Molecule Information

General Information of the Molecule (ID: Mol04324)

• Name: ATP-dependent translocase ABCB1 (ABCB1) ,Homo sapiens
• Synonyms: ATP-binding cassette sub-family B member 1 ; Multidrug resistance protein 1; P-glycoprotein 1; Phospholipid transporter ABCB1 ; CD_antigen=CD243
• Molecule Type: Protein
• Gene Name: ABCB1
• Gene ID: 5243
• Sequence:
  MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAII
  HGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYS
  G IGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDD
  VS KINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILS
  SFT DKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITAN
  ISIG AAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAF
  ANARG AAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLN
  LKVQSG QTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVV
  SQEPVLF ATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLS
  GGQKQRIA IARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLST
  VRNADVIAG FDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDA
  LEMSSNDSRS SLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWP
  YFVVGVFCAII NGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFI
  TFFLQGFTFGKA GEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKG
  AIGSRLAVITQNI ANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKD
  KKELEGSGKIATEA IENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFT
  QAMMYFSYAGCFRFG AYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKIS
  AAHIIMIIEKTPLIDS YSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKG
  QTLALVGSSGCGKSTVV QLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPIL
  FDCSIAENIAYGDNSRVV SQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQK
  QRIAIARALVRQPHILLLD EATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNA
  DLIVVFQNGRVKEHGTHQQL LAQKGIYFSMVSVQAGTKRQ
• Function: Translocates drugs and phospholipids across the membrane. Catalyzes the flop of phospholipids from thecytoplasmic to the exoplasmic leaflet of the apical membrane.Participates mainly to the flop of phosphatidylcholine,phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins. Energy-dependent efflux pump responsible fordecreased drug accumulation in multidrug-resistant cells.{ECO:0000269|PubMed:2897240, ECO:0000269|PubMed:35507548,ECO:0000269|PubMed:35970996, ECO:0000269|PubMed:8898203,ECO:0000269|PubMed:9038218}.
• Uniprot ID: MDR1_HUMAN
• Ensembl ID: ENSG0000008556315
• HGNC ID: HGNC:40

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

Clinical Trial Drug(s) 1 drug(s) in total

Tanespimycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Acute lymphoblastic leukemia [ICD-11: 2B33.3] [1]

• Resistant Disease: Acute lymphoblastic leukemia [ICD-11: 2B33.3]
• Resistant Drug: Tanespimycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: kCL22 cells; Pleural effusion; Homo sapiens (Human); CVCL_2091
• In Vitro Model: Sup-B15 cells; Bone marrow; Homo sapiens (Human); CVCL_0103
• In Vivo Model: NSG mice model; Mus musculus
• Experiment for Molecule Alteration: Immunofluorescence staining assay; Western blot assay
• Experiment for Drug Resistance: Colony forming unit assay; Caspase 3/7 Glo assay
• Mechanism Description: Tanespimycin and Coumermycin A1 was attained by MDR1 efflux pump overexpression.

References

• Ref 1: Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells. Cell Death Dis. 2023 Dec 6;14(12):799.