ERAP2

Summary

ERAP2 (endoplasmic reticulum aminopeptidase 2, HGNC:29499) is a protein-coding gene on chromosome 5q15, encoding Endoplasmic reticulum aminopeptidase 2 (Q6P179). Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.

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.

Source: NCBI Gene 64167 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 12 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_022350

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29499
Approved symbol	ERAP2
Name	endoplasmic reticulum aminopeptidase 2
Location	5q15
Locus type	gene with protein product
Status	Approved
Aliases	L-RAP, LRAP
Ensembl gene	ENSG00000164308
Ensembl biotype	protein_coding
OMIM	609497
Entrez	64167

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000379904, ENST00000437043, ENST00000507346, ENST00000508077, ENST00000510309, ENST00000510373, ENST00000512869, ENST00000513084, ENST00000513368, ENST00000515095, ENST00000515387, ENST00000714228, ENST00000851668, ENST00000851669, ENST00000959438, ENST00000959439

RefSeq mRNA: 4 — MANE Select: NM_022350 NM_001130140, NM_001329229, NM_001329233, NM_022350

CCDS: CCDS4086, CCDS87316, CCDS87317

Canonical transcript exons

ENST00000437043 — 19 exons

Exon	Start	End
ENSE00001083348	96892299	96892453
ENSE00001083349	96886655	96886789
ENSE00001083351	96889185	96889305
ENSE00001083354	96883792	96883930
ENSE00001083358	96879564	96880260
ENSE00002048366	96876500	96876527
ENSE00002084274	96908961	96909117
ENSE00003465035	96895246	96895359
ENSE00003510796	96902274	96902353
ENSE00003554877	96896373	96896504
ENSE00003577997	96900121	96900189
ENSE00003612783	96901506	96901681
ENSE00003674037	96903377	96903560
ENSE00003694183	96896732	96896863
ENSE00004011717	96913317	96913457
ENSE00004011718	96915688	96915769
ENSE00004011719	96912637	96912798
ENSE00004011720	96909580	96909764
ENSE00004011721	96917462	96919703

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 94.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6027 / max 434.3614, expressed in 1346 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57710	15.4472	1342
57708	0.1177	59
57709	0.0378	7

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.37	gold quality
granulocyte	CL:0000094	93.21	gold quality
lymph node	UBERON:0000029	92.83	gold quality
superficial temporal artery	UBERON:0001614	91.21	gold quality
visceral pleura	UBERON:0002401	91.06	gold quality
epithelium of nasopharynx	UBERON:0001951	90.75	gold quality
leukocyte	CL:0000738	90.59	gold quality
monocyte	CL:0000576	90.25	gold quality
mononuclear cell	CL:0000842	90.08	gold quality
colonic epithelium	UBERON:0000397	89.80	gold quality
vermiform appendix	UBERON:0001154	89.34	gold quality
calcaneal tendon	UBERON:0003701	88.40	gold quality
spleen	UBERON:0002106	87.24	gold quality
ileal mucosa	UBERON:0000331	86.74	gold quality
blood	UBERON:0000178	86.63	gold quality
jejunal mucosa	UBERON:0000399	86.50	gold quality
caecum	UBERON:0001153	86.05	gold quality
palpebral conjunctiva	UBERON:0001812	85.67	gold quality
bone marrow cell	CL:0002092	85.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.35	gold quality
apex of heart	UBERON:0002098	85.05	gold quality
germinal epithelium of ovary	UBERON:0001304	84.88	gold quality
pleura	UBERON:0000977	84.75	gold quality
small intestine	UBERON:0002108	84.75	gold quality
duodenum	UBERON:0002114	84.26	gold quality
tonsil	UBERON:0002372	83.91	gold quality
gall bladder	UBERON:0002110	83.66	gold quality
mucosa of transverse colon	UBERON:0004991	83.50	gold quality
right lung	UBERON:0002167	83.29	gold quality
bone marrow	UBERON:0002371	83.12	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.00
E-CURD-10	no	692.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF1, IRF2, NFKB1, RELA, SPI1

miRNA regulators (miRDB)

64 targeting ERAP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Literature-anchored findings (GeneRIF, showing 40)

• oxytocinase subfamily of M1 aminopeptidases play important roles in the maintenance of homeostasis including maintenance of normal pregnancy, memory retention, blood pressure regulation and antigen presentation [review] (PMID:16054015)
• low and/or imbalanced expression of ERAP1 and probably ERAP2 may cause improper Ag processing and favor tumor escape from immune surveillance (PMID:16585582)
• Dramatic genetic effect on LRAP expression. (PMID:17129607)
• ERAP2, which encodes an aminopeptidase, did not show preferential parent-of-origin expression, but rather, cis-acting nonimprinted differential allelic control (PMID:18369178)
• Results describe the altered expression of endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 in transformed non-lymphoid human tissues. (PMID:18393273)
• Novel preeclampsia risk locus, ERAP2, in a region of known genetic linkage to this pregnancy-specific disorder. (PMID:19578876)
• Data show the downregulation of MHC class I, ERAP1, and ERAP2 in aggressive NB cells is attributable to a low transcriptional availability of NF-kappaB, possibly due to an unknown suppressor other than MYCN. (PMID:20103633)
• heterogeneous expression in melanoma cell lines (PMID:20419298)
• The ERAP1 and ERAP2 polymorphisms associated with ankylosing spondylitis (AS) do not influence the serum cytokine receptor levels in patients with AS. (PMID:20595269)
• data suggest that genetic diversity in ERAP1 and ERAP2 has been maintained by balancing selection and that variants in ERAP2 confer resistance to HIV-1 infection possibly via the presentation of a distinctive peptide repertoire to CD8(+) T cells (PMID:20843824)
• Data show that the differences between the ERAP2 splice forms provide important insights into the potential mechanism for the action of selection. (PMID:20976248)
• ERAP2 was found to have bimodal expression in human skeletal muscle tissue. (PMID:21299892)
• S1 specificity pocket of the aminopeptidases that generate antigenic peptides. (PMID:21314638)
• strong evidence that ERAP2 plays a role in the development of preeclampsia (PMID:21569342)
• assessed frequency of rs2248374 SNP in ERAP2 in ankylosing spondylitis (AS) cases and controls and found no association with AS (PMID:21719416)
• The molecular structure of glycosylated human ERAP2 has been determined to 3.08 A resolution by molecular replacement using ERAP1 as a search model and refined. (PMID:22106953)
• crystals of ERAP2 belonged to an orthorhombic space group and diffracted anisotropically to 3.3 A resolution in the best direction on an in-house X-ray source (PMID:22505422)
• The common ERAP2 single nucleotide polymorphism rs2549782 that codes for amino acid variation Asp392Lys leads to alterations in both the activity and the specificity of the enzyme. (PMID:22837489)
• ERAP2 haplotype A is correlated with resistance to HIV-1 infection, possibly secondarily to its effect on antigen processing and presentation. (PMID:23435305)
• Generation and destruction of antigenic peptides by endoplasmic reticulum resident aminopeptidases ERAP1 and ERAP2 have been shown in the last few years to be important for correct functioning and regulation of the adaptive immune response. (PMID:23545452)
• ERAP1 and ERAP2 might be involved in the development of immune escape mechanisms of renal cell carcinoma. (PMID:23696916)
• The association and co-localization of ERAP2 and EpCAM at the surface of breast cancer cells is a unique and novel finding that provides new ideas on EpCAM processing and on how antigen presentation may be regulated in cancer. (PMID:23988446)
• concerted aminoproteolytic activity of ERAP 1 and ERAP2 (PMID:24223975)
• Data indicate that dimerization of endoplasmic reticulum aminopeptidases ERAP1/2 creates complexes with superior peptide-trimming efficacy. (PMID:24928998)
• The risk allele of the polymorphism near ERAP2 is strongly associated with birdshot chorioretinopathy. (PMID:24957906)
• Studies indicate the critical role of M1 aminopeptidases ERAP1, ERAP2 and NPEPPS in immune-mediated diseases. (PMID:25142031)
• ERAP2 is associated with ankylosing spondylitis in HLA-B27 positive and HLA-B27 negative patients. (PMID:25917849)
• ERAP2 variation does not have a significant effect on PBMC intracellular and cell surface HLA-class I expression and heavy chain formation, markers of ER stress or inflammatory cytokine production. (PMID:26088389)
• ERAP2 might be associated with CLNM in PTMC. (PMID:26148615)
• ERAP-2 significantly influences the B*27:05-bound peptidome by destroying some ligands and decreasing the abundance of many more ligands with N-terminal basic residues, while increasing the abundance of nonamers. The former effects are best explained by direct ERAP-2 trimming. The effects on peptide length might be attributed to ERAP-2-induced activation of ERAP-1 trimming. These data support the notion of a peptide-media (PMID:27110896)
• Increased expression of ERAP2 in GC-responders before therapy warrants further investigation into their role as potential predictors for the response to GC, and in the inflammatory process of rheumatoid arthritis. (PMID:27384923)
• ERAP1 and ERAP2 heterodimers have a role in mediating the processing pathway of MHC class I antigens (PMID:27514473)
• study reveals fine-mapped AID risk variants that act as eQTLs with ERAP2 in thymus (PMID:27829666)
• ERAP2 deficiency causes increased MHC class I free heavy chain expression and up-regulation of the unfolded protein response pathway in anklyosing spondylitis. (PMID:28029742)
• ERAP1 and ERAP2 have significant and distinct effects on the HLA-B*27 peptidome, suggesting that both enzymes largely act as separate entities in vivo. This may explain their different patterns of association with AS. (PMID:28063628)
• there is a significant association of ERAP2 with psoriatic arthritis and HLA-B27 negative psoriatic arthritis, while ERAP1 association is restricted only to HLA-B27 positive disease (PMID:28083616)
• This review focuses on the ambivalent role of HLA-B27 in autoimmunity and viral protection correlating its functions to the quantitative and qualitative effects of ERAP1 and ERAP2 polymorphisms on their enzymatic activity. (PMID:28759104)
• These results indicated that the ERAP gene may play a critical role in HCV chronicity in this Chinese Han population (PMID:29037997)
• Increased aminopeptidase expression governed by altered transcript dynamics at both ERAP1 and ERAP2 is a key mechanism driving the degree to which these enzymes contribute to immune-mediated disease. (PMID:29108111)
• this study shows the association of ERAP2 single nucleotide polymorphism and its haplotypes with psoriasis vulgaris, and its dependence on the presence or absence of the HLA-C*06:02 allele and age at disease onset (PMID:29183862)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	erap2	ENSDARG00000098618
drosophila_melanogaster	CG7653	FBGN0028935
drosophila_melanogaster	CG9806	FBGN0030222
drosophila_melanogaster	CG2111	FBGN0030223
drosophila_melanogaster	CG6071	FBGN0036186
drosophila_melanogaster	CG5849	FBGN0038897
drosophila_melanogaster	CG3502	FBGN0046253
drosophila_melanogaster	CG31233	FBGN0051233
drosophila_melanogaster	CG31343	FBGN0051343
drosophila_melanogaster	CG31445	FBGN0051445
drosophila_melanogaster	SP1029	FBGN0263236
drosophila_melanogaster	CG46339	FBGN0285963
caenorhabditis_elegans	F49B2.6	WBGENE00009865
caenorhabditis_elegans		WBGENE00011587
caenorhabditis_elegans		WBGENE00012776

