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Q6P179 (ERAP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endoplasmic reticulum aminopeptidase 2

EC=3.4.11.-
Alternative name(s):
Leukocyte-derived arginine aminopeptidase
Short name=L-RAP
Gene names
Name:ERAP2
Synonyms:LRAP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length960 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.7 Ref.8

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

Heterodimer with ERAP1. Ref.7 Ref.12

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein Ref.1.

Tissue specificity

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

Induction

By IFNG/IFN-gamma. Ref.2 Ref.7 Ref.9

Post-translational modification

N-glycosylated. Ref.1 Ref.12

Miscellaneous

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

Sequence similarities

Belongs to the peptidase M1 family.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6P179-1)

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.
Isoform 2 (identifier: Q6P179-2)

The sequence of this isoform differs from the canonical sequence as follows:
     525-532: LAFLGENA → VRIKRVTE
     533-960: Missing.
Isoform 3 (identifier: Q6P179-3)

The sequence of this isoform differs from the canonical sequence as follows:
     238-282: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q6P179-4)

The sequence of this isoform differs from the canonical sequence as follows:
     324-350: DLIAIPDFAPGAMENWGLITYRETSLL → GMFKFHIIVFIFAHKTCFDLFPLSLSM
     351-960: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 960960Endoplasmic reticulum aminopeptidase 2
PRO_0000315719

Regions

Topological domain1 – 2020Cytoplasmic Potential
Transmembrane21 – 4020Helical; Signal-anchor for type II membrane protein; Potential
Topological domain41 – 960920Lumenal Potential
Region334 – 3385Substrate binding

Sites

Active site3711Proton acceptor Ref.12
Metal binding3701Zinc; catalytic
Metal binding3741Zinc; catalytic
Metal binding3931Zinc; catalytic
Binding site2001Substrate
Site4551Transition state stabilizer

Amino acid modifications

Glycosylation851N-linked (GlcNAc...) Ref.12
Glycosylation1191N-linked (GlcNAc...) Ref.6
Glycosylation4051N-linked (GlcNAc...) Ref.12
Glycosylation6501N-linked (GlcNAc...) Ref.12
Disulfide bond421 ↔ 460 Ref.12
Disulfide bond759 ↔ 766 Ref.12

Natural variations

Alternative sequence238 – 28245Missing in isoform 3.
VSP_030671
Alternative sequence324 – 35027DLIAI…ETSLL → GMFKFHIIVFIFAHKTCFDL FPLSLSM in isoform 4.
VSP_030672
Alternative sequence351 – 960610Missing in isoform 4.
VSP_030673
Alternative sequence525 – 5328LAFLGENA → VRIKRVTE in isoform 2.
VSP_030674
Alternative sequence533 – 960428Missing in isoform 2.
VSP_030675
Natural variant2141P → L.
Corresponds to variant rs3733905 [ dbSNP | Ensembl ].
VAR_038285
Natural variant3921K → N. Ref.1 Ref.2
Corresponds to variant rs2549782 [ dbSNP | Ensembl ].
VAR_038286
Natural variant4111L → R.
Corresponds to variant rs34261036 [ dbSNP | Ensembl ].
VAR_051569
Natural variant6691L → Q.
Corresponds to variant rs17408150 [ dbSNP | Ensembl ].
VAR_038287

Experimental info

Sequence conflict1291R → K in AAH17927. Ref.5

Secondary structure

............................................................................................................................................... 960
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: 261EFC06870D644E

FASTA960110,462
        10         20         30         40         50         60 
MFHSSAMVNS HRKPMFNIHR GFYCLTAILP QICICSQFSV PSSYHFTEDP GAFPVATNGE 

        70         80         90        100        110        120 
RFPWQELRLP SVVIPLHYDL FVHPNLTSLD FVASEKIEVL VSNATQFIIL HSKDLEITNA 

       130        140        150        160        170        180 
TLQSEEDSRY MKPGKELKVL SYPAHEQIAL LVPEKLTPHL KYYVAMDFQA KLGDGFEGFY 

       190        200        210        220        230        240 
KSTYRTLGGE TRILAVTDFE PTQARMAFPC FDEPLFKANF SIKIRRESRH IALSNMPKVK 

       250        260        270        280        290        300 
TIELEGGLLE DHFETTVKMS TYLVAYIVCD FHSLSGFTSS GVKVSIYASP DKRNQTHYAL 

       310        320        330        340        350        360 
QASLKLLDFY EKYFDIYYPL SKLDLIAIPD FAPGAMENWG LITYRETSLL FDPKTSSASD 

       370        380        390        400        410        420 
KLWVTRVIAH ELAHQWFGNL VTMEWWNDIW LKEGFAKYME LIAVNATYPE LQFDDYFLNV 

       430        440        450        460        470        480 
CFEVITKDSL NSSRPISKPA ETPTQIQEMF DEVSYNKGAC ILNMLKDFLG EEKFQKGIIQ 

       490        500        510        520        530        540 
YLKKFSYRNA KNDDLWSSLS NSCLESDFTS GGVCHSDPKM TSNMLAFLGE NAEVKEMMTT 

       550        560        570        580        590        600 
WTLQKGIPLL VVKQDGCSLR LQQERFLQGV FQEDPEWRAL QERYLWHIPL TYSTSSSNVI 

       610        620        630        640        650        660 
HRHILKSKTD TLDLPEKTSW VKFNVDSNGY YIVHYEGHGW DQLITQLNQN HTLLRPKDRV 

       670        680        690        700        710        720 
GLIHDVFQLV GAGRLTLDKA LDMTYYLQHE TSSPALLEGL SYLESFYHMM DRRNISDISE 

       730        740        750        760        770        780 
NLKRYLLQYF KPVIDRQSWS DKGSVWDRML RSALLKLACD LNHAPCIQKA AELFSQWMES 

       790        800        810        820        830        840 
SGKLNIPTDV LKIVYSVGAQ TTAGWNYLLE QYELSMSSAE QNKILYALST SKHQEKLLKL 

       850        860        870        880        890        900 
IELGMEGKVI KTQNLAALLH AIARRPKGQQ LAWDFVRENW THLLKKFDLG SYDIRMIISG 

       910        920        930        940        950        960 
TTAHFSSKDK LQEVKLFFES LEAQGSHLDI FQTVLETITK NIKWLEKNLP TLRTWLMVNT 

« Hide

Isoform 2 [UniParc].

Checksum: DA0F49B61F79B920
Show »

FASTA53260,952
Isoform 3 [UniParc].

Checksum: 10075BE1C076377F
Show »

FASTA915105,526
Isoform 4 [UniParc].

Checksum: 189B8EF5D9D4BD11
Show »

FASTA35040,088

References

« Hide 'large scale' references
[1]"Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases."
Tanioka T., Hattori A., Masuda S., Nomura Y., Nakayama H., Mizutani S., Tsujimoto M.
J. Biol. Chem. 278:32275-32283(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY, SUBCELLULAR LOCATION, GLYCOSYLATION, TOPOLOGY, TISSUE SPECIFICITY, VARIANT ASN-392.
[2]"Regulation of the human leukocyte-derived arginine aminopeptidase/endoplasmic reticulum-aminopeptidase 2 gene by interferon-gamma."
Tanioka T., Hattori A., Mizutani S., Tsujimoto M.
FEBS J. 272:916-928(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION BY IFNG, VARIANT ASN-392.
[3]"Molecular characterization of aminopeptidase MAMS."
Schomburg L.
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
Tissue: Skeletal muscle and Skin.
[6]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-119.
Tissue: Plasma.
[7]"Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum."
Saveanu L., Carroll O., Lindo V., Del Val M., Lopez D., Lepelletier Y., Greer F., Schomburg L., Fruci D., Niedermann G., van Endert P.M.
Nat. Immunol. 6:689-697(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INDUCTION BY IFNG.
[8]"The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a 'molecular ruler' mechanism."
Chang S.-C., Momburg F., Bhutani N., Goldberg A.L.
Proc. Natl. Acad. Sci. U.S.A. 102:17107-17112(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Expression of endoplasmic reticulum aminopeptidases in EBV-B cell lines from healthy donors and in leukemia/lymphoma, carcinoma, and melanoma cell lines."
Fruci D., Ferracuti S., Limongi M.Z., Cunsolo V., Giorda E., Fraioli R., Sibilio L., Carroll O., Hattori A., van Endert P.M., Giacomini P.
J. Immunol. 176:4869-4879(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GENE REGULATION.
[10]"Inactivation of RB1 in mantle-cell lymphoma detected by nonsense-mediated mRNA decay pathway inhibition and microarray analysis."
Pinyol M., Bea S., Pla L., Ribrag V., Bosq J., Rosenwald A., Campo E., Jares P.
Blood 109:5422-5429(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"The crystal structure of human endoplasmic reticulum aminopeptidase 2 reveals the atomic basis for distinct roles in antigen processing."
Birtley J.R., Saridakis E., Stratikos E., Mavridis I.M.
Biochemistry 51:286-295(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.08 ANGSTROMS) OF 3-960 IN COMPLEX WITH SUBSTRATE, GLYCOSYLATION AT ASN-85; ASN-219; ASN-405 AND ASN-650, ACTIVE SITE, ZINC-BINDING SITES, SUBUNIT, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS4086.1. [Q6P179-1]
RefSeqNP_001123612.1. NM_001130140.1. [Q6P179-1]
NP_071745.1. NM_022350.3. [Q6P179-1]
UniGeneHs.482910.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3SE6X-ray3.08A/B1-960[»]
4E36X-ray3.22A/B1-960[»]
4JBSX-ray2.79A/B3-960[»]
ProteinModelPortalQ6P179.
SMRQ6P179. Positions 54-960.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ6P179. 1 interaction.
STRING9606.ENSP00000342447.

Chemistry

ChEMBLCHEMBL5043.

Protein family/group databases

MEROPSM01.024.

PTM databases

PhosphoSiteQ6P179.

Polymorphism databases

DMDM166232401.

Proteomic databases

MaxQBQ6P179.
PaxDbQ6P179.
PeptideAtlasQ6P179.
PRIDEQ6P179.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379904; ENSP00000369235; ENSG00000164308. [Q6P179-3]
ENST00000437043; ENSP00000400376; ENSG00000164308. [Q6P179-1]
ENST00000510309; ENSP00000425758; ENSG00000164308. [Q6P179-4]
ENST00000513084; ENSP00000421849; ENSG00000164308. [Q6P179-2]
GeneID64167.
KEGGhsa:64167.
UCSCuc003kmq.3. human. [Q6P179-1]
uc003kms.3. human. [Q6P179-3]

Organism-specific databases

CTD64167.
GeneCardsGC05P096238.
H-InvDBHIX0005053.
HGNCHGNC:29499. ERAP2.
HPACAB025618.
HPA034498.
MIM609497. gene.
neXtProtNX_Q6P179.
PharmGKBPA162385208.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0308.
HOGENOMHOG000106482.
HOVERGENHBG108296.
InParanoidQ6P179.
KOK13723.
OMAYLDINRE.
OrthoDBEOG754HNR.
PhylomeDBQ6P179.
TreeFamTF300395.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SABIO-RKQ6P179.

Gene expression databases

ArrayExpressQ6P179.
BgeeQ6P179.
CleanExHS_ERAP2.
GenevestigatorQ6P179.

Family and domain databases

InterProIPR024571. ERAP1-like_C_dom.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view]
PANTHERPTHR11533. PTHR11533. 1 hit.
PfamPF11838. ERAP1_C. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]
PRINTSPR00756. ALADIPTASE.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi64167.
NextBio66072.
PROQ6P179.
SOURCESearch...

Entry information

Entry nameERAP2_HUMAN
AccessionPrimary (citable) accession number: Q6P179
Secondary accession number(s): Q7Z5K1 expand/collapse secondary AC list , Q8TD32, Q8WVJ4, Q9HBX2
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: July 9, 2014
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM