Phosphatidylcholine translocator ABCB4

Details

Name
Phosphatidylcholine translocator ABCB4
Synonyms
  • ATP-binding cassette sub-family B member 4
  • MDR3
  • Multidrug resistance protein 3
  • P-glycoprotein 3
  • PGY3
Gene Name
ABCB4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006998|Phosphatidylcholine translocator ABCB4
MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLG
TIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYY
SGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDD
ISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSA
FSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANIS
MGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANA
RGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQ
SGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPV
LFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQR
IAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVI
AGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKS
RLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIA
NGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAG
EILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIA
NLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAI
ENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGA
YLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSY
SEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQ
LLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYG
DNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQP
QILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEH
GTHQQLLAQKGIYFSMVSVQAGTQNL
Number of residues
1286
Molecular Weight
141521.845
Theoretical pI
8.74
GO Classification
Functions
ATP binding / ATPase activity, coupled to transmembrane movement of substances / phosphatidylcholine transporter activity / phosphatidylcholine-translocating ATPase activity / xenobiotic-transporting ATPase activity
Processes
bile acid secretion / cellular lipid metabolic process / cellular response to bile acid / lipid homeostasis / lipid metabolic process / phospholipid translocation / positive regulation of cholesterol transport / positive regulation of phospholipid translocation / positive regulation of phospholipid transport / response to drug / response to fenofibrate / small molecule metabolic process / transmembrane transport / transport
Components
apical plasma membrane / clathrin-coated vesicle / cytoplasm / extracellular exosome / integral component of plasma membrane / intercellular canaliculus / membrane / membrane raft / plasma membrane
General Function
Xenobiotic-transporting atpase activity
Specific 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 of 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:7957936, PubMed:8898203, PubMed:9366571, PubMed:17523162, PubMed:23468132, PubMed:24806754, PubMed:24723470, PubMed:24594635, PubMed:21820390). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to fu rther enrichment of SM and cholesterol in raft membranes in hepatocytes (PubMed:23468132). Required for proper phospholipid bile formation (By similarity). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:24045840). 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 (By similarity).
