TAP2_MOUSE
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 03-AUG-2022, entry version 178.
DE RecName: Full=Antigen peptide transporter 2;
DE Short=APT2;
DE EC=7.4.2.- {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 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 EPD; P36371; -.
DR PaxDb; P36371; -.
DR PeptideAtlas; P36371; -.
DR PRIDE; P36371; -.
DR ProteomicsDB; 263068; -.
DR DNASU; 21355; -.
DR Ensembl; ENSMUST00000025197; ENSMUSP00000025197; ENSMUSG00000024339.
DR GeneID; 21355; -.
DR KEGG; mmu:21355; -.
DR UCSC; uc008cbx.2; mouse.
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; ERQRMTI; -.
DR OrthoDB; 684058at2759; -.
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; 20 hits in 77 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 126 other tissues.
DR ExpressionAtlas; P36371; baseline and differential.
DR Genevisible; P36371; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; 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:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
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:1904680; F:peptide transmembrane transporter activity; 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 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..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
