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P21447

- MDR1A_MOUSE

UniProt

P21447 - MDR1A_MOUSE

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Protein
Multidrug resistance protein 1A
Gene
Abcb1a, Abcb4, Mdr1a, Mdr3, Pgy-3, Pgy3
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 1 By similarity
Nucleotide bindingi1066 – 10738ATP 2 By similarity

GO - Molecular functioni

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

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 – 4343Cytoplasmic By similarity
Add
BLAST
Transmembranei44 – 6623Helical
Add
BLAST
Topological domaini67 – 11246Extracellular By similarity
Add
BLAST
Transmembranei113 – 13321Helical
Add
BLAST
Topological domaini134 – 18249Cytoplasmic By similarity
Add
BLAST
Transmembranei183 – 20422Helical
Add
BLAST
Topological domaini205 – 2117Extracellular By similarity
Transmembranei212 – 23221Helical
Add
BLAST
Topological domaini233 – 29058Cytoplasmic By similarity
Add
BLAST
Transmembranei291 – 31222Helical
Add
BLAST
Topological domaini313 – 32614Extracellular By similarity
Add
BLAST
Transmembranei327 – 34822Helical
Add
BLAST
Topological domaini349 – 707359Cytoplasmic By similarity
Add
BLAST
Transmembranei708 – 72821Helical
Add
BLAST
Topological domaini729 – 75224Extracellular By similarity
Add
BLAST
Transmembranei753 – 77321Helical
Add
BLAST
Topological domaini774 – 82855Cytoplasmic By similarity
Add
BLAST
Transmembranei829 – 84921Helical
Add
BLAST
Topological domaini850 – 8501Extracellular By similarity
Transmembranei851 – 87020Helical
Add
BLAST
Topological domaini871 – 93060Cytoplasmic By similarity
Add
BLAST
Transmembranei931 – 95323Helical
Add
BLAST
Topological domaini954 – 96916Extracellular By similarity
Add
BLAST
Transmembranei970 – 99122Helical
Add
BLAST
Topological domaini992 – 1276285Cytoplasmic By similarity
Add
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 1A
PRO_0000093336Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP21447.
PaxDbiP21447.
PRIDEiP21447.

PTM databases

PhosphoSiteiP21447.

Expressioni

Gene expression databases

ArrayExpressiP21447.
BgeeiP21447.
GenevestigatoriP21447.

Interactioni

Subunit structurei

Interacts with PSMB5 By similarity.

Protein-protein interaction databases

IntActiP21447. 1 interaction.
MINTiMINT-4101695.

Structurei

Secondary structure

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:
PDBe
RCSB PDB
PDBj
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.

Miscellaneous databases

EvolutionaryTraceiP21447.

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1132.
GeneTreeiENSGT00530000062896.
HOVERGENiHBG080809.
InParanoidiQ5I1Y5.
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

MELEEDLKGR ADKNFSKMGK KSKKEKKEKK PAVSVLTMFR YAGWLDRLYM     50
LVGTLAAIIH GVALPLMMLI FGDMTDSFAS VGNVSKNSTN MSEADKRAMF 100
AKLEEEMTTY AYYYTGIGAG VLIVAYIQVS FWCLAAGRQI HKIRQKFFHA 150
IMNQEIGWFD VHDVGELNTR LTDDVSKINE GIGDKIGMFF QAMATFFGGF 200
IIGFTRGWKL TLVILAISPV LGLSAGIWAK ILSSFTDKEL HAYAKAGAVA 250
EEVLAAIRTV IAFGGQKKEL ERYNNNLEEA KRLGIKKAIT ANISMGAAFL 300
LIYASYALAF WYGTSLVISK EYSIGQVLTV FFSVLIGAFS VGQASPNIEA 350
FANARGAAYE VFKIIDNKPS IDSFSKSGHK PDNIQGNLEF KNIHFSYPSR 400
KEVQILKGLN LKVKSGQTVA LVGNSGCGKS TTVQLMQRLY DPLDGMVSID 450
GQDIRTINVR YLREIIGVVS QEPVLFATTI AENIRYGRED VTMDEIEKAV 500
KEANAYDFIM KLPHQFDTLV GERGAQLSGG QKQRIAIARA LVRNPKILLL 550
DEATSALDTE SEAVVQAALD KAREGRTTIV IAHRLSTVRN ADVIAGFDGG 600
VIVEQGNHDE LMREKGIYFK LVMTQTAGNE IELGNEACKS KDEIDNLDMS 650
SKDSGSSLIR RRSTRKSICG PHDQDRKLST KEALDEDVPP ASFWRILKLN 700
STEWPYFVVG IFCAIINGGL QPAFSVIFSK VVGVFTNGGP PETQRQNSNL 750
FSLLFLILGI ISFITFFLQG FTFGKAGEIL TKRLRYMVFK SMLRQDVSWF 800
DDPKNTTGAL TTRLANDAAQ VKGATGSRLA VIFQNIANLG TGIIISLIYG 850
WQLTLLLLAI VPIIAIAGVV EMKMLSGQAL KDKKELEGSG KIATEAIENF 900
RTVVSLTREQ KFETMYAQSL QIPYRNAMKK AHVFGITFSF TQAMMYFSYA 950
ACFRFGAYLV TQQLMTFENV LLVFSAIVFG AMAVGQVSSF APDYAKATVS 1000
ASHIIRIIEK TPEIDSYSTQ GLKPNMLEGN VQFSGVVFNY PTRPSIPVLQ 1050
GLSLEVKKGQ TLALVGSSGC GKSTVVQLLE RFYDPMAGSV FLDGKEIKQL 1100
NVQWLRAQLG IVSQEPILFD CSIAENIAYG DNSRVVSYEE IVRAAKEANI 1150
HQFIDSLPDK YNTRVGDKGT QLSGGQKQRI AIARALVRQP HILLLDEATS 1200
ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VIQNGKVKEH 1250
GTHQQLLAQK GIYFSMVSVQ AGAKRS 1276
Length:1,276
Mass (Da):140,647
Last modified:June 16, 2009 - v3
Checksum:i542E101DF18DDC52
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti526 – 5272QL → HV in AAA39514. 1 Publication
Sequence conflicti526 – 5272QL → HV in AAA03243. 1 Publication
Sequence conflicti939 – 9391S → F in AAA39517. 1 Publication
Sequence conflicti1036 – 10361V → F in AAA39517. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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:
PDBe
RCSB PDB
PDBj
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 Q5I1Y5.
KOi K05658.
OMAi FWALISV.
OrthoDBi EOG7Z3F4H.
PhylomeDBi P21447.
TreeFami TF105193.

Enzyme and pathway databases

Reactomei REACT_196555. Abacavir transmembrane transport.

Miscellaneous databases

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

Gene expression databases

ArrayExpressi P21447.
Bgeei P21447.
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: September 3, 2014
This is version 130 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

Similar proteinsi