Molecule Information

General Information of the Molecule (ID: Mol00494)

• Name: Multidrug resistance protein 3 (ABCB4) ,Homo sapiens
• Synonyms: ATP-binding cassette sub-family B member 4; Multidrug resistance protein 3; P-glycoprotein 3; MDR3; PGY3
• Molecule Type: Protein
• Gene Name: ABCB4
• Gene ID: 5244
• Location: chr7:87401696-87480435[-]
• Sequence:
  MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSLG
  TIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYY
  SGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDD
  ISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSA
  FSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANIS
  MGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAFSVGQAAPCIDAFANA
  RGAAYVIFDIIDNNPKIDSFSERGHKPDSIKGNLEFNDVHFSYPSRANVKILKGLNLKVQ
  SGQTVALVGSSGCGKSTTVQLIQRLYDPDEGTINIDGQDIRNFNVNYLREIIGVVSQEPV
  LFSTTIAENICYGRGNVTMDEIKKAVKEANAYEFIMKLPQKFDTLVGERGAQLSGGQKQR
  IAIARALVRNPKILLLDEATSALDTESEAEVQAALDKAREGRTTIVIAHRLSTVRNADVI
  AGFEDGVIVEQGSHSELMKKEGVYFKLVNMQTSGSQIQSEEFELNDEKAATRMAPNGWKS
  RLFRHSTQKNLKNSQMCQKSLDVETDGLEANVPPVSFLKVLKLNKTEWPYFVVGTVCAIA
  NGGLQPAFSVIFSEIIAIFGPGDDAVKQQKCNIFSLIFLFLGIISFFTFFLQGFTFGKAG
  EILTRRLRSMAFKAMLRQDMSWFDDHKNSTGALSTRLATDAAQVQGATGTRLALIAQNIA
  NLGTGIIISFIYGWQLTLLLLAVVPIIAVSGIVEMKLLAGNAKRDKKELEAAGKIATEAI
  ENIRTVVSLTQERKFESMYVEKLYGPYRNSVQKAHIYGITFSISQAFMYFSYAGCFRFGA
  YLIVNGHMRFRDVILVFSAIVFGAVALGHASSFAPDYAKAKLSAAHLFMLFERQPLIDSY
  SEEGLKPDKFEGNITFNEVVFNYPTRANVPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQ
  LLERFYDPLAGTVFVDFGFQLLDGQEAKKLNVQWLRAQLGIVSQEPILFDCSIAENIAYG
  DNSRVVSQDEIVSAAKAANIHPFIETLPHKYETRVGDKGTQLSGGQKQRIAIARALIRQP
  QILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEH
  GTHQQLLAQKGIYFSMVSVQAGTQNL
• Function: [Isoform 1]: 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. 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. Required for proper phospholipid bile formation. Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner. Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane. In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts. Does not confer multidrug resistance.
• Uniprot ID: MDR3_HUMAN
• Ensembl ID: ENSG00000005471
• HGNC ID: HGNC:45

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Endometrial cancer [1]

• Resistant Disease: Endometrial cancer [ICD-11: 2C76.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell autophagy; Inhibition; hsa04140
• In Vitro Model: Ishikawa cells; Endometrium; Homo sapiens (Human); CVCL_2529
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
• Mechanism Description: HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.

Miltefosine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Leishmaniasis [2]

• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Resistant Drug: Miltefosine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: In addition, the overexpression of ABC transporters ABCB4(MDR1), ABCG4, and ABCG6 has also been described to be associated with an increased resistance to several alkyl-lysophospholipids analogues, including MIL in Leishmania, due to a reduced intracellular accumulation because of increased efflux of the drug across the plasma membrane.

References

• Ref 1: Autophagy regulated by lncRNA HOTAIR contributes to the cisplatin-induced resistance in endometrial cancer cells. Biotechnol Lett. 2017 Oct;39(10):1477-1484. doi: 10.1007/s10529-017-2392-4. Epub 2017 Jul 18.
• Ref 2: Drug resistance and treatment failure in leishmaniasis: A 21st century challenge .PLoS Negl Trop Dis. 2017 Dec 14;11(12):e0006052. doi: 10.1371/journal.pntd.0006052. eCollection 2017 Dec. 10.1371/journal.pntd.0006052