TISIDB

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Endoplasmic reticulum membrane Single-pass type II membrane protein
Domain	PF11838 ERAP1-like C-terminal domain PF01433 Peptidase family M1
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. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0002250 adaptive immune response GO:0002474 antigen processing and presentation of peptide antigen via MHC class I GO:0002483 antigen processing and presentation of endogenous peptide antigen GO:0003013 circulatory system process GO:0006509 membrane protein ectodomain proteolysis GO:0008015 blood circulation GO:0008217 regulation of blood pressure GO:0019882 antigen processing and presentation GO:0019883 antigen processing and presentation of endogenous antigen GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I GO:0033619 membrane protein proteolysis GO:0043171 peptide catabolic process GO:0045088 regulation of innate immune response GO:0045444 fat cell differentiation GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0048002 antigen processing and presentation of peptide antigen GO:0048514 blood vessel morphogenesis GO:1901342 regulation of vasculature development GO:1901565 organonitrogen compound catabolic process GO:1904018 positive regulation of vasculature development
Molecular Function	GO:0004175 endopeptidase activity GO:0004177 aminopeptidase activity GO:0005126 cytokine receptor binding GO:0005138 interleukin-6 receptor binding GO:0005149 interleukin-1 receptor binding GO:0005151 interleukin-1, Type II receptor binding GO:0008235 metalloexopeptidase activity GO:0008237 metallopeptidase activity GO:0008238 exopeptidase activity GO:0033218 amide binding GO:0042277 peptide binding GO:0070006 metalloaminopeptidase activity GO:0070851 growth factor receptor binding
Cellular Component	GO:0005788 endoplasmic reticulum lumen

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983170: Antigen Presentation R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-168256: Immune System

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ERAP1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between ERAP1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25592150	Cervix Carcinoma; Medulloblastoma; Lymphoma; Melanoma	Inhibit immunity (NK cell function)	Notably, ERAP1 inhibition enhanced the ability of NK cells to kill freshly established human lymphoblastoid cell lines from autologous or allogeneic sources, thereby promoting NK cytotoxic activity against target cells that would not be expected because of KIR-KIR ligand matching.
23610143	Colorectal Carcinoma	Inhibit immunity (T cell function)	BALB/c mice with reduced ERAAP expression challenged with CT26 induced protective immunity that was mediated by CD8(+) T cells. Furthermore, boosting the tumor immunogenicity through inhibition of ERAAP function with the small molecule inhibitor leucinethiol in vitro, or in established tumors in vivo, abrogated tumor growth and prolonged survival.
21252114	Lymphoma	Inhibit immunity	The endoplasmic reticulum aminopeptidase ERAAP is involved in the final trimming of peptides for presentation by MHC class I (MHC-I) molecules. Herein, we show that ERAAP silencing results in MHC-I peptide-loading defects eliciting rejection of the murine T-cell lymphoma RMA in syngeneic mice. Because a large fraction of human tumors express high levels of the homologous ERAP1 and/or ERAP2, the present findings highlight a convenient, novel target for cancer immunotherapy.

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of ERAP1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: -1.85; FDR: 0.02000	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	STARS Score: 5.48; FDR: 0.001	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of ERAP1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.298	0.365
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.17	0.926
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.401	0.742
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.334	0.425
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.021	0.993
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.73	0.82
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.394	0.391
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.639	0.72
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.165	0.932
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.398	0.793
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.758	0.745
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.072	0.392

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ERAP1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ERAP1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ERAP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ERAP1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ERAP1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ERAP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ERAP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ERAP1
Name	endoplasmic reticulum aminopeptidase 1
Aliases	ARTS-1; A-LAP; PILS-AP; KIAA0525; ERAAP1; aminopeptidase regulator of TNFR1 shedding; adipocyte-derived leuc ......
Chromosomal Location	5q15
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ERAP1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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