TAP1_HUMAN
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 03-AUG-2022, entry version 224.
DE RecName: Full=Antigen peptide transporter 1;
DE Short=APT1;
DE EC=7.4.2.- {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 Evidence={ECO:0000269|PubMed:11274390, ECO:0000269|PubMed:25377891,
CC 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=18; IntAct=EBI-747259, EBI-780781;
CC Q03518; O15533: TAPBP; NbExp=14; 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 -!- 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: Higly 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";
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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; CCDS4758.1; -. [Q03518-1]
DR PIR; S13427; A41538.
DR RefSeq; NP_000584.2; NM_000593.5.
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 SMR; Q03518; -.
DR BioGRID; 112753; 167.
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; Q03518; -.
DR PeptideAtlas; Q03518; -.
DR PRIDE; Q03518; -.
DR ProteomicsDB; 58214; -.
DR Antibodypedia; 4017; 339 antibodies from 40 providers.
DR CPTC; Q03518; 1 antibody.
DR DNASU; 6890; -.
DR Ensembl; ENST00000354258.5; ENSP00000346206.5; ENSG00000168394.12. [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 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; LGIMLWG; -.
DR OrthoDB; 684058at2759; -.
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; 21 hits in 1082 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 97 other tissues.
DR ExpressionAtlas; Q03518; baseline and differential.
DR Genevisible; Q03518; HS.
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; TAS:Reactome.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA: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:0015440; F:ABC-type peptide transporter activity; IBA:GO_Central.
DR GO; GO:0043531; F:ADP binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
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; IMP:UniProtKB.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; IEA:InterPro.
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 DisProt; DP01306; -.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 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; IPR013306; Tap1/ABCB2.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR PANTHER; PTHR24221:SF249; PTHR24221:SF249; 1.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR TIGRFAMs; TIGR00958; 3a01208; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
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
