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P21447

- MDR1A_MOUSE

UniProt

P21447 - MDR1A_MOUSE

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Protein

Multidrug resistance protein 1A

Gene

Abcb1a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.1 Publication

Catalytic activityi

ATP + H2O + xenobiotic(In) = ADP + phosphate + xenobiotic(Out).

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi423 – 4308ATP 1PROSITE-ProRule annotation
Nucleotide bindingi1066 – 10738ATP 2PROSITE-ProRule annotation

GO - Molecular functioni

  1. ATPase activity, coupled Source: MGI
  2. ATPase activity, coupled to transmembrane movement of substances Source: RefGenome
  3. ATP binding Source: UniProtKB-KW
  4. xenobiotic-transporting ATPase activity Source: UniProtKB-EC

GO - Biological processi

  1. ATP catabolic process Source: GOC
  2. circadian rhythm Source: Ensembl
  3. drug transport Source: MGI
  4. lactation Source: Ensembl
  5. negative regulation of cell death Source: Ensembl
  6. response to cadmium ion Source: Ensembl
  7. response to hypoxia Source: Ensembl
  8. response to vitamin D Source: Ensembl
  9. transmembrane transport Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Transport

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_196555. Abacavir transmembrane transport.
REACT_237882. ABC-family proteins mediated transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Multidrug resistance protein 1A (EC:3.6.3.44)
Alternative name(s):
ATP-binding cassette sub-family B member 1A
MDR1A
Multidrug resistance protein 3
P-glycoprotein 3
Gene namesi
Name:Abcb1a
Synonyms:Abcb4, Mdr1a, Mdr3, Pgy-3, Pgy3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:97570. Abcb1a.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4343CytoplasmicBy similarityAdd
BLAST
Transmembranei44 – 6623HelicalAdd
BLAST
Topological domaini67 – 11246ExtracellularBy similarityAdd
BLAST
Transmembranei113 – 13321HelicalAdd
BLAST
Topological domaini134 – 18249CytoplasmicBy similarityAdd
BLAST
Transmembranei183 – 20422HelicalAdd
BLAST
Topological domaini205 – 2117ExtracellularBy similarity
Transmembranei212 – 23221HelicalAdd
BLAST
Topological domaini233 – 29058CytoplasmicBy similarityAdd
BLAST
Transmembranei291 – 31222HelicalAdd
BLAST
Topological domaini313 – 32614ExtracellularBy similarityAdd
BLAST
Transmembranei327 – 34822HelicalAdd
BLAST
Topological domaini349 – 707359CytoplasmicBy similarityAdd
BLAST
Transmembranei708 – 72821HelicalAdd
BLAST
Topological domaini729 – 75224ExtracellularBy similarityAdd
BLAST
Transmembranei753 – 77321HelicalAdd
BLAST
Topological domaini774 – 82855CytoplasmicBy similarityAdd
BLAST
Transmembranei829 – 84921HelicalAdd
BLAST
Topological domaini850 – 8501ExtracellularBy similarity
Transmembranei851 – 87020HelicalAdd
BLAST
Topological domaini871 – 93060CytoplasmicBy similarityAdd
BLAST
Transmembranei931 – 95323HelicalAdd
BLAST
Topological domaini954 – 96916ExtracellularBy similarityAdd
BLAST
Transmembranei970 – 99122HelicalAdd
BLAST
Topological domaini992 – 1276285CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: RefGenome
  2. intercellular canaliculus Source: MGI
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12761276Multidrug resistance protein 1APRO_0000093336Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi83 – 831N-linked (GlcNAc...)Sequence Analysis
Glycosylationi87 – 871N-linked (GlcNAc...)Sequence Analysis
Glycosylationi90 – 901N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP21447.
PaxDbiP21447.
PRIDEiP21447.

PTM databases

PhosphoSiteiP21447.

Expressioni

Gene expression databases

BgeeiP21447.
ExpressionAtlasiP21447. baseline and differential.
GenevestigatoriP21447.

Interactioni

Subunit structurei

Interacts with PSMB5.By similarity

Protein-protein interaction databases

IntActiP21447. 1 interaction.
MINTiMINT-4101695.