Paralogs (11): TRHDE (ENSG00000072657), LTA4H (ENSG00000111144), LNPEP (ENSG00000113441), ENPEP (ENSG00000138792), NPEPPS (ENSG00000141279), RNPEPL1 (ENSG00000142327), AOPEP (ENSG00000148120), ERAP1 (ENSG00000164307), ANPEP (ENSG00000166825), LVRN (ENSG00000172901), RNPEP (ENSG00000176393)

Protein

Protein identifiers

Endoplasmic reticulum aminopeptidase 2 — Q6P179 (reviewed: Q6P179)

Alternative names: Leukocyte-derived arginine aminopeptidase

All UniProt accessions (6): A0AAQ5BHS6, D6RF46, D6RGW0, Q6P179, H0Y9X9, H0YAL8

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Heterodimer with ERAP1.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitously expressed. Highly expressed in spleen and leukocytes.

Post-translational modifications. N-glycosylated.

Cofactor. Binds 1 zinc ion per subunit.

Induction. By IFNG/IFN-gamma.

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

Similarity. Belongs to the peptidase M1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6P179-1	1	yes
Q6P179-2	2
Q6P179-3	3
Q6P179-4	4

RefSeq proteins (4): NP_001123612, NP_001316158, NP_001316162, NP_071745* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001930	Peptidase_M1	Family
IPR014782	Peptidase_M1_dom	Domain
IPR024571	ERAP1-like_C_dom	Domain
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR034016	M1_APN-typ	Family
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily
IPR045357	Aminopeptidase_N-like_N	Domain
IPR050344	Peptidase_M1_aminopeptidases	Family

Pfam: PF01433, PF11838, PF17900

Enzyme classification (BRENDA):

• EC 3.4.11.1 — leucyl aminopeptidase (BRENDA: 101 organisms, 467 substrates, 423 inhibitors, 209 Km, 161 kcat entries)
• EC 3.4.11.6 — aminopeptidase B (BRENDA: 35 organisms, 222 substrates, 305 inhibitors, 95 Km, 61 kcat entries)

Substrate kinetics (BRENDA)

137 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-ARG-2-NAPHTHYLAMIDE	—	22
LEU-GLY	1.5–8.4	10
L-LEU-4-NITROANILIDE	0.035–12.7	9
LEU-4-NITROANILIDE	0.22–8.8	8
L-LEU-7-AMIDO-4-METHYLCOUMARIN	0.012–1.38	7
L-LEUCINE-4-METHYLCOUMARYL-7-AMIDE	0.015–0.35	6
LEUCYL-4-METHYLCOUMARYL-7-AMIDE	0.0131–0.173	6
L-LYS-2-NAPHTHYLAMIDE	0.0001–0.333	6
BETA-CYCLOHEXYL-L-ALANYL-4-METHYLCOUMARYL-7-AMID	0.0011–0.539	5
LEU-P-NITROANILIDE	0.17–0.97	5
LEUCINAMIDE	4.02–17	5
ARG-7-AMIDO-4-METHYLCOUMARIN	0.0159–0.603	5
L-ARG-7-AMIDO-4-METHYLCOUMARIN	0.048–0.208	5
L-ALANINE-4-METHYLCOUMARYL-7-AMIDE	0.054–1.16	4
L-LEU-GLY	1.8–7.2	4

UniProt features (119 total): helix 41, strand 41, turn 9, glycosylation site 5, splice variant 5, binding site 5, sequence variant 4, topological domain 2, disulfide bond 2, chain 1, site 1, transmembrane region 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6EA4	X-RAY DIFFRACTION	2.45
5AB0	X-RAY DIFFRACTION	2.5
7PFS	X-RAY DIFFRACTION	2.7
5AB2	X-RAY DIFFRACTION	2.73
4JBS	X-RAY DIFFRACTION	2.79
5J6S	X-RAY DIFFRACTION	2.8
5K1V	X-RAY DIFFRACTION	2.9
7P7P	X-RAY DIFFRACTION	3
5CU5	X-RAY DIFFRACTION	3.02
3SE6	X-RAY DIFFRACTION	3.08
7NSK	X-RAY DIFFRACTION	3.1
7NUP	X-RAY DIFFRACTION	3.1
7SH0	X-RAY DIFFRACTION	3.2
4E36	X-RAY DIFFRACTION	3.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P179-F1	93.52	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 455 (transition state stabilizer); 371 (proton acceptor)

Ligand- & substrate-binding residues (5): 200; 334–338; 370; 374; 393

Disulfide bonds (2): 421–460, 759–766

Glycosylation sites (5): 85, 119, 219, 405, 650

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC

MSigDB gene sets: 109 (showing top): GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOMF_METALLOPEPTIDASE_ACTIVITY, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_PEPTIDE_METABOLIC_PROCESS, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN_VIA_MHC_CLASS_I, GOBP_ADAPTIVE_IMMUNE_RESPONSE, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, RODRIGUES_DCC_TARGETS_DN, GOBP_PEPTIDE_CATABOLIC_PROCESS

GO Biological Process (7): adaptive immune response (GO:0002250), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), proteolysis (GO:0006508), regulation of blood pressure (GO:0008217), antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:0019885), peptide catabolic process (GO:0043171), immune system process (GO:0002376)

GO Molecular Function (9): endopeptidase activity (GO:0004175), aminopeptidase activity (GO:0004177), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
peptidase activity	2
immune response	1
antigen processing and presentation of peptide antigen	1
protein metabolic process	1
blood circulation	1
regulation of biological quality	1
antigen processing and presentation of peptide antigen via MHC class I	1
antigen processing and presentation of endogenous peptide antigen	1
peptide metabolic process	1
catabolic process	1
biological_process	1
exopeptidase activity	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERAP2	TPP2	P29144	901
ERAP2	HLA-C	P04222	721
ERAP2	CAST	P20810	680
ERAP2	PDIA3	P30101	667
ERAP2	TAPBP	O15533	631
ERAP2	CALR	P27797	625
ERAP2	B2M	P01884	608
ERAP2	HLA-B	P01889	597
ERAP2	ERAP1	Q9NZ08	557
ERAP2	IFNG	P01579	537
ERAP2	TAPBPL	Q9BX59	511
ERAP2	HLA-A	P01891	505
ERAP2	VCAN	P13611	503
ERAP2	HLA-DQB2	P05538	449
ERAP2	LILRB1	Q8NHL6	435

IntAct

16 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
ERAP1	ERAP2	psi-mi:“MI:0915”(physical association)	0.460
ERAP1	ERAP2	psi-mi:“MI:0403”(colocalization)	0.460
ERAP2	env	psi-mi:“MI:0570”(protein cleavage)	0.440
ERAP2	RPL27	psi-mi:“MI:0915”(physical association)	0.400
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
MFSD3	NME4	psi-mi:“MI:0914”(association)	0.350
SLC22A11	CNOT1	psi-mi:“MI:0914”(association)	0.350
TCTN1	TOR1A	psi-mi:“MI:2364”(proximity)	0.270
TCTN1	PLOD2	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
	ERAP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): ERAP2 (Proximity Label-MS), ERAP2 (Affinity Capture-MS), ERAP2 (Affinity Capture-MS), ERAP2 (Affinity Capture-MS), ERAP2 (Proximity Label-MS), ERAP2 (Proximity Label-MS), ERAP2 (Proximity Label-MS), ERAP2 (Proximity Label-MS), ERAP2 (Proximity Label-MS), ERAP2 (Proximity Label-MS), ERAP2 (Affinity Capture-RNA), ERAP2 (Affinity Capture-MS), ERAP2 (Proximity Label-MS), ERAP2 (Proximity Label-MS), ERAP2 (Proximity Label-MS)

ESM2 similar proteins: A0A6J2ATK2, A5HUI5, A6QPT7, D3UW23, M3XFH7, O57579, O88917, O88923, O94910, O95490, O97817, O97827, O97831, P15144, P15145, P15541, P15684, P16406, P42658, P42659, P46101, P50123, P79098, P79143, P79171, P97449, P97629, Q07075, Q10737, Q22523, Q2KHK3, Q2M2H8, Q32LQ0, Q5RFP3, Q6P179, Q6Q4G3, Q7Q2T8, Q7TT41, Q80TR1, Q80TS3

