Molecule Information

General Information of the Molecule (ID: Mol00515)

• Name: ATP-binding cassette sub-family C5 (ABCC5) ,Homo sapiens
• Synonyms: Multi-specific organic anion transporter C; MOAT-C; Multidrug resistance-associated protein 5; SMRP; pABC11; MRP5
• Molecule Type: Protein
• Gene Name: ABCC5
• Gene ID: 10057
• Location: chr3:183919934-184017939[-]
• Sequence:
  MKDIDIGKEYIIPSPGYRSVRERTSTSGTHRDREDSKFRRTRPLECQDALETAARAEGLS
  LDASMHSQLRILDEEHPKGKYHHGLSALKPIRTTSKHQHPVDNAGLFSCMTFSWLSSLAR
  VAHKKGELSMEDVWSLSKHESSDVNCRRLERLWQEELNEVGPDAASLRRVVWIFCRTRLI
  LSIVCLMITQLAGFSGPAFMVKHLLEYTQATESNLQYSLLLVLGLLLTEIVRSWSLALTW
  ALNYRTGVRLRGAILTMAFKKILKLKNIKEKSLGELINICSNDGQRMFEAAAVGSLLAGG
  PVVAILGMIYNVIILGPTGFLGSAVFILFYPAMMFASRLTAYFRRKCVAATDERVQKMNE
  VLTYIKFIKMYAWVKAFSQSVQKIREEERRILEKAGYFQSITVGVAPIVVVIASVVTFSV
  HMTLGFDLTAAQAFTVVTVFNSMTFALKVTPFSVKSLSEASVAVDRFKSLFLMEEVHMIK
  NKPASPHIKIEMKNATLAWDSSHSSIQNSPKLTPKMKKDKRASRGKKEKVRQLQRTEHQA
  VLAEQKGHLLLDSDERPSPEEEEGKHIHLGHLRLQRTLHSIDLEIQEGKLVGICGSVGSG
  KTSLISAILGQMTLLEGSIAISGTFAYVAQQAWILNATLRDNILFGKEYDEERYNSVLNS
  CCLRPDLAILPSSDLTEIGERGANLSGGQRQRISLARALYSDRSIYILDDPLSALDAHVG
  NHIFNSAIRKHLKSKTVLFVTHQLQYLVDCDEVIFMKEGCITERGTHEELMNLNGDYATI
  FNNLLLGETPPVEINSKKETSGSQKKSQDKGPKTGSVKKEKAVKPEEGQLVQLEEKGQGS
  VPWSVYGVYIQAAGGPLAFLVIMALFMLNVGSTAFSTWWLSYWIKQGSGNTTVTRGNETS
  VSDSMKDNPHMQYYASIYALSMAVMLILKAIRGVVFVKGTLRASSRLHDELFRRILRSPM
  KFFDTTPTGRILNRFSKDMDEVDVRLPFQAEMFIQNVILVFFCVGMIAGVFPWFLVAVGP
  LVILFSVLHIVSRVLIRELKRLDNITQSPFLSHITSSIQGLATIHAYNKGQEFLHRYQEL
  LDDNQAPFFLFTCAMRWLAVRLDLISIALITTTGLMIVLMHGQIPPAYAGLAISYAVQLT
  GLFQFTVRLASETEARFTSVERINHYIKTLSLEAPARIKNKAPSPDWPQEGEVTFENAEM
  RYRENLPLVLKKVSFTIKPKEKIGIVGRTGSGKSSLGMALFRLVELSGGCIKIDGVRISD
  IGLADLRSKLSIIPQEPVLFSGTVRSNLDPFNQYTEDQIWDALERTHMKECIAQLPLKLE
  SEVMENGDNFSVGERQLLCIARALLRHCKILILDEATAAMDTETDLLIQETIREAFADCT
  MLTIAHRLHTVLGSDRIMVLAQGQVVEFDTPSVLLSNDSSRFYAMFAAAENKVAVKG
• Function: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins. Confers resistance to the antiviral agent PMEA. Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated. Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway. May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells.
• Uniprot ID: MRP5_HUMAN
• Ensembl ID: ENSG00000114770
• HGNC ID: HGNC:56

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) 8 drug(s) in total

Adefovir

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glaucoma [1]

• Resistant Disease: Glaucoma [ICD-11: 9C61.0]
• Resistant Drug: Adefovir
• Molecule Alteration: Expression; Regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SIRC cells; Colon; Homo sapiens (Human); CVCL_2724
• In Vitro Model: SV40-HCEC cells; Kidney; Homo sapiens (Human); CVCL_1272
• Experiment for Molecule Alteration: RT-PCR; Immunoprecipitation assay; Western blot analysis; Immunostaining assay
• Experiment for Drug Resistance: Trypan blue exclusion test assay
• Mechanism Description: Taken together immunolocalization on human cornea, in vitro efflux in human, rabbit corneal and MRP5 over expressing cells, ex vivo and in vivo studies in intact rabbit cornea suggest that MRP5 on cornea can significantly lower the permeability of antiviral and glaucoma drugs.

Disease Class: Glaucoma [1]

• Resistant Disease: Glaucoma [ICD-11: 9C61.0]
• Resistant Drug: Adefovir
• Molecule Alteration: Expression; Regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SIRC cells; Colon; Homo sapiens (Human); CVCL_2724
• In Vitro Model: SV40-HCEC cells; Kidney