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Protein

Endoplasmic reticulum aminopeptidase 2

Gene

ERAP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

Miscellaneous

Defects in the expression of this gene may cause improper antigen processing, possibly leading to favor tumor escape from the immune surveillance.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei200Substrate1 Publication1
Metal bindingi370Zinc; catalytic1
Active sitei371Proton acceptorPROSITE-ProRule annotation1 Publication1
Metal bindingi374Zinc; catalytic1
Metal bindingi393Zinc; catalytic1
Sitei455Transition state stabilizer1

GO - Molecular functioni

  • aminopeptidase activity Source: HGNC
  • endopeptidase activity Source: Reactome
  • metalloaminopeptidase activity Source: GO_Central
  • metallopeptidase activity Source: HGNC
  • peptide binding Source: GO_Central
  • zinc ion binding Source: HGNC

GO - Biological processi

Keywordsi

Molecular functionAminopeptidase, Hydrolase, Metalloprotease, Protease
Biological processAdaptive immunity, Immunity
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.11.1 2681
3.4.11.6 2681
ReactomeiR-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC
SABIO-RKiQ6P179

Protein family/group databases

MEROPSiM01.024

Names & Taxonomyi

Protein namesi
Recommended name:
Endoplasmic reticulum aminopeptidase 2 (EC:3.4.11.-)
Alternative name(s):
Leukocyte-derived arginine aminopeptidase
Short name:
L-RAP
Gene namesi
Name:ERAP2
Synonyms:LRAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000164308.16
HGNCiHGNC:29499 ERAP2
MIMi609497 gene
neXtProtiNX_Q6P179

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 20CytoplasmicSequence analysisAdd BLAST20
Transmembranei21 – 40Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST20
Topological domaini41 – 960LumenalSequence analysisAdd BLAST920

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi64167
OpenTargetsiENSG00000164308
PharmGKBiPA162385208

Chemistry databases

ChEMBLiCHEMBL5043
GuidetoPHARMACOLOGYi1567

Polymorphism and mutation databases

BioMutaiERAP2
DMDMi166232401

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003157191 – 960Endoplasmic reticulum aminopeptidase 2Add BLAST960

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi85N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi119N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi219N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi405N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi421 ↔ 4601 Publication
Glycosylationi650N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi759 ↔ 7661 Publication

Post-translational modificationi

N-glycosylated.3 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ6P179
MaxQBiQ6P179
PaxDbiQ6P179
PeptideAtlasiQ6P179
PRIDEiQ6P179
ProteomicsDBi66824
66825 [Q6P179-2]
66826 [Q6P179-3]
66827 [Q6P179-4]

PTM databases

GlyConnecti1204
iPTMnetiQ6P179
PhosphoSitePlusiQ6P179

Expressioni

Tissue specificityi

Ubiquitously expressed. Highly expressed in spleen and leukocytes.1 Publication

Inductioni

By IFNG/IFN-gamma.2 Publications

Gene expression databases

BgeeiENSG00000164308 Expressed in 197 organ(s), highest expression level in leukocyte
CleanExiHS_ERAP2
ExpressionAtlasiQ6P179 baseline and differential
GenevisibleiQ6P179 HS

Organism-specific databases

HPAiCAB025618
HPA034498
HPA064360

Interactioni

Subunit structurei

Heterodimer with ERAP1.2 Publications

Protein-protein interaction databases

BioGridi122092, 1 interactor
CORUMiQ6P179
IntActiQ6P179, 2 interactors
STRINGi9606.ENSP00000400376

Chemistry databases

BindingDBiQ6P179

Structurei

Secondary structure

1960
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6P179
SMRiQ6P179
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni334 – 338Substrate binding5

Sequence similaritiesi

Belongs to the peptidase M1 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1046 Eukaryota
COG0308 LUCA
GeneTreeiENSGT00760000119082
HOGENOMiHOG000106482
HOVERGENiHBG108296
InParanoidiQ6P179
KOiK13723
OMAiAKNDDLW
OrthoDBiEOG091G01GH
PhylomeDBiQ6P179
TreeFamiTF300395

