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Identification
HMDB Protein ID HMDBP01901
Secondary Accession Numbers
  • 7307
  • HMDBP04199
Name Multidrug resistance protein 3
Synonyms
  1. ATP-binding cassette sub-family B member 4
  2. P-glycoprotein 3
Gene Name ABCB4
Protein Type Transporter
Biological Properties
General Function Involved in ATP binding
Specific Function Mediates ATP-dependent export of organic anions and drugs from the cytoplasm. Hydrolyzes ATP with low efficiency. Human MDR3 is not capable of conferring drug resistance. Mediates the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
active transmembrane transporter activity
primary active transmembrane transporter activity
p-p-bond-hydrolysis-driven transmembrane transporter activity
atpase activity, coupled to transmembrane movement of substances
binding
nucleotide binding
catalytic activity
hydrolase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
transmembrane transporter activity
atpase activity
transporter activity
nucleoside-triphosphatase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
Process
establishment of localization
transport
transmembrane transport
Cellular Location
  1. Cell membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:7
Locus 7q21.1
SNPs ABCB4
Gene Sequence
>3861 bp
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
CTCCTGGAGCGGTTCTACGACCCCTTGGCGGGGACAGTGTTTGTGGACTTTGGTTTTCAG
CTTCTCGATGGTCAAGAAGCAAAGAAACTCAATGTCCAGTGGCTCAGAGCTCAACTCGGA
ATCGTGTCTCAGGAGCCTATCCTATTTGACTGCAGCATTGCCGAGAATATTGCCTATGGA
GACAACAGCCGGGTTGTATCACAGGATGAAATTGTGAGTGCAGCCAAAGCTGCCAACATA
CATCCTTTCATCGAGACGTTACCCCACAAATATGAAACAAGAGTGGGAGATAAGGGGACT
CAGCTCTCAGGAGGTCAAAAACAGAGGATTGCTATTGCCCGAGCCCTCATCAGACAACCT
CAAATCCTCCTGTTGGATGAAGCTACATCAGCTCTGGATACTGAAAGTGAAAAGGTTGTC
CAAGAAGCCCTGGACAAAGCCAGAGAAGGCCGCACCTGCATTGTGATTGCTCACCGCCTG
TCCACCATCCAGAATGCAGACTTAATAGTGGTGTTTCAGAATGGGAGAGTCAAGGAGCAT
GGCACGCATCAGCAGCTGCTGGCACAGAAAGGCATCTATTTTTCAATGGTCAGTGTCCAG
GCTGGGACACAGAACTTATGA
Protein Properties
Number of Residues 1286
Molecular Weight 141521.8
Theoretical pI 8.74
Pfam Domain Function
Signals
  • None
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
Protein Sequence
>Multidrug resistance protein 3
MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLG
TIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYY
SGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDD
ISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSA
FSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANIS
MGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANA
RGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQ
SGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPV
LFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQR
IAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVI
AGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKS
RLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIA
NGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAG
EILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIA
NLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAI
ENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGA
YLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSY
SEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQ
LLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYG
DNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQP
QILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEH
GTHQQLLAQKGIYFSMVSVQAGTQNL
GenBank ID Protein 9961250
UniProtKB/Swiss-Prot ID P21439
UniProtKB/Swiss-Prot Entry Name MDR3_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_018849.2
GeneCard ID ABCB4
GenAtlas ID ABCB4
