TAP2 (transporter 2, ATP binding cassette subfamily B member)

Gene

• Entrez ID: 6891
• Gene name: Transporter 2, ATP binding cassette subfamily B member
• Gene symbol: TAP2
• Synonyms: ABC18, ABCB3, APT2, D6S217E, PSF-2, PSF2, RING11
• Chromosome: 6
• Chromosome location: 6p21.32
• Summary: 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. [provided by RefSeq, Feb 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs61736923	G>A,C	Pathogenic	Stop gained, coding sequence variant, missense variant
rs1222208628	C>T	Likely-pathogenic	Splice donor variant
rs1321880935	TG>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1562331529	C>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT744053	hsa-miR-4323	PAR-CLIP	26701625
MIRT744053	hsa-miR-4323	PAR-CLIP	27292025
MIRT747063	hsa-miR-4690-3p	PAR-CLIP	26701625
MIRT747063	hsa-miR-4690-3p	PAR-CLIP	27292025
MIRT751191	hsa-miR-5685	PAR-CLIP	26701625
MIRT751191	hsa-miR-5685	PAR-CLIP	27292025
MIRT757326	hsa-miR-6840-3p	PAR-CLIP	26701625
MIRT757326	hsa-miR-6840-3p	PAR-CLIP	27292025

Transcription factors

Transcription factor	Regulation	Reference
IRF1	Unknown	18694960
NFKB1	Unknown	18694960
RELA	Unknown	18694960

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002250	Process	Adaptive immune response	IEA
GO:0002474	Process	Antigen processing and presentation of peptide antigen via MHC class I	TAS
GO:0002479	Process	Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS
GO:0002489	Process	Antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent	IMP	1538751
GO:0005515	Function	Protein binding	IPI	9427624, 12213826, 15793001, 16828748, 17055437, 18802093, 19201886, 19297616, 26789246, 28514442
GO:0005524	Function	ATP binding	IDA	7673167
GO:0005524	Function	ATP binding	IMP	15793001
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0015031	Process	Protein transport	IEA
GO:0015433	Function	ABC-type peptide antigen transporter activity	IBA	21873635
GO:0015433	Function	ABC-type peptide antigen transporter activity	IDA	25377891
GO:0015433	Function	ABC-type peptide antigen transporter activity	IMP	1538751, 25656091
GO:0015440	Function	ABC-type peptide transporter activity	IBA	21873635
GO:0015833	Process	Peptide transport	IBA	21873635
GO:0016020	Component	Membrane	HDA	19946888
GO:0016021	Component	Integral component of membrane	IBA	21873635
GO:0016021	Component	Integral component of membrane	IDA	8955196
GO:0016032	Process	Viral process	IEA
GO:0016607	Component	Nuclear speck	IDA
GO:0016887	Function	ATPase activity	IEA
GO:0019885	Process	Antigen processing and presentation of endogenous peptide antigen via MHC class I	IBA	21873635
GO:0019885	Process	Antigen processing and presentation of endogenous peptide antigen via MHC class I	IDA	8496691
GO:0019885	Process	Antigen processing and presentation of endogenous peptide antigen via MHC class I	IMP	1538751
GO:0023029	Function	MHC class Ib protein binding	IPI	10605026
GO:0030176	Component	Integral component of endoplasmic reticulum membrane	IDA	7673167, 22638925
GO:0030670	Component	Phagocytic vesicle membrane	TAS
GO:0033116	Component	Endoplasmic reticulum-Golgi intermediate compartment membrane	TAS
GO:0042288	Function	MHC class I protein binding	IBA	21873635
GO:0042605	Function	Peptide antigen binding	IDA	7500034
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042824	Component	MHC class I peptide loading complex	IBA	21873635
GO:0042824	Component	MHC class I peptide loading complex	IDA	17947644
GO:0042825	Component	TAP complex	IDA	15518576, 17947644
GO:0046967	Process	Cytosol to endoplasmic reticulum transport	IMP	7538543
GO:0046968	Process	Peptide antigen transport	IDA	8496691
GO:0046968	Process	Peptide antigen transport	IMP	1538751
GO:0046978	Function	TAP1 binding	IBA	21873635
GO:0046978	Function	TAP1 binding	IPI	1538751, 15518576
GO:0046980	Function	Tapasin binding	ISS
GO:0055085	Process	Transmembrane transport	IBA	21873635
GO:0098656	Process	Anion transmembrane transport	IEA
GO:1904680	Function	Peptide transmembrane transporter activity	IGI	7673167
GO:1990668	Process	Vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane	TAS

Other IDs

• MIM: 170261
• HGNC: 44
• e!Ensembl: ENSG00000204267

Protein

• UniProt ID: Q03519
• Protein name: Antigen peptide transporter 2 (APT2) (EC 7.4.2.-) (ATP-binding cassette sub-family B member 3) (Peptide supply factor 2) (Peptide transporter PSF2) (PSF-2) (Peptide transporter TAP2) (Peptide transporter involved in antigen processing 2) (Really interesting new gene 11 protein) (RING11)
• Protein 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 (PubMed:25656091, PubMed:25377891). Uses the chemical energy of ATP to export peptides against the concentration gradient (PubMed:25377891). 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 (PubMed:25377891, PubMed:25656091, PubMed:11274390). 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 (PubMed:7500034, PubMed:9256420, PubMed:11274390). As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation (PubMed:26611325, PubMed:1538751, PubMed:25377891).
• PDB: 5U1D
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00664	ABC_membrane	152 → 421	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	486 → 635	ABC transporter	Domain

• Sequence:

  MRLPDLRPWTSLLLVDAALLWLLQGPLGTLLPQGLPGLWLEGTLRLGGLWGLLKLRGLLG
  FVGTLLLPLCLATPLTVSLRALVAGASRAPPARVASAPWSWLLVGYGAAGLSWSLWAVLS
  PPGAQEKEQDQVNNKVLMWRLLKLSRPDLPLLVAAFFFLVLAVLGETLIPHYSGRVIDIL
  GGDFDPHAFASAIFFMCLFSFGSSLSAGCRGGCFTYTMSRINLRIREQLFSSLLRQDLGF
  FQETKTGELNSRLSSDTTLMSNWLPLNANVLLRSLVKVVGLYGFMLSISPRLTLLSLLHM
  PFTIAAEKVYNTRHQEVLREIQDAVARAGQVVREAVGGLQTVRSFGAEEHEVCRYKEALE
  QCRQLYWRRDLERALYLLVRRVLHLGVQMLMLSCGLQQMQDGELTQGSLLSFMIYQESVG
  SYVQTLVYIYGDMLSNVGAAEKVFSYMDRQPNLPSPGTLAPTTLQGVVKFQDVSFAYPNR
  PDRPVLKGLTFTLRPGEVTALVGPNGSGKSTVAALLQNLYQPTGGQVLLDEKPISQYEHC
  YLHSQVVSVGQEPVLFSGSVRNNIAYGLQSCEDDKVMAAAQAAHADDFIQEMEHGIYTDV
  GEKGSQLAAGQKQRLAIARALVRDPRVLILDEATSALDVQCEQALQDWNSRGDRTVLVIA
  HRLQTVQRAHQILVLQEGKLQKLAQL

• Sequence length: 686