TAP2

Summary

TAP2 (transporter 2, ATP binding cassette subfamily B member, HGNC:44) is a protein-coding gene on chromosome 6p21.32, encoding Antigen peptide transporter 2 (Q03519). ABC transporter associated with antigen processing.

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules.

Source: NCBI Gene 6891 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MHC class I deficiency (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 28
• Clinical variants (ClinVar): 443 total — 17 pathogenic, 4 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001290043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44
Approved symbol	TAP2
Name	transporter 2, ATP binding cassette subfamily B member
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	PSF2, RING11, D6S217E
Ensembl gene	ENSG00000204267
Ensembl biotype	protein_coding
OMIM	170261
Entrez	6891

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 retained_intron

ENST00000374897, ENST00000464100, ENST00000485701, ENST00000652259, ENST00000698440, ENST00000698441, ENST00000698448, ENST00000698449, ENST00000705716, ENST00000861086, ENST00000861087, ENST00000861088, ENST00000933348, ENST00000933349

RefSeq mRNA: 2 — MANE Select: NM_001290043 NM_001290043, NM_018833

CCDS: CCDS4755, CCDS78129

Canonical transcript exons

ENST00000374897 — 12 exons

Exon	Start	End
ENSE00001827028	32825415	32829034
ENSE00003484041	32837741	32838237
ENSE00003488003	32837537	32837651
ENSE00003492231	32830267	32830440
ENSE00003516527	32832627	32832824
ENSE00003568498	32832333	32832461
ENSE00003622178	32835154	32835359
ENSE00003631951	32830618	32830806
ENSE00003671152	32829930	32830089
ENSE00003685114	32829400	32829536
ENSE00003693733	32835643	32835773
ENSE00003900427	32838653	32838739

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.2004 / max 230.5637, expressed in 1789 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73024	15.1636	1755
73020	4.3078	1169
73023	2.5964	1101
73018	0.6529	336
73019	0.6265	282
73021	0.5814	277
73022	0.2717	127

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	97.02	gold quality
lymph node	UBERON:0000029	96.63	gold quality
monocyte	CL:0000576	95.93	gold quality
leukocyte	CL:0000738	95.85	gold quality
granulocyte	CL:0000094	95.74	gold quality
duodenum	UBERON:0002114	95.11	gold quality
apex of heart	UBERON:0002098	95.06	gold quality
spleen	UBERON:0002106	94.98	gold quality
stromal cell of endometrium	CL:0002255	94.46	gold quality
mucosa of transverse colon	UBERON:0004991	93.36	gold quality
blood	UBERON:0000178	93.22	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.95	gold quality
upper lobe of left lung	UBERON:0008952	92.80	gold quality
small intestine	UBERON:0002108	92.74	gold quality
esophagus mucosa	UBERON:0002469	92.42	gold quality
right lung	UBERON:0002167	92.35	gold quality
endometrium	UBERON:0001295	91.09	gold quality
bone marrow cell	CL:0002092	90.76	gold quality
lung	UBERON:0002048	90.56	gold quality
gall bladder	UBERON:0002110	90.18	gold quality
vagina	UBERON:0000996	89.65	gold quality
bone marrow	UBERON:0002371	89.57	gold quality
ectocervix	UBERON:0012249	89.45	gold quality
omental fat pad	UBERON:0010414	89.42	gold quality
adipose tissue	UBERON:0001013	89.40	gold quality
metanephros cortex	UBERON:0010533	89.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.33	gold quality
esophagus	UBERON:0001043	89.08	gold quality
rectum	UBERON:0001052	89.08	gold quality
tonsil	UBERON:0002372	89.07	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, IRF1, IRF7, NFKB1, RELA, TAPBP

miRNA regulators (miRDB)

119 targeting TAP2, 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-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6756-5P	99.82	67.97	2466

Literature-anchored findings (GeneRIF, showing 40)