HGNC ID HGNC:45
References
General References
  1. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. [PubMed:12690205 ]
  2. van der Bliek AM, Kooiman PM, Schneider C, Borst P: Sequence of mdr3 cDNA encoding a human P-glycoprotein. Gene. 1988 Nov 30;71(2):401-11. [PubMed:2906314 ]
  3. Smit JJ, Mol CA, van Deemter L, Wagenaar E, Schinkel AH, Borst P: Characterization of the promoter region of the human MDR3 P-glycoprotein gene. Biochim Biophys Acta. 1995 Mar 14;1261(1):44-56. [PubMed:7893760 ]
  4. Van der Bliek AM, Baas F, Ten Houte de Lange T, Kooiman PM, Van der Velde-Koerts T, Borst P: The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver. EMBO J. 1987 Nov;6(11):3325-31. [PubMed:2892668 ]
  5. Lincke CR, Smit JJ, van der Velde-Koerts T, Borst P: Structure of the human MDR3 gene and physical mapping of the human MDR locus. J Biol Chem. 1991 Mar 15;266(8):5303-10. [PubMed:2002063 ]
  6. de Vree JM, Jacquemin E, Sturm E, Cresteil D, Bosma PJ, Aten J, Deleuze JF, Desrochers M, Burdelski M, Bernard O, Oude Elferink RP, Hadchouel M: Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):282-7. [PubMed:9419367 ]
  7. Dixon PH, Weerasekera N, Linton KJ, Donaldson O, Chambers J, Egginton E, Weaver J, Nelson-Piercy C, de Swiet M, Warnes G, Elias E, Higgins CF, Johnston DG, McCarthy MI, Williamson C: Heterozygous MDR3 missense mutation associated with intrahepatic cholestasis of pregnancy: evidence for a defect in protein trafficking. Hum Mol Genet. 2000 May 1;9(8):1209-17. [PubMed:10767346 ]
  8. Jacquemin E, De Vree JM, Cresteil D, Sokal EM, Sturm E, Dumont M, Scheffer GL, Paul M, Burdelski M, Bosma PJ, Bernard O, Hadchouel M, Elferink RP: The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood. Gastroenterology. 2001 May;120(6):1448-58. [PubMed:11313315 ]
  9. Rosmorduc O, Hermelin B, Poupon R: MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis. Gastroenterology. 2001 May;120(6):1459-67. [PubMed:11313316 ]
  10. Lucena JF, Herrero JI, Quiroga J, Sangro B, Garcia-Foncillas J, Zabalegui N, Sola J, Herraiz M, Medina JF, Prieto J: A multidrug resistance 3 gene mutation causing cholelithiasis, cholestasis of pregnancy, and adulthood biliary cirrhosis. Gastroenterology. 2003 Apr;124(4):1037-42. [PubMed:12671900 ]
  11. Rosmorduc O, Hermelin B, Boelle PY, Parc R, Taboury J, Poupon R: ABCB4 gene mutation-associated cholelithiasis in adults. Gastroenterology. 2003 Aug;125(2):452-9. [PubMed:12891548 ]
  12. Mullenbach R, Linton KJ, Wiltshire S, Weerasekera N, Chambers J, Elias E, Higgins CF, Johnston DG, McCarthy MI, Williamson C: ABCB4 gene sequence variation in women with intrahepatic cholestasis of pregnancy. J Med Genet. 2003 May;40(5):e70. [PubMed:12746424 ]
  13. Pauli-Magnus C, Lang T, Meier Y, Zodan-Marin T, Jung D, Breymann C, Zimmermann R, Kenngott S, Beuers U, Reichel C, Kerb R, Penger A, Meier PJ, Kullak-Ublick GA: Sequence analysis of bile salt export pump (ABCB11) and multidrug resistance p-glycoprotein 3 (ABCB4, MDR3) in patients with intrahepatic cholestasis of pregnancy. Pharmacogenetics. 2004 Feb;14(2):91-102. [PubMed:15077010 ]
  14. Lang T, Haberl M, Jung D, Drescher A, Schlagenhaufer R, Keil A, Mornhinweg E, Stieger B, Kullak-Ublick GA, Kerb R: Genetic variability, haplotype structures, and ethnic diversity of hepatic transporters MDR3 (ABCB4) and bile salt export pump (ABCB11). Drug Metab Dispos. 2006 Sep;34(9):1582-99. Epub 2006 Jun 8. [PubMed:16763017 ]
  15. Lang C, Meier Y, Stieger B, Beuers U, Lang T, Kerb R, Kullak-Ublick GA, Meier PJ, Pauli-Magnus C: Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury. Pharmacogenet Genomics. 2007 Jan;17(1):47-60. [PubMed:17264802 ]