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P21447 (MDR1A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Abcb1a
Synonyms:Abcb4, Mdr1a, Mdr3, Pgy-3, Pgy3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length1276 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. Ref.8

Catalytic activity

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

Subunit structure

Interacts with PSMB5 By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Miscellaneous

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

Sequence similarities

Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily. [View classification]

Contains 2 ABC transmembrane type-1 domains.

Contains 2 ABC transporter domains.

Ontologies

Keywords
   Biological processTransport
   Cellular componentCell membrane
Membrane
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionHydrolase
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcircadian rhythm

Inferred from electronic annotation. Source: Compara

drug transport

Inferred from direct assay PubMed 11741934. Source: MGI

lactation

Inferred from electronic annotation. Source: Compara

negative regulation of cell death

Inferred from electronic annotation. Source: Compara

response to cadmium ion

Inferred from electronic annotation. Source: Compara

response to hypoxia

Inferred from electronic annotation. Source: Compara

response to vitamin D

Inferred from electronic annotation. Source: Compara

   Cellular_componentGolgi membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

apical plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral to membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

intercellular canaliculus

Inferred from direct assay PubMed 12068294. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ATPase activity, coupled to transmembrane movement of substances

Inferred from Biological aspect of Ancestor. Source: RefGenome

xenobiotic-transporting ATPase activity

Inferred from electronic annotation. Source: EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12761276Multidrug resistance protein 1A
PRO_0000093336

Regions

Topological domain1 – 4343Cytoplasmic By similarity
Transmembrane44 – 6623Helical
Topological domain67 – 11246Extracellular By similarity
Transmembrane113 – 13321Helical
Topological domain134 – 18249Cytoplasmic By similarity
Transmembrane183 – 20422Helical
Topological domain205 – 2117Extracellular By similarity
Transmembrane212 – 23221Helical
Topological domain233 – 29058Cytoplasmic By similarity
Transmembrane291 – 31222Helical
Topological domain313 – 32614Extracellular By similarity
Transmembrane327 – 34822Helical
Topological domain349 – 707359Cytoplasmic By similarity
Transmembrane708 – 72821Helical
Topological domain729 – 75224Extracellular By similarity
Transmembrane753 – 77321Helical
Topological domain774 – 82855Cytoplasmic By similarity
Transmembrane829 – 84921Helical
Topological domain8501Extracellular By similarity
Transmembrane851 – 87020Helical
Topological domain871 – 93060Cytoplasmic By similarity
Transmembrane931 – 95323Helical
Topological domain954 – 96916Extracellular By similarity
Transmembrane970 – 99122Helical
Topological domain992 – 1276285Cytoplasmic By similarity
Domain50 – 353304ABC transmembrane type-1 1
Domain388 – 624237ABC transporter 1
Domain707 – 996290ABC transmembrane type-1 2
Domain1031 – 1269239ABC transporter 2
Nucleotide binding423 – 4308ATP 1 By similarity
Nucleotide binding1066 – 10738ATP 2 By similarity

Amino acid modifications

Modified residue6671Phosphoserine Ref.7
Glycosylation831N-linked (GlcNAc...) Potential
Glycosylation871N-linked (GlcNAc...) Potential
Glycosylation901N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict526 – 5272QL → HV in AAA39514. Ref.2
Sequence conflict526 – 5272QL → HV in AAA03243. Ref.5
Sequence conflict9391S → F in AAA39517. Ref.1
Sequence conflict10361V → F in AAA39517. Ref.1

Secondary structure

1 ................................................................................................................................................................................... 1276
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P21447 [UniParc].

Last modified June 16, 2009. Version 3.
Checksum: 542E101DF18DDC52

FASTA1,276140,647
        10         20         30         40         50         60 
MELEEDLKGR ADKNFSKMGK KSKKEKKEKK PAVSVLTMFR YAGWLDRLYM LVGTLAAIIH 

        70         80         90        100        110        120 
GVALPLMMLI FGDMTDSFAS VGNVSKNSTN MSEADKRAMF AKLEEEMTTY AYYYTGIGAG 

       130        140        150        160        170        180 
VLIVAYIQVS FWCLAAGRQI HKIRQKFFHA IMNQEIGWFD VHDVGELNTR LTDDVSKINE 

       190        200        210        220        230        240 
GIGDKIGMFF QAMATFFGGF IIGFTRGWKL TLVILAISPV LGLSAGIWAK ILSSFTDKEL 

       250        260        270        280        290        300 
HAYAKAGAVA EEVLAAIRTV IAFGGQKKEL ERYNNNLEEA KRLGIKKAIT ANISMGAAFL 

       310        320        330        340        350        360 
LIYASYALAF WYGTSLVISK EYSIGQVLTV FFSVLIGAFS VGQASPNIEA FANARGAAYE 

       370        380        390        400        410        420 
VFKIIDNKPS IDSFSKSGHK PDNIQGNLEF KNIHFSYPSR KEVQILKGLN LKVKSGQTVA 

