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3.A.1.209.1
MHC heterodimeric peptide exporter (TAP) (from cytoplasm to the endoplasmic reticulum) (TAP1=ABCB2; TAP2=ABCB3) (defects in TAP1 or TAP2 cause immunodeficiency) (TAP1/TAP2 is stabilized by tapasin isoforms 1, 2 and 3) (Raghuraman et al., 2002). TAP1 has 10 TMSs, 4 unique N-terminal TMSs and 6 TMSs that form the translocation pore with N- and C-termini in the cytosol (Schrodt et al., 2006). The TAP2 nucleotide binding site appears to be the main catalytic active site driving transport suggesting asymmetry in the transporter (Perria et al., 2006). The TAP complex shows strict coupling between peptide binding and ATP hydrolysis, revealing no basal ATPase activity in the absence of peptides (Herget et al., 2009).  There are three binding sites on TAP1 for tapasis which interconnects TAP and MHC class I, promotes TAP stability and facilitates heterodimerization (Leonhardt et al. 2014).  TAP is the target of GN1 (TC#8.B.25.1.1), a virally encoded protein inhibitor of viral peptide exposure on the cell surface (Verweij et al. 2008; Rufer et al. 2015). Tapasin (448 aas; O15533) stabilizes TAP2 (Papadopoulos and Momburg 2007). Tapasin is involved in the association of MHC class I with the transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading). TAP plays a key role in the adaptive immune defense against infected or malignantly transformed cells by translocating proteasomal degradation products into the lumen of the endoplasmic reticulum for loading onto MHC class I molecules. TAP transports peptides from 8 to 40 residues, including even branched or modified molecules, suggestive of structural flexibility of the substrate-binding pocket. The bound peptides in side-chains' mobility was strongly restricted at the ends of the peptide, whereas the central region was flexible. Peptides bind to TAP in an extended kinked structure, analogous to those bound to MHC class I proteins (Herget et al., 2011). TAP translocates proteasomal degradation products from the cytosol into the lumen of the endoplasmic reticulum, where these peptides are loaded onto MHC class I molecules by a macromolecular peptide-loading complex (PLC) and subsequently shuttled to the cell surface for inspection by cytotoxic T lymphocytes. As a central adapter protein, tapasin (O15533) (Li et al. 2000) recruits other components of the PLC at the N-terminal domains of TAP. Koch et al. 2006 found that the N-terminal domains of human TAP1 and TAP2 independently bind to tapasin, thus providing two separate loading platforms for PLC assembly. Tapasin binding is dependent on the first N-terminal TMS of TAP1 and TAP2, demonstrating that these two helices contribute independently to the recruitment of tapasin and associated factors (Koch et al. 2006). The endoplasmic reticulum-resident human cytomegalovirus glycoprotein US6 (gpUS6) inhibits peptide translocation by the transporter associated with antigen processing (TAP) to prevent loading of major histocompatibility complex class I molecules and antigen presentation to CD8+ T cells. gpUS6 associates with preformed TAP1/2 heterodimers (Halenius et al. 2006).

Accession Number:Q03519
Protein Name:TAP2 aka ABCB3 aka PSF2 aka RING11 aka Y1
Length:686
Molecular Weight:75664.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Endoplasmic reticulum membrane1 / Multi-pass membrane protein2
Substrate peptides

Cross database links:

Genevestigator: Q03519
eggNOG: prNOG10289
DIP: DIP-322N
RefSeq: NP_000535.3    NP_061313.2   
Entrez Gene ID: 6891   
Pfam: PF00664    PF00005   
Drugbank: Drugbank Link   
OMIM: 170261  gene
604571  phenotype
KEGG: hsa:6891   

Gene Ontology

GO:0030176 C:integral to endoplasmic reticulum membrane
GO:0005634 C:nucleus
GO:0042825 C:TAP complex
GO:0005524 F:ATP binding
GO:0015433 F:peptide antigen-transporting ATPase activity
GO:0046978 F:TAP1 binding
GO:0002489 P:antigen processing and presentation of endo...
GO:0019885 P:antigen processing and presentation of endo...
GO:0046967 P:cytosol to ER transport
GO:0006955 P:immune response
GO:0019060 P:intracellular transport of viral proteins i...
GO:0046968 P:peptide antigen transport
GO:0055085 P:transmembrane transport

References (21)

