Molecule Information

General Information of the Molecule (ID: Mol00516)

• Name: ATP-binding cassette sub-family C10 (ABCC10) ,Homo sapiens
• Synonyms: Multidrug resistance-associated protein 7; MRP7; SIMRP7
• Molecule Type: Protein
• Gene Name: ABCC10
• Gene ID: 89845
• Location: chr6:43427366-43450427[+]
• Sequence:
  MERLLAQLCGSSAAWPLPLWEGDTTGHCFTQLVLSALPHALLAVLSACYLGTPRSPDYIL
  PCSPGWRLRLAASFLLSVFPLLDLLPVALPPGAGPGPIGLEVLAGCVAAVAWISHSLALW
  VLAHSPHGHSRGPLALALVALLPAPALVLTVLWHCQRGTLLPPLLPGPMARLCLLILQLA
  ALLAYALGWAAPGGPREPWAQEPLLPEDQEPEVAEDGESWLSRFSYAWLAPLLARGACGE
  LRQPQDICRLPHRLQPTYLARVFQAHWQEGARLWRALYGAFGRCYLALGLLKLVGTMLGF
  SGPLLLSLLVGFLEEGQEPLSHGLLYALGLAGGAVLGAVLQNQYGYEVYKVTLQARGAVL
  NILYCKALQLGPSRPPTGEALNLLGTDSERLLNFAGSFHEAWGLPLQLAITLYLLYQQVG
  VAFVGGLILALLLVPVNKVIATRIMASNQEMLQHKDARVKLVTELLSGIRVIKFCGWEQA
  LGARVEACRARELGRLRVIKYLDAACVYLWAALPVVISIVIFITYVLMGHQLTATKVFTA
  LALVRMLILPLNNFPWVINGLLEAKVSLDRIQLFLDLPNHNPQAYYSPDPPAEPSTVLEL
  HGALFSWDPVGTSLETFISHLEVKKGMLVGIVGKVGCGKSSLLAAIAGELHRLRGHVAVR
  GLSKGFGLATQEPWIQFATIRDNILFGKTFDAQLYKEVLEACALNDDLSILPAGDQTEVG
  EKGVTLSGGQRARIALARAVYQEKELYLLDDPLAAVDADVANHLLHRCILGMLSYTTRLL
  CTHRTEYLERADAVLLMEAGRLIRAGPPSEILPLVQAVPKAWAENGQESDSATAQSVQNP
  EKTKEGLEEEQSTSGRLLQEESKKEGAVALHVYQAYWKAVGQGLALAILFSLLLMQATRN
  AADWWLSHWISQLKAENSSQEAQPSTSPASMGLFSPQLLLFSPGNLYIPVFPLPKAAPNG
  SSDIRFYLTVYATIAGVNSLCTLLRAVLFAAGTLQAAATLHRRLLHRVLMAPVTFFNATP
  TGRILNRFSSDVACADDSLPFILNILLANAAGLLGLLAVLGSGLPWLLLLLPPLSIMYYH
  VQRHYRASSRELRRLGSLTLSPLYSHLADTLAGLSVLRATGATYRFEEENLRLLELNQRC
  QFATSATMQWLDIRLQLMGAAVVSAIAGIALVQHQQGLANPGLVGLSLSYALSLTGLLSG
  LVSSFTQTEAMLVSVERLEEYTCDLPQEPQGQPLQLGTGWLTQGGVEFQDVVLAYRPGLP
  NALDGVTFCVQPGEKLGIVGRTGSGKSSLLLVLFRLLEPSSGRVLLDGVDTSQLELAQLR
  SQLAIIPQEPFLFSGTVRENLDPQGLHKDRALWQALKQCHLSEVITSMGGLDGELGEGGR
  SLSLGQRQLLCLARALLTDAKILCIDEATASVDQKTDQLLQQTICKRFANKTVLTIAHRL
  NTILNSDRVLVLQAGRVVELDSPATLRNQPHSLFQQLLQSSQQGVPASLGGP
• Function: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Lipophilic anion transporter that mediates ATP-dependent transport of glucuronide conjugates such as estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4). Mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs, such as, docetaxel and paclitaxel. Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP.
• Uniprot ID: MRP7_HUMAN
• Ensembl ID: ENSG00000124574
• HGNC ID: HGNC:52

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 Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Esophageal carcinoma [1]

• Sensitive Disease: Esophageal carcinoma [ICD-11: 2B70.4]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: EC109 cells; Esophagus; Homo sapiens (Human); CVCL_6898
• In Vitro Model: HEEpiC cells; Esophagus; Homo sapiens (Human); N.A.
• In Vitro Model: TE10 cells; Esophagus; Homo sapiens (Human); CVCL_1760
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: ABCC10, a drug resistance gene, was identified as a functional and direct target gene of miR-let-7g/i. Luciferase reporter assay confirmed that let-7g and let-7i combined directly with 3'UTR of ABCC10, in consequence, inhibiting ABCC10 expression and enhancing cellular sensitivity to drugs.

Cytarabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Leukemia [2]

• Resistant Disease: Leukemia [ICD-11: 2B33.6]
• Resistant Drug: Cytarabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Uptake and accumulation of cytarabine is also regulated by transmembrane transporter proteins of the ABC family, also called human multidrug resistance-associated protein (MRP) family, namely ABCC10 (MRP7) and ABCC11 (MRP8) specifically committed to efflux of deoxynucleotides inactive metabolites and to temper intracellular pools of phosphorylated deoxynucleotides. The drug accumulation may be substantially reduced when the expression of hENT1 transporter is deficient, or the activity of ABC drug efflux transporter proteins is elevated.

Disease Class: Lymphoma [2]

• Resistant Disease: Lymphoma [ICD-11: 2A90- 2A85]
• Resistant Drug: Cytarabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Uptake and accumulation of cytarabine is also regulated by transmembrane transporter proteins of the ABC family, also called human multidrug resistance-associated protein (MRP) family, namely ABCC10 (MRP7) and ABCC11 (MRP8) specifically committed to efflux of deoxynucleotides inactive metabolites and to temper intracellular pools of phosphorylated deoxynucleotides. The drug accumulation may be substantially reduced when the expression of hENT1 transporter is deficient, or the activity of ABC drug efflux transporter proteins is elevated.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lymphoma [ICD-11: 2A90- 2A85]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Tonsil tissue
• The Specified Disease: Lymphoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.91E-02; Fold-change: -3.03E-01; Z-score: -7.03E-01

Esophageal cancer [ICD-11: 2B70]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Esophagus
• The Specified Disease: Esophageal cancer
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.34E-02; Fold-change: 3.68E-01; Z-score: 1.17E+00

References

• Ref 1: BAG3-mediated miRNA let-7g and let-7i inhibit proliferation and enhance apoptosis of human esophageal carcinoma cells by targeting the drug transporter ABCC10. Cancer Lett. 2016 Feb 1;371(1):125-33. doi: 10.1016/j.canlet.2015.11.031. Epub 2015 Dec 3.
• Ref 2: Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers. Cancers (Basel). 2021 Feb 25;13(5):966. doi: 10.3390/cancers13050966.