Pfam Domain Function
Transmembrane Regions
51-73 119-139 189-210 218-238 297-318 333-354 712-732 756-776 832-852 854-873 934-956 973-994
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020704|Phosphatidylcholine translocator ABCB4 (ABCB4)
ATGGATCTTGAGGCGGCAAAGAACGGAACAGCCTGGCGCCCCACGAGCGCGGAGGGCGAC
TTTGAACTGGGCATCAGCAGCAAACAAAAAAGGAAAAAAACGAAGACAGTGAAAATGATT
GGAGTATTAACATTGTTTCGATACTCCGATTGGCAGGATAAATTGTTTATGTCGCTGGGT
ACCATCATGGCCATAGCTCACGGATCAGGTCTCCCCCTCATGATGATAGTATTTGGAGAG
ATGACTGACAAATTTGTTGATACTGCAGGAAACTTCTCCTTTCCAGTGAACTTTTCCTTG
TCGCTGCTAAATCCAGGCAAAATTCTGGAAGAAGAAATGACTAGATATGCATATTACTAC
TCAGGATTGGGTGCTGGAGTTCTTGTTGCTGCCTATATACAAGTTTCATTTTGGACTTTG
GCAGCTGGTCGACAGATCAGGAAAATTAGGCAGAAGTTTTTTCATGCTATTCTACGACAG
GAAATAGGATGGTTTGACATCAACGACACCACTGAACTCAATACGCGGCTAACAGATGAC
ATCTCCAAAATCAGTGAAGGAATTGGTGACAAGGTTGGAATGTTCTTTCAAGCAGTAGCC
ACGTTTTTTGCAGGATTCATAGTGGGATTCATCAGAGGATGGAAGCTCACCCTTGTGATA
ATGGCCATCAGCCCTATTCTAGGACTCTCTGCAGCCGTTTGGGCAAAGATACTCTCGGCA
TTTAGTGACAAAGAACTAGCTGCTTATGCAAAAGCAGGCGCCGTGGCAGAAGAGGCTCTG
GGGGCCATCAGGACTGTGATAGCTTTCGGGGGCCAGAACAAAGAGCTGGAAAGGTATCAG
AAACATTTAGAAAATGCCAAAGAGATTGGAATTAAAAAAGCTATTTCAGCAAACATTTCC
ATGGGTATTGCCTTCCTGTTAATATATGCATCATATGCACTGGCCTTCTGGTATGGATCC
ACTCTAGTCATATCAAAAGAATATACTATTGGAAATGCAATGACAGTTTTTTTTTCAATC
CTAATTGGAGCTTTCAGTGTTGGCCAGGCTGCCCCATGTATTGATGCTTTTGCCAATGCA
AGAGGAGCAGCATATGTGATCTTTGATATTATTGATAATAATCCTAAAATTGACAGTTTT
TCAGAGAGAGGACACAAACCAGACAGCATCAAAGGGAATTTGGAGTTCAATGATGTTCAC
TTTTCTTACCCTTCTCGAGCTAACGTCAAGATCTTGAAGGGCCTCAACCTGAAGGTGCAG
AGTGGGCAGACGGTGGCCCTGGTTGGAAGTAGTGGCTGTGGGAAGAGCACAACGGTCCAG
CTGATACAGAGGCTCTATGACCCTGATGAGGGCACAATTAACATTGATGGGCAGGATATT
AGGAACTTTAATGTAAACTATCTGAGGGAAATCATTGGTGTGGTGAGTCAGGAGCCGGTG
CTGTTTTCCACCACAATTGCTGAAAATATTTGTTATGGCCGTGGAAATGTAACCATGGAT
GAGATAAAGAAAGCTGTCAAAGAGGCCAACGCCTATGAGTTTATCATGAAATTACCACAG
AAATTTGACACCCTGGTTGGAGAGAGAGGGGCCCAGCTGAGTGGTGGGCAGAAGCAGAGG
ATCGCCATTGCACGTGCCCTGGTTCGCAACCCCAAGATCCTTCTGCTGGATGAGGCCACG
TCAGCATTGGACACAGAAAGTGAAGCTGAGGTACAGGCAGCTCTGGATAAGGCCAGAGAA
GGCCGGACCACCATTGTGATAGCACACCGACTGTCTACGGTCCGAAATGCAGATGTCATC
GCTGGGTTTGAGGATGGAGTAATTGTGGAGCAAGGAAGCCACAGCGAACTGATGAAGAAG
GAAGGGGTGTACTTCAAACTTGTCAACATGCAGACATCAGGAAGCCAGATCCAGTCAGAA
GAATTTGAACTAAATGATGAAAAGGCTGCCACTAGAATGGCCCCAAATGGCTGGAAATCT
CGCCTATTTAGGCATTCTACTCAGAAAAACCTTAAAAATTCACAAATGTGTCAGAAGAGC
CTTGATGTGGAAACCGATGGACTTGAAGCAAATGTGCCACCAGTGTCCTTTCTGAAGGTC
CTGAAACTGAATAAAACAGAATGGCCCTACTTTGTCGTGGGAACAGTATGTGCCATTGCC
AATGGGGGGCTTCAGCCGGCATTTTCAGTCATATTCTCAGAGATCATAGCGATTTTTGGA
CCAGGCGATGATGCAGTGAAGCAGCAGAAGTGCAACATATTCTCTTTGATTTTCTTATTT
CTGGGAATTATTTCTTTTTTTACTTTCTTCCTTCAGGGTTTCACGTTTGGGAAAGCTGGC
GAGATCCTCACCAGAAGACTGCGGTCAATGGCTTTTAAAGCAATGCTAAGACAGGACATG
AGCTGGTTTGATGACCATAAAAACAGTACTGGTGCACTTTCTACAAGACTTGCCACAGAT
GCTGCCCAAGTCCAAGGAGCCACAGGAACCAGGTTGGCTTTAATTGCACAGAATATAGCT
AACCTTGGAACTGGTATTATCATATCATTTATCTACGGTTGGCAGTTAACCCTATTGCTA
TTAGCAGTTGTTCCAATTATTGCTGTGTCAGGAATTGTTGAAATGAAATTGTTGGCTGGA
AATGCCAAAAGAGATAAAAAAGAACTGGAAGCTGCTGGAAAGATTGCAACAGAGGCAATA
GAAAATATTAGGACAGTTGTGTCTTTGACCCAGGAAAGAAAATTTGAATCAATGTATGTT
GAAAAATTGTATGGACCTTACAGGAATTCTGTGCAGAAGGCACACATCTATGGAATTACT
TTTAGTATCTCACAAGCATTTATGTATTTTTCCTATGCCGGTTGTTTTCGATTTGGTGCA
TATCTCATTGTGAATGGACATATGCGCTTCAGAGATGTTATTCTGGTGTTTTCTGCAATT
