ID TAP1_HUMAN Reviewed; 748 AA. AC Q03518; Q16149; Q96CP4; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 23-FEB-2022, sequence version 3. DT 27-MAR-2024, entry version 233. DE RecName: Full=Antigen peptide transporter 1; DE Short=APT1; DE EC=7.4.2.14 {ECO:0000269|PubMed:11274390, ECO:0000269|PubMed:25377891, ECO:0000269|PubMed:25656091}; DE AltName: Full=ATP-binding cassette sub-family B member 2; DE AltName: Full=Peptide supply factor 1 {ECO:0000303|PubMed:1946428}; DE AltName: Full=Peptide transporter PSF1; DE Short=PSF-1 {ECO:0000303|PubMed:1946428}; DE AltName: Full=Peptide transporter TAP1; DE AltName: Full=Peptide transporter involved in antigen processing 1; DE AltName: Full=Really interesting new gene 4 protein; DE Short=RING4 {ECO:0000303|PubMed:1538751}; GN Name=TAP1 {ECO:0000303|PubMed:10605026, ECO:0000312|HGNC:HGNC:43}; GN Synonyms=ABCB2, PSF1, RING4, Y3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2259383; DOI=10.1038/348741a0; RA Trowsdale J., Hanson I., Mockridge I., Beck S., Townsend A., Kelly A.; RT "Sequences encoded in the class II region of the MHC related to the 'ABC' RT superfamily of transporters."; RL Nature 348:741-744(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1453454; DOI=10.1016/0022-2836(92)90832-5; RA Beck S., Kelly A., Radley E., Khurshid F., Alderton R.P., Trowsdale J.; RT "DNA sequence analysis of 66 kb of the human MHC class II region encoding a RT cluster of genes for antigen processing."; RL J. Mol. Biol. 228:433-441(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8568858; DOI=10.1006/jmbi.1996.0001; RA Beck S., Abdulla S., Alderton R.P., Glynne R.J., Gut I.G., Hosking L.K., RA Jackson A., Kelly A., Newell W.R., Sanseau P., Radley E., Thorpe K.L., RA Trowsdale J.; RT "Evolutionary dynamics of non-coding sequences within the class II region RT of the human MHC."; RL J. Mol. Biol. 255:1-13(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-333; LEU-458; GLY-637 AND GLN-648, RP AND POLYMORPHISM. RC TISSUE=Blood; RX PubMed=8248212; DOI=10.1073/pnas.90.23.11079; RA Jackson D.G., Capra J.D.; RT "TAP1 alleles in insulin-dependent diabetes mellitus: a newly defined RT centromeric boundary of disease susceptibility."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11079-11083(1993). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 123-552. RX PubMed=2259384; DOI=10.1038/348744a0; RA Spies T., Bresnahan M., Bahram S., Arnold D., Blanck G., Mellins E., RA Pious D., Demars R.; RT "A gene in the human major histocompatibility complex class II region RT controlling the class I antigen presentation pathway."; RL Nature 348:744-747(1990). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 631-663, VARIANTS GLY-637 AND GLN-648, AND RP POLYMORPHISM. RX PubMed=8168860; DOI=10.1007/bf00189240; RA Szafer F., Oksenberg J.R., Steinman L.; RT "New allelic polymorphisms in TAP genes."; RL Immunogenetics 39:374-374(1994). RN [10] RP INDUCTION BY IFNG. RX PubMed=1946428; DOI=10.1073/pnas.88.22.10094; RA Bahram S., Arnold D., Bresnahan M., Strominger J.L., Spies T.; RT "Two putative subunits of a peptide pump encoded in the human major RT histocompatibility complex class II region."; RL Proc. Natl. Acad. Sci. U.S.A. 88:10094-10098(1991). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=1589036; DOI=10.1038/357342a0; RA Kleijmeer M.J., Kelly A., Geuze H.J., Slot J.W., Townsend A., Trowsdale J.; RT "Location of MHC-encoded transporters in the endoplasmic reticulum and cis- RT Golgi."; RL Nature 357:342-344(1992). RN [12] RP FUNCTION, AND INTERACTION WITH TAP2. RX PubMed=1538751; DOI=10.1038/355641a0; RA Kelly A., Powis S.H., Kerr L.A., Mockridge I., Elliott T., Bastin J., RA Uchanska-Ziegler B., Ziegler A., Trowsdale J., Townsend A.; RT "Assembly and function of the two ABC transporter proteins encoded in the RT human major histocompatibility complex."; RL Nature 355:641-644(1992). RN [13] RP FUNCTION. RX PubMed=7500034; DOI=10.1084/jem.182.6.1883; RA van Endert P.M., Riganelli D., Greco G., Fleischhauer K., Sidney J., RA Sette A., Bach J.F.; RT "The peptide-binding motif for the human transporter associated with RT antigen processing."; RL J. Exp. Med. 182:1883-1895(1995). RN [14] RP INTERACTION WITH HERPES SIMPLEX VIRUS US12/ICP47 (MICROBIAL INFECTION). RX PubMed=7760936; DOI=10.1038/375415a0; RA Frueh K., Ahn K., Djaballah H., Sempe P., van Endert P.M., Tampe R., RA Peterson P.A., Yang Y.; RT "A viral inhibitor of peptide transporters for antigen presentation."; RL Nature 375:415-418(1995). RN [15] RP INTERACTION WITH HLA-A*02-B2M. RX