P21440 · MDR3_MOUSE

  • Protein
    Phosphatidylcholine translocator ABCB4
  • Gene
    Abcb4
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi between hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:7592705, PubMed:7814632, PubMed:7912658, PubMed:8106172, PubMed:8725158, PubMed:9366571).
Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (By similarity).
Required for proper phospholipid bile formation (PubMed:8106172).
Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:7814632, PubMed:8725158).
May promote biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:9366571).
In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390).
Does not confer multidrug resistance (PubMed:1990275).

Catalytic activity

Activity regulation

Translocation activity is inhibited by the ATPase inhibitor vanadate and the calcium channel blocker verapamil (PubMed:7912658).
Translocation activity is enhanced by the addition of the bile salt taurocholate (PubMed:7592705).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site403ATP 1 (UniProtKB | ChEBI)
Binding site429-434ATP 1 (UniProtKB | ChEBI)
Binding site474ATP 1 (UniProtKB | ChEBI)
Binding site533ATP 2 (UniProtKB | ChEBI)
Binding site1043ATP 2 (UniProtKB | ChEBI)
Binding site1068-1074ATP 2 (UniProtKB | ChEBI)
Binding site1114ATP 2 (UniProtKB | ChEBI)
Binding site1174-1176ATP 1 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentclathrin-coated vesicle
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentfocal adhesion
Cellular ComponentGolgi membrane
Cellular Componentintercellular canaliculus
Cellular Componentmembrane
Cellular Componentmembrane raft
Cellular Componentnucleoplasm
Cellular Componentplasma membrane
Molecular FunctionABC-type transporter activity
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular FunctionATPase-coupled transmembrane transporter activity
Molecular Functionphosphatidylcholine floppase activity
Biological Processbile acid secretion
Biological Processcellular response to bile acid
Biological Processlipid homeostasis
Biological Processphospholipid translocation
Biological Processpositive regulation of cholesterol transport
Biological Processpositive regulation of phospholipid translocation
Biological Processpositive regulation of phospholipid transport
Biological Processresponse to fenofibrate

Keywords

Enzyme and pathway databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    Phosphatidylcholine translocator ABCB4
  • EC number
  • Alternative names
    • ATP-binding cassette sub-family B member 4
    • Multidrug resistance protein 2
    • Multidrug resistance protein 3
    • P-glycoprotein 2
    • P-glycoprotein 3

Gene names

    • Name
      Abcb4
    • Synonyms
      Mdr2
      , Pgy-2, Pgy2

Organism names

  • Taxonomic identifier
  • Strain
    • BALB/cJ
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P21440
  • Secondary accessions
    • B9EK77
    • Q6LCL9

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Apical cell membrane
; Multi-pass membrane protein
Membrane raft
Cytoplasm
Note: Transported from the Golgi to the apical bile canalicular membrane in a RACK1-dependent manner. Redistributed into pseudocanaliculi formed between cells in a bezafibrate- or PPARA-dependent manner (By similarity).
Localized at the apical canalicular membrane of the epithelial cells lining the lumen of the bile canaliculi and biliary ductules (PubMed:1381362, PubMed:8106172, PubMed:8615769).
Localized preferentially in lipid nonraft domains of canalicular plasma membranes (PubMed:23468132).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-47Cytoplasmic
Transmembrane48-70Helical
Topological domain71-115Extracellular
Transmembrane116-136Helical
Topological domain137-185Cytoplasmic
Transmembrane186-207Helical
Topological domain208-212Extracellular
Transmembrane213-235Helical
Topological domain236-293Cytoplasmic
Transmembrane294-315Helical
Topological domain316-329Extracellular
Transmembrane330-351Helical
Topological domain352-708Cytoplasmic
Transmembrane709-729Helical
Topological domain730-752Extracellular
Transmembrane753-773Helical
Topological domain774-828Cytoplasmic
Transmembrane829-849Helical
Topological domain850Extracellular
Transmembrane851-870Helical
Topological domain871-930Cytoplasmic
Transmembrane931-953Helical
Topological domain954-969Extracellular
Transmembrane970-991Helical
Topological domain992-1276Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Mice show severe necrotic damage of hepatocytes, strong portal inflammation, proliferation and destruction of the canalicular and small bile ductular tracts (PubMed:8106172).
Display almost complete reduction of biliary phospholipid secretion, although bile salt secretion is normal (PubMed:7814632, PubMed:8106172, PubMed:8725158, PubMed:9366571).
Show also reduced cholesterol secretion (PubMed:8106172, PubMed:9366571).
Knockout mice lacking both ABCB4 and ATP8B1 show lower hepatic damage compared with the single ABCB4 knockout mice (PubMed:21820390).
Display equivalent reduction of biliary phosphatidylcholine (PC) secretion as the single ABCB4 knockout mice (PubMed:21820390).
Biliary cholesterol secretion is higher compared to the single ABCB4 knockout mice (PubMed:21820390).
Bile salt secretion is normal in both single ABCB4 knockout mice and double ABCB4 and ATP8B1 knockout mice (PubMed:21820390).
Biliary excretion of canalicular ectoenzymes, aminopeptidase N and alkaline phosphatase is strongly reduced compared to single ATP8B1 knockout mice (PubMed:21820390).