Family and domain databases

CDDicd09601 M1_APN_2, 1 hit
InterProiView protein in InterPro
IPR024571 ERAP1-like_C_dom
IPR033528 ERAP2
IPR034016 M1_APN-typ
IPR001930 Peptidase_M1
IPR014782 Peptidase_M1_N
PANTHERiPTHR11533 PTHR11533, 1 hit
PTHR11533:SF239 PTHR11533:SF239, 1 hit
PfamiView protein in Pfam
PF11838 ERAP1_C, 1 hit
PF01433 Peptidase_M1, 1 hit
PRINTSiPR00756 ALADIPTASE
PROSITEiView protein in PROSITE
PS00142 ZINC_PROTEASE, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q6P179-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MFHSSAMVNS HRKPMFNIHR GFYCLTAILP QICICSQFSV PSSYHFTEDP
60 70 80 90 100
GAFPVATNGE RFPWQELRLP SVVIPLHYDL FVHPNLTSLD FVASEKIEVL
110 120 130 140 150
VSNATQFIIL HSKDLEITNA TLQSEEDSRY MKPGKELKVL SYPAHEQIAL
160 170 180 190 200
LVPEKLTPHL KYYVAMDFQA KLGDGFEGFY KSTYRTLGGE TRILAVTDFE
210 220 230 240 250
PTQARMAFPC FDEPLFKANF SIKIRRESRH IALSNMPKVK TIELEGGLLE
260 270 280 290 300
DHFETTVKMS TYLVAYIVCD FHSLSGFTSS GVKVSIYASP DKRNQTHYAL
310 320 330 340 350
QASLKLLDFY EKYFDIYYPL SKLDLIAIPD FAPGAMENWG LITYRETSLL
360 370 380 390 400
FDPKTSSASD KLWVTRVIAH ELAHQWFGNL VTMEWWNDIW LKEGFAKYME
410 420 430 440 450
LIAVNATYPE LQFDDYFLNV CFEVITKDSL NSSRPISKPA ETPTQIQEMF
460 470 480 490 500
DEVSYNKGAC ILNMLKDFLG EEKFQKGIIQ YLKKFSYRNA KNDDLWSSLS
510 520 530 540 550
NSCLESDFTS GGVCHSDPKM TSNMLAFLGE NAEVKEMMTT WTLQKGIPLL
560 570 580 590 600
VVKQDGCSLR LQQERFLQGV FQEDPEWRAL QERYLWHIPL TYSTSSSNVI
610 620 630 640 650
HRHILKSKTD TLDLPEKTSW VKFNVDSNGY YIVHYEGHGW DQLITQLNQN
660 670 680 690 700
HTLLRPKDRV GLIHDVFQLV GAGRLTLDKA LDMTYYLQHE TSSPALLEGL
710 720 730 740 750
SYLESFYHMM DRRNISDISE NLKRYLLQYF KPVIDRQSWS DKGSVWDRML
760 770 780 790 800
RSALLKLACD LNHAPCIQKA AELFSQWMES SGKLNIPTDV LKIVYSVGAQ
810 820 830 840 850
TTAGWNYLLE QYELSMSSAE QNKILYALST SKHQEKLLKL IELGMEGKVI
860 870 880 890 900
KTQNLAALLH AIARRPKGQQ LAWDFVRENW THLLKKFDLG SYDIRMIISG
910 920 930 940 950
TTAHFSSKDK LQEVKLFFES LEAQGSHLDI FQTVLETITK NIKWLEKNLP
960
TLRTWLMVNT
Length:960
Mass (Da):110,462
Last modified:January 15, 2008 - v2
Checksum:i261EFC06870D644E
GO
Isoform 2 (identifier: Q6P179-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     525-532: LAFLGENA → VRIKRVTE
     533-960: Missing.

Show »
Length:532
Mass (Da):60,952
Checksum:iDA0F49B61F79B920
GO
Isoform 3 (identifier: Q6P179-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     238-282: Missing.

