[TAP1] 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. [provided by RefSeq].
RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 9 spliced variants.
AceView synopsis, each blue text links to tables and details
Note that this locus is complex: it appears to produce several proteins with no sequence overlap. Expression: According to AceView, this gene is expressed at high level, 2.9 times the average gene in this release. The sequence of this gene is defined by 328 GenBank accessions from 291 cDNA clones, some from uterus tumor (seen 17 times), thymus (14), skin (13), lung (12), thalamus (12), t-lymphocytes (11), uterus (11) and 82 other tissues. We annotate structural defects or features in 10 cDNA clones. Alternative mRNA variants and regulation: The gene contains 14 distinct introns (13 gt-ag, 1 other). Transcription produces 12 different mRNAs, 9 alternatively spliced variants and 3 unspliced forms. There are 6 probable alternative promotors, 4 non overlapping alternative last exons and 5 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of a cassette exon, overlapping exons with different boundaries, splicing versus retention of 2 introns. 2628 bp of this gene are antisense to spliced gene PSMB9.aAug10, raising the possibility of regulated alternate expression.
2 variants were isolated in vivo, despite the fact that they are predicted targets of nonsense mediated mRNA decay (NMD).
Efficacy of translation may be reduced by the presence of a shorter translated product (uORF) initiating at an AUG upstream of the main open reading frame (in variant aAug10, cAug10, dAug10). Function: There are 162 articles specifically referring to this gene in PubMed. Functionally, the gene has been tested for association to diseases (OMIM: Bare lymphocyte syndrome, type I; Other sources: Arthritis, Rheumatoid; Bronchiolitis, Viral; Carcinoma, Renal Cell; Chromosome Deletion; Colonic Neoplasms; Coronary Artery Disease; Diabetes Mellitus, Type 1; diabetes, type 1 and 12 others), proposed to participate in pathways (ABC transporters, Antigen processing and presentation, Phagosome, Primary immunodeficiency) and processes (defense response, interspecies interaction between organisms, protection from natural killer cell mediated cytotoxicity, protein transport, transmembrane transport). Proteins are expected to have molecular functions (ATPase activity, ATPase activity, coupled to transmembrane movement of substances, nucleotide binding, protein heterodimerization activity, protein homodimerization activity, TAP1 binding, transporter activity) and to localize in various compartments (cytoplasm, membrane, mitochondrion, nucleus, plasma membrane and 4 others). Putative protein interactors have been described (COPG, ESR1, HLA-F, HLA-G, HLA_, KRTAP4-12, MDFI, PDIA3, PSMA1ANDCOPB1, PSMB5, PSMB8, TAP2ANDHLA-DOB, TAPBP). Protein coding potential: 8 spliced and the unspliced mRNAs putatively encode good proteins, altogether 9 different isoforms (6 complete, 1 COOH complete, 2 partial), some containing domains ABC transporter transmembrane region, ABC transporter [Pfam], some transmembrane domains, a coiled coil stretch [Psort2]. The remaining 3 mRNA variants (1 spliced, 2 unspliced; 2 partial) appear not to encode good proteins.
2 isoforms are annotated using as Met a Kozak-compatible non-AUG start, thereby gaining a minimum of 76 amino acids N-terminal to the first AUG.
Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12. Map on chromosome 6, links to other databases and other names Map: This gene TAP1 maps on chromosome 6, at 6p21.3 according to Entrez Gene. In AceView, it covers 9.13 kb, from 32822112 to 32812979 (NCBI 37, August 2010), on the reverse strand. Links to: manual annotations from OMIM_604571, GAD, KEGG_02010, KEGG_04145, KEGG_04612, KEGG_05340, the SNP view, gene overviews from Entrez Gene 6890, GeneCards, expression data from ECgene, UniGene, molecular and other annotations from UCSC, or our GOLD analysis.
The previous AceView annotation is here. Other names: The gene is also known as TAP1, DAAP-57C1.5, APT1, PSF1, ABC17, ABCB2, RING4, TAP1N, D6S114E, FLJ26666, FLJ41500 or TAP1*0102N, LOC6890. It has been described as antigen peptide transporter 1, PSF-1, ABC transporter, MHC 1, peptide supply factor 1, peptide transporter PSF1, peptide transporter TAP1, really interesting new gene 4 protein, ATP-binding cassette sub-family B member 2, transporter associated with antigen processing, peptide transporter involved in antigen processing 1, ATP-binding cassette, sub-family B (MDR/TAP), member 2, transporter, ATP-binding cassette, major histocompatibility complex, 1. Closest AceView homologs in other species ? The closest mouse gene, according to BlastP, is the AceView gene Tap1 (e=10-97). The closest C.elegans genes, according to BlastP, are the AceView/WormGenes haf-9 (e=3 10-51), haf-4 (e=2 10-48), which may contain interesting functional annotation. The closest A.thaliana genes, according to BlastP, are the AceView genes ATTAP2 (e=10-41), ATTAP1 (e=2 10-40), which may contain interesting functional annotation
RNA-seq gene expression profile across 16 selected tissues from the Non-Human Primates Reference Transcriptome Resource (link to NHPRTR project).