• Regulation of transporters associated with antigen processing (TAPs) by nucleotide binding to, and hydrolysis by, Walker consensus sequences (PMID:11774612)
• Analysis of TAP2 polymorphisms in Finnish individuals with type I diabetes. (PMID:11916171)
• There was a significant difference in the frequencies at position 665 of TAP 2 gene. TAP genes might have modifying effects on the cystic fibrosis phenotype. (PMID:12026214)
• examination of TAP1 and TAP2 gene polymorphisms in rheumatoid arthritis patients revealed an association between a particular amino acid residue, namely Thr565 in the TAP2 gene, and rheumatoid arthritis (PMID:12047361)
• IFN-gamma and LPS upregulated the expression of TAP1 and TAP2 in primary human macrophages (PMID:12234057)
• cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport (PMID:12505156)
• A major role for tapasin as a stabilizer of the TAP peptide transporter and consequences for MHC class I expression (PMID:12594855)
• Mutations in the ABC-transporter signature motifs of TAP2 inhibit the translocation of peptide without affecting binding of either peptide or ATP by TAP. This motif is required after peptide binding to facilitate peptide translocation by TAP. (PMID:12645939)
• The binding sites contributing to the substrate specificity and subcellular localization of this protein are identified. (PMID:12682044)
• TAP2*Bky2 or its haplotype with DRB1*08032 may be involved in SS-A/Ro antibody production not only in SS but also SLE, indicating that TAP2*Bky2 may be a susceptible gene not only to the disease of SS but also to the SS-A/Ro autoantibody production. (PMID:12729048)
• peptide binding induces a conformation that triggers ATP hydrolysis in both subunits of the TAP complex within the catalytic cycle (PMID:12777379)
• Expression of TAP2 is not identical to TAP1 in primary melanoma lesions. (PMID:12777979)
• this allele is preferentially associated with the large conserved haplotype HLA DQA1*0501-DQB1*0201-DRB1*0301 and restricted to populations of African origin (PMID:12786999)
• detected the presence of 17 nucleotide sequence variations in the entire coding region of TAP2 in an indigenous Zimbabwean population (Shona ethnic group) (PMID:12826376)
• TAP2 gene polymorphism is not linked to renal cell carcinoma (PMID:12963978)
• There exists decreased expression of TAP in both childhood ALL and AML, which probably contributes to the escape of leukemia cells from immune surveillance. (PMID:14558951)
• the N-terminal domains of TAP1 and TAP2 are essential for recruitment of tapasin, consequently mediating assembly of the macromolecular peptide-loading complex (PMID:14679198)
• The results of this study provide genetic evidence that TAP2 gene codon 565 polymorphism may play a role in rheumatoid arthritis. (PMID:14749980)
• Evidence is provided that that the extended haplotype of TAP2 is distinct in pauciarticular and polyarticular rheumatoid factor negative juvenile idiopathic arthritis patients. (PMID:15343265)
• interaction of TAP1 and TAP2 and P-glycoprotein with proteasome subunits beta-5 and beta-5i suggest direct targeting of antigenic peptides to the ER via a TAP-proteasome association and a possible role for P-glycoprotein (PMID:15488952)
• TAP1-2 gene polymorphisms may, by way of post-transcriptional changes and altered regulation of gene expression, be involve the immune system in the development of primary open-angle glaucoma (PMID:15887980)
• Transmembrane segment 1 (TM1) of core-TAP2 is critical for its heterodimerization with core-TAP1. (PMID:16061226)
• Results suggest the possible role of TAP2 gene polymorphism in the genetic susceptibility to systemic sclerosis . (PMID:16112028)
• N-terminal domains of TAP1 and TAP2 are important for tapasin binding and for optimal peptide loading onto major histocompatibility complex class I molecules. (PMID:16174096)
• allelic frequency of TAP1 and TAP2 and the alleles shared in mother-infant were compared in pre-eclampsia and controls (PMID:16191421)
• TAP variants lacking TAP2 N-terminal domain build peptide-loading complexes (PLC) that fail to generate stable MHC I-peptide complexes, which correlates with a substantially reduced recruitment of accessory chaperones into the PLC (PMID:16210614)
• The TAP2-2 MspI polymorphism might be associated with calcium stone disease. (PMID:16215317)
• The data revealed a nonanalogous multipolar bridging of the transporter associated with antigen processing (TAP) transmembrane domains by cytomegalovirus glycoprotein US6 (PMID:16356928)
• Several TAP gene polymorphisms were examined and a TAP2 SNP (rs241448) associated with AD found in two independent case-control samples, especially in carriers of the APOE4 allele. (PMID:16595160)
• Two Pemphigus vulgaris (PV) TAP2 risk alleles were identified (TAP2*C and TAP2*D) implying that TAP2 genes are involved in susceptibility to development of PV. (PMID:16690408)
• These data reveal that the single-site polymorphism of the TAP2 gene at codon 665 may be an indicator for predicting Graves Disease development. (PMID:16721835)
• The main active site required for peptide translocation by TAP1-TAP2 complexes resides at the TAP2 nucleotide binding site. (PMID:17068338)
• Evidence of TAP2 association with type 1 diabetes that is independent of HLA DR-DQ may be based on allele dependence of splicing into isoforms known to have differential peptide selectivities. (PMID:17192492)
• results indicate that TAP gene polymorphisms may have had a role in the development of bronchiectasis in our patient group (PMID:17245734)
• TAP2-651 site is associated with the risk of HBV infection (PMID:17525827)
• study found strong associations of psoriasis with variant alleles of LMP and TAP (PMID:17581627)
• TAP subunits alternate in the recruitment and loading of a single MHC class I (PMID:17947644)
• TAP1 but not TAP2 gene polymorphism may be an important factor contributing to the genetic susceptibility in the development of allergic rhinitis in the Korean population (PMID:17982230)
• First report on the role of TAP2 polymorphisms involved in the diverse pathogenesis of dengue virus infection. (PMID:18071882)
• TAP1 and TAP2 expression restores both antigen presentation and immunogenicity in A375 melanoma cells and concomitantly increases IL-12 and IFN-gamma production in tumor antigen-specific cytotoxic T lymphocytes. (PMID:18385764)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tap2	ENSMUSG00000024339
rattus_norvegicus	Tap2	ENSRNOG00000000455
caenorhabditis_elegans		WBGENE00001817
caenorhabditis_elegans		WBGENE00001818
caenorhabditis_elegans		WBGENE00003995
caenorhabditis_elegans		WBGENE00003999
caenorhabditis_elegans		WBGENE00004000
caenorhabditis_elegans		WBGENE00004001
caenorhabditis_elegans		WBGENE00004002
caenorhabditis_elegans		WBGENE00004003
caenorhabditis_elegans		WBGENE00004006
caenorhabditis_elegans		WBGENE00004008

