TAP2_RAT
ID TAP2_RAT Reviewed; 703 AA.
AC P36372;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Antigen peptide transporter 2;
DE Short=APT2;
DE EC=7.4.2.- {ECO:0000305|PubMed:17018292};
DE AltName: Full=ATP-binding cassette sub-family B member 3;
GN Name=Tap2; Synonyms=Abcb3, Mtp2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1758495; DOI=10.1038/354528a0;
RA Powis S.J., Townsend A.R.M., Deverson E.V., Bastin J., Butcher G.W.,
RA Howard J.C.;
RT "Restoration of antigen presentation to the mutant cell line RMA-S by an
RT MHC-linked transporter.";
RL Nature 354:528-531(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS TAP2L PHE-352 AND ARG-603.
RX PubMed=1350326; DOI=10.1038/357211a0;
RA Powis S.J., Deverson E.V., Coadwell W.J., Ciruela A., Huskisson N.S.,
RA Smith H., Butcher G.W., Howard J.C.;
RT "Effect of polymorphism of an MHC-linked transporter on the peptides
RT assembled in a class I molecule.";
RL Nature 357:211-215(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=PVG-RT1L(LEW);
RX PubMed=8206525; DOI=10.1007/bf00163963;
RA Joly E., Deverson E.V., Coadwell W.L., Guenther E., Howard J.C.,
RA Butcher G.W.;
RT "The distribution of Tap2 alleles among laboratory rat RT1 haplotypes.";
RL Immunogenetics 40:45-53(1994).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 608-ALA-VAL-609 AND
RP GLU-632.
RX PubMed=17018292; DOI=10.1016/j.molcel.2006.07.034;
RA Procko E., Ferrin-O'Connell I., Ng S.L., Gaudet R.;
RT "Distinct structural and functional properties of the ATPase sites in an
RT asymmetric ABC transporter.";
RL Mol. Cell 24:51-62(2006).
CC -!- FUNCTION: ABC transporter associated with antigen processing
CC (PubMed:17018292). In complex with TAP1 mediates unidirectional
CC translocation of peptide antigens from cytosol to endoplasmic reticulum
CC (ER) for loading onto MHC class I (MHCI) molecules (By similarity).
CC Uses the chemical energy of ATP to export peptides against the
CC concentration gradient (By similarity). During the transport cycle
CC alternates between 'inward-facing' state with peptide binding site
CC facing the cytosol to 'outward-facing' state with peptide binding site
CC facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2
CC induces a switch to hydrolysis-competent 'outward-facing' conformation
CC ready for peptide loading onto nascent MHCI molecules. Subsequently ATP
CC hydrolysis resets the transporter to the 'inward facing' state for a
CC new cycle (By similarity). As a component of the peptide loading
CC complex (PLC), acts as a molecular scaffold essential for peptide-MHCI
CC assembly and antigen presentation (By similarity).
CC {ECO:0000250|UniProtKB:Q03519, ECO:0000269|PubMed:17018292}.
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:0000305|PubMed:17018292};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65973;
CC Evidence={ECO:0000305|PubMed:17018292};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q03519};
CC -!- SUBUNIT: Heterodimer of TAP1 and TAP2 (TAP1-TAP2). A component of the
CC peptide loading complex (PLC), interacts via TAPBP with MHCI
CC heterodimer; this interaction mediates peptide-MHCI assembly.
CC {ECO:0000250|UniProtKB:Q03519}.
CC -!- INTERACTION:
CC P36372; Q77CE4: gN; Xeno; NbExp=2; IntAct=EBI-11304494, EBI-11303846;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q03519}; Multi-pass membrane protein
CC {ECO:0000255}. Note=The transmembrane segments seem to form a pore in
CC the membrane. {ECO:0000250|UniProtKB:Q03519}.
CC -!- DOMAIN: The peptide-binding site is shared between the cytoplasmic
CC loops of TAP1 and TAP2. {ECO:0000250|UniProtKB:Q03519}.
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 -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC MHC peptide exporter (TC 3.A.1.209) subfamily. {ECO:0000305}.
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DR EMBL; X63854; CAA45339.1; -; mRNA.
DR EMBL; X75305; CAA53053.1; -; mRNA.
DR PIR; S38400; S38400.
DR RefSeq; NP_114445.2; NM_032056.3.
DR AlphaFoldDB; P36372; -.
DR SMR; P36372; -.
DR BioGRID; 246934; 7.
DR IntAct; P36372; 3.
DR STRING; 10116.ENSRNOP00000000527; -.
DR jPOST; P36372; -.
DR PaxDb; P36372; -.
DR PRIDE; P36372; -.
DR GeneID; 24812; -.
DR KEGG; rno:24812; -.
DR UCSC; RGD:3818; rat.
DR CTD; 6891; -.
DR RGD; 3818; Tap2.
DR eggNOG; KOG0058; Eukaryota.
DR InParanoid; P36372; -.
DR OrthoDB; 684058at2759; -.
DR PhylomeDB; P36372; -.
DR BRENDA; 7.4.2.14; 5301.
DR Reactome; R-RNO-1236974; ER-Phagosome pathway.
DR Reactome; R-RNO-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR PRO; PR:P36372; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0042824; C:MHC class I peptide loading complex; IDA:UniProtKB.
DR GO; GO:0042825; C:TAP complex; IDA:UniProtKB.
DR GO; GO:0015433; F:ABC-type peptide antigen transporter activity; ISO:RGD.
DR GO; GO:0015440; F:ABC-type peptide transporter activity; IBA:GO_Central.
DR GO; GO:0043531; F:ADP binding; IDA:RGD.
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:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042288; F:MHC class I protein binding; IDA:UniProtKB.
DR GO; GO:0023029; F:MHC class Ib protein binding; ISO:RGD.
DR GO; GO:0000166; F:nucleotide binding; IDA:RGD.
DR GO; GO:0042605; F:peptide antigen binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0046978; F:TAP1 binding; IPI:UniProtKB.
DR GO; GO:0046979; F:TAP2 binding; IPI:UniProtKB.
DR GO; GO:0046980; F:tapasin binding; IDA:RGD.
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:MGI.
DR GO; GO:0002485; P:antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent; ISO:RGD.
DR GO; GO:0002489; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent; ISO:RGD.
DR GO; GO:0002481; P:antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent; ISO:RGD.
DR GO; GO:0046967; P:cytosol to endoplasmic reticulum transport; ISO:RGD.
DR GO; GO:0046968; P:peptide antigen transport; ISO:RGD.
DR GO; GO:0015833; P:peptide transport; IMP:RGD.
DR GO; GO:0002591; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class I; IMP:RGD.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IDA:MGI.
DR GO; GO:0042270; P:protection from natural killer cell mediated cytotoxicity; IMP:RGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0002237; P:response to molecule of bacterial origin; ISO:RGD.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
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; IPR005293; Tap2/ABCB3.
DR InterPro; IPR039421; Type_1_exporter.
DR PANTHER; PTHR24221; PTHR24221; 1.
DR Pfam; PF00664; ABC_membrane; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR PRINTS; PR01897; TAP2PROTEIN.
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 Adaptive immunity; ATP-binding; Endoplasmic reticulum; Immunity; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Peptide transport;
KW Protein transport; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..703
FT /note="Antigen peptide transporter 2"
FT /id="PRO_0000093331"
FT TOPO_DOM 1..6
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..27
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 28..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 78..98
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 120..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 170..187
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 209..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 288..293
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 294..314
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 315..374
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 375..395
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 396..408
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 409..429
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 430..703
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 152..435
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 468..702
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 301..389
FT /note="Part of the peptide-binding site"
FT /evidence="ECO:0000250|UniProtKB:Q03519"
FT REGION 414..433
FT /note="Part of the peptide-binding site"
FT /evidence="ECO:0000250|UniProtKB:Q03519"
FT BINDING 503..510
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT SITE 16
FT /note="Inter-subunit salt bridge with TAPBP"
FT /evidence="ECO:0000250|UniProtKB:Q03519"
FT VARIANT 352
FT /note="V -> F (in TAP2L)"
FT /evidence="ECO:0000269|PubMed:1350326"
FT VARIANT 603
FT /note="K -> R (in TAP2L)"
FT /evidence="ECO:0000269|PubMed:1350326"
FT MUTAGEN 608..609
FT /note="AV->SG: Has negligible effect on ATPase activity."
FT /evidence="ECO:0000269|PubMed:17018292"
FT MUTAGEN 632
FT /note="E->D: Impairs peptide loading onto MHCI."
FT /evidence="ECO:0000269|PubMed:17018292"
FT MUTAGEN 632
FT /note="E->Q: Has negligible effect on ATPase activity."
FT /evidence="ECO:0000269|PubMed:17018292"
SQ SEQUENCE 703 AA; 77713 MW; E545993A8F784250 CRC64;
MALSHPRPWA SLLLVDLALL GLLQSSLGTL LPPGLPGLWL EGTLRLGVLW GLLKVGGLLR
LVGTFLPLLC LTNPLFFSLR ALVGSTMSTS VVRVASASWG WLLADYGAVA LSLAVWAVLS
PAGAQEKEPG QENNRALMIR LLRLSKPDLP FLIVAFIFLA MAVWWEMFIP HYSGRVIDIL
GGDFDPDAFA SAIFFMCLFS VGSSLSAGCR GGSFLFAESR INLRIREQLF SSLLRQDLAF
FQETKTGELN SRLSSDTSLM SQWLSLNANI LLRSLVKVVG LYYFMLQVSP RLTFLSLLDL
PLTIAAEKVY NPRHQAVLKE IQDAVAKAGQ VVREAVGGLQ TVRSFGAEEQ EVRRYKEALE
RCRQLWWRRD LEKSLYLVIQ RVMALGMQVL ILNVGVQQIL AGEVTRGGLL SFLLYQEEVG
HHVQNLVYMY GDMLSNVGAA EKVFSYLDRR PNLPNPGTLA PPRLEGRVEF QDVSFSYPSR
PEKPVLQGLT FTLHPGKVTA LVGPNGSGKS TVAALLQNLY QPTGGQLLLD GEPLVQYDHH
YLHRQVVLVG QEPVLFSGSV KDNIAYGLRD CEDAQVMAAA QAACADDFIG EMTNGINTEI
GEKGSQLAVG QKQRLAIARA LVRNPRVLIL DEATSALDAE CEQALQTWRS QEDRTMLVIA
HRLHTVQNAD QVLVLKQGQL VEHDQLRDEQ DVYAHLVQQR LEA