GTATTTGGTGCAGTGGCTCTAGGACATGCCAGTTCATTTGCTCCAGACTATGCTAAAGCT
AAGCTGTCTGCAGCCCACTTATTCATGCTGTTTGAAAGACAACCTCTGATTGACAGCTAC
AGTGAAGAGGGGCTGAAGCCTGATAAATTTGAAGGAAATATAACATTTAATGAAGTCGTG
TTCAACTATCCCACCCGAGCAAACGTGCCAGTGCTTCAGGGGCTGAGCCTGGAGGTGAAG
AAAGGCCAGACACTAGCCCTGGTGGGCAGCAGTGGCTGTGGGAAGAGCACGGTGGTCCAG
CTCCTGGAGCGGTTCTACGACCCCTTGGCGGGGACAGTGCTTCTCGATGGTCAAGAAGCA
AAGAAACTCAATGTCCAGTGGCTCAGAGCTCAACTCGGAATCGTGTCTCAGGAGCCTATC
CTATTTGACTGCAGCATTGCCGAGAATATTGCCTATGGAGACAACAGCCGGGTTGTATCA
CAGGATGAAATTGTGAGTGCAGCCAAAGCTGCCAACATACATCCTTTCATCGAGACGTTA
CCCCACAAATATGAAACAAGAGTGGGAGATAAGGGGACTCAGCTCTCAGGAGGTCAAAAA
CAGAGGATTGCTATTGCCCGAGCCCTCATCAGACAACCTCAAATCCTCCTGTTGGATGAA
GCTACATCAGCTCTGGATACTGAAAGTGAAAAGGTTGTCCAAGAAGCCCTGGACAAAGCC
AGAGAAGGCCGCACCTGCATTGTGATTGCTCACCGCCTGTCCACCATCCAGAATGCAGAC
TTAATAGTGGTGTTTCAGAATGGGAGAGTCAAGGAGCATGGCACGCATCAGCAGCTGCTG
GCACAGAAAGGCATCTATTTTTCAATGGTCAGTGTCCAGGCTGGGACACAGAACTTATGA
Chromosome Location
7
Locus
7q21.1
External Identifiers
ResourceLink
UniProtKB IDP21439
UniProtKB Entry NameMDR3_HUMAN
GenBank Protein ID307181
GenBank Gene IDM23234
HGNC IDHGNC:45
General References
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  8. van Helvoort A, Smith AJ, Sprong H, Fritzsche I, Schinkel AH, Borst P, van Meer G: MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell. 1996 Nov 1;87(3):507-17. [PubMed:8898203]
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  15. Morita SY, Tsuda T, Horikami M, Teraoka R, Kitagawa S, Terada T: Bile salt-stimulated phospholipid efflux mediated by ABCB4 localized in nonraft membranes. J Lipid Res. 2013 May;54(5):1221-30. doi: 10.1194/jlr.M032425. Epub 2013 Mar 6. [PubMed:23468132]
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  31. Poupon R, Rosmorduc O, Boelle PY, Chretien Y, Corpechot C, Chazouilleres O, Housset C, Barbu V: Genotype-phenotype relationships in the low-phospholipid-associated cholelithiasis syndrome: a study of 156 consecutive patients. Hepatology. 2013 Sep;58(3):1105-10. doi: 10.1002/hep.26424. Epub 2013 Jul 29. [PubMed:23533021]
  32. Degiorgio D, Corsetto PA, Rizzo AM, Colombo C, Seia M, Costantino L, Montorfano G, Tomaiuolo R, Bordo D, Sansanelli S, Li M, Tavian D, Rastaldi MP, Coviello DA: Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein targeting to the plasma membrane but promote MDR3 dysfunction. Eur J Hum Genet. 2014 May;22(5):633-9. doi: 10.1038/ejhg.2013.214. Epub 2013 Sep 18. [PubMed:24045840]
  33. Gautherot J, Delautier D, Maubert MA, Ait-Slimane T, Bolbach G, Delaunay JL, Durand-Schneider AM, Firrincieli D, Barbu V, Chignard N, Housset C, Maurice M, Falguieres T: Phosphorylation of ABCB4 impacts its function: insights from disease-causing mutations. Hepatology. 2014 Aug;60(2):610-21. doi: 10.1002/hep.27170. Epub 2014 May 19. [PubMed:24723470]
  34. Gordo-Gilart R, Andueza S, Hierro L, Martinez-Fernandez P, D'Agostino D, Jara P, Alvarez L: Functional analysis of ABCB4 mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity. Gut. 2015 Jan;64(1):147-55. doi: 10.1136/gutjnl-2014-306896. Epub 2014 Mar 4. [PubMed:24594635]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06207SilodosinapprovedunknownsubstrateDetails
DB06414EtravirineapprovedunknowninhibitorDetails