       430        440        450        460        470        480 
LVGNSGCGKS TTVQLMQRLY DPLDGMVSID GQDIRTINVR YLREIIGVVS QEPVLFATTI 

       490        500        510        520        530        540 
AENIRYGRED VTMDEIEKAV KEANAYDFIM KLPHQFDTLV GERGAQLSGG QKQRIAIARA 

       550        560        570        580        590        600 
LVRNPKILLL DEATSALDTE SEAVVQAALD KAREGRTTIV IAHRLSTVRN ADVIAGFDGG 

       610        620        630        640        650        660 
VIVEQGNHDE LMREKGIYFK LVMTQTAGNE IELGNEACKS KDEIDNLDMS SKDSGSSLIR 

       670        680        690        700        710        720 
RRSTRKSICG PHDQDRKLST KEALDEDVPP ASFWRILKLN STEWPYFVVG IFCAIINGGL 

       730        740        750        760        770        780 
QPAFSVIFSK VVGVFTNGGP PETQRQNSNL FSLLFLILGI ISFITFFLQG FTFGKAGEIL 

       790        800        810        820        830        840 
TKRLRYMVFK SMLRQDVSWF DDPKNTTGAL TTRLANDAAQ VKGATGSRLA VIFQNIANLG 

       850        860        870        880        890        900 
TGIIISLIYG WQLTLLLLAI VPIIAIAGVV EMKMLSGQAL KDKKELEGSG KIATEAIENF 

       910        920        930        940        950        960 
RTVVSLTREQ KFETMYAQSL QIPYRNAMKK AHVFGITFSF TQAMMYFSYA ACFRFGAYLV 

       970        980        990       1000       1010       1020 
TQQLMTFENV LLVFSAIVFG AMAVGQVSSF APDYAKATVS ASHIIRIIEK TPEIDSYSTQ 

      1030       1040       1050       1060       1070       1080 
GLKPNMLEGN VQFSGVVFNY PTRPSIPVLQ GLSLEVKKGQ TLALVGSSGC GKSTVVQLLE 

      1090       1100       1110       1120       1130       1140 
RFYDPMAGSV FLDGKEIKQL NVQWLRAQLG IVSQEPILFD CSIAENIAYG DNSRVVSYEE 

      1150       1160       1170       1180       1190       1200 
IVRAAKEANI HQFIDSLPDK YNTRVGDKGT QLSGGQKQRI AIARALVRQP HILLLDEATS 

      1210       1220       1230       1240       1250       1260 
ALDTESEKVV QEALDKAREG RTCIVIAHRL STIQNADLIV VIQNGKVKEH GTHQQLLAQK 

      1270 
GIYFSMVSVQ AGAKRS

« Hide

References

« Hide 'large scale' references
[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, MASS SPECTROMETRY.
Strain: OF1.
Tissue: Hippocampus.
[7]"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry."
Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M.
J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667, MASS SPECTROMETRY.
Tissue: Melanoma.
[8]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		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.
IPIIPI00311780.
PIRDVMS1A. A34175.
A34786.
RefSeqNP_035206.2. NM_011076.2.
UniGeneMm.207354.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3G5UX-ray3.80A/B1-1276[»]
3G60X-ray4.40A/B1-1276[»]
3G61X-ray4.35A/B1-1276[»]
ProteinModelPortalP21447.
ModBaseSearch...

PTM databases

PhosphoSiteP21447.

Proteomic databases

PaxDbP21447.
PRIDEP21447.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000047753; ENSMUSP00000041204; ENSMUSG00000040584.
GeneID18671.
KEGGmmu:18671.
UCSCuc008wkl.1. mouse.

Organism-specific databases

CTD18671.
MGIMGI:97570. Abcb1a.

Phylogenomic databases

eggNOGCOG1132.
GeneTreeENSGT00530000062896.
HOVERGENHBG080809.
InParanoidQ5I1Y5.
KOK05658.
OMAEQKFENM.
OrthoDBEOG42FSGR.

Enzyme and pathway databases

ReactomeREACT_112621. Metabolism.

Gene expression databases

ArrayExpressP21447.
BgeeP21447.
GenevestigatorP21447.
GermOnlineENSMUSG00000040584. Mus musculus.

Family and domain databases

InterProIPR003593. AAA+_ATPase.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR017940. ABC_transporter_type1.
IPR001140. ABC_transptr_TM_dom.
IPR011527. ABC_transptrTM_dom_typ1.
[Graphical view]
PfamPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
[Graphical view]
SMARTSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMSSF90123. ABC_TM_1. 2 hits.
PROSITEPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 2 hits.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

BindingDBP21447.
ChEMBLCHEMBL2573.
EvolutionaryTraceP21447.
NextBio294686.
SOURCESearch...

Entry information

Entry nameMDR1A_MOUSE
AccessionPrimary (citable) accession number: P21447
Secondary accession number(s): Q5I1Y5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: June 16, 2009
Last modified: April 3, 2013
This is version 118 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents