TAP1_RAT
ID TAP1_RAT Reviewed; 725 AA.
AC P36370;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Antigen peptide transporter 1;
DE Short=APT1;
DE EC=7.4.2.- {ECO:0000305|PubMed:17018292};
DE AltName: Full=ATP-binding cassette sub-family B member 2;
DE AltName: Full=Peptide transporter TAP1;
GN Name=Tap1; Synonyms=Abcb2, Mtp1;
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=1979660; DOI=10.1038/348738a0;
RA Deverson E.V., Gow I.R., Coadwell W.J., Monaco J.J., Butcher G.W.,
RA Howard J.C.;
RT "MHC class II region encoding proteins related to the multidrug resistance
RT family of transmembrane transporters.";
RL Nature 348:738-741(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BDIX; TISSUE=Lymphocyte;
RA Deverson E.V.;
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 465-725 IN COMPLEX WITH ATP AND
RP MAGNESIUM, COFACTOR, DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS
RP OF 621-SER-GLY-622; ASP-645; ASP-651 AND GLN-678.
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).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 465-725 IN COMPLEX WITH ATP AND
RP MAGNESIUM, COFACTOR, AND MUTAGENESIS OF ASP-251.
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).
CC -!- FUNCTION: ABC transporter associated with antigen processing
CC (PubMed:17018292). In complex with TAP2 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:Q03518, 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:0000269|PubMed:17018292, ECO:0000269|PubMed:25377891};
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. Interacts
CC with PSMB5 and PSMB8. {ECO:0000250|UniProtKB:Q03518}.
CC -!- INTERACTION:
CC P36370; Q99JC6: Tapbp; NbExp=2; IntAct=EBI-11303917, EBI-11304538;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q03518}; Multi-pass membrane protein
CC {ECO:0000255}. Note=The transmembrane segments seem to form a pore in
CC the membrane.
CC -!- DOMAIN: The peptide-binding site is shared between the cytoplasmic
CC loops of TAP1 and TAP2. {ECO:0000250|UniProtKB:Q03518}.
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:0000269|PubMed:17018292}.
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=CAA40742.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X57523; CAA40742.1; ALT_INIT; mRNA.
DR EMBL; Y10231; CAA71280.1; -; mRNA.
DR PIR; S13426; S13426.
DR PDB; 2IXE; X-ray; 2.00 A; A/D=465-725.
DR PDB; 2IXF; X-ray; 2.00 A; A/B/C/D=465-725.
DR PDB; 2IXG; X-ray; 2.70 A; A=465-725.
DR PDB; 4K8O; X-ray; 2.65 A; A=465-725.
DR PDBsum; 2IXE; -.
DR PDBsum; 2IXF; -.
DR PDBsum; 2IXG; -.
DR PDBsum; 4K8O; -.
DR AlphaFoldDB; P36370; -.
DR SMR; P36370; -.
DR IntAct; P36370; 3.
DR STRING; 10116.ENSRNOP00000000529; -.
DR iPTMnet; P36370; -.
DR PhosphoSitePlus; P36370; -.
DR jPOST; P36370; -.
DR PaxDb; P36370; -.
DR UCSC; RGD:3817; rat.
DR RGD; 3817; Tap1.
DR eggNOG; KOG0058; Eukaryota.
DR InParanoid; P36370; -.
DR PhylomeDB; P36370; -.
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 EvolutionaryTrace; P36370; -.
DR PRO; PR:P36370; -.
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:0016887; F:ATP hydrolysis activity; IDA:RGD.
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; 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:1904680; F:peptide transmembrane transporter activity; 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; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0006952; P:defense response; ISO:RGD.
DR GO; GO:0046968; P:peptide antigen transport; TAS:RGD.
DR GO; GO:0015833; P:peptide transport; IMP:RGD.
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: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; 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; ATP-binding; Endoplasmic reticulum;
KW Immunity; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Peptide transport; Protein transport; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..725
FT /note="Antigen peptide transporter 1"
FT /id="PRO_0000093328"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 30..38
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..60
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 61..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 89..110
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 132..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 185..204
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 205..225
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 226..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 297..305
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..326
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 327..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..416
FT /note="Helical; Name=9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 417..420
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 421..441
FT /note="Helical; Name=10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 442..725
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 164..447
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 480..719
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 352..397
FT /note="Part of the peptide-binding site"
FT /evidence="ECO:0000250|UniProtKB:Q03518"
FT REGION 430..464
FT /note="Part of the peptide-binding site"
FT /evidence="ECO:0000250|UniProtKB:Q03518"
FT BINDING 515..523
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434,
FT ECO:0000269|PubMed:17018292, ECO:0007744|PDB:2IXE,
FT ECO:0007744|PDB:2IXF, ECO:0007744|PDB:2IXG,
FT ECO:0007744|PDB:4K8O"
FT BINDING 522
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:17018292,
FT ECO:0000269|PubMed:25377891, ECO:0007744|PDB:2IXE,
FT ECO:0007744|PDB:2IXF, ECO:0007744|PDB:4K8O"
FT BINDING 618..624
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17018292,
FT ECO:0000269|PubMed:25377891, ECO:0007744|PDB:2IXE,
FT ECO:0007744|PDB:2IXF, ECO:0007744|PDB:4K8O"
FT BINDING 678
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:17018292,
FT ECO:0000269|PubMed:25377891, ECO:0007744|PDB:2IXE,
FT ECO:0007744|PDB:2IXG, ECO:0007744|PDB:4K8O"
FT SITE 17
FT /note="Inter-subunit salt bridge with TAPBP"
FT /evidence="ECO:0000250|UniProtKB:Q03518"
FT MUTAGEN 621..622
FT /note="SG->AV: Complete loss of ATPase activity; when
FT associated with N-645. Impairs peptide loading onto MHCI."
FT /evidence="ECO:0000269|PubMed:17018292"
FT MUTAGEN 645
FT /note="D->E: Increases ATPase activity by 8-fold; when
FT associated with H-678."
FT /evidence="ECO:0000269|PubMed:17018292"
FT MUTAGEN 645
FT /note="D->N: Complete loss of ATPase activity; when
FT associated with A-621 and V-622."
FT /evidence="ECO:0000269|PubMed:17018292"
FT MUTAGEN 645
FT /note="D->Q: Impairs ATPase activity; when associated with
FT H-678."
FT /evidence="ECO:0000269|PubMed:17018292"
FT MUTAGEN 651
FT /note="D->A,N: Decreases ATP-driven nucleotide binding
FT domain (NBD) dimerization."
FT /evidence="ECO:0000269|PubMed:25377891"
FT MUTAGEN 678
FT /note="Q->H: Increases ATPase activity by 8-fold; when
FT associated with E-645. Impairs ATPase activity; when
FT associated with Q-645."
FT /evidence="ECO:0000269|PubMed:17018292"
FT TURN 466..469
FT /evidence="ECO:0007829|PDB:2IXF"
FT STRAND 480..487
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 498..505
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 510..514
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 521..528
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 535..541
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 546..548
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 551..557
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 558..561
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 569..571
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 572..577
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 586..595
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 599..604
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 608..610
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 615..617
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 622..634
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 639..645
FT /evidence="ECO:0007829|PDB:2IXE"
FT TURN 646..649
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 652..664
FT /evidence="ECO:0007829|PDB:2IXE"
FT TURN 666..670
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 671..676
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 680..683
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 687..693
FT /evidence="ECO:0007829|PDB:2IXE"
FT STRAND 696..701
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 703..709
FT /evidence="ECO:0007829|PDB:2IXE"
FT HELIX 712..718
FT /evidence="ECO:0007829|PDB:2IXE"
SQ SEQUENCE 725 AA; 79150 MW; 3FA7215D0AC22EE0 CRC64;
MAAHAWPTAA LLLLLVDWLL LRPVLPGIFS LLVPEVPLLR VWAVGLSRWA ILGLGVRGVL
GVTAGARGWL AALQPLVAAL GLALPGLASF RKLSAWGALR EGDNAGLLHW NSRLDAFVLS
YVAALPAAAL WHKLGGFWAP SGHKGAGDML CRMLGFLDSK KGRLHLVLVL LILSCLGEMA
IPFFTGRITD WILQDKTAPS FARNMWLMCI LTIASTVLEF AGDGIYNITM GHMHSRVHGE
VFRAVLHQET GFFLKNPTGS ITSRVTEDTS NVCESISDKL NLFLWYLGRG LCLLAFMIWG
SFYLTVVTLL SLPLLFLLPR RLGKVYQSLA VKVQESLAKS TQVALEALSA MPTVRSFANE
EGEAQKFRQK LEEMKPLNKK EALAYVTEVW TMSVSGMLLK VGILYLGGQL VVRGAVSSGN
LVSFVLYQLQ FTRAVEVLLS IYPSMQKSVG ASEKIFEYLD RTPCSPLSGS LAPLNMKGLV
KFQDVSFAYP NHPNVQVLQG LTFTLYPGKV TALVGPNGSG KSTVAALLQN LYQPTGGKVL
LDGEPLVQYD HHYLHTQVAA VGQEPLLFGR SFRENIAYGL TRTPTMEEIT AVAMESGAHD
FISGFPQGYD TEVGETGNQL SGGQRQAVAL ARALIRKPRL LILDDATSAL DAGNQLRVQR
LLYESPEWAS RTVLLITQQL SLAERAHHIL FLKEGSVCEQ GTHLQLMERG GCYRSMVEAL
AAPSD