Structurei

Secondary structure

1
1276
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi36 – 394
Helixi45 – 517
Helixi55 – 595
Helixi63 – 708
Helixi74 – 807
Helixi84 – 874
Helixi93 – 11422
Helixi122 – 13514
Helixi139 – 15113
Helixi167 – 17913
Helixi189 – 1968
Helixi211 – 22010
Helixi228 – 24518
Turni249 – 2513
Helixi257 – 2615
Helixi269 – 28214
Helixi289 – 2935
Helixi298 – 31114
Helixi316 – 3194
Beta strandi320 – 3223
Helixi327 – 3359
Helixi344 – 35411
Helixi360 – 3634
Beta strandi388 – 3958
Beta strandi411 – 4133
Beta strandi418 – 4214
Helixi432 – 4354
Turni436 – 4383
Beta strandi446 – 4483
Helixi454 – 4563
Helixi459 – 4657
Helixi480 – 4867
Helixi493 – 50210
Helixi506 – 5116
Helixi515 – 5173
Helixi532 – 54312
Beta strandi546 – 5527
Helixi559 – 57315
Beta strandi577 – 5815
Helixi585 – 5884
Beta strandi592 – 5954
Helixi608 – 6136
Helixi618 – 6247
Helixi695 – 7028
Helixi712 – 7165
Helixi721 – 73111
Helixi743 – 75715
Helixi761 – 7688
Helixi779 – 79416
Helixi798 – 8014
Helixi810 – 82112
Helixi828 – 83811
Helixi844 – 8474
Helixi854 – 86613
Helixi870 – 8756
Helixi879 – 8868
Helixi892 – 8976
Turni901 – 9055
Helixi909 – 93325
Helixi937 – 95418
Beta strandi961 – 9633
Helixi970 – 9778
Beta strandi989 – 9913
Helixi996 – 100914
Beta strandi1013 – 10164
Turni1024 – 10274
Beta strandi1031 – 10344
Beta strandi1036 – 10383
Helixi1043 – 10453
Beta strandi1054 – 10563
Beta strandi1061 – 10655
Helixi1073 – 10797
Beta strandi1089 – 10913
Helixi1102 – 11054
Beta strandi1112 – 11154
Beta strandi1120 – 11223
Helixi1123 – 11275
Helixi1138 – 114811
Helixi1151 – 11544
Turni1157 – 11593
Helixi1160 – 11623
Helixi1177 – 118812
Beta strandi1194 – 11974
Beta strandi1199 – 12013
Helixi1204 – 121714
Beta strandi1223 – 12264
Helixi1232 – 12343
Beta strandi1237 – 12426
Beta strandi1247 – 12493
Helixi1253 – 12586
Helixi1263 – 12708

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3G5UX-ray3.80A/B1-1276[»]
3G60X-ray4.40A/B1-1276[»]
3G61X-ray4.35A/B1-1276[»]
4KSBX-ray3.80A1-1276[»]
4KSCX-ray4.00A1-1276[»]
4KSDX-ray4.10A1-1276[»]
4LSGX-ray3.80A/B1-1276[»]
4M1MX-ray3.80A/B1-1276[»]
4M2SX-ray4.40A/B1-1276[»]
4M2TX-ray4.35A/B1-1276[»]
ProteinModelPortaliP21447.
SMRiP21447. Positions 31-626.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21447.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini50 – 353304ABC transmembrane type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini388 – 624237ABC transporter 1PROSITE-ProRule annotationAdd
BLAST
Domaini707 – 996290ABC transmembrane type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini1031 – 1269239ABC transporter 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 2 ABC transmembrane type-1 domains.PROSITE-ProRule annotation
Contains 2 ABC transporter domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1132.
GeneTreeiENSGT00530000062896.
HOVERGENiHBG080809.
InParanoidiP21447.
KOiK05658.
OMAiFWALISV.
OrthoDBiEOG7Z3F4H.
PhylomeDBiP21447.
TreeFamiTF105193.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR001140. ABC_transptr_TM_dom.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view]
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P21447-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MELEEDLKGR ADKNFSKMGK KSKKEKKEKK PAVSVLTMFR YAGWLDRLYM
60 70 80 90 100
LVGTLAAIIH GVALPLMMLI FGDMTDSFAS VGNVSKNSTN MSEADKRAMF
110 120 130 140 150
AKLEEEMTTY AYYYTGIGAG VLIVAYIQVS FWCLAAGRQI HKIRQKFFHA
160 170 180 190 200
IMNQEIGWFD VHDVGELNTR LTDDVSKINE GIGDKIGMFF QAMATFFGGF
210 220 230 240 250
IIGFTRGWKL TLVILAISPV LGLSAGIWAK ILSSFTDKEL HAYAKAGAVA
260 270 280 290 300
EEVLAAIRTV IAFGGQKKEL ERYNNNLEEA KRLGIKKAIT ANISMGAAFL
310 320 330 340 350
LIYASYALAF WYGTSLVISK EYSIGQVLTV FFSVLIGAFS VGQASPNIEA
360 370 380 390 400
FANARGAAYE VFKIIDNKPS IDSFSKSGHK PDNIQGNLEF KNIHFSYPSR
410 420 430 440 450
KEVQILKGLN LKVKSGQTVA LVGNSGCGKS TTVQLMQRLY DPLDGMVSID
460 470 480 490 500
GQDIRTINVR YLREIIGVVS QEPVLFATTI AENIRYGRED VTMDEIEKAV
510 520 530 540 550
KEANAYDFIM KLPHQFDTLV GERGAQLSGG QKQRIAIARA LVRNPKILLL
560 570 580 590 600
DEATSALDTE SEAVVQAALD KAREGRTTIV IAHRLSTVRN ADVIAGFDGG
610 620 630 640 650
VIVEQGNHDE LMREKGIYFK LVMTQTAGNE IELGNEACKS KDEIDNLDMS
660 670 680 690 700
SKDSGSSLIR RRSTRKSICG PHDQDRKLST KEALDEDVPP ASFWRILKLN
710 720 730 740 750
STEWPYFVVG IFCAIINGGL QPAFSVIFSK VVGVFTNGGP PETQRQNSNL
760 770 780 790 800
FSLLFLILGI ISFITFFLQG FTFGKAGEIL TKRLRYMVFK SMLRQDVSWF
810 820 830 840 850
DDPKNTTGAL TTRLANDAAQ VKGATGSRLA VIFQNIANLG TGIIISLIYG
860 870 880 890 900
WQLTLLLLAI VPIIAIAGVV EMKMLSGQAL KDKKELEGSG KIATEAIENF
910 920 930 940 950
RTVVSLTREQ KFETMYAQSL QIPYRNAMKK AHVFGITFSF TQAMMYFSYA
960 970 980 990 1000
ACFRFGAYLV TQQLMTFENV LLVFSAIVFG AMAVGQVSSF APDYAKATVS
1010 1020 1030 1040 1050
ASHIIRIIEK TPEIDSYSTQ GLKPNMLEGN VQFSGVVFNY PTRPSIPVLQ
1060 1070 1080 1090 1100
GLSLEVKKGQ TLALVGSSGC GKSTVVQLLE RFYDPMAGSV FLDGKEIKQL
1110 1120 1130 1140 1150
NVQWLRAQLG IVSQEPILFD CSIAENIAYG DNSRVVSYEE IVRAAKEANI
1160 1170 1180 1190 1200
HQFIDSLPDK YNTRVGDKGT QLSGGQKQRI AIARALVRQP HILLLDEATS
1210 1220 1230 1240 1250
ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VIQNGKVKEH
1260 1270
GTHQQLLAQK GIYFSMVSVQ AGAKRS
Length:1,276
Mass (Da):140,647
Last modified:June 16, 2009 - v3
Checksum:i542E101DF18DDC52
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti526 – 5272QL → HV in AAA39514. (PubMed:1972547)Curated
Sequence conflicti526 – 5272QL → HV in AAA03243. (PubMed:2473069)Curated
Sequence conflicti939 – 9391S → F in AAA39517. (PubMed:1969610)Curated
Sequence conflicti1036 – 10361V → F in AAA39517. (PubMed:1969610)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30697 mRNA. Translation: AAA39517.1.
M33581 mRNA. Translation: AAA39514.1.
M33580 Genomic DNA. Translation: AAA39518.1.
AY864315 mRNA. Translation: AAW56448.1.
CH466600 Genomic DNA. Translation: EDL14677.1.
M24417 mRNA. Translation: AAA03243.1.
CCDSiCCDS19084.1.
PIRiA34175. DVMS1A.
A34786.
RefSeqiNP_035206.2. NM_011076.2.
XP_006503618.1. XM_006503555.1.
XP_006503619.1. XM_006503556.1.
UniGeneiMm.207354.