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 50 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00000933371-1276Phosphatidylcholine translocator ABCB4
Modified residue24Phosphoserine
Glycosylation88N-linked (GlcNAc...) asparagine
Glycosylation94N-linked (GlcNAc...) asparagine

Post-translational modification

Phosphorylated. Phosphorylation is required for PC efflux activity. Phosphorylation occurs on serine and threonine residues in a protein kinase A- or C-dependent manner. May be phosphorylated on Thr-41 and Ser-46.
Glycosylated.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in the liver (PubMed:1381362, PubMed:8615769) (at protein level). Expressed in adrenal, liver, muscle, spleen and heart (PubMed:2471060).
Expressed in multidrug-resistant cell lines (PubMed:1969609).

Induction

Up-regulated by compounds that cause peroxisome proliferation, such as ciprofibrate and clofibrate (at protein level) (PubMed:8615769).
Up-regulated by compounds that cause peroxisome proliferation, such as fenofibrate, ciprofibrate, clofibrate, bezafibrate and gemfibrozil (PubMed:12381268, PubMed:8615769).

Gene expression databases

Interaction

Subunit

May interact with RACK1. Interacts with HAX1.

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain54-356ABC transmembrane type-1 1
Domain391-627ABC transporter 1
Region622-646Interaction with HAX1
Domain708-996ABC transmembrane type-1 2
Domain1031-1269ABC transporter 2

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,276
  • Mass (Da)
    140,377
  • Last updated
    2011-06-28 v2
  • Checksum
    30BC72EDDFA4388C
MDLEAARNGTARRLDGDFELGSISNQGREKKKKVNLIGLLTLFRYSDWQDKLFMFLGTLMAIAHGSGLPLMMIVFGEMTDKFVDNTGNFSLPVNFSLSMLNPGRILEEEMTRYAYYYSGLGGGVLVAAYIQVSFWTLAAGRQIKKIRQKFFHAILRQEMGWFDIKGTTELNTRLTDDVSKISEGIGDKVGMFFQAIATFFAGFIVGFIRGWKLTLVIMAISPILGLSTAVWAKILSTFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKKIGIKKAISANISMGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANARGAAYVIFDIIDNNPKIDSFSERGHKPDNIKGNLEFSDVHFSYPSRANIKILKGLNLKVKSGQTVALVGNSGCGKSTTVQLLQRLYDPTEGKISIDGQDIRNFNVRCLREIIGVVSQEPVLFSTTIAENIRYGRGNVTMDEIEKAVKEANAYDFIMKLPQKFDTLVGDRGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTIRNADVIAGFEDGVIVEQGSHSELMKKEGIYFRLVNMQTAGSQILSEEFEVELSDEKAAGDVAPNGWKARIFRNSTKKSLKSPHQNRLDEETNELDANVPPVSFLKVLKLNKTEWPYFVVGTVCAIANGALQPAFSIILSEMIAIFGPGDDAVKQQKCNMFSLVFLGLGVLSFFTFFLQGFTFGKAGEILTTRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNTANLGTGIIISFIYGWQLTLLLLSVVPFIAVAGIVEMKMLAGNAKRDKKEMEAAGKIATEAIENIRTVVSLTQERKFESMYVEKLHGPYRNSVRKAHIYGITFSISQAFMYFSYAGCFRFGSYLIVNGHMRFKDVILVFSAIVLGAVALGHASSFAPDYAKAKLSAAYLFSLFERQPLIDSYSGEGLWPDKFEGSVTFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPMAGSVLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYGDNSRVVPHDEIVRAAKEANIHPFIETLPQKYNTRVGDKGTQLSGGQKQRIAIARALIRQPRVLLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVIENGKVKEHGTHQQLLAQKGIYFSMVNIQAGTQNL

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0G2JDM4A0A0G2JDM4_MOUSEAbcb4882

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict257in Ref. 1; AAA39516
Sequence conflict828in Ref. 1; AAA39516

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
J03398
EMBL· GenBank· DDBJ
AAA39516.1
EMBL· GenBank· DDBJ
mRNA
CH466600
EMBL· GenBank· DDBJ
EDL14681.1
EMBL· GenBank· DDBJ
Genomic DNA
BC150687
EMBL· GenBank· DDBJ
AAI50688.1
EMBL· GenBank· DDBJ
mRNA
M74151
EMBL· GenBank· DDBJ
AAA39515.1
EMBL· GenBank· DDBJ
Genomic DNA
U46839
EMBL· GenBank· DDBJ
AAC52722.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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