Diamond homologs: A0A6J2ATK2, A6NEC2, A6QPT7, M3XFH7, O57579, P15144, P15145, P15541, P15684, P46557, P50123, P79098, P79143, P79171, P97449, P97629, Q07075, Q10736, Q10836, Q2KHK3, Q32LQ0, Q5RFP3, Q6P179, Q6Q4G3, Q7Q2T8, Q8C129, Q8K093, Q95334, Q9EQH2, Q9JJ22, Q9UIQ6, Q9UKU6, A5HUI5, D3UW23, O93654, O93655, P0DQU2, P16406, P32454, P37893

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ERAP2	“down-regulates quantity”	oligopeptide	“chemical modification”
ERAP2	“up-regulates quantity”	“peptide antigen”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

12 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2880 predictions. Top by Δscore:

Variant	Effect	Δscore
5:96877889:A:AG	acceptor_gain	1.0000
5:96886650:TGTA:T	acceptor_loss	1.0000
5:96886651:GTAG:G	acceptor_loss	1.0000
5:96886652:TAG:T	acceptor_loss	1.0000
5:96886653:A:C	acceptor_loss	1.0000
5:96886785:TCAAG:T	donor_loss	1.0000
5:96886786:CAAG:C	donor_loss	1.0000
5:96886787:AAGG:A	donor_loss	1.0000
5:96886788:AGGTG:A	donor_loss	1.0000
5:96886789:GGT:G	donor_loss	1.0000
5:96886790:G:GA	donor_loss	1.0000
5:96886791:T:A	donor_loss	1.0000
5:96895356:ATTT:A	donor_gain	1.0000
5:96895360:G:GG	donor_gain	1.0000
5:96896862:AT:A	donor_gain	1.0000
5:96896864:G:GG	donor_gain	1.0000
5:96903524:GA:G	donor_gain	1.0000
5:96903526:G:GG	donor_gain	1.0000
5:96908959:A:AG	acceptor_gain	1.0000
5:96908959:AGT:A	acceptor_gain	1.0000
5:96908960:G:GA	acceptor_gain	1.0000
5:96908960:GT:G	acceptor_gain	1.0000
5:96908960:GTG:G	acceptor_gain	1.0000
5:96908960:GTGCA:G	acceptor_gain	1.0000
5:96909087:G:GT	donor_gain	1.0000
5:96909113:TCAAG:T	donor_loss	1.0000
5:96909114:CAAG:C	donor_loss	1.0000
5:96909115:AAG:A	donor_loss	1.0000
5:96909116:AGGT:A	donor_loss	1.0000
5:96909117:GGTT:G	donor_loss	1.0000

AlphaMissense

6355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:96883846:C:G	C210W	0.987
5:96886697:T:C	F253L	0.984
5:96886699:T:A	F253L	0.984
5:96886699:T:G	F253L	0.984
5:96895246:T:A	W376R	0.983
5:96895246:T:C	W376R	0.983
5:96883868:G:C	A218P	0.981
5:96883874:T:C	F220L	0.980
5:96883876:T:A	F220L	0.980
5:96883876:T:G	F220L	0.980
5:96892343:T:A	W339R	0.978
5:96892343:T:C	W339R	0.978
5:96895288:T:A	W390R	0.976
5:96895288:T:C	W390R	0.976
5:96880130:G:C	A149P	0.975
5:96895276:T:A	W386R	0.975
5:96895276:T:C	W386R	0.975
5:96901554:T:A	W541R	0.974
5:96901554:T:C	W541R	0.974
5:96880125:A:C	Q147P	0.971
5:96892350:T:C	L341P	0.970
5:96879869:T:C	F62L	0.969
5:96879871:T:A	F62L	0.969
5:96879871:T:G	F62L	0.969
5:96883844:T:C	C210R	0.969
5:96895278:G:C	W386C	0.968
5:96895278:G:T	W386C	0.968
5:96892443:T:C	L372P	0.967
5:96902281:T:A	W586R	0.967
5:96902281:T:C	W586R	0.967

dbSNP variants (sampled 300 via entrez): RS1000047069 (5:96906128 T>C), RS1000060125 (5:96879390 T>C), RS1000074611 (5:96885581 G>A,T), RS1000146343 (5:96885907 G>A,C), RS1000224287 (5:96912523 A>G), RS1000346644 (5:96891594 C>T), RS1000400998 (5:96902553 G>A,C), RS1000406884 (5:96905528 C>A,T), RS1000433359 (5:96883664 C>A), RS1000617864 (5:96901342 C>T), RS1000624338 (5:96874769 T>A,C), RS1000646233 (5:96907220 A>G), RS1000661084 (5:96881130 C>A,T), RS1000712553 (5:96908698 A>G), RS1000718868 (5:96874984 A>T)

Disease associations

OMIM: gene MIM:609497 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000879_16	Crohn’s disease	1.000000e-10
GCST001725_70	Inflammatory bowel disease	6.000000e-13
GCST002501_1	Birdshot chorioretinopathy	2.000000e-09
GCST002826_1	Urate levels (BMI interaction)	2.000000e-06
GCST003097_13	Pediatric autoimmune diseases	9.000000e-08
GCST004131_97	Inflammatory bowel disease	1.000000e-10
GCST004132_104	Crohn’s disease	1.000000e-14
GCST005528_16	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	7.000000e-09
GCST005529_27	Ankylosing spondylitis	6.000000e-14
GCST005529_28	Ankylosing spondylitis	5.000000e-17
GCST005537_227	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-21
GCST005951_148	Body mass index	4.000000e-09
GCST006273_5	Diastolic blood pressure night-to-day ratio in hypertension	9.000000e-06
GCST006585_449	Blood protein levels	0.000000e+00
GCST007362_1	Acute anterior uveitis (with or without ankylosing spondylitis)	2.000000e-16
GCST90010715_9	Arthritis (juvenile idiopathic)	3.000000e-09
GCST90011899_135	Aspartate aminotransferase levels	8.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831223 (PROTEIN FAMILY), CHEMBL5043 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 328 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2103847	TOSEDOSTAT	2	328

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2248374	ERAP1, ERAP2		0.00	0
rs17524572	ERAP1, ERAP2		0.00	0
rs1363907	ERAP1, ERAP2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M1: Aminopeptidase N

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 2g [PMID: 27390066]	Inhibition	6.82	pKi
compound 3v [PMID: 27390066]	Inhibition	6.21	pKi
compound 17 [PMID: 23916253]	Inhibition	5.05	pIC50

ChEMBL bioactivities

185 potent at pChembl≥5 of 256 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL5527891
7.96	IC50	11	nM	CHEMBL3416733
7.72	IC50	19	nM	CHEMBL5512459
7.47	IC50	34	nM	CHEMBL6177450
7.46	IC50	35	nM	CHEMBL5555425
7.43	IC50	37	nM	CHEMBL4101200
7.43	IC50	37	nM	CHEMBL5517929
7.30	IC50	50	nM	CHEMBL3416733
7.26	IC50	55	nM	CHEMBL4097268
7.25	IC50	56	nM	CHEMBL4095882
7.10	IC50	80	nM	CHEMBL3416733
7.08	IC50	84	nM	CHEMBL4099107
7.08	IC50	83	nM	CHEMBL4077855
7.02	IC50	96	nM	CHEMBL4091951
6.98	IC50	105	nM	CHEMBL4094131
6.96	IC50	109	nM	CHEMBL4099693
6.96	IC50	110	nM	CHEMBL6166774
6.96	IC50	110	nM	CHEMBL6173724
6.93	IC50	118	nM	CHEMBL4081682
6.91	IC50	123	nM	CHEMBL4081073
6.89	IC50	129	nM	CHEMBL4070078
6.89	IC50	128	nM	CHEMBL4066723
6.89	IC50	130	nM	CHEMBL4080145
6.89	IC50	130	nM	CHEMBL6168455
6.84	IC50	144	nM	CHEMBL4089555
6.82	Ki	152	nM	CHEMBL3355101
6.82	IC50	150	nM	CHEMBL6175320
6.82	IC50	150	nM	CHEMBL6174407
6.73	Ki	185	nM	CHEMBL3355104
6.72	IC50	190	nM	CHEMBL4069425
6.70	Ki	200	nM	CHEMBL4065841
6.70	IC50	200	nM	CHEMBL6176373
6.69	Ki	205	nM	CHEMBL3355105
6.68	IC50	211	nM	CHEMBL4077711
6.66	IC50	217	nM	CHEMBL4104383
6.65	IC50	225	nM	CHEMBL4085707
6.62	IC50	237	nM	CHEMBL3416727
6.62	Ki	241	nM	CHEMBL3355106
6.61	IC50	243	nM	CHEMBL4095735
6.61	IC50	246	nM	CHEMBL4069576
6.60	IC50	250	nM	CHEMBL5195885
6.60	IC50	250	nM	CHEMBL6170475
6.58	IC50	260	nM	CHEMBL6169997
6.57	IC50	271	nM	CHEMBL4088020
6.51	IC50	310	nM	CHEMBL6176747
6.46	Ki	350	nM	CHEMBL327844
6.46	IC50	345	nM	CHEMBL4103640
6.42	IC50	380	nM	CHEMBL6164147
6.41	IC50	390	nM	CHEMBL1852660
6.38	IC50	412	nM	CHEMBL4074464

PubChem BioAssay actives

145 with measured affinity, of 341 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-N-hydroxy-3-(4-methoxyphenyl)-2-[4-[[(5-pyridin-2-ylthiophen-2-yl)sulfonylamino]methyl]triazol-1-yl]propanamide	2066904: Inhibition of ERAP2 (unknown origin) using R-AMC as substrate	ic50	0.0040	uM
[(2S)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1199906: Inhibition of human recombinant ERAP2 expressed in baculovirus infected cabbage looper ovary Hi5 cells using L-arginyl-7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorescence assay	ic50	0.0110	uM
(2S)-N-hydroxy-3-(4-methoxyphenyl)-2-[4-[[(5-phenylthiophen-2-yl)sulfonylamino]methyl]triazol-1-yl]propanamide	2066904: Inhibition of ERAP2 (unknown origin) using R-AMC as substrate	ic50	0.0190	uM
(2S)-N-hydroxy-3-(4-phenoxyphenyl)-2-[4-[[(5-pyridin-2-ylthiophen-2-yl)sulfonylamino]methyl]triazol-1-yl]propanamide	2066904: Inhibition of ERAP2 (unknown origin) using R-AMC as substrate	ic50	0.0350	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]pent-4-ynyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.0370	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]but-3-ynyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	2066904: Inhibition of ERAP2 (unknown origin) using R-AMC as substrate	ic50	0.0370	uM
[(2S)-2-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.0550	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(4-hydroxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.0560	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(2-hydroxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.0830	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.0840	uM
[(2S)-2-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.0960	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[(3,5-diphenylphenyl)methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1050	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1090	uM
[(2S)-2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1180	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(2-chlorophenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1230	uM
[(2S)-2-[[(2S)-1-amino-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1280	uM
[(2S)-2-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1290	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(2-methoxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1300	uM
[(1R)-1-amino-3-phenylpropyl]-[(2S)-2-[(2S)-2-carbamoylpyrrolidine-1-carbonyl]-4-methylpentyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1440	uM
2-[[[1-amino-3-(4-nitrophenyl)propyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1314019: Inhibition of human ERAP2 preincubated for 30 to 60 mins followed by addition of Arg-AMC as substrate measured for 15 mins by spectrofluorimetric method	ki	0.1520	uM
2-[[[1-amino-3-[4-(hydroxymethyl)phenyl]propyl]-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1314019: Inhibition of human ERAP2 preincubated for 30 to 60 mins followed by addition of Arg-AMC as substrate measured for 15 mins by spectrofluorimetric method	ki	0.1850	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.1900	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-4,4-diphenylbutyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1443778: Inhibition of recombinant human ERAP2 using L-arginyl-7-amido-4-methyl coumarin as substrate by fluorimetric assay	ki	0.2000	uM
2-[[(1-amino-3-pyridin-3-ylpropyl)-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1314019: Inhibition of human ERAP2 preincubated for 30 to 60 mins followed by addition of Arg-AMC as substrate measured for 15 mins by spectrofluorimetric method	ki	0.2050	uM
[(2S)-2-[[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.2110	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(3-methoxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.2170	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(3-chlorophenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.2250	uM
(2S)-2-[[3-amino-4-[[(2S)-2-aminohexanoyl]amino]benzoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1199906: Inhibition of human recombinant ERAP2 expressed in baculovirus infected cabbage looper ovary Hi5 cells using L-arginyl-7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorescence assay	ic50	0.2370	uM
2-[[(1-amino-3-pyridin-4-ylpropyl)-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1314019: Inhibition of human ERAP2 preincubated for 30 to 60 mins followed by addition of Arg-AMC as substrate measured for 15 mins by spectrofluorimetric method	ki	0.2410	uM
(4S)-5-amino-4-[[(2S)-2-[[[(1R)-1-amino-3-phenylpropyl]-hydroxyphosphoryl]methyl]-4-methylpentanoyl]amino]-5-oxopentanoic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.2430	uM
[(2S)-2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]-4,4-diphenylbutyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.2460	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-(3,4,5-trifluorophenoxy)butanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893372: Inhibition of recombinant ERAP2 (unknown origin) expressed in baculovirus infected Hi-5 insect cells using R-AMC as substrate by flourescence assay	ic50	0.2500	uM
[(1R)-1-amino-3-phenylpropyl]-[(2S)-2-[[(2S)-1,6-diamino-1-oxohexan-2-yl]carbamoyl]-4-methylpentyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.2710	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(4-chlorophenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.3450	uM
2-[[(1-amino-3-phenylpropyl)-hydroxyphosphoryl]methyl]-3-phenylpropanoic acid	1314019: Inhibition of human ERAP2 preincubated for 30 to 60 mins followed by addition of Arg-AMC as substrate measured for 15 mins by spectrofluorimetric method	ki	0.3500	uM
7-amino-1-bromo-4-phenyl-5,7,8,9-tetrahydrobenzo[7]annulen-6-one	2066907: Inhibition of human recombinant ERAP2 expressed in baculovirus infected sf9 cells using R-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ic50	0.3900	uM
[(2S)-2-(1-adamantylmethyl)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469763: Inhibition of ERAP2 (unknown origin) expressed in Hi5 cells by in vitro fluorimetric assay	ic50	0.4120	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-5-(3-chlorophenoxy)-2-hydroxypentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893372: Inhibition of recombinant ERAP2 (unknown origin) expressed in baculovirus infected Hi-5 insect cells using R-AMC as substrate by flourescence assay	ic50	0.4600	uM
methyl (2S)-2-[[4-amino-3-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]benzoyl]amino]-3-(4-hydroxyphenyl)propanoate	1199906: Inhibition of human recombinant ERAP2 expressed in baculovirus infected cabbage looper ovary Hi5 cells using L-arginyl-7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorescence assay	ic50	0.5180	uM
[(1R)-1-amino-3-phenylpropyl]-[(2S)-2-carbamoyl-4-methylpentyl]phosphinic acid	2066904: Inhibition of ERAP2 (unknown origin) using R-AMC as substrate	ic50	0.5470	uM
[(1R)-1-amino-3-phenylpropyl]-[(2R)-2-carbamoyl-4-methylpentyl]phosphinic acid	2066904: Inhibition of ERAP2 (unknown origin) using R-AMC as substrate	ic50	0.5710	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-5-(3-chlorophenoxy)-2-hydroxypentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoate	1893372: Inhibition of recombinant ERAP2 (unknown origin) expressed in baculovirus infected Hi-5 insect cells using R-AMC as substrate by flourescence assay	ic50	0.5800	uM
methyl (2S)-2-[[(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-5-(4-hydroxyphenoxy)pentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate	1893372: Inhibition of recombinant ERAP2 (unknown origin) expressed in baculovirus infected Hi-5 insect cells using R-AMC as substrate by flourescence assay	ic50	0.5800	uM
(2S)-2-[[4-amino-3-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]benzoyl]amino]-3-(1H-indol-3-yl)propanoic acid	1199906: Inhibition of human recombinant ERAP2 expressed in baculovirus infected cabbage looper ovary Hi5 cells using L-arginyl-7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorescence assay	ic50	0.5890	uM
(2S)-2-amino-4-methylpentane-1-thiol	2066910: Inhibition of C-terminal Hexa-histidine-tagged human recombinant ERAP2 expressed in Sf9 cells using R-AMC as substrate incubated for 15 mins by Michaelis-Menten analysis	ic50	0.6100	uM
(1-amino-2-piperidin-1-ylethyl)phosphonic acid	1314019: Inhibition of human ERAP2 preincubated for 30 to 60 mins followed by addition of Arg-AMC as substrate measured for 15 mins by spectrofluorimetric method	ki	0.6220	uM
[1-amino-2-(hexylamino)ethyl]phosphonic acid	1314019: Inhibition of human ERAP2 preincubated for 30 to 60 mins followed by addition of Arg-AMC as substrate measured for 15 mins by spectrofluorimetric method	ki	0.6320	uM
benzyl (2S)-2-[[2-(3-hydroxy-2-oxo-1-pyridinyl)acetyl]amino]-3-(1H-indol-3-yl)propanoate	1611467: Competitive inhibition of human recombinant ERAP2 expressed in baculovirus infected sf9 cells using R-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis	ki	0.7000	uM
benzyl (2S)-2-[[3-amino-4-[[(2S)-2-aminohexanoyl]amino]benzoyl]amino]-3-(1H-indol-3-yl)propanoate	1199906: Inhibition of human recombinant ERAP2 expressed in baculovirus infected cabbage looper ovary Hi5 cells using L-arginyl-7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorescence assay	ic50	0.7090	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-5,5-diphenylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1524643: Inhibition of ERAP2 (unknown origin)	ic50	0.7400	uM

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	3
Cyclosporine	affects expression, decreases expression	3
(+)-JQ1 compound	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
ochratoxin A	affects cotreatment, increases expression	1
potassium chromate(VI)	decreases expression	1
chloropicrin	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
trametinib	increases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, increases expression	1
Capecitabine	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Citrinin	affects cotreatment, increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

46 unique, capped per target: 40 binding, 4 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334276	ADMET	Stability in pH 2 HCl assessed as aminopeptidase (unknown origin)-mediated compound hydrolysis by measuring parent compound remaining at 200 uM up to 6 hrs by RP-HPLC analysis	Astratides: Insulin-Modulating, Insecticidal, and Antifungal Cysteine-Rich Peptides from Astragalus membranaceus. — J Nat Prod
CHEMBL1041813	Binding	Inhibition of LRAP at 10 uM	Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis. — J Med Chem
CHEMBL3561976	Functional	PubChem BioAssay. MLPCN ERAP2 Measured in Biochemical System Using Plate Reader - 7016-02_Inhibitor_Dose_DryPowder_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C5VF	P50	Transformed cell line

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.