- Primates: Apes (HUM: Human (Illumina BodyMap 2), CHP: Chimpanzee), Old World monkeys (PTM: Pig-Tailed Macaque, JMI Japanese Macaque, RMI Rhesus Macaque Indian, RMC Rhesus Macaque Chinese, CMM Cynomolgus Macaque Mauritian, CMC Cynomolgus Macaque Chinese, BAB Olive Baboon, SMY Sooty Mangabey); New World monkeys (MST common Marmoset, SQM Squirrel Monkey, OWL Owl Monkey); and Lemurs (MLM Mouse Lemur, RTL Ring-Tailed Lemur).
- The level for significantly expressed genes is color coded in 8 equal sized bins (light to dark green). Light gray is for weak not-accurately measured expression (2 to 8 reads above intergenic background); dark gray for no expression or no sequence conservation (0 read in gene). The plot to the right shows the distribution of measured expression values in all tissues for all genes (blue) and for this gene (green), in Magic index = log2(1000 sFPKM).
You may also examine the strand-specific genome coverage plots on the experimental AceView/Magic hub at UCSC, by tissue or by species. Tracks may be slow to load; please reload if some tracks come up yellow-greenish, and thanks to UCSC for the great work!. Read more...
About UCSC tracks: you may enjoy the plots for the summed coverage over all primates' libraries (top track), summarizing 3 terabases of stranded RNA-seq. Fragments mapping on the + strand of the genome (from genes on the + strand) are red (or dark), on minus strand blue (or light) and antisense transcribed areas are black or overlaid. The vertical scale for each track is self-adapting. Homozygous SNPs tracks are also presented.
About mapping: Primates body map RNA-seq data were stringently mapped to the human genome using the NCBI Magic pipeline. Normalized results are shown as significant FPKM (sFPKM), which includes corrections on F, K and M, computed from parameters measured directly in each RNA-seq experiment, to render the expression measures more significant and more robust to experimental biases. Only fragments with both reads mapped uniquely and over at least 80+80 bases ending with 8 exact bases on each side of each read, and facing each other in a single site or gene, are included in the computation of the sFPKM/index, in the coverage plots, and in the determination of homozygous SNPs (minimum coverage 10, minimum allele frequency 95%). But be aware that genes whose sequence evolved to become too distant from Human cannot be measured well, this bias can be appreciated in the per-species coverage plots at UCSC.
About libraries: For non-human primates, total RNA libraries used TruSeq, ribozero and the stranded UDG protocol. The human 2010 libraries used the polyA selected non-stranded protocol, with short reads (50, 75 or 50+50 bases); furthermore the insert lengths are larger in human than in the non-human primates (average insert size 187 bp in non-human primates versus 232 bp in human). These protocol differences may impact expression measures for the non polyadenylated genes (or genes with shorter or occasional polyA tails), for the pseudogenes or close gene families (specificity is reduced in humans due to shorter reads), and for the very short genes.
Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript. Read more...
Mouse over the ending of each transcript gives tissues from which the supporting cDNAs were extracted. Details on tissue of origin for each intron and exon is available from the intron and exons table.
Click on any transcript to open the specific mRNA page, to see the exact cDNA clone support and eventual SNPs and to get details on tissues, sequences, mRNA and protein annotations. Proteins supported by a single continuous cDNA sequence lead to underlining the name/ending of the variant. Names not underlined result from cDNA concatenation in the coding region and should be experimentally checked.
Introns are depicted by broken lines; the height of the top of each intron reflects the relative number of clones supporting this intron. ]^[ A pink broken line denotes an intron with standard boundaries (gt-ag or gc-ag) that is exactly supported (i.e. a cDNA sequence exactly matches the genome over 16 bp, 8 on both sides of the intron). ] ^ ] A blue broken line denotes non-standard introns, exactly supported, but with non-standard at-ac or any other boundaries. ]-[ Pink and ] - ] blue straight lines represent 'fuzzy' introns of the standard and non-standard types respectively, those introns do not follow the 16 bp rule. Black straight lines ]-[denote gaps in the alignments.
Exons: Wide filled pink areas represent putative protein coding regions, narrow empty pink boxes represent the 5'UTR (on the left) and 3' UTR (on the right). Flags identify validated endings: cap site on the 5' side, polyadenylation site on the 3' side. Filled flags correspond to frequent events while empty flags have lesser supporting cDNAs (yet all are validated); at the 3' side, black flags are associated to the main AATAAA signal, blue flags to any single letter variant of the main . More explanations are given in the gene help file
To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.
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