensus CDS
      CCDS87317.1
      UniProtKB/TrEMBL
      B2R769
      Related
      ENSP00000369235.4, ENST00000379904.8
      Conserved Domains (3) summary
      cd09601
      Location:76 → 503
      M1_APN_2; Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)
      pfam01433
      Location:68 → 413
      Peptidase_M1; Peptidase family M1
      pfam11838
      Location:576 → 893
      ERAP1_C; ERAP1-like C-terminal domain

    3. NM_001329233.1 → NP_001316162.1  endoplasmic reticulum aminopeptidase 2 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 3' UTR, lacks multiple exons in the 3' coding region and its 3' terminal exon extends past a known splice donor site, compared to variant 1. It encodes isoform 3 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AV688559, BC017927, BC065240, BU430967, DA990479
      Consensus CDS
      CCDS87316.1
      UniProtKB/Swiss-Prot
      Q6P179
      Related
      ENSP00000425758.1, ENST00000510309.1
      Conserved Domains (1) summary
      cl14813
      Location:76 → 325
      GluZincin; Peptidase Gluzincin family (thermolysin-like proteinases, TLPs) includes peptidases M1, M2, M3, M4, M13, M32 and M36 (fungalysins)

    4. NM_022350.5 → NP_071745.1  endoplasmic reticulum aminopeptidase 2 isoform 1

      See identical proteins and their annotated locations for NP_071745.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1 and 2 both encode the same protein (isoform 1).
      Source sequence(s)
      AC008850, AF191545, AK312864, AV688559, CA311579
      Consensus CDS
      CCDS4086.1
      UniProtKB/Swiss-Prot
      Q6P179, Q7Z5K1, Q8TD32, Q8WVJ4, Q9HBX2
      UniProtKB/TrEMBL
      B2R769
      Related
      ENSP00000400376.3, ENST00000437043.8
      Conserved Domains (3) summary
      cd09601
      Location:76 → 548
      M1_APN_2; Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)
      pfam01433
      Location:68 → 458
      Peptidase_M1; Peptidase family M1
      pfam11838
      Location:621 → 938
      ERAP1_C; ERAP1-like C-terminal domain

    RNA

    1. NR_137637.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AB163917, AC008850, AC009126, AV688559, BC065240, BU430967, CA311579, DA990479

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      96875939..96919716
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011543544.3 → XP_011541846.1  endoplasmic reticulum aminopeptidase 2 isoform X1

      UniProtKB/TrEMBL
      A0AAQ5BHS6, B2R769
      Related
      ENSP00000519508.1, ENST00000714228.1
      Conserved Domains (3) summary
      cd09601
      Location:76 → 525
      M1_APN_2; Peptidase M1 Aminopeptidase N family incudes tricorn interacting factor F3, Endoplasmic reticulum aminopeptidase 1 (ERAP1), Aminopeptidase Q (APQ)
      pfam01433
      Location:68 → 458
      Peptidase_M1; Peptidase family M1
      pfam11838
      Location:598 → 915
      ERAP1_C; ERAP1-like C-terminal domain

    2. XM_047417490.1 → XP_047273446.1  endoplasmic reticulum aminopeptidase 2 isoform X1

      UniProtKB/TrEMBL
      A0AAQ5BHS6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      97376720..97420596
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353077.1 → XP_054209052.1  endoplasmic reticulum aminopeptidase 2 isoform X1

    2. XM_054353078.1 → XP_054209053.1  endoplasmic reticulum aminopeptidase 2 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6P179.2 GenPept UniProtKB/Swiss-Prot:Q6P179

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