Paralogs (10): ABCB5 (ENSG00000004846), ABCB4 (ENSG00000005471), ABCB11 (ENSG00000073734), ABCB1 (ENSG00000085563), ABCB6 (ENSG00000115657), ABCB7 (ENSG00000131269), ABCB10 (ENSG00000135776), ABCB9 (ENSG00000150967), TAP1 (ENSG00000168394), ABCB8 (ENSG00000197150)

Protein

Protein identifiers

Antigen peptide transporter 2 — Q03519 (reviewed: Q03519)

Alternative names: ATP-binding cassette sub-family B member 3, Peptide supply factor 2, Peptide transporter PSF2, Peptide transporter TAP2, Peptide transporter involved in antigen processing 2, Really interesting new gene 11 protein

All UniProt accessions (6): A0A8V8TNI0, A0A8V8TNJ0, A0A994J4Y7, Q03519, Q5JNW1, Q9UP03

UniProt curated annotations — full annotation on UniProt →

Function. ABC transporter associated with antigen processing. In complex with TAP1 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export peptides against the concentration gradient. During the transport cycle alternates between ‘inward-facing’ state with peptide binding site facing the cytosol to ‘outward-facing’ state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent ‘outward-facing’ conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the ‘inward facing’ state for a new cycle. Typically transports intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome. Binds peptides with free N- and C-termini, the first three and the C-terminal residues being critical. Preferentially selects peptides having a highly hydrophobic residue at position 3 and hydrophobic or charged residues at the C-terminal anchor. Proline at position 2 has the most destabilizing effect. As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation.

Subunit / interactions. Heterodimer of TAP1 and TAP2 (TAP1-TAP2). A component of the peptide loading complex (PLC), interacts via TAPBP with MHCI heterodimer; this interaction mediates peptide-MHCI assembly. Recruits TAPBP in a 1:1 stoichiometry. Interacts with classical MHCI such as HLA-A*02-B2M; this interaction is obligatory for the loading of peptide epitopes. Interacts with non-classical MHCI molecules including HLA-E-B2M and HLA-F-B2M as well as PLC component CALR before the peptide loading. (Microbial infection) Interacts with Epstein-Barr virus BLNF2a. (Microbial infection) Interacts with herpes simplex virus US12/ICP47. (Microbial infection) Interacts with adenovirus E3-19K glycoprotein, which binds TAP1-TAP2 and acts as a TAPBP inhibitor, preventing TAP1-TAP2 association with MHCI.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. MHC class I deficiency 2 (MHC1D2) [MIM:620813] An autosomal recessive, progressive disorder characterized by chronic bacterial infections of the upper and lower respiratory tract apparent in the first or second decades of life, nasal polyps, and ulcers with granulomatous inflammation affecting the nasal cavity, upper respiratory tract, or skin. Patients may develop bronchiectasis and respiratory failure. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited at high ER lumenal peptide concentrations. (Microbial infection) Inhibited by herpes simplex virus US12/ICP47 protein, which blocks the peptide-binding site of TAP1-TAP2. (Microbial infection) Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of TAP1-TAP2 complex and inhibits peptide translocation by specifically blocking ATP-binding and preventing TAP1-TAP2 conformational rearrangement induced by peptide binding.

Domain organisation. The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2. The nucleotide-binding domain (NBD) mediates ATP hydrolysis coupled to peptide translocation. Two ATP molecules are accommodated at distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD of one subunit, while the NBD from the second subunit completes the active site by contributing the C loop motif (LSGGQ). Each ATP molecule is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which is necessary for ATP hydrolysis.

Polymorphism. 4 common alleles are officially recognized: TAP201:01 (TAP2A or PSF2A or RING11A), TAP201:02 (TAP2E), TAP201:03 (TAP2F), and TAP202:01 (TAP2B or PSF2B or RING11B). Other relatively common alleles have been identified: TAP201D, TAP201E, TAP201F, TAP201G, TAP201H, TAP202B, TAP202C (TAP202:02), TAP202D, TAP202E, TAP202F, TAP203A and TAP204A. The sequence shown is that of TAP201:01. The allele TAP2*Bky2 is commonly found only in the Japanese population. It may be associated with susceptibility to Sjoegren syndrome, an autoimmune disorder characterized by abnormal dryness of the conjunctiva, cornea and mouth due to exocrine glands dysfunction.

Similarity. Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q03519-1	1	yes
Q03519-2	2

RefSeq proteins (2): NP_001276972, NP_061313 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR005293	Tap2/ABCB3	Family
IPR011527	ABC1_TM_dom	Domain
IPR013305	ABC_Tap-like	Family
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR039421	Type_1_exporter	Family

Pfam: PF00005, PF00664

Enzyme classification (BRENDA):

• EC 7.4.2.14 — ABC-type antigen peptide transporter (BRENDA: 10 organisms, 90 substrates, 37 inhibitors, 4 Km, 0 kcat entries)
• EC 7.4.2.5 — bacterial ABC-type protein transporter (BRENDA: 33 organisms, 105 substrates, 44 inhibitors, 13 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.05–2.33	11
8-AZIDO-ATP	0.103	1
ATP	0.197	1
RRYNASTEL	0.0006	1
RRYQKSTEL	0.0002	1

Catalyzed reactions (Rhea), 1 shown:

• a peptide antigen(in) + ATP + H2O = a peptide antigen(out) + ADP + phosphate + H(+) (RHEA:65972)

UniProt features (85 total): helix 26, strand 11, topological domain 10, sequence variant 10, transmembrane region 9, turn 6, sequence conflict 3, domain 2, region of interest 2, mutagenesis site 2, chain 1, binding site 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

21 structures.

PDB	Method	Resolution (Å)
9O9D	ELECTRON MICROSCOPY	2.44
9RCV	ELECTRON MICROSCOPY	2.7
9OCJ	ELECTRON MICROSCOPY	3
9N63	ELECTRON MICROSCOPY	3.1
9O94	ELECTRON MICROSCOPY	3.1
9N66	ELECTRON MICROSCOPY	3.2
9OCH	ELECTRON MICROSCOPY	3.3
9OCI	ELECTRON MICROSCOPY	3.3
9N62	ELECTRON MICROSCOPY	3.4
8T4E	ELECTRON MICROSCOPY	3.5
8T4F	ELECTRON MICROSCOPY	3.5
8T4G	ELECTRON MICROSCOPY	3.5
8T46	ELECTRON MICROSCOPY	3.6
9N61	ELECTRON MICROSCOPY	3.6
9N64	ELECTRON MICROSCOPY	3.7
9N65	ELECTRON MICROSCOPY	3.7
8T4H	ELECTRON MICROSCOPY	3.8
9OCG	ELECTRON MICROSCOPY	3.8
8T4J	ELECTRON MICROSCOPY	3.9
5U1D	ELECTRON MICROSCOPY	3.97
8T4I	ELECTRON MICROSCOPY	5.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03519-F1	82.98	0.39

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 (1): 16 (inter-subunit salt bridge with tapbp)

Ligand- & substrate-binding residues (1): 503–510

Mutagenesis-validated functional residues (2):

Position	Phenotype
16	complete loss of interaction with tapbp, resulting in impaired plc assembly and antigen presentation.
638	inactive in peptide transport when associated with ‘a-734’ of tap1.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 340 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, KEGG_ABC_TRANSPORTERS, GOBP_POSITIVE_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY

GO Biological Process (15): T cell mediated cytotoxicity (GO:0001913), positive regulation of T cell mediated cytotoxicity (GO:0001916), response to molecule of bacterial origin (GO:0002237), antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent (GO:0002481), antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent (GO:0002485), antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent (GO:0002489), protein transport (GO:0015031), antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:0019885), cytosol to endoplasmic reticulum transport (GO:0046967), peptide antigen transport (GO:0046968), transmembrane transport (GO:0055085), adaptive immune response (GO:0002250), immune system process (GO:0002376), peptide antigen assembly with MHC class I protein complex (GO:0002502), peptide transport (GO:0015833)

GO Molecular Function (14): ATP binding (GO:0005524), ABC-type peptide antigen transporter activity (GO:0015433), ABC-type peptide transporter activity (GO:0015440), ATP hydrolysis activity (GO:0016887), MHC class Ib protein binding (GO:0023029), peptide antigen binding (GO:0042605), metal ion binding (GO:0046872), TAP1 binding (GO:0046978), tapasin binding (GO:0046980), peptide transmembrane transporter activity (GO:1904680), nucleotide binding (GO:0000166), protein binding (GO:0005515), MHC protein binding (GO:0042287), ABC-type transporter activity (GO:0140359)

GO Cellular Component (8): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), nuclear speck (GO:0016607), phagocytic vesicle membrane (GO:0030670), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), MHC class I peptide loading complex (GO:0042824), TAP complex (GO:0042825)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	2
Antigen processing-Cross presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
antigen processing and presentation of peptide antigen via MHC class I	2
peptide transport	2
membrane protein complex	2
endoplasmic reticulum protein-containing complex	2
leukocyte mediated cytotoxicity	1
T cell mediated immunity	1
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
response to bacterium	1
response to external biotic stimulus	1
antigen processing and presentation of exogenous peptide antigen via MHC class Ib	1
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway	1
antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway	1
intracellular protein localization	1
establishment of protein localization	1
antigen processing and presentation of endogenous peptide antigen	1
intercellular transport	1
intracellular transport	1
transmembrane transport	1
antigen processing and presentation of peptide antigen	1
cellular process	1
immune response	1
biological_process	1
MHC class I protein complex assembly	1
peptide antigen assembly with MHC protein complex	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ABC-type peptide transporter activity	1
ABC-type transporter activity	1
peptide transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
MHC protein binding	1
antigen binding	1
peptide binding	1
cation binding	1
TAP binding	1

Protein interactions and networks

STRING

1234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAP2	TAP1	Q03518	987
TAP2	PSMB9	P28065	859
TAP2	PSMB8	P28062	812
TAP2	ADM2	Q7Z4H4	710
TAP2	SRPRA	P08240	652
TAP2	TAPBP	O15533	597
TAP2	Q5Y7H0	Q5Y7H0	564
TAP2	LAMP2	P13473	554
TAP2	ABCE1	P61221	552
TAP2	PSMB10	P40306	500
TAP2	SUPT6H	Q7KZ85	484
TAP2	ABCC4	O15439	478
TAP2	HLA-B	P01889	444
TAP2	HLA-DRA	P01903	442
TAP2	HLA-DQB1	P01917	437

IntAct

133 interactions, top by confidence:

A	B	Type	Score
TAP2	TAP1	psi-mi:“MI:0915”(physical association)	0.940
TAP1	TAP2	psi-mi:“MI:0407”(direct interaction)	0.940
RAD51D	RAD51B	psi-mi:“MI:0914”(association)	0.850
TAP1	TAPBP	psi-mi:“MI:0914”(association)	0.800
TAPBP	TAP1	psi-mi:“MI:0914”(association)	0.800
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TAPBP	TAP2	psi-mi:“MI:0915”(physical association)	0.680
TAP2	TAPBP	psi-mi:“MI:0914”(association)	0.680
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
TAP1		psi-mi:“MI:0915”(physical association)	0.670
TAPBP		psi-mi:“MI:0915”(physical association)	0.620
TAPBP		psi-mi:“MI:0914”(association)	0.620
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
B2M	TAPBP	psi-mi:“MI:0915”(physical association)	0.570
gN	TAPBP	psi-mi:“MI:0914”(association)	0.560

BioGRID (140): TAP2 (Proximity Label-MS), TAP2 (Proximity Label-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), TAP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, A0A0U1RPR8, A0A125QXJ1, A0A7N9VSG0, A1Y9I9, B2GUP8, B2RX12, B6CZ56, B6CZ62, O15438, O70595, O88269, O88563, O95255, P21958, P36370, P36371, P36372, P51839, P58428, Q03518, Q03519, Q09427, Q09428, Q09429, Q28433, Q5RFQ9, Q5RKI8, Q5T3U5, Q8K0H7, Q8LPQ6, Q8R420, Q8R4P9, Q8TE96, Q924H9, Q96J65, Q96J66, Q99758, Q9CXJ4, Q9DC29

Diamond homologs: A0A179H0T5, A0A1U8QG99, A0A3G9H9H1, A1B9K8, A1USS5, I1RF50, I1S2J9, K3VYH8, O06967, O07550, O52618, P08716, P0A2V0, P0A2V1, P10089, P18767, P21958, P22638, P23596, P23702, P23886, P26050, P29018, P36370, P40416, P44407, P63392, P63394, P70864, P77265, P9WER4, P9WQJ6, P9WQJ7, P9WQJ8, P9WQJ9, Q03024, Q03518, Q03519, Q080T2, Q0BFU0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	7	34.5×	4e-07
DAP12 interactions	5	29.7×	8e-05
ER-Phagosome pathway	9	14.6×	2e-06
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	8	8.7×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	6	10.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	4
Uncertain significance	193
Likely benign	151
Benign	32