PubMed=8805302; DOI=10.1016/s0960-9822(02)00611-5; RA Lewis J.W., Neisig A., Neefjes J., Elliott T.; RT "Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally RT relevant interaction with TAP."; RL Curr. Biol. 6:873-883(1996). RN [16] RP ACTIVITY REGULATION (MICROBIAL INFECTION), AND INHIBITION BY US12/ICP47. RX PubMed=8670825; DOI=10.1002/j.1460-2075.1996.tb00689.x; RA Ahn K., Meyer T.H., Uebel S., Sempe P., Djaballah H., Yang Y., RA Peterson P.A., Frueh K., Tampe R.; RT "Molecular mechanism and species specificity of TAP inhibition by herpes RT simplex virus ICP47."; RL EMBO J. 15:3247-3255(1996). RN [17] RP INTERACTION WITH HLA-A*02-B2M. RX PubMed=8630735; DOI=10.1016/s1074-7613(00)80416-1; RA Peace-Brewer A.L., Tussey L.G., Matsui M., Li G., Quinn D.G., RA Frelinger J.A.; RT "A point mutation in HLA-A*0201 results in failure to bind the TAP complex RT and to present virus-derived peptides to CTL."; RL Immunity 4:505-514(1996). RN [18] RP PEPTIDE-BINDING SITE. RX PubMed=8955196; RA Nijenhuis M., Hammerling G.J.; RT "Multiple regions of the transporter associated with antigen processing RT (TAP) contribute to its peptide binding site."; RL J. Immunol. 157:5467-5477(1996). RN [19] RP TISSUE SPECIFICITY, INDUCTION, AND INDUCTION (MICROBIAL INFECTION). RX PubMed=9310490; RA Zeidler R., Eissner G., Meissner P., Uebel S., Tampe R., Lazis S., RA Hammerschmidt W.; RT "Downregulation of TAP1 in B lymphocytes by cellular and Epstein-Barr RT virus-encoded interleukin-10."; RL Blood 90:2390-2397(1997). RN [20] RP ACTIVITY REGULATION (MICROBIAL INFECTION), AND INHIBITION BY US6 RP GLYCOPROTEIN. RX PubMed=9175839; DOI=10.1016/s1074-7613(00)80349-0; RA Ahn K., Gruhler A., Galocha B., Jones T.R., Wiertz E.J.H.J., Ploegh H.L., RA Peterson P.A., Yang Y., Frueh K.; RT "The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide RT translocation by TAP."; RL Immunity 6:613-621(1997). RN [21] RP FUNCTION. RX PubMed=9256420; DOI=10.1073/pnas.94.17.8976; RA Uebel S., Kraas W., Kienle S., Wiesmueller K.H., Jung G., Tampe R.; RT "Recognition principle of the TAP transporter disclosed by combinatorial RT peptide libraries."; RL Proc. Natl. Acad. Sci. U.S.A. 94:8976-8981(1997). RN [22] RP SUBUNIT, AND INTERACTION WITH HLA-E-B2M. RX PubMed=9427624; DOI=10.1016/s0960-9822(98)70014-4; RA Braud V.M., Allan D.S., Wilson D., McMichael A.J.; RT "TAP- and tapasin-dependent HLA-E surface expression correlates with the RT binding of an MHC class I leader peptide."; RL Curr. Biol. 8:1-10(1998). RN [23] RP INTERACTION WITH ADENOVIRUS E3-19K GLYCOPROTEIN (MICROBIAL INFECTION). RX PubMed=10227971; RA Bennett E.M., Bennink J.R., Yewdell J.W., Brodsky F.M.; RT "Adenovirus E19 has two mechanisms for affecting class I MHC expression."; RL J. Immunol. 162:5049-5052(1999). RN [24] RP SUBUNIT, AND INTERACTION WITH HLA-F. RX PubMed=10605026; DOI=10.4049/jimmunol.164.1.319; RA Wainwright S.D., Biro P.A., Holmes C.H.; RT "HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib RT protein with a restricted expression pattern."; RL J. Immunol. 164:319-328(2000). RN [25] RP ACTIVITY REGULATION (MICROBIAL INFECTION), AND INHIBITION BY US6 RP GLYCOPROTEIN. RX PubMed=11157746; DOI=10.1093/emboj/20.3.387; RA Hewitt E.W., Gupta S.S., Lehner P.J.; RT "The human cytomegalovirus gene product US6 inhibits ATP binding by TAP."; RL EMBO J. 20:387-396(2001). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=11274390; DOI=10.1073/pnas.061467898; RA Gorbulev S., Abele R., Tampe R.; RT "Allosteric crosstalk between peptide-binding, transport, and ATP RT hydrolysis of the ABC transporter TAP."; RL Proc. Natl. Acad. Sci. U.S.A. 98:3732-3737(2001). RN [27] RP INTERACTION WITH PSMB5 AND PSMB8. RX PubMed=15488952; DOI=10.1016/j.molimm.2004.07.005; RA Begley G.S., Horvath A.R., Taylor J.C., Higgins C.F.; RT "Cytoplasmic domains of the transporter associated with antigen processing RT and P-glycoprotein interact with subunits of the proteasome."; RL Mol. Immunol. 42:137-141(2005). RN [28] RP INTERACTION WITH EPSTEIN-VIRUS/EBV PROTEIN BNLF2A (MICROBIAL INFECTION). RX PubMed=19201886; DOI=10.4049/jimmunol.0803218; RA Horst D., van Leeuwen D., Croft N.P., Garstka M.A., Hislop A.D., RA Kremmer E., Rickinson A.B., Wiertz E.J.H.J., Ressing M.E.; RT "Specific targeting of the EBV lytic phase protein BNLF2a to the RT transporter associated with antigen processing results in impairment of HLA RT class I-restricted antigen presentation."; RL J. Immunol. 182:2313-2324(2009). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [30] RP SUBCELLULAR LOCATION, AND INTERACTION WITH TAPBP. RX PubMed=22638925; DOI=10.1007/s00018-012-1005-6; RA Hulpke S., Tomioka M., Kremmer E., Ueda K., Abele R., Tampe R.; RT "Direct evidence that the N-terminal extensions of the TAP complex act as RT autonomous interaction scaffolds for the assembly of the MHC I peptide- RT loading complex."; RL Cell. Mol. Life Sci. 69:3317-3327(2012). RN [31] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, RP ACTIVITY REGULATION, AND MUTAGENESIS OF ASP-674. RX PubMed=25377891; DOI=10.1038/ncomms6419; RA Grossmann N., Vakkasoglu A.S., Hulpke S., Abele R., Gaudet R., Tampe R.; RT "Mechanistic determinants of the directionality and energetics of active RT export by a heterodimeric ABC transporter."; RL Nat. Commun. 5:5419-5419(2014). RN [32] RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND ACTIVITY REGULATION RP (MICROBIAL INFECTION). RX PubMed=25656091; DOI=10.1038/ncomms7199; RA Fischbach H., Doering M., Nikles D., Lehnert E., Baldauf C., Kalinke U., RA Tampe R.; RT "Ultrasensitive quantification of TAP-dependent antigen RT compartmentalization in scarce primary immune cell subsets."; RL Nat. Commun. 6:6199-6199(2015). RN [33] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [34] RP FUNCTION, SUBUNIT, INTERACTION WITH TAPBP, SITE, AND MUTAGENESIS OF ASP-32. RX PubMed=26611325; DOI=10.1038/srep17341; RA Blees A., Reichel K., Trowitzsch S., Fisette O., Bock C., Abele R., RA Hummer G., Schaefer L.V., Tampe R.; RT "Assembly of the MHC I peptide-loading complex determined by a conserved RT ionic lock-switch."; RL Sci. Rep. 5:17341-17341(2015). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 489-748 IN COMPLEX WITH ADP AND RP MAGNESIUM, AND COFACTOR. RX PubMed=11532960; DOI=10.1093/emboj/20.17.4964; RA Gaudet R., Wiley D.C.; RT "Structure of the ABC ATPase domain of human TAP1, the transporter RT associated with antigen processing."; RL EMBO J. 20:4964-4972(2001). RN [36] RP VARIANTS VAL-333 AND GLY-637, AND POLYMORPHISM. RX PubMed=1570316; DOI=10.1073/pnas.89.9.3932; RA Colonna M., Bresnahan M., Bahram S., Strominger J.L., Spies T.; RT "Allelic variants of the human putative peptide transporter involved in RT antigen processing."; RL Proc. Natl. Acad. Sci. U.S.A. 89:3932-3936(1992). RN [37] RP VARIANT GLN-659. RX PubMed=8640228; DOI=10.1038/ng0696-210; RA Chen H.L., Gabrilovich D., Tampe R., Girgis K.R., Nadaf S., Carbone D.P.; RT "A functionally defective allele of TAP1 results in loss of MHC class I RT antigen presentation in a human lung cancer."; RL Nat. Genet. 13:210-213(1996). RN [38] RP INVOLVEMENT IN BLS1. RX PubMed=10074494; DOI=10.1172/jci5335; RA Furukawa H., Murata S., Yabe T., Shimbara N., Keicho N., Kashiwase K., RA Watanabe K., Ishikawa Y., Akaza T., Tadokoro K., Tohma S., Inoue T., RA Tokunaga K., Yamamoto K., Tanaka K., Juji T.; RT "Splice acceptor site mutation of the transporter associated with antigen RT processing-1 gene in human bare lymphocyte syndrome."; RL J. Clin. Invest. 103:755-758(1999). RN [39] RP VARIANTS VAL-333; VAL-370; LEU-458; ILE-518; GLY-637 AND GLN-648, AND RP POLYMORPHISM. RX PubMed=11250043; DOI=10.1016/s0198-8859(00)00259-7; RA Tang J., Freedman D.O., Allen S., Karita E., Musonda R., Braga C., RA Margolick J., Kaslow R.A.; RT "TAP1 polymorphisms in several human ethnic groups: characteristics, RT evolution, and genotyping strategies."; RL Hum. Immunol. 62:256-268(2001). RN [40] RP VARIANTS SER-7; ARG-17; VAL-333; VAL-370; CYS-419; LEU-458; GLY-637 AND RP GLN-648, AND POLYMORPHISM. RX PubMed=12878362; DOI=10.1016/s0198-8859(03)00110-1; RA Lajoie J., Zijenah L.S., Faucher M.C., Ward B.J., Roger M.; RT "Novel TAP1 polymorphisms in indigenous Zimbabweans: their potential RT implications on TAP function and in human diseases."; RL Hum. Immunol. 64:823-829(2003). CC -!- FUNCTION: ABC transporter associated with antigen processing. In CC complex with TAP2 mediates unidirectional translocation of peptide CC antigens from cytosol to endoplasmic reticulum (ER) for loading onto CC MHC class I (MHCI) molecules (PubMed:25656091, PubMed:25377891). Uses CC the chemical energy of ATP to export peptides against the concentration CC gradient (PubMed:25377891). During the transport cycle alternates CC between 'inward-facing' state with peptide binding site facing the CC cytosol to 'outward-facing' state with peptide binding site facing the CC ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a CC switch to hydrolysis-competent 'outward-facing' conformation ready for CC peptide loading onto nascent MHCI molecules. Subsequently ATP CC hydrolysis resets the transporter to the 'inward facing' state for a CC new cycle (PubMed:25377891, PubMed:25656091, PubMed:11274390). CC Typically transports intracellular peptide antigens of 8 to 13 amino CC acids that arise from cytosolic proteolysis via IFNG-induced CC immunoproteasome. Binds peptides with free N- and C-termini, the first CC three and the C-terminal residues being critical. Preferentially CC selects peptides having a highly hydrophobic residue at position 3 and CC hydrophobic or charged residues at the C-terminal anchor. Proline at CC position 2 has the most destabilizing effect (PubMed:7500034, CC PubMed:9256420, PubMed:11274390). As a component of the peptide loading CC complex (PLC), acts as a molecular scaffold essential for peptide-MHCI CC assembly and antigen presentation (PubMed:26611325, PubMed:1538751, CC PubMed:25377891). {ECO:0000269|PubMed:11274390, CC ECO:0000269|PubMed:1538751, ECO:0000269|PubMed:25377891, CC ECO:0000269|PubMed:25656091, ECO:0000269|PubMed:26611325, CC ECO:0000269|PubMed:7500034, ECO:0000269|PubMed:9256420}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a peptide antigen(in) + ATP + H2O = a peptide antigen(out) + CC ADP + H(+) + phosphate; Xref=Rhea:RHEA:65972, Rhea:RHEA-COMP:16941, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:166823, ChEBI:CHEBI:456216; CC EC=7.4.2.14; Evidence={ECO:0000269|PubMed:11274390, CC ECO:0000269|PubMed:25377891, ECO:0000269|PubMed:25656091}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65973; CC Evidence={ECO:0000305|PubMed:11274390, ECO:0000305|PubMed:25377891, CC ECO:0000305|PubMed:25656091}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:11532960, ECO:0000269|PubMed:25377891, CC ECO:0007744|PDB:1JJ7}; CC -!- ACTIVITY REGULATION: Inhibited at high ER lumenal peptide CC concentrations. {ECO:0000269|PubMed:25377891}. CC -!- ACTIVITY REGULATION: (Microbial infection) Inhibited by herpes simplex CC virus US12/ICP47 protein, which blocks the peptide-binding site of CC TAP1-TAP2. {ECO:0000269|PubMed:25656091, ECO:0000269|PubMed:8670825}. CC -!- ACTIVITY REGULATION: (Microbial infection) Inhibited by human CC cytomegalovirus US6 glycoprotein, which binds to the lumenal side of CC TAP1-TAP2 complex and inhibits peptide translocation by specifically CC blocking ATP-binding and preventing TAP1-TAP2 conformational CC rearrangement induced by peptide binding. {ECO:0000269|PubMed:11157746, CC ECO:0000269|PubMed:25656091, ECO:0000269|PubMed:9175839}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.3 mM for ATP {ECO:0000269|PubMed:11274390}; CC KM=0.099 mM for ATP {ECO:0000269|PubMed:25377891}; CC Vmax=2 umol/min/mg enzyme toward ATP {ECO:0000269|PubMed:11274390}; CC -!- SUBUNIT: Heterodimer of TAP1 and TAP2 (TAP1-TAP2) (PubMed:1538751). A CC component of the peptide loading complex (PLC), interacts via TAPBP CC with MHCI heterodimer; this interaction mediates peptide-MHCI assembly CC (PubMed:26611325). Recruits TAPBP in a 1:1 stoichiometry CC (PubMed:22638925). Interacts with classical MHCI such as HLA-A*02-B2M; CC this interaction is obligatory for the loading of peptide epitopes CC (PubMed:8805302, PubMed:8630735). Interacts with non-classical MHCI CC molecules including HLA-E-B2M and HLA-F-B2M as well as PLC component CC CALR before the peptide loading (PubMed:9427624, PubMed:10605026). CC Interacts with PSMB5 and PSMB8 (PubMed:15488952). CC {ECO:0000269|PubMed:10605026, ECO:0000269|PubMed:1538751, CC ECO:0000269|PubMed:15488952, ECO:0000269|PubMed:22638925, CC ECO:0000269|PubMed:26611325, ECO:0000269|PubMed:8630735, CC ECO:0000269|PubMed:8805302, ECO:0000269|PubMed:9427624}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus CC BNLF2a. {ECO:0000269|PubMed:19201886}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus CC US12/ICP47. {ECO:0000269|PubMed:7760936}. CC -!- SUBUNIT: (Microbial infection) Interacts with adenovirus E3-19K CC glycoprotein, which binds TAP1-TAP2 and acts as a TAPBP inhibitor, CC preventing TAP1-TAP2 association with MHCI. CC {ECO:0000269|PubMed:10227971}. CC -!- INTERACTION: CC Q03518; Q13520: AQP6; NbExp=3; IntAct=EBI-747259, EBI-13059134; CC Q03518; P27797: CALR; NbExp=2; IntAct=EBI-747259, EBI-1049597; CC Q03518; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-747259, EBI-781551; CC Q03518; P60508: ERVFRD-1; NbExp=3; IntAct=EBI-747259, EBI-17973325; CC Q03518; P57678: GEMIN4; NbExp=3; IntAct=EBI-747259, EBI-356700; CC Q03518; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-747259, EBI-13345167; CC Q03518; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-747259, EBI-11973993; CC Q03518; P07237: P4HB; NbExp=4; IntAct=EBI-747259, EBI-395883; CC Q03518; P30101: PDIA3; NbExp=5; IntAct=EBI-747259, EBI-979862; CC Q03518; Q6ZMZ0: RNF19B; NbExp=3; IntAct=EBI-747259, EBI-2466594; CC Q03518; Q14973: SLC10A1; NbExp=3; IntAct=EBI-747259, EBI-3923031; CC Q03518; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-747259, EBI-18159983; CC Q03518; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-747259, EBI-17295964; CC Q03518; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-747259, EBI-17280858; CC Q03518; Q03519: TAP2; NbExp=14; IntAct=EBI-747259, EBI-780781; CC Q03518; O15533: TAPBP; NbExp=13; IntAct=EBI-747259, EBI-874801; CC Q03518; Q13769: THOC5; NbExp=4; IntAct=EBI-747259, EBI-5280316; CC Q03518; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-747259, EBI-8638294; CC Q03518; P0C739: BNLF2a; Xeno; NbExp=9; IntAct=EBI-747259, EBI-9346744; CC Q03518; Q77CE4: gN; Xeno; NbExp=6; IntAct=EBI-747259, EBI-11303846; CC Q03518-2; Q03519: TAP2; NbExp=4; IntAct=EBI-31441209, EBI-780781; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:1589036, ECO:0000269|PubMed:22638925}; Multi-pass CC membrane protein {ECO:0000255}. Note=The transmembrane segments seem to CC form a pore in the membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; CC IsoId=Q03518-1; Sequence=Displayed; CC Name=2; CC IsoId=Q03518-2; Sequence=VSP_061432; CC -!- TISSUE SPECIFICITY: Highly expressed in professional APCs monocytes and CC dendritic cells as well as in lymphocyte subsets T cells, B cells and CC NK cells. {ECO:0000269|PubMed:25656091, ECO:0000269|PubMed:9310490}. CC -!- INDUCTION: Up-regulated by IFNG (PubMed:1946428). Down-regulated by CC IL10 (PubMed:9310490). {ECO:0000269|PubMed:1946428, CC ECO:0000269|PubMed:9310490}. CC -!- INDUCTION: (Microbial infection) Down-regulated by BCRF1/viral IL10. CC {ECO:0000269|PubMed:9310490}. CC -!- DOMAIN: The peptide-binding site is shared between the cytoplasmic CC loops of TAP1 and TAP2. {ECO:0000269|PubMed:8955196}. CC -!- DOMAIN: The nucleotide-binding domain (NBD) mediates ATP hydrolysis CC coupled to peptide translocation. Two ATP molecules are accommodated at CC distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. CC Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD CC of one subunit, while the NBD from the second subunit completes the CC active site by contributing the C loop motif (LSGGQ). Each ATP molecule CC is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which CC is necessary for ATP hydrolysis. {ECO:0000250|UniProtKB:P36370}. CC -!- POLYMORPHISM: There are five common alleles; TAP1*01:01 (PSF1A), CC TAP1*02:01 (PSF1B), TAP1*03:01 (PSF1C), TAP1*01:04 and TAP1*x. The CC sequence of TAP1*01:01 is shown here. {ECO:0000269|PubMed:11250043, CC ECO:0000269|PubMed:12878362, ECO:0000269|PubMed:1570316, CC ECO:0000269|PubMed:8168860, ECO:0000269|PubMed:8248212}. CC -!- DISEASE: Bare lymphocyte syndrome 1 (BLS1) [MIM:604571]: A HLA class I CC deficiency. Contrary to bare lymphocyte syndromes type 2 and type 3, CC which are characterized by early-onset severe combined CC immunodeficiency, class I antigen deficiencies are not accompanied by CC particular pathologic manifestations during the first years of life. CC Systemic infections have not been described. Chronic bacterial CC infections, often beginning in the first decade of life, are restricted CC to the respiratory tract. {ECO:0000269|PubMed:10074494}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family. CC MHC peptide exporter (TC 3.A.1.209) subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA47025.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAA60785.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=TAP1base; Note=TAP1 mutation db; CC URL="http://structure.bmc.lu.se/idbase/TAP1base/"; CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins; CC URL="http://abcm2.hegelab.org/search"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X57522; CAA40741.1; -; mRNA. DR EMBL; X66401; CAA47025.1; ALT_INIT; Genomic_DNA. DR EMBL; X87344; CAA60785.1; ALT_INIT; Genomic_DNA. DR EMBL; AL669918; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL671681; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL935043; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX927138; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR762476; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR933844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR753889; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX03647.1; -; Genomic_DNA. DR EMBL; BC014081; AAH14081.1; -; mRNA. DR EMBL; L21204; AAC12902.1; -; mRNA. DR EMBL; L21205; AAC12903.1; -; mRNA. DR EMBL; L21206; AAC12904.1; -; mRNA. DR EMBL; L21207; AAC12905.1; -; mRNA. DR EMBL; L21208; AAC12906.1; -; mRNA. DR EMBL; X57521; CAA40740.1; -; mRNA. DR EMBL; S70274; AAD14056.1; -; mRNA. DR CCDS; CCDS4758.2; -. [Q03518-1] DR PIR; S13427; A41538. DR RefSeq; NP_000584.2; NM_000593.5. [Q03518-1] DR RefSeq; NP_001278951.1; NM_001292022.1. DR PDB; 1JJ7; X-ray; 2.40 A; A=489-748. DR PDB; 5U1D; EM; 3.97 A; A=1-748. DR PDBsum; 1JJ7; -. DR PDBsum; 5U1D; -. DR AlphaFoldDB; Q03518; -. DR EMDB; EMD-8482; -. DR SMR; Q03518; -. DR BioGRID; 112753; 173. DR CORUM; Q03518; -. DR DIP; DIP-35626N; -. DR IntAct; Q03518; 65. DR MINT; Q03518; -. DR STRING; 9606.ENSP00000346206; -. DR ChEMBL; CHEMBL4523275; -. DR DrugBank; DB01259; Lapatinib. DR TCDB; 3.A.1.209.1; the atp-binding cassette (abc) superfamily. DR GlyGen; Q03518; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q03518; -. DR MetOSite; Q03518; -. DR PhosphoSitePlus; Q03518; -. DR SwissPalm; Q03518; -. DR BioMuta; TAP1; -. DR DMDM; 215273957; -. DR EPD; Q03518; -. DR jPOST; Q03518; -. DR MassIVE; Q03518; -. DR MaxQB; Q03518; -. DR PaxDb; 9606-ENSP00000346206; -. DR PeptideAtlas; Q03518; -. DR ProteomicsDB; 58214; -. DR Pumba; Q03518; -. DR Antibodypedia; 4017; 384 antibodies from 40 providers. DR CPTC; Q03518; 1 antibody. DR DNASU; 6890; -. DR Ensembl; ENST00000354258.5; ENSP00000346206.5; ENSG00000168394.13. [Q03518-1] DR Ensembl; ENST00000383235.4; ENSP00000372722.4; ENSG00000206297.7. [Q03518-2] DR Ensembl; ENST00000414467.2; ENSP00000405356.2; ENSG00000226173.4. [Q03518-2] DR Ensembl; ENST00000418205.2; ENSP00000401149.2; ENSG00000227816.4. [Q03518-2] DR Ensembl; ENST00000424897.2; ENSP00000413080.2; ENSG00000230705.4. [Q03518-2] DR Ensembl; ENST00000439781.2; ENSP00000415660.2; ENSG00000224212.4. [Q03518-2] DR Ensembl; ENST00000440894.2; ENSP00000402316.2; ENSG00000232367.5. [Q03518-2] DR GeneID; 6890; -. DR KEGG; hsa:6890; -. DR MANE-Select; ENST00000354258.5; ENSP00000346206.5; NM_000593.6; NP_000584.3. DR UCSC; uc003ocg.4; human. [Q03518-1] DR AGR; HGNC:43; -. DR CTD; 6890; -. DR DisGeNET; 6890; -. DR GeneCards; TAP1; -. DR HGNC; HGNC:43; TAP1. DR HPA; ENSG00000168394; Low tissue specificity. DR MalaCards; TAP1; -. DR MIM; 170260; gene. DR MIM; 604571; phenotype. DR neXtProt; NX_Q03518; -. DR OpenTargets; ENSG00000168394; -. DR Orphanet; 34592; Immunodeficiency by defective expression of MHC class I. DR PharmGKB; PA35021; -. DR VEuPathDB; HostDB:ENSG00000168394; -. DR eggNOG; KOG0058; Eukaryota. DR GeneTree; ENSGT00940000159023; -. DR HOGENOM; CLU_000604_84_3_1; -. DR InParanoid; Q03518; -. DR OMA; FNQFFVG; -. DR OrthoDB; 5487044at2759; -. DR PhylomeDB; Q03518; -. DR TreeFam; TF105197; -. DR BRENDA; 7.4.2.14; 2681. DR BRENDA; 7.4.2.5; 2681. DR PathwayCommons; Q03518; -. DR Reactome; R-HSA-1236974; ER-Phagosome pathway. DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC. DR SignaLink; Q03518; -. DR SIGNOR; Q03518; -. DR BioGRID-ORCS; 6890; 23 hits in 1165 CRISPR screens. DR ChiTaRS; TAP1; human. DR EvolutionaryTrace; Q03518; -. DR GeneWiki; TAP1; -. DR GenomeRNAi; 6890; -. DR Pharos; Q03518; Tbio. DR PRO; PR:Q03518; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q03518; Protein. DR Bgee; ENSG00000168394; Expressed in granulocyte and 99 other cell types or tissues. DR ExpressionAtlas; Q03518; baseline and differential. DR GO; GO:0034451; C:centriolar satellite; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0042824; C:MHC class I peptide loading complex; IDA:UniProtKB. DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome. DR GO; GO:0042825; C:TAP complex; IDA:UniProtKB. DR GO; GO:0015433; F:ABC-type peptide antigen transporter activity; IDA:UniProtKB. DR GO; GO:0043531; F:ADP binding; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042288; F:MHC class I protein binding; IEA:Ensembl. DR GO; GO:0023029; F:MHC class Ib protein binding; IPI:UniProtKB. DR GO; GO:0042605; F:peptide antigen binding; IDA:UniProtKB. DR GO; GO:1904680; F:peptide transmembrane transporter activity; IMP:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0046978; F:TAP1 binding; ISS:UniProtKB. DR GO; GO:0046979; F:TAP2 binding; IPI:UniProtKB. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; IDA:UniProt. DR GO; GO:0046967; P:cytosol to endoplasmic reticulum transport; IMP:UniProtKB. DR GO; GO:0006952; P:defense response; IEA:Ensembl. DR GO; GO:0015833; P:peptide transport; IMP:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central. DR CDD; cd18589; ABC_6TM_TAP1; 1. DR CDD; cd03248; ABCC_TAP; 1. DR DisProt; DP01306; -. DR Gene3D; 1.20.1560.10; ABC transporter type 1, transmembrane domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR011527; ABC1_TM_dom. DR InterPro; IPR036640; ABC1_TM_sf. DR InterPro; IPR013305; ABC_Tap-like. DR InterPro; IPR003439; ABC_transporter-like_ATP-bd. DR InterPro; IPR017871; ABC_transporter-like_CS. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR039421; Type_1_exporter. DR NCBIfam; TIGR00958; 3a01208; 1. DR PANTHER; PTHR43394; ATP-DEPENDENT PERMEASE MDL1, MITOCHONDRIAL; 1. DR PANTHER; PTHR43394:SF15; TRANSPORTER 1, ATP BINDING CASSETTE SUBFAMILY B MEMBER; 1. DR Pfam; PF00664; ABC_membrane; 1. DR Pfam; PF00005; ABC_tran; 1. DR PIRSF; PIRSF002773; ABC_prm/ATPase_B; 1. DR PRINTS; PR01896; TAP1PROTEIN. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF90123; ABC transporter transmembrane region; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS50929; ABC_TM1F; 1. DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1. DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1. DR Genevisible; Q03518; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative initiation; ATP-binding; KW Endoplasmic reticulum; Host-virus interaction; Immunity; Magnesium; KW Membrane; Metal-binding; Nucleotide-binding; Peptide transport; KW Protein transport; Reference proteome; Translocase; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..748 FT /note="Antigen peptide transporter 1" FT /id="PRO_0000093326" FT TOPO_DOM 1..15 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 16..36 FT /note="Helical; Name=1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 37..53 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 54..76 FT /note="Helical; Name=2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 77..92 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 93..113 FT /note="Helical; Name=3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 114..133 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 134..154 FT /note="Helical; Name=4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 155..186 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 187..207 FT /note="Helical; Name=5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 208..227 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 228..248 FT /note="Helical; Name=6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 249..298 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 299..319 FT /note="Helical; Name=7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 320..328 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 329..349 FT /note="Helical; Name=8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 350..418 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 419..439 FT /note="Helical; Name=9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 440..443 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 444..464 FT /note="Helical; Name=10" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT TOPO_DOM 465..748 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 187..470 FT /note="ABC transmembrane type-1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441" FT DOMAIN 503..742 FT /note="ABC transporter" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434" FT REGION 375..420 FT /note="Part of the peptide-binding site" FT /evidence="ECO:0000269|PubMed:8955196" FT REGION 453..487 FT /note="Part of the peptide-binding site" FT /evidence="ECO:0000269|PubMed:8955196" FT BINDING 538..546 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P36370, FT ECO:0000255|PROSITE-ProRule:PRU00434" FT BINDING 545 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:11532960, FT ECO:0007744|PDB:1JJ7" FT BINDING 641..647 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P36370" FT BINDING 701 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P36370" FT SITE 32 FT /note="Inter-subunit salt bridge with TAPBP" FT /evidence="ECO:0000269|PubMed:26611325" FT VAR_SEQ 1 FT /note="M -> MAELLASAGSACSWDFPRAPPSFPPPAASRGGLGGTRSFRPHRGAES FT PRPGRDRDGVRVPM (in isoform 2)" FT /id="VSP_061432" FT VARIANT 7 FT /note="P -> S (in dbSNP:rs375389015)" FT /evidence="ECO:0000269|PubMed:12878362" FT /id="VAR_016801" FT VARIANT 17 FT /note="G -> R (in dbSNP:rs57640466)" FT /evidence="ECO:0000269|PubMed:12878362" FT /id="VAR_016802" FT VARIANT 110 FT /note="L -> V (in dbSNP:rs2228108)" FT /id="VAR_048137" FT VARIANT 244 FT /note="V -> L (in dbSNP:rs36229525)" FT /id="VAR_060987" FT VARIANT 286 FT /note="S -> F (in dbSNP:rs2228111)" FT /id="VAR_048138" FT VARIANT 333 FT /note="I -> V (in allele TAP1*02:01, allele TAP1*03:01, FT allele TAP1*04:01 and allele TAP1*x; dbSNP:rs1057141)" FT /evidence="ECO:0000269|PubMed:11250043, FT ECO:0000269|PubMed:12878362, ECO:0000269|PubMed:1570316, FT ECO:0000269|PubMed:8248212" FT /id="VAR_000092" FT VARIANT 370 FT /note="A -> V (in allele TAP1*x; dbSNP:rs2127679)" FT /evidence="ECO:0000269|PubMed:11250043, FT ECO:0000269|PubMed:12878362" FT /id="VAR_013151" FT VARIANT 419 FT /note="G -> C (in dbSNP:rs2228110)" FT /evidence="ECO:0000269|PubMed:12878362" FT /id="VAR_016803" FT VARIANT 458 FT /note="V -> L (in allele TAP1*04:01; dbSNP:rs41550019)" FT /evidence="ECO:0000269|PubMed:11250043, FT ECO:0000269|PubMed:12878362, ECO:0000269|PubMed:8248212" FT /id="VAR_013152" FT VARIANT 518 FT /note="V -> I (in allele TAP1*x; dbSNP:rs41561219)" FT /evidence="ECO:0000269|PubMed:11250043" FT /id="VAR_013153" FT VARIANT 637 FT /note="D -> G (in allele TAP1*02:01, allele TAP1*04:01 and FT allele TAP1*x; dbSNP:rs1135216)" FT /evidence="ECO:0000269|PubMed:11250043, FT ECO:0000269|PubMed:12878362, ECO:0000269|PubMed:1570316, FT ECO:0000269|PubMed:8168860, ECO:0000269|PubMed:8248212" FT /id="VAR_000093" FT VARIANT 648 FT /note="R -> Q (in allele TAP1*04:01; dbSNP:rs1057149)" FT /evidence="ECO:0000269|PubMed:11250043, FT ECO:0000269|PubMed:12878362, ECO:0000269|PubMed:8168860, FT ECO:0000269|PubMed:8248212" FT /id="VAR_013154" FT VARIANT 659 FT /note="R -> Q (in a lung cancer cell line deficient in MHC FT class I presentation; dbSNP:rs121917702)" FT /evidence="ECO:0000269|PubMed:8640228" FT /id="VAR_013173" FT VARIANT 708 FT /note="Q -> R (in dbSNP:rs1057149)" FT /id="VAR_047514" FT MUTAGEN 32 FT /note="D->K: Complete loss of interaction with TAPBP, FT resulting in impaired PLC assembly and antigen FT presentation." FT /evidence="ECO:0000269|PubMed:26611325" FT MUTAGEN 674 FT /note="D->A: Impairs allosteric coupling of peptide FT transport to ATP hydrolysis, converting the unidirectional FT active pump into a passive bidirectional nucleotide-gated FT facilitator. Inactive in peptide transport when associated FT with 'A-638' of TAP2." FT /evidence="ECO:0000269|PubMed:25377891" FT STRAND 503..510 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 520..528 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 533..537 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 544..551 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 558..564 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 569..571 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 574..580 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 581..584 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 592..594 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 595..600 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 609..618 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 622..626 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 631..633 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 641..643 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 645..657 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 662..668 FT /evidence="ECO:0007829|PDB:1JJ7" FT TURN 669..672 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 675..686 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 689..693 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 695..699 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 703..707 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 710..716 FT /evidence="ECO:0007829|PDB:1JJ7" FT STRAND 719..724 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 726..732 FT /evidence="ECO:0007829|PDB:1JJ7" FT HELIX 735..740 FT /evidence="ECO:0007829|PDB:1JJ7" SQ SEQUENCE 748 AA; 80965 MW; E703ECCC09417002 CRC64; MASSRCPAPR GCRCLPGASL AWLGTVLLLL ADWVLLRTAL PRIFSLLVPT ALPLLRVWAV GLSRWAVLWL GACGVLRATV GSKSENAGAQ GWLAALKPLA AALGLALPGL ALFRELISWG APGSADSTRL LHWGSHPTAF VVSYAAALPA AALWHKLGSL WVPGGQGGSG NPVRRLLGCL GSETRRLSLF LVLVVLSSLG EMAIPFFTGR LTDWILQDGS ADTFTRNLTL MSILTIASAV LEFVGDGIYN NTMGHVHSHL QGEVFGAVLR QETEFFQQNQ TGNIMSRVTE DTSTLSDSLS ENLSLFLWYL VRGLCLLGIM LWGSVSLTMV TLITLPLLFL LPKKVGKWYQ LLEVQVRESL AKSSQVAIEA LSAMPTVRSF ANEEGEAQKF REKLQEIKTL NQKEAVAYAV NSWTTSISGM LLKVGILYIG GQLVTSGAVS SGNLVTFVLY QMQFTQAVEV LLSIYPRVQK AVGSSEKIFE YLDRTPRCPP SGLLTPLHLE GLVQFQDVSF AYPNRPDVLV LQGLTFTLRP GEVTALVGPN GSGKSTVAAL LQNLYQPTGG QLLLDGKPLP QYEHRYLHRQ VAAVGQEPQV FGRSLQENIA YGLTQKPTME EITAAAVKSG AHSFISGLPQ GYDTEVDEAG SQLSGGQRQA VALARALIRK PCVLILDDAT SALDANSQLQ VEQLLYESPE RYSRSVLLIT QHLSLVEQAD HILFLEGGAI REGGTHQQLM EKKGCYWAMV QAPADAPE //