ID   TAP2_MOUSE              Reviewed;         702 AA.
AC   P36371;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   27-MAR-2024, entry version 186.
DE   RecName: Full=Antigen peptide transporter 2;
DE            Short=APT2;
DE            EC=7.4.2.14 {ECO:0000250|UniProtKB:Q03519};
DE   AltName: Full=ATP-binding cassette sub-family B member 3;
DE   AltName: Full=Histocompatibility antigen modifier 2;
GN   Name=Tap2; Synonyms=Abcb3, Ham-2, Ham2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1339432; DOI=10.1016/s0021-9258(19)49745-7;
RA   Yang Y., Frueh K., Chambers J., Waters J.B., Wu L., Spies T.,
RA   Peterson P.A.;
RT   "Major histocompatibility complex (MHC)-encoded HAM2 is necessary for
RT   antigenic peptide loading onto class I MHC molecules.";
RL   J. Biol. Chem. 267:11669-11672(1992).
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: ABC transporter associated with antigen processing. In
CC       complex with TAP1 mediates unidirectional translocation of peptide
CC       antigens from cytosol to endoplasmic reticulum (ER) for loading onto
CC       MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export
CC       peptides against the concentration gradient. 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. As a component of the peptide loading complex (PLC), acts as
CC       a molecular scaffold essential for peptide-MHCI assembly and antigen
CC       presentation. {ECO:0000250|UniProtKB:Q03519}.
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:0000250|UniProtKB:Q03519};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65973;
CC         Evidence={ECO:0000250|UniProtKB:Q03519};
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   -!- 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; M90459; AAA39609.1; -; mRNA.
DR   CCDS; CCDS28644.1; -.
DR   PIR; A44135; A44135.
DR   RefSeq; NP_035660.3; NM_011530.3.
DR   AlphaFoldDB; P36371; -.
DR   SMR; P36371; -.
DR   BioGRID; 203967; 6.
DR   IntAct; P36371; 2.
DR   STRING; 10090.ENSMUSP00000025197; -.
DR   iPTMnet; P36371; -.
DR   PhosphoSitePlus; P36371; -.
DR   SwissPalm; P36371; -.
DR   EPD; P36371; -.
DR   PaxDb; 10090-ENSMUSP00000025197; -.
DR   PeptideAtlas; P36371; -.
DR   ProteomicsDB; 263068; -.
DR   Pumba; P36371; -.
DR   DNASU; 21355; -.
DR   Ensembl; ENSMUST00000025197.6; ENSMUSP00000025197.6; ENSMUSG00000024339.13.
DR   GeneID; 21355; -.
DR   KEGG; mmu:21355; -.
DR   UCSC; uc008cbx.2; mouse.
DR   AGR; MGI:98484; -.
DR   CTD; 6891; -.
DR   MGI; MGI:98484; Tap2.
DR   VEuPathDB; HostDB:ENSMUSG00000024339; -.
DR   eggNOG; KOG0058; Eukaryota.
DR   GeneTree; ENSGT00940000160499; -.
DR   HOGENOM; CLU_000604_84_3_1; -.
DR   InParanoid; P36371; -.
DR   OMA; NMLTWPV; -.
DR   OrthoDB; 5487044at2759; -.
DR   PhylomeDB; P36371; -.
DR   TreeFam; TF105197; -.
DR   BRENDA; 7.4.2.14; 3474.
DR   Reactome; R-MMU-1236974; ER-Phagosome pathway.
DR   Reactome; R-MMU-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR   BioGRID-ORCS; 21355; 22 hits in 82 CRISPR screens.
DR   ChiTaRS; Tap2; mouse.
DR   PRO; PR:P36371; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; P36371; Protein.
DR   Bgee; ENSMUSG00000024339; Expressed in thymus and 128 other cell types or tissues.
DR   ExpressionAtlas; P36371; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR   GO; GO:0016020; C:membrane; ISO:MGI.
DR   GO; GO:0042824; C:MHC class I peptide loading complex; ISO:MGI.
DR   GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR   GO; GO:0042825; C:TAP complex; ISO:MGI.
DR   GO; GO:0015433; F:ABC-type peptide antigen transporter activity; ISO:MGI.
DR   GO; GO:0015440; F:ABC-type peptide transporter activity; IBA:GO_Central.
DR   GO; GO:0043531; F:ADP binding; ISO:MGI.
DR   GO; GO:0005524; F:ATP binding; ISO:MGI.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0042288; F:MHC class I protein binding; ISO:MGI.
DR   GO; GO:0023029; F:MHC class Ib protein binding; ISO:MGI.
DR   GO; GO:0000166; F:nucleotide binding; ISO:MGI.
DR   GO; GO:0042605; F:peptide antigen binding; ISO:MGI.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0046978; F:TAP1 binding; IPI:UniProtKB.
DR   GO; GO:0046979; F:TAP2 binding; ISO:MGI.
DR   GO; GO:0046980; F:tapasin binding; ISS:UniProtKB.
DR   GO; GO:0019885; P:antigen processing and presentation of endogenous peptide antigen via MHC class I; ISO:MGI.
DR   GO; GO:0002485; P:antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent; IDA:MGI.
DR   GO; GO:0002489; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent; IDA:MGI.
DR   GO; GO:0002481; P:antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent; IMP:MGI.
DR   GO; GO:0046967; P:cytosol to endoplasmic reticulum transport; ISO:MGI.
DR   GO; GO:0046968; P:peptide antigen transport; ISO:MGI.
DR   GO; GO:0015833; P:peptide transport; ISO:MGI.
DR   GO; GO:0002591; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class I; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR   GO; GO:0002237; P:response to molecule of bacterial origin; IMP:MGI.
DR   GO; GO:0001913; P:T cell mediated cytotoxicity; IDA:MGI.
DR   GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR   CDD; cd18590; ABC_6TM_TAP2; 1.
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; IPR005293; Tap2/ABCB3.
DR   InterPro; IPR039421; Type_1_exporter.
DR   NCBIfam; TIGR00958; 3a01208; 1.
DR   PANTHER; PTHR24221:SF237; ANTIGEN PEPTIDE TRANSPORTER 2; 1.
DR   PANTHER; PTHR24221; ATP-BINDING CASSETTE SUB-FAMILY B; 1.
DR   Pfam; PF00664; ABC_membrane; 1.
DR   Pfam; PF00005; ABC_tran; 1.
DR   PIRSF; PIRSF002773; ABC_prm/ATPase_B; 1.
DR   PRINTS; PR01897; TAP2PROTEIN.
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; P36371; MM.
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..702
FT                   /note="Antigen peptide transporter 2"
FT                   /id="PRO_0000093330"
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..147
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        148..168
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT   TOPO_DOM        169..186
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        187..207
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT   TOPO_DOM        208..265
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        266..286
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT   TOPO_DOM        287..292
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        293..313
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT   TOPO_DOM        314..373
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        374..394
FT                   /note="Helical; Name=8"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT   TOPO_DOM        395..407
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        408..428
FT                   /note="Helical; Name=9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT   TOPO_DOM        429..702
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          151..434
FT                   /note="ABC transmembrane type-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT   DOMAIN          467..701
FT                   /note="ABC transporter"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT   REGION          300..388
FT                   /note="Part of the peptide-binding site"
FT                   /evidence="ECO:0000250|UniProtKB:Q03519"
FT   REGION          413..432
FT                   /note="Part of the peptide-binding site"
FT                   /evidence="ECO:0000250|UniProtKB:Q03519"
FT   BINDING         502..509
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"
SQ   SEQUENCE   702 AA;  77445 MW;  F93DFA38B057AC0A CRC64;
     MALSYLRPWV SLLLADMALL GLLQGSLGNL LPQGLPGLWI EGTLRLGVLW GLLKVGELLG
     LVGTLLPLLC LATPLFFSLR ALVGGTASTS VVRVASASWG WLLAGYGAVA LSWAVWAVLS
     PAGVQEKEPG QENRTLMKRL LKLSRPDLPF LIAAFFFLVV AVWGETLIPR YSGRVIDILG
     GDFDPDAFAS AIFFMCLFSV GSSFSAGCRG GSFLFTMSRI NLRIREQLFS SLLRQDLGFF
     QETKTGELNS RLSSDTSLMS RWLPFNANIL LRSLVKVVGL YFFMLQVSPR LTFLSLLDLP
     LTIAAEKVYN PRHQAVLKEI QDAVAKAGQV VREAVGGLQT VRSFGAEEQE VSHYKEALER
     CRQLWWRRDL EKDVYLVIRR VMALGMQVLI LNCGVQQILA GEVTRGGLLS FLLYQEEVGQ
     YVRNLVYMYG DMLSNVGAAE KVFSYLDRKP NLPQPGILAP PWLEGRVEFQ DVSFSYPRRP
     EKPVLQGLTF TLHPGTVTAL VGPNGSGKST VAALLQNLYQ PTGGQLLLDG EPLTEYDHHY
     LHRQVVLVGQ EPVLFSGSVK DNIAYGLRDC EDAQVMAAAQ AACADDFIGE MTNGINTEIG
     EKGGQLAVGQ KQRLAIARAL VRNPRVLILD EATSALDAQC EQALQNWRSQ GDRTMLVIAH
     RLHTVQNADQ VLVLKQGRLV EHDQLRDGQD VYAHLVQQRL EA
//