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
13727	NM_001290043.2(TAP2):c.817C>T (p.Arg273Ter)	Pathogenic
13728	NM_001290043.2(TAP2):c.979del (p.Arg327fs)	Pathogenic
1443971	NM_001290043.2(TAP2):c.1260del (p.Ser421fs)	Pathogenic
1452277	NM_001290043.2(TAP2):c.824del (p.Leu275fs)	Pathogenic
1456619	NM_001290043.2(TAP2):c.373del (p.Gln125fs)	Pathogenic
1459385	NM_001290043.2(TAP2):c.1101G>A (p.Trp367Ter)	Pathogenic
1928904	NM_001290043.2(TAP2):c.1837C>T (p.Gln613Ter)	Pathogenic
1996596	NM_001290043.2(TAP2):c.1606C>T (p.Gln536Ter)	Pathogenic
2075917	NM_001290043.2(TAP2):c.224del (p.Leu75fs)	Pathogenic
2164746	NM_001290043.2(TAP2):c.815del (p.Leu272fs)	Pathogenic
2727952	NM_001290043.2(TAP2):c.1636-1G>A	Pathogenic
2734845	NM_001290043.2(TAP2):c.1867C>T (p.Arg623Ter)	Pathogenic
2833232	NM_001290043.2(TAP2):c.117del (p.Trp39fs)	Pathogenic
3013838	NM_001290043.2(TAP2):c.63G>A (p.Trp21Ter)	Pathogenic
3721305	NM_001290043.2(TAP2):c.178G>T (p.Gly60Ter)	Pathogenic
4740154	NM_001290043.2(TAP2):c.226_229del (p.Thr76fs)	Pathogenic
571072	NM_001290043.2(TAP2):c.958del (p.Glu320fs)	Pathogenic
2501118	NM_001290043.2(TAP2):c.814_815delinsC (p.Leu272fs)	Likely pathogenic
2803894	NM_001290043.2(TAP2):c.1635+1G>C	Likely pathogenic
534707	NM_001290043.2(TAP2):c.1272+1G>A	Likely pathogenic
626224	NM_001290043.2(TAP2):c.217_218del (p.Thr73fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

4362 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32835662:G:C	F240L	0.983
6:32835662:G:T	F240L	0.983
6:32835664:A:G	F240L	0.983
6:32830654:A:C	F475L	0.979
6:32830654:A:T	F475L	0.979
6:32830656:A:G	F475L	0.979
6:32830036:G:C	N563K	0.974
6:32830036:G:T	N563K	0.974
6:32830372:G:C	S510R	0.973
6:32830372:G:T	S510R	0.973
6:32830374:T:G	S510R	0.973
6:32832369:A:C	F412L	0.971
6:32832369:A:T	F412L	0.971
6:32832371:A:G	F412L	0.971
6:32835696:A:G	L229P	0.971
6:32835773:G:C	S203R	0.971
6:32835773:G:T	S203R	0.971
6:32837538:T:G	S203R	0.971
6:32829479:G:T	A618D	0.968
6:32835277:G:C	S274R	0.968
6:32835277:G:T	S274R	0.968
6:32835279:T:G	S274R	0.968
6:32835753:C:G	R210P	0.967
6:32835705:C:G	R226P	0.963
6:32835292:A:C	N269K	0.961
6:32835292:A:T	N269K	0.961
6:32832767:C:G	A335P	0.956
6:32835740:G:C	F214L	0.956
6:32835740:G:T	F214L	0.956
6:32835742:A:G	F214L	0.956

dbSNP variants (sampled 300 via entrez): RS1000062830 (6:32837340 T>C), RS1000347208 (6:32823947 T>A), RS1000369239 (6:32836930 C>T), RS1000397988 (6:32823714 A>G), RS1000565875 (6:32823878 A>C,G), RS1000783292 (6:32824229 A>C), RS1001735997 (6:32839175 G>A), RS1001745938 (6:32838849 G>A), RS1001902308 (6:32832039 C>T), RS1002001453 (6:32836292 T>C), RS1002077172 (6:32825467 G>A), RS1002158995 (6:32829802 G>A), RS1002375975 (6:32832450 C>A,G), RS1002569448 (6:32835065 C>G,T), RS1002825847 (6:32822139 C>T)

Disease associations

OMIM: gene MIM:170261 | disease phenotypes: MIM:604571, MIM:620813

GenCC curated gene-disease

Disease	Classification	Inheritance
MHC class I deficiency	Strong	Autosomal recessive
MHC class I deficiency 1	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MHC class I deficiency	Strong	AR

