Human Gene TAP1 (uc003ocg.3) Description and Page Index
Description: Homo sapiens transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) (TAP1), mRNA. RefSeq Summary (NM_000593): 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]. Transcript (Including UTRs) Position: hg19 chr6:32,812,986-32,821,748 Size: 8,763 Total Exon Count: 11 Strand: - Coding Region Position: hg19 chr6:32,813,356-32,821,593 Size: 8,238 Coding Exon Count: 11
ID:TAP1_HUMAN DESCRIPTION: RecName: Full=Antigen peptide transporter 1; Short=APT1; AltName: Full=ATP-binding cassette sub-family B member 2; AltName: Full=Peptide supply factor 1; AltName: Full=Peptide transporter PSF1; Short=PSF-1; AltName: Full=Peptide transporter TAP1; AltName: Full=Peptide transporter involved in antigen processing 1; AltName: Full=Really interesting new gene 4 protein; FUNCTION: Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules. SUBUNIT: Heterodimer of TAP1 and TAP2. Interacts with Epstein-Barr virus BNLF2a. Interacts with PSMB5 and PSMB8. INTERACTION: P27797:CALR; NbExp=2; IntAct=EBI-747259, EBI-1049597; P07237:P4HB; NbExp=4; IntAct=EBI-747259, EBI-395883; P30101:PDIA3; NbExp=4; IntAct=EBI-747259, EBI-979862; Q03519:TAP2; NbExp=6; IntAct=EBI-747259, EBI-780781; O15533:TAPBP; NbExp=7; IntAct=EBI-747259, EBI-874801; SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Note=The transmembrane segments seem to form a pore in the membrane. INDUCTION: By IFNG/IFN-gamma. DOMAIN: The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2. POLYMORPHISM: There are five common alleles; TAP1*01:01 (PSF1A), TAP1*02:01 (PSF1B), TAP1*03:01 (PSF1C), TAP1*01:04 and TAP1*x. The sequence of TAP1*01:01 is shown here. DISEASE: Defects in TAP1 are a cause of bare lymphocyte syndrome type 1 (BLS1) [MIM:604571]; also called HLA class I deficiency. BLS1 is a class I antigen deficiency that is not accompanied by particular pathologic manifestations during the first years of life. Systemic infections have not been described. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract. SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily. SIMILARITY: Contains 1 ABC transmembrane type-1 domain. SIMILARITY: Contains 1 ABC transporter domain. CAUTION: It is uncertain whether Met-1 or Met-61 is the initiator. SEQUENCE CAUTION: Sequence=CAA47025.1; Type=Erroneous initiation; Sequence=CAA60785.1; Type=Erroneous initiation; WEB RESOURCE: Name=TAP1base; Note=TAP1 mutation db; URL="http://bioinf.uta.fi/TAP1base/"; WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins; URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=Q03518";
Genetic Association Studies of Complex Diseases and Disorders
asthma Hang, L. W. et al. 2003, TAP1 gene AccI polymorphism is associated with atopic bronchial asthma., Journal of clinical laboratory analysis. 2003 ;17(2):57-60.
The results show that the AccI polymorphism may be an indicator for atopic bronchial asthma.
cervical cancer Gostout BS 2003, , Gynecologic oncology. 2003 Mar;88(3):326-32.
We demonstrated a significant association between immune response genes and the risk of cervical cancer. Our data create a compelling argument for a gene or a cluster of genes in the HLA region of chromosome 6 that regulates host immune responses to human papillomavirus infection in a manner that results in inherited susceptibility or resistance to the transforming properties of oncogenic papillomaviruses.
cystic fibrosis Ozbas-Gerceker, F. et al. 2002, Analysis of the modifying effects of TAP 1/2 genes on cystic fibrosis phenotype., The Turkish journal of pediatrics. 2002 Apr-Jun;44(2):91-7.
We demonstrated that TAP genes might have modifying effects on the CF phenotype.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q03518
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002250 adaptive immune response GO:0002376 immune system process GO:0002474 antigen processing and presentation of peptide antigen via MHC class I GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent GO:0006952 defense response GO:0015031 protein transport GO:0015833 peptide transport GO:0016032 viral process GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I GO:0046967 cytosol to ER transport GO:0055085 transmembrane transport GO:1990668 vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane