Target Information
| Target General Information | Top | |||||
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| Target ID |
T65818
(Former ID: TTDI03171)
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| Target Name |
Endoplasmic reticulum aminopeptidase 2 (ERAP2)
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| Synonyms |
Leukocyte-derived arginine aminopeptidase; LRAP; L-RAP
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| Gene Name |
ERAP2
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
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. Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.11.-
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| Sequence |
MFHSSAMVNSHRKPMFNIHRGFYCLTAILPQICICSQFSVPSSYHFTEDPGAFPVATNGE
RFPWQELRLPSVVIPLHYDLFVHPNLTSLDFVASEKIEVLVSNATQFIILHSKDLEITNA TLQSEEDSRYMKPGKELKVLSYPAHEQIALLVPEKLTPHLKYYVAMDFQAKLGDGFEGFY KSTYRTLGGETRILAVTDFEPTQARMAFPCFDEPLFKANFSIKIRRESRHIALSNMPKVK TIELEGGLLEDHFETTVKMSTYLVAYIVCDFHSLSGFTSSGVKVSIYASPDKRNQTHYAL QASLKLLDFYEKYFDIYYPLSKLDLIAIPDFAPGAMENWGLITYRETSLLFDPKTSSASD KLWVTRVIAHELAHQWFGNLVTMEWWNDIWLKEGFAKYMELIAVNATYPELQFDDYFLNV CFEVITKDSLNSSRPISKPAETPTQIQEMFDEVSYNKGACILNMLKDFLGEEKFQKGIIQ YLKKFSYRNAKNDDLWSSLSNSCLESDFTSGGVCHSDPKMTSNMLAFLGENAEVKEMMTT WTLQKGIPLLVVKQDGCSLRLQQERFLQGVFQEDPEWRALQERYLWHIPLTYSTSSSNVI HRHILKSKTDTLDLPEKTSWVKFNVDSNGYYIVHYEGHGWDQLITQLNQNHTLLRPKDRV GLIHDVFQLVGAGRLTLDKALDMTYYLQHETSSPALLEGLSYLESFYHMMDRRNISDISE NLKRYLLQYFKPVIDRQSWSDKGSVWDRMLRSALLKLACDLNHAPCIQKAAELFSQWMES SGKLNIPTDVLKIVYSVGAQTTAGWNYLLEQYELSMSSAEQNKILYALSTSKHQEKLLKL IELGMEGKVIKTQNLAALLHAIARRPKGQQLAWDFVRENWTHLLKKFDLGSYDIRMIISG TTAHFSSKDKLQEVKLFFESLEAQGSHLDIFQTVLETITKNIKWLEKNLPTLRTWLMVNT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 1-ETHOXY-2-(2-ETHOXYETHOXY)ETHANE | Ligand Info | |||||
| Structure Description | Endoplasmic reticulum aminopeptidase 2 complexed with a hydroxamic ligand | PDB:7NSK | ||||
| Method | X-ray diffraction | Resolution | 3.10 Å | Mutation | Yes | [2] |
| PDB Sequence |
AFPVATNGER
61 FPWQELRLPS71 VVIPLHYDLF81 VHPNLTSLDF91 VASEKIEVLV101 SNATQFIILH 111 SKDLEITNAT121 LQSEEDSRYM131 KPGKELKVLS141 YPAHEQIALL151 VPEKLTPHLK 161 YYVAMDFQAK171 LGDGFEGFYK181 STYRTLGGET191 RILAVTDFEP201 TQARMAFPCF 211 DEPLFKANFS221 IKIRRESRHI231 ALSNMPKVKT241 IELEGGLLED251 HFETTVKMST 261 YLVAYIVCDF271 HSLSGFTSSG281 VKVSIYASPD291 KRNQTHYALQ301 ASLKLLDFYE 311 KYFDIYYPLS321 KLDLIAIPDF331 APGAMENWGL341 ITYRETSLLF351 DPKTSSASDK 361 LWVTRVIAHE371 LAHQWFGNLV381 TMEWWNDIWL391 NEGFAKYMEL401 IAVNATYPEL 411 QFDDYFLNVC421 FEVITKDSLN431 SSRPISKPAE441 TPTQIQEMFD451 EVSYNKGACI 461 LNMLKDFLGE471 EKFQKGIIQY481 LKKFSYRNAK491 NDDLWSSLSN501 SCLESDFTSG 511 GVCHSDPKMT521 SNMLAFLGEN531 AEVKEMMTTW541 TLQKGIPLLV551 VKQDGCSLRL 561 QQERFLQGVF571 QEDPEWRALQ581 ERYLWHIPLT591 YSTSSSNVIH601 RHILKSKTDT 611 LDLPEKTSWV621 KFNVDSNGYY631 IVHYEGHGWD641 QLITQLNQNH651 TLLRPKDRVG 661 LIHDVFQLVG671 AGRLTLDKAL681 DMTYYLQHET691 SSPALLEGLS701 YLESFYHMMD 711 RRNISDISEN721 LKRYLLQYFK731 PVIDRQSWSD741 KGSVWDRMLR751 SALLKLACDL 761 NHAPCIQKAA771 ELFSQWMESS781 GKLNIPTDVL791 KIVYSVGAQT801 TAGWNYLLEQ 811 YELSMSSAEQ821 NKILYALSTS831 KHQEKLLKLI841 ELGMEGKVIK851 TQNLAALLHA 861 IARRPKGQQL871 AWDFVRENWT881 HLLKKFDLGS891 YDIRMIISGT901 TAHFSSKDKL 911 QEVKLFFESL921 EAQGSHLDIF931 QTVLETITKN941 IKWLEKNLPT951 LRTWLMVNTR 961 HH
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| Ligand Name: L-lysine | Ligand Info | |||||
| Structure Description | ERAP2 bound to Aryl Sulfonamide Uncompetitive Inhibitor | PDB:6EA4 | ||||
| Method | X-ray diffraction | Resolution | 2.45 Å | Mutation | Yes | [3] |
| PDB Sequence |
FPVATNGERF
62 PWQELRLPSV72 VIPLHYDLFV82 HPNLTSLDFV92 ASEKIEVLVS102 NATQFIILHS 112 KDLEITNATL122 QSEEDSRYMK132 PGKELKVLSY142 PAHEQIALLV152 PEKLTPHLKY 162 YVAMDFQAKL172 GDGFEGFYKS182 TYRTLGGETR192 ILAVTDFEPT202 QARMAFPCFD 212 EPLFKANFSI222 KIRRESRHIA232 LSNMPKVKTI242 ELEGGLLEDH252 FETTVKMSTY 262 LVAYIVCDFH272 SLSGFTSSGV282 KVSIYASPDK292 RNQTHYALQA302 SLKLLDFYEK 312 YFDIYYPLSK322 LDLIAIPDFA332 PGAMENWGLI342 TYRETSLLFD352 PKTSSASDKL 362 WVTRVIAHEL372 AHQWFGNLVT382 MEWWNDIWLN392 EGFAKYMELI402 AVNATYPELQ 412 FDDYFLNVCF422 EVITKDSLNS432 SRPISKPAET442 PTQIQEMFDE452 VSYNKGACIL 462 NMLKDFLGEE472 KFQKGIIQYL482 KKFSYRNAKN492 DDLWSSLSNE530 NAEVKEMMTT 540 WTLQKGIPLL550 VVKQDGCSLR560 LQQERFLQGV570 FQEDPEWRAL580 QERYLWHIPL 590 TYSTSSSNVI600 HRHILKSKTD610 TLDLPEKTSW620 VKFNVDSNGY630 YIVHYEGHGW 640 DQLITQLNQN650 HTLLRPKDRV660 GLIHDVFQLV670 GAGRLTLDKA680 LDMTYYLQHE 690 TSSPALLEGL700 SYLESFYHMM710 DRRNISDISE720 NLKRYLLQYF730 KPVIDRQSWS 740 DKGSVWDRML750 RSALLKLACD760 LNHAPCIQKA770 AELFSQWMES780 SGKLNIPTDV 790 LKIVYSVGAQ800 TTAGWNYLLE810 QYELSMSSAE820 QNKILYALST830 SKHQEKLLKL 840 IELGMEGKVI850 KTQNLAALLH860 AIARRPKGQQ870 LAWDFVRENW880 THLLKKFDLG 890 SYDIRMIISG900 TTAHFSSKDK910 LQEVKLFFES920 LEAQGSHLDI930 FQTVLETITK 940 NIKWLEKNLP950 TLRTWLMVNT960 RHH
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Cofactor of initiator function (CIF) | 23.188 (48/207) | 3.60E-04 | |
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Novel selective inhibitors of aminopeptidases that generate antigenic peptides. Bioorg Med Chem Lett. 2013 Sep 1;23(17):4832-6. | |||||
| REF 2 | Endoplasmic reticulum aminopeptidase 2 in complex with a phosphinic ligand | |||||
| REF 3 | Crystal structure of human ER aminopeptidase 1 bound to aryl sulfonamide inhibitor. | |||||
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