Genome annotation databases

EnsembliENSMUST00000047753; ENSMUSP00000041204; ENSMUSG00000040584.
GeneIDi18671.
KEGGimmu:18671.
UCSCiuc008wkl.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M30697 mRNA. Translation: AAA39517.1 .
M33581 mRNA. Translation: AAA39514.1 .
M33580 Genomic DNA. Translation: AAA39518.1 .
AY864315 mRNA. Translation: AAW56448.1 .
CH466600 Genomic DNA. Translation: EDL14677.1 .
M24417 mRNA. Translation: AAA03243.1 .
CCDSi CCDS19084.1.
PIRi A34175. DVMS1A.
A34786.
RefSeqi NP_035206.2. NM_011076.2.
XP_006503618.1. XM_006503555.1.
XP_006503619.1. XM_006503556.1.
UniGenei Mm.207354.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3G5U X-ray 3.80 A/B 1-1276 [» ]
3G60 X-ray 4.40 A/B 1-1276 [» ]
3G61 X-ray 4.35 A/B 1-1276 [» ]
4KSB X-ray 3.80 A 1-1276 [» ]
4KSC X-ray 4.00 A 1-1276 [» ]
4KSD X-ray 4.10 A 1-1276 [» ]
4LSG X-ray 3.80 A/B 1-1276 [» ]
4M1M X-ray 3.80 A/B 1-1276 [» ]
4M2S X-ray 4.40 A/B 1-1276 [» ]
4M2T X-ray 4.35 A/B 1-1276 [» ]
ProteinModelPortali P21447.
SMRi P21447. Positions 31-626.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P21447. 1 interaction.
MINTi MINT-4101695.

Chemistry

BindingDBi P21447.
ChEMBLi CHEMBL2573.

PTM databases

PhosphoSitei P21447.

Proteomic databases

MaxQBi P21447.
PaxDbi P21447.
PRIDEi P21447.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000047753 ; ENSMUSP00000041204 ; ENSMUSG00000040584 .
GeneIDi 18671.
KEGGi mmu:18671.
UCSCi uc008wkl.1. mouse.

Organism-specific databases

CTDi 18671.
MGIi MGI:97570. Abcb1a.

Phylogenomic databases

eggNOGi COG1132.
GeneTreei ENSGT00530000062896.
HOVERGENi HBG080809.
InParanoidi P21447.
KOi K05658.
OMAi FWALISV.
OrthoDBi EOG7Z3F4H.
PhylomeDBi P21447.
TreeFami TF105193.

Enzyme and pathway databases

Reactomei REACT_196555. Abacavir transmembrane transport.
REACT_237882. ABC-family proteins mediated transport.

Miscellaneous databases

EvolutionaryTracei P21447.
NextBioi 294686.
PROi P21447.
SOURCEi Search...

Gene expression databases

Bgeei P21447.
ExpressionAtlasi P21447. baseline and differential.
Genevestigatori P21447.

Family and domain databases

Gene3Di 3.40.50.300. 2 hits.
InterProi IPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR001140. ABC_transptr_TM_dom.
IPR027417. P-loop_NTPase.
[Graphical view ]
Pfami PF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view ]
SMARTi SM00382. AAA. 2 hits.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
PROSITEi PS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities."
    Devault A., Gros P.
    Mol. Cell. Biol. 10:1652-1663(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Structural analysis of the mouse mdr1a (P-glycoprotein) promoter reveals the basis for differential transcript heterogeneity in multidrug-resistant J774.2 cells."
    Hsu S.I.H., Cohen D., Kirschner L.S., Lothstein L., Hartstein M., Horwitz S.B.
    Mol. Cell. Biol. 10:3596-3606(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  3. "Heterologus expression of mouse mdr1a (Abcb1a), (P-glycoprotein), using the insect cell baculovirus expression system."
    Pimprale S.S., Xiao G., Patten C., Crespi C.
    Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Differential overexpression of three mdr gene family members in multidrug-resistant J774.2 mouse cells. Evidence that distinct P-glycoprotein precursors are encoded by unique mdr genes."
    Hsu S.I.H., Lothstein L., Horwitz S.B.
    J. Biol. Chem. 264:12053-12062(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 173-1276.
    Strain: BALB/c.
  6. Lubec G., Sunyer B., Chen W.-Q.
    Submitted (JAN-2009) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 273-282, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: OF1.
    Tissue: Hippocampus.
  7. "Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding."
    Aller S.G., Yu J., Ward A., Weng Y., Chittaboina S., Zhuo R., Harrell P.M., Trinh Y.T., Zhang Q., Urbatsch I.L., Chang G.
    Science 323:1718-1722(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) IN COMPLEXES WITH INHIBITORS, FUNCTION, TOPOLOGY.

Entry informationi

Entry nameiMDR1A_MOUSE
AccessioniPrimary (citable) accession number: P21447
Secondary accession number(s): Q5I1Y5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: June 16, 2009
Last modified: November 26, 2014
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

In mouse the MDR gene family includes three or more related but distinct cellular genes.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3