[1] “DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing.”  Beck S.et.al.   1453454
[2] “Polymorphism in a second ABC transporter gene located within the class II region of the human major histocompatibility complex.”  Powis S.H.et.al.   1741401
[3] “Two putative subunits of a peptide pump encoded in the human major histocompatibility complex class II region.”  Bahram S.et.al.   1946428
[4] “Alleles and haplotypes of the MHC-encoded ABC transporters TAP1 and TAP2.”  Powis S.H.et.al.   8428770
[5] “Novel splicing of the human MHC-encoded peptide transporter confers unique properties.”  Yan G.et.al.   9916708
[6] “Evolutionary dynamics of non-coding sequences within the class II region of the human MHC.”  Beck S.et.al.   8568858
[7] “The DNA sequence and analysis of human chromosome 6.”  Mungall A.J.et.al.   14574404
[8] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[9] “Novel human TAP2*103 allele shows further polymorphism in the ATP-binding domain.”  Cano P.et.al.   7792761
[10] “New TAP2 polymorphisms in Africans.”  Tang J.et.al.   9672156
[11] “Polymorphisms in the TAP2 gene and their association with rheumatoid arthritis.”  Singal D.P.et.al.   8162639
[12] “Multiple regions of the transporter associated with antigen processing (TAP) contribute to its peptide binding site.”  Nijenhuis M.et.al.   8955196
[13] “Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus ICP47.”  Ahn K.et.al.   8670825
[14] “The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP.”  Ahn K.et.al.   9175839
[15] “The human cytomegalovirus gene product US6 inhibits ATP binding by TAP.”  Hewitt E.W.et.al.   11157746
[16] “Adenovirus E19 has two mechanisms for affecting class I MHC expression.”  Bennett E.M.et.al.   10227971
[17] “Specific targeting of the EBV lytic phase protein BNLF2a to the transporter associated with antigen processing results in impairment of HLA class I-restricted antigen presentation.”  Horst D.et.al.   19201886
[18] “Allelic variants of the human putative peptide transporter involved in antigen processing.”  Colonna M.et.al.   1570316
[19] “Homozygous human TAP peptide transporter mutation in HLA class I deficiency.”  de la Salle H.et.al.   7517574
[20] “Association of a new allele of the TAP2 gene, TAP2*Bky2 (Val577), with susceptibility to Sjogren's syndrome.”  Kumagai S.et.al.   9324024
[21] “Genotyping TAP2 variants in North American Caucasians, Brazilians, and Africans.”  Tang J.et.al.   11294565

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MRLPDLRPWT SLLLVDAALL WLLQGPLGTL LPQGLPGLWL EGTLRLGGLW GLLKLRGLLG 
61:	FVGTLLLPLC LATPLTVSLR ALVAGASRAP PARVASAPWS WLLVGYGAAG LSWSLWAVLS 
121:	PPGAQEKEQD QVNNKVLMWR LLKLSRPDLP LLVAAFFFLV LAVLGETLIP HYSGRVIDIL 
181:	GGDFDPHAFA SAIFFMCLFS FGSSLSAGCR GGCFTYTMSR INLRIREQLF SSLLRQDLGF 
241:	FQETKTGELN SRLSSDTTLM SNWLPLNANV LLRSLVKVVG LYGFMLSISP RLTLLSLLHM 
301:	PFTIAAEKVY NTRHQEVLRE IQDAVARAGQ VVREAVGGLQ TVRSFGAEEH EVCRYKEALE 
361:	QCRQLYWRRD LERALYLLVR RVLHLGVQML MLSCGLQQMQ DGELTQGSLL SFMIYQESVG 
421:	SYVQTLVYIY GDMLSNVGAA EKVFSYMDRQ PNLPSPGTLA PTTLQGVVKF QDVSFAYPNR 
481:	PDRPVLKGLT FTLRPGEVTA LVGPNGSGKS TVAALLQNLY QPTGGQVLLD EKPISQYEHC 
541:	YLHSQVVSVG QEPVLFSGSV RNNIAYGLQS CEDDKVMAAA QAAHADDFIQ EMEHGIYTDV 
601:	GEKGSQLAAG QKQRLAIARA LVRDPRVLIL DEATSALDVQ CEQALQDWNS RGDRTVLVIA 
661:	HRLQTVQRAH QILVLQEGKL QKLAQL