MDR_LEITA
ID MDR_LEITA Reviewed; 1548 AA.
AC P21441;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Multidrug resistance protein;
DE EC=7.6.2.2;
DE AltName: Full=P-glycoprotein;
GN Name=PGPA;
OS Leishmania tarentolae (Sauroleishmania tarentolae).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania;
OC lizard Leishmania.
OX NCBI_TaxID=5689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1969794; DOI=10.1002/j.1460-2075.1990.tb08206.x;
RA Ouellette M., Fase-Fowler F., Borst P.;
RT "The amplified H circle of methotrexate-resistant Leishmania tarentolae
RT contains a novel P-glycoprotein gene.";
RL EMBO J. 9:1027-1033(1990).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- MISCELLANEOUS: In this organism, this protein is encoded by a gene,
CC located in 'H circle', a 68 kb duplex DNA circle containing a 30 kb
CC inverted repeat. Acquired resistance to methotrexate in the organism is
CC associated with the amplification of h circles with increasing level of
CC LTPGPA gene transcription.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCB family.
CC Multidrug resistance exporter (TC 3.A.1.201) subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X17154; CAA35038.1; -; Genomic_DNA.
DR PIR; S09248; DVLNS.
DR AlphaFoldDB; P21441; -.
DR SMR; P21441; -.
DR TCDB; 3.A.1.208.6; the atp-binding cassette (abc) superfamily.
DR PRIDE; P21441; -.
DR VEuPathDB; TriTrypDB:LtaPh_2303061; -.
DR BioCyc; MetaCyc:MON-21693; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR CDD; cd18579; ABC_6TM_ABCC_D1; 1.
DR CDD; cd18580; ABC_6TM_ABCC_D2; 1.
DR Gene3D; 1.20.1560.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR044746; ABCC_6TM_D1.
DR InterPro; IPR044726; ABCC_6TM_D2.
DR InterPro; IPR000938; CAP-Gly_domain.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR SMART; SM00382; AAA; 2.
DR SMART; SM01052; CAP_GLY; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 2.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 3: Inferred from homology;
KW Antibiotic resistance; ATP-binding; Glycoprotein; Membrane;
KW Nucleotide-binding; Repeat; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1548
FT /note="Multidrug resistance protein"
FT /id="PRO_0000093346"
FT TOPO_DOM 1..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..256
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 266..287
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 349..367
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 375..392
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 463..480
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 500..519
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 520..932
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 933..950
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 975..993
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1051..1070
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1072..1088
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1164..1182
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 1186..1205
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TOPO_DOM 1206..1548
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 231..514
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 634..855
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 940..1221
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1286..1521
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 667..674
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 1320..1327
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1095
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1548 AA; 172236 MW; AFE4CC405C77B2EA CRC64;
MVDNGHVTIA MADLGTVVEI AQVRCQQEAQ RKFAEQLDEL WGGEPAYTPT VEDQASWFQQ
LYYGWIGDYI YKAAAGNITE ADLPPPTRST RTYHIGRKLS RQAHADIDAS RRWQGYIGCE
VVYKSEAEAK GVLRWVGHLQ QSDYPRSLVA GVEWRMPPRH RRLAVLGSAA ALHNGVVHGE
RLFWPHEDNY LCSCEPVEQL YVKSKYNLIP PRPPPSPDLL RTLFKVHWYH VWAQILPKLL
SDVTALMLPV LLEYFVKYLN ADNATWGWGL GLALTIFLTN VIQSCSAHKY DHISIRTAAL
FETSSMALLF EKCFTVSRRS LQRPDMSVGR IMNMVGNDVD NIGSLNWYVM YFWSAPLQLV
LCLLLLIRLV GWLRVPGMAV LFVTLPLQAV ISKHVQDVSE RMASVVDLRI KRTNELLSGV
RIVKFMGWEP VFLARIQDAR SRELRCLRDV HVANVFFMFV NDATPTLVIA VVFILYHVSG
KVLKPEVVFP TIALLNTMRV SFFMIPIIIS SILQCFVSAK RVTAFIECPD THSQVQDIAS
IDVPDAAAIF KGASIHTYLP VKLPRCKSRL TAMQRSTLWF RRRGVPETEW YEVDSPDASA
SSLAVHSTTV HMGSTQTVIT DSDGAAGEDE KGEVEEGDRE YYQLVSKELL RNVSLTIPKG
KLTMVIGSTG SGKSTLLGAL MGEYSVESGE LWAERSIAYV PQQAWIMNAT LRGNILFFDE
ERAEDLQDVI RCCQLEADLA QFCGGLDTEI GEMGVNLSGG QKARVSLARA VYANRDVYLL
DDPLSALDAH VGQRIVQDVI LGRLRGKTRV LATHQIHLLP LADYIVVLQH GSIVFAGDFA
AFSATALEET LRGELKGSKD VESCSSDVDT ESATAETAPY VAKAKGLNAE QETSLAGGED
PLRSDVEAGR LMTTEEKATG KVPWSTYVAY LKSCGGLEAW GCLLATFALT ECVTAASSVW
LSIWSTGSLM WSADTYLYVY LFIVFLEIFG SPLRFFLCYY LIRIGSRNMH RDLLESIGVA
RMSFFDTTPV GRVLNRFTKD MSILDNTLND GYLYLLEYFF SMCSTVIIMV VVQPFVLVAI
VPCVYSYYKL MQVYNASNRE TRRIKSIAHS PVFTLLEESL QGQRTIATYG KLHLVLQEAL
GRLDVVYSAL YMQNVSNRWL GVRLEFLSCV VTFMVAFIGV IGKMEGASSQ NIGLISLSLT
MSMTLTETLN WLVRQVAMVE ANMNSVERVL HYTQEVEHEH VPEMGELVAQ LVRSESGRGA
NVTETVVIES AGAASSALHP VQAGSLVLEG VQMRYREGLP LVLRGVSFQI APREKVGIVG
RTGSGKSTLL LTFMRMVEVC GGVIHVNGRE MSAYGLRDVR RHFSMIPQDP VLFDGTVRQN
VDPFLEASSA EVWAALELVG LRERVASESE GIDSRVLEGG SNYSVGQRQL MCMARALLKR
GSGFILMDEA TANIDPALDR QIQATVMSAF SAYTVITIAH RLHTVAQYDK IIVMDHGVVA
EMGSPRELVM NHQSMFHSMV ESLGSRGSKD FYELLMGRRI VQPAVLSD