Note: No experimental confirmation available.
Show »
Length:915
Mass (Da):105,526
Checksum:i10075BE1C076377F
GO
Isoform 4 (identifier: Q6P179-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     324-350: DLIAIPDFAPGAMENWGLITYRETSLL → GMFKFHIIVFIFAHKTCFDLFPLSLSM
     351-960: Missing.

Note: No experimental confirmation available.
Show »
Length:350
Mass (Da):40,088
Checksum:i189B8EF5D9D4BD11
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RGW0D6RGW0_HUMAN
Endoplasmic reticulum aminopeptidas...
ERAP2
694Annotation score:
H0YAL8H0YAL8_HUMAN
Endoplasmic reticulum aminopeptidas...
ERAP2
163Annotation score:
H0Y9X9H0Y9X9_HUMAN
Endoplasmic reticulum aminopeptidas...
ERAP2
79Annotation score:
D6RF46D6RF46_HUMAN
Endoplasmic reticulum aminopeptidas...
ERAP2
29Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti129R → K in AAH17927 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_038285214P → L. Corresponds to variant dbSNP:rs3733905Ensembl.1
Natural variantiVAR_038286392K → N2 PublicationsCorresponds to variant dbSNP:rs2549782Ensembl.1
Natural variantiVAR_051569411L → R. Corresponds to variant dbSNP:rs34261036EnsemblClinVar.1
Natural variantiVAR_038287669L → Q. Corresponds to variant dbSNP:rs17408150Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030671238 – 282Missing in isoform 3. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_030672324 – 350DLIAI…ETSLL → GMFKFHIIVFIFAHKTCFDL FPLSLSM in isoform 4. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_030673351 – 960Missing in isoform 4. 1 PublicationAdd BLAST610
Alternative sequenceiVSP_030674525 – 532LAFLGENA → VRIKRVTE in isoform 2. 1 Publication8
Alternative sequenceiVSP_030675533 – 960Missing in isoform 2. 1 PublicationAdd BLAST428

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB109031 mRNA Translation: BAC78818.1
AB163917 mRNA Translation: BAD90015.1
AY028805 mRNA Translation: AAK37776.1
AF191545 mRNA Translation: AAG28383.1
CH471084 Genomic DNA Translation: EAW96080.1
BC065240 mRNA Translation: AAH65240.1
BC017927 mRNA Translation: AAH17927.1
CCDSiCCDS4086.1 [Q6P179-1]
CCDS87316.1 [Q6P179-4]
CCDS87317.1 [Q6P179-3]
RefSeqiNP_001123612.1, NM_001130140.2 [Q6P179-1]
NP_001316158.1, NM_001329229.1 [Q6P179-3]
NP_001316162.1, NM_001329233.1 [Q6P179-4]
NP_071745.1, NM_022350.4 [Q6P179-1]
UniGeneiHs.482910

Genome annotation databases

EnsembliENST00000379904; ENSP00000369235; ENSG00000164308 [Q6P179-3]
ENST00000437043; ENSP00000400376; ENSG00000164308 [Q6P179-1]
ENST00000510309; ENSP00000425758; ENSG00000164308 [Q6P179-4]
ENST00000513084; ENSP00000421849; ENSG00000164308 [Q6P179-2]
GeneIDi64167
KEGGihsa:64167
UCSCiuc003kmq.4 human [Q6P179-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB109031 mRNA Translation: BAC78818.1
AB163917 mRNA Translation: BAD90015.1
AY028805 mRNA Translation: AAK37776.1
AF191545 mRNA Translation: AAG28383.1
CH471084 Genomic DNA Translation: EAW96080.1
BC065240 mRNA Translation: AAH65240.1
BC017927 mRNA Translation: AAH17927.1
CCDSiCCDS4086.1 [Q6P179-1]
CCDS87316.1 [Q6P179-4]
CCDS87317.1 [Q6P179-3]
RefSeqiNP_001123612.1, NM_001130140.2 [Q6P179-1]
NP_001316158.1, NM_001329229.1 [Q6P179-3]
NP_001316162.1, NM_001329233.1 [Q6P179-4]
NP_071745.1, NM_022350.4 [Q6P179-1]
UniGeneiHs.482910

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3SE6X-ray3.08A/B1-960[»]
4E36X-ray3.22A/B1-960[»]
4JBSX-ray2.79A/B3-960[»]
5AB0X-ray2.50A/C1-960[»]
5AB2X-ray2.73A/B1-960[»]
5CU5X-ray3.02A/B1-960[»]
5J6SX-ray2.80A/B1-960[»]
5K1VX-ray2.90A/B1-960[»]
ProteinModelPortaliQ6P179
SMRiQ6P179
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122092, 1 interactor
CORUMiQ6P179
IntActiQ6P179, 2 interactors
STRINGi9606.ENSP00000400376

Chemistry databases

BindingDBiQ6P179
ChEMBLiCHEMBL5043
GuidetoPHARMACOLOGYi1567

Protein family/group databases

MEROPSiM01.024

PTM databases

GlyConnecti1204
iPTMnetiQ6P179
PhosphoSitePlusiQ6P179

Polymorphism and mutation databases

BioMutaiERAP2
DMDMi166232401

Proteomic databases

EPDiQ6P179
MaxQBiQ6P179
PaxDbiQ6P179
PeptideAtlasiQ6P179
PRIDEiQ6P179
ProteomicsDBi66824
66825 [Q6P179-2]
66826 [Q6P179-3]
66827 [Q6P179-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379904; ENSP00000369235; ENSG00000164308 [Q6P179-3]
ENST00000437043; ENSP00000400376; ENSG00000164308 [Q6P179-1]
ENST00000510309; ENSP00000425758; ENSG00000164308 [Q6P179-4]
ENST00000513084; ENSP00000421849; ENSG00000164308 [Q6P179-2]
GeneIDi64167
KEGGihsa:64167
UCSCiuc003kmq.4 human [Q6P179-1]

Organism-specific databases

CTDi64167
DisGeNETi64167
EuPathDBiHostDB:ENSG00000164308.16
GeneCardsiERAP2
H-InvDBiHIX0005053
HGNCiHGNC:29499 ERAP2
HPAiCAB025618
HPA034498
HPA064360
MIMi609497 gene
neXtProtiNX_Q6P179
OpenTargetsiENSG00000164308
PharmGKBiPA162385208
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1046 Eukaryota
COG0308 LUCA
GeneTreeiENSGT00760000119082
HOGENOMiHOG000106482
HOVERGENiHBG108296
InParanoidiQ6P179
KOiK13723
OMAiAKNDDLW
OrthoDBiEOG091G01GH
PhylomeDBiQ6P179
TreeFamiTF300395

Enzyme and pathway databases

BRENDAi3.4.11.1 2681
3.4.11.6 2681
ReactomeiR-HSA-983170 Antigen Presentation: Folding, assembly and peptide loading of class I MHC
SABIO-RKiQ6P179

Miscellaneous databases

ChiTaRSiERAP2 human
GenomeRNAii64167
PROiPR:Q6P179
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164308 Expressed in 197 organ(s), highest expression level in leukocyte
CleanExiHS_ERAP2
ExpressionAtlasiQ6P179 baseline and differential
GenevisibleiQ6P179 HS

Family and domain databases

CDDicd09601 M1_APN_2, 1 hit
InterProiView protein in InterPro
IPR024571 ERAP1-like_C_dom
IPR033528 ERAP2
IPR034016 M1_APN-typ
IPR001930 Peptidase_M1
IPR014782 Peptidase_M1_N
PANTHERiPTHR11533 PTHR11533, 1 hit
PTHR11533:SF239 PTHR11533:SF239, 1 hit
PfamiView protein in Pfam
PF11838 ERAP1_C, 1 hit
PF01433 Peptidase_M1, 1 hit
PRINTSiPR00756 ALADIPTASE
PROSITEiView protein in PROSITE
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiERAP2_HUMAN
AccessioniPrimary (citable) accession number: Q6P179
Secondary accession number(s): Q7Z5K1
, Q8TD32, Q8WVJ4, Q9HBX2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: October 10, 2018
This is version 129 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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