TISIDB

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
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; Multi-pass membrane protein. Note=The transmembrane segments seem to form a pore in the membrane.
Domain	PF00664 ABC transporter transmembrane region PF00005 ABC transporter
Function	Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules.

> Gene Ontology [ TOP ]
Biological Process	GO:0002250 adaptive immune response GO:0002428 antigen processing and presentation of peptide antigen via MHC class Ib GO:0002474 antigen processing and presentation of peptide antigen via MHC class I GO:0002475 antigen processing and presentation via MHC class Ib GO:0002476 antigen processing and presentation of endogenous peptide antigen via MHC class Ib GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib GO:0002478 antigen processing and presentation of exogenous peptide antigen GO:0002481 antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent GO:0002483 antigen processing and presentation of endogenous peptide antigen GO:0002484 antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway GO:0002485 antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent GO:0002488 antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway GO:0002489 antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent GO:0002577 regulation of antigen processing and presentation GO:0002579 positive regulation of antigen processing and presentation GO:0002583 regulation of antigen processing and presentation of peptide antigen GO:0002585 positive regulation of antigen processing and presentation of peptide antigen GO:0002589 regulation of antigen processing and presentation of peptide antigen via MHC class I GO:0002591 positive regulation of antigen processing and presentation of peptide antigen via MHC class I GO:0015833 peptide transport GO:0019058 viral life cycle GO:0019060 intracellular transport of viral protein in host cell GO:0019882 antigen processing and presentation GO:0019883 antigen processing and presentation of endogenous antigen GO:0019884 antigen processing and presentation of exogenous antigen GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I GO:0030581 symbiont intracellular protein transport in host GO:0042886 amide transport GO:0043900 regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0044766 multi-organism transport GO:0046719 regulation by virus of viral protein levels in host cell GO:0046794 transport of virus GO:0046967 cytosol to ER transport GO:0048002 antigen processing and presentation of peptide antigen GO:0050792 regulation of viral process GO:0051701 interaction with host GO:0051708 intracellular protein transport in other organism involved in symbiotic interaction GO:0075733 intracellular transport of virus GO:1902579 multi-organism localization GO:1902581 multi-organism cellular localization GO:1902583 multi-organism intracellular transport
Molecular Function	GO:0003823 antigen binding GO:0015197 peptide transporter activity GO:0015399 primary active transmembrane transporter activity GO:0015405 P-P-bond-hydrolysis-driven transmembrane transporter activity GO:0015433 peptide antigen-transporting ATPase activity GO:0015440 peptide-transporting ATPase activity GO:0016820 hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances GO:0016887 ATPase activity GO:0022804 active transmembrane transporter activity GO:0023029 MHC class Ib protein binding GO:0033218 amide binding GO:0042277 peptide binding GO:0042287 MHC protein binding GO:0042288 MHC class I protein binding GO:0042605 peptide antigen binding GO:0042623 ATPase activity, coupled GO:0042626 ATPase activity, coupled to transmembrane movement of substances GO:0043492 ATPase activity, coupled to movement of substances GO:0043531 ADP binding GO:0046977 TAP binding GO:0046978 TAP1 binding GO:0046979 TAP2 binding
Cellular Component	GO:0018995 host GO:0030176 integral component of endoplasmic reticulum membrane GO:0031227 intrinsic component of endoplasmic reticulum membrane GO:0042824 MHC class I peptide loading complex GO:0042825 TAP complex GO:0043657 host cell GO:0044215 other organism GO:0044216 other organism cell GO:0044217 other organism part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa02010 ABC transporters hsa04145 Phagosome hsa04612 Antigen processing and presentation
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983170: Antigen Presentation R-HSA-1236975: Antigen processing-Cross presentation R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-1236974: ER-Phagosome pathway R-HSA-168256: Immune System

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TAP1 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 TAP1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29341428	Breast Carcinoma	Promote immunity (T cell function)	Gene expression analysis of the sorted tumor cells revealed that the Aldefluor+ tumor cells has decreased expression of transporter associated with antigen processing (TAP) genes and co-stimulatory molecule CD80, which would decrease susceptibility to T cells.
16517708	Head and Neck Squamous Cell Carcinoma	Promote immunity (T cell function)	First, lack of recognition of SCCHN cells by CTL is associated with marked down-regulation of the IFN-gamma-inducible APM components low-m.w. protein 2, TAP1, TAP2, and tapasin.
28783722	Melanoma	Promote immunity (T cell function); essential for immunotherapy	We observed that the reduction in the overall survival of these patients was significantly associated with loss of expression of B2M and TAP1 in tumours biopsied before ipilimumab treatment. Loss of expression of these 19 genes within tumours could diminish or extinguish the presentation of tumour antigens (including HLA-A, HLA-F, B2M, TAP1 and TAP2); T cell co- stimulation (ICAM1, CLECL1, LILRA1 and LILRA3); or cytokine production and signalling (JAK2 and STAT1) in the tumour microenvironment that drive infiltration and activation of T cells, and thus serve as a principal mechanism in immune evasion.
27496866	Head and Neck Carcinoma	Promote immunity (T cell function); essential for immunotherapy	CD137 agonist mAb urelumab enhanced cetuximab-activated NK-cell survival, DC maturation, and tumor antigen cross-presentation. Urelumab boosted DC maturation markers, CD86 and HLA DR, and antigen-processing machinery (APM) components TAP1/2, leading to increased tumor antigen cross-presentation. These results suggest a beneficial effect of combination immunotherapy using cetuximab and CD137 agonist in HNC.
18519766	Ovarian Cancinoma	Promote immunity (infiltration)	The majority of APM component expression examined was significantly associated with both intratumoral and peritumoral T-cell infiltration (P < 0.05). The expression of APM components and the presence of intratumoral T-cell infiltrates were significantly associated with improved survival (all P < or = 0.01);
17541610	Astrocytoma	Promote immunity	Among human WHO grade II-IV astrocytomas, downregulation of LMP2, TAP1 and beta2m correlated with grade of malignancy. Our results support the hypothesis that coordinated downregulation or impaired upregulation of certain HLA class I APM components may serve as a mechanism for astrocytoma cells to evade the host's immune response, even if HLA class I antigen surface expression is not altered.
16140964	Lung Carcinoma	Promote immunity	Fluorescence-activated cell sorting and ELISPOT analysis showed that AdhTAP1 treatment significantly increased dendritic cell cross-presentation and cross-priming of tumor antigens. Furthermore, ex vivo and in vivo AdhTAP1 treatment significantly retarded tumor growth and increased survival of mice bearing CMT.64 tumors. Fluorescence-activated cell sorting analysis and immunohistochemical staining showed a significant increase in CD8+ and CD4+ T cells and CD11c+ dendritic cells infiltrating the tumors.

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
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 TAP1 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: 2.55; FDR: 0.000150	Sensitive 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	Second most enriched score: 1.05	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	STARS Score: 6.00; FDR: 0.000	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 6.41; FDR: 0.001	Resistant to T cell-mediated killing
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	Total # shRNA with >= 4-fold: 2	Resistant to T-cell proliferation

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
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 TAP1 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	0.312	0.431
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.479	0.732
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.189	0.863
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	1.054	0.0241
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1.167	0.625
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.918	0.775
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.77	0.142
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.159	0.514
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.264	0.9
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.311	0.561
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	1.033	0.768
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.412	0.0153

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TAP1 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	7.4	1.4	6	0.177
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	7.4	1.7	5.7	0.231
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	22.2	0	22.2	0.12
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	50	0	50	0.109
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
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	15.4	-15.4	0.482
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	16.7	-16.7	1

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TAP1. 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	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TAP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TAP1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TAP1. 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	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TAP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TAP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TAP1
Name	transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Aliases	RING4; D6S114E; ABCB2; ABC17; PSF-1; RING4*0102N; TAP1N; ABC transporter, MHC 1; ATP-binding cassette sub-fa ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TAP1 collected from DrugBank database.

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

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