TAP1 (transporter 1, ATP binding cassette subfamily B member)

Gene

• Entrez ID: 6890
• Gene name: Transporter 1, ATP binding cassette subfamily B member
• Gene symbol: TAP1
• Synonyms: ABC17, ABCB2, APT1, D6S114E, PSF-1, PSF1, RING4, TAP1*0102N, TAP1N
• 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. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2228106	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs56366814	G>A	Conflicting-interpretations-of-pathogenicity	Intron variant
rs121917702	C>T	Pathogenic, likely-benign	Missense variant, coding sequence variant
rs1470217821	G>C	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006669	hsa-miR-346	Immunocytochemistry, In situ hybridization, qRT-PCR, Western blot	22002058
MIRT732463	hsa-miR-21-5p	Luciferase reporter assay, Western blot	25327529

Transcription factors

Transcription factor	Regulation	Reference
IRF1	Activation	18694960
IRF1	Unknown	9632673
IRF2	Activation	15778351
NFKB1	Unknown	18694960
RELA	Unknown	18694960
STAT1	Unknown	15778351;9632673

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:0005515	Function	Protein binding	IPI	12213826, 15793001, 16828748, 17055437, 18802093, 19165146, 19201886, 19297616, 22810586, 26789246, 28514442, 30833792, 32296183
GO:0005524	Function	ATP binding	IDA	7673167, 11133832
GO:0005524	Function	ATP binding	IMP	15793001
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006952	Process	Defense response	IEA
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	25656091
GO:0015440	Function	ABC-type peptide transporter activity	IBA	21873635
GO:0015833	Process	Peptide transport	IBA	21873635
GO:0015833	Process	Peptide transport	IMP	11133832, 17418234
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: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	IMP	11133832
GO:0023029	Function	MHC class Ib protein binding	IPI	10605026
GO:0030176	Component	Integral component of endoplasmic reticulum membrane	IDA	7673167, 11133832, 15577206, 22638925
GO:0030670	Component	Phagocytic vesicle membrane	TAS
GO:0033116	Component	Endoplasmic reticulum-Golgi intermediate compartment membrane	TAS
GO:0034451	Component	Centriolar satellite	IDA
GO:0042288	Function	MHC class I protein binding	IBA	21873635
GO:0042605	Function	Peptide antigen binding	IDA	7500034
GO:0042605	Function	Peptide antigen binding	NAS	11133832
GO:0042626	Function	ATPase-coupled transmembrane transporter activity	IBA	21873635
GO:0042803	Function	Protein homodimerization activity	ISS
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	11133832, 15518576, 17947644
GO:0043531	Function	ADP binding	IDA	11532960
GO:0046967	Process	Cytosol to endoplasmic reticulum transport	IMP	7538543
GO:0046978	Function	TAP1 binding	IBA	21873635
GO:0046978	Function	TAP1 binding	ISS
GO:0046979	Function	TAP2 binding	IPI	1538751, 11133832, 15518576
GO:0055085	Process	Transmembrane transport	IBA	21873635
GO:0098656	Process	Anion transmembrane transport	IEA
GO:1904680	Function	Peptide transmembrane transporter activity	IGI	7673167
GO:1904680	Function	Peptide transmembrane transporter activity	IMP	17418234
GO:1990668	Process	Vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane	TAS

Other IDs

• MIM: 170260
• HGNC: 43
• e!Ensembl: ENSG00000168394

Protein

• UniProt ID: Q03518
• Protein name: Antigen peptide transporter 1 (APT1) (EC 7.4.2.-) (ATP-binding cassette sub-family B member 2) (Peptide supply factor 1) (Peptide transporter PSF1) (PSF-1) (Peptide transporter TAP1) (Peptide transporter involved in antigen processing 1) (Really interesting new gene 4 protein) (RING4)
• Protein function: ABC transporter associated with antigen processing. In complex with TAP2 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: 1JJ7, 5U1D
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00664	ABC_membrane	247 → 518	ABC transporter transmembrane region	Family
  PF00005	ABC_tran	581 → 731	ABC transporter	Domain

• Sequence:

  MAELLASAGSACSWDFPRAPPSFPPPAASRGGLGGTRSFRPHRGAESPRPGRDRDGVRVP
  MASSRCPAPRGCRCLPGASLAWLGTVLLLLADWVLLRTALPRIFSLLVPTALPLLRVWAV
  GLSRWAVLWLGACGVLRATVGSKSENAGAQGWLAALKPLAAALGLALPGLALFRELISWG
  APGSADSTRLLHWGSHPTAFVVSYAAALPAAALWHKLGSLWVPGGQGGSGNPVRRLLGCL
  GSETRRLSLFLVLVVLSSLGEMAIPFFTGRLTDWILQDGSADTFTRNLTLMSILTIASAV
  LEFVGDGIYNNTMGHVHSHLQGEVFGAVLRQETEFFQQNQTGNIMSRVTEDTSTLSDSLS
  ENLSLFLWYLVRGLCLLGIMLWGSVSLTMVTLITLPLLFLLPKKVGKWYQLLEVQVRESL
  AKSSQVAIEALSAMPTVRSFANEEGEAQKFREKLQEIKTLNQKEAVAYAVNSWTTSISGM
  LLKVGILYIGGQLVTSGAVSSGNLVTFVLYQMQFTQAVEVLLSIYPRVQKAVGSSEKIFE
  YLDRTPRCPPSGLLTPLHLEGLVQFQDVSFAYPNRPDVLVLQGLTFTLRPGEVTALVGPN
  GSGKSTVAALLQNLYQPTGGQLLLDGKPLPQYEHRYLHRQVAAVGQEPQVFGRSLQENIA
  YGLTQKPTMEEITAAAVKSGAHSFISGLPQGYDTEVDEAGSQLSGGQRQAVALARALIRK
  PCVLILDDATSALDANSQLQVEQLLYESPERYSRSVLLITQHLSLVEQADHILFLEGGAI
  REGGTHQQLMEKKGCYWAMVQAPADAPE

• Sequence length: 808