Mondo (3): MHC class I deficiency (MONDO:0011476), MHC class I deficiency 2 (MONDO:0971011), MHC class I deficiency 1 (MONDO:0971006)

Orphanet (1): Immunodeficiency by defective expression of MHC class I (Orphanet:34592)

HPO phenotypes

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

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST001009_2	Nephropathy	2.000000e-12
GCST001826_5	Lymphoma	2.000000e-09
GCST001876_6	Pubertal anthropometrics	9.000000e-07
GCST002655_18	IgA nephropathy	2.000000e-09
GCST002830_6	Urate levels in lean individuals	8.000000e-06
GCST002876_7	Type 1 diabetes and autoimmune thyroid diseases	4.000000e-22
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_150	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST005542_4	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	2.000000e-06
GCST005606_13	Response to hepatitis B vaccine	1.000000e-08
GCST007564_33	Asthma or allergic disease (pleiotropy)	8.000000e-35
GCST008572_1	Composite immunoglobulin trait (IgA/IgG)	3.000000e-10
GCST008916_16	Asthma	3.000000e-17
GCST008916_27	Asthma	5.000000e-31
GCST008916_90	Asthma	4.000000e-15
GCST008921_2	Asthma and major depressive disorder	3.000000e-13
GCST010083_360	Hemoglobin levels	1.000000e-24
GCST011773_19	Type 1 diabetes (age at diagnosis)	4.000000e-06
GCST011773_20	Type 1 diabetes (age at diagnosis)	2.000000e-06
GCST012227_932	Hip circumference adjusted for BMI	3.000000e-09
GCST012227_934	Hip circumference adjusted for BMI	3.000000e-08
GCST90002388_83	Lymphocyte count	1.000000e-11
GCST90002401_42	Platelet distribution width	2.000000e-19
GCST90020028_1278	Hip circumference adjusted for BMI	9.000000e-09
GCST90020029_1577	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0001382	puberty
EFO:0004531	urate measurement
EFO:0004645	response to vaccine
EFO:0004509	hemoglobin measurement
EFO:0004918	age at diagnosis
EFO:0008039	BMI-adjusted hip circumference
EFO:0004587	lymphocyte count
EFO:0007984	platelet component distribution width
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523654 (PROTEIN COMPLEX), CHEMBL6067543 (SINGLE PROTEIN)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2071543	PSMB8, TAP1, TAP2		0.00	0
rs9357155	PSMB8, TAP2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCB subfamily

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.06	Kd	87.13	nM	CHEMBL5653589
7.06	ED50	87.13	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 9 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149545: Binding affinity to human TAP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0871	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	increases abundance, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Cadmium	increases abundance, increases expression, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression, decreases expression	2
Tretinoin	affects expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
tamibarotene	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
monomethylarsonous acid	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Aspirin	affects response to substance	1
Copper	affects binding, decreases expression	1
Daunorubicin	affects response to substance	1
Diethylstilbestrol	increases expression	1
Disulfiram	affects binding, decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4380178	Binding	Inhibition of TAP1/2 in human HeLa cells stably expressing H-2 Kb infected with vaccinia virus containing Ub-SIINFEKL epitope assessed as suppression of Ub-SIINFEKL binding to MHC1 H-2 Kb at cell surface by measuring reduction in 25D1 stain	Discovery of Selective Inhibitors of Endoplasmic Reticulum Aminopeptidase 1. — J Med Chem

Cellosaurus cell lines

8 cell lines: 4 transformed cell line, 3 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5NE	STF-1	Finite cell line	Male
CVCL_B2I6	Abcam HeLa TAP2 KO	Cancer cell line	Female
CVCL_D7HM	Ubigene HEK293T TAP2 KO	Transformed cell line	Female
CVCL_DP20	ST-EAH	Transformed cell line	Male
CVCL_DP21	ST-EMO	Transformed cell line	Male
CVCL_E2LI	HAP1 TAP2 (-) 1	Cancer cell line	Male
CVCL_E2LJ	HAP1 TAP2 (-) 2	Cancer cell line	Male
CVCL_F744	STF1-169	Transformed cell line	Male

Clinical trials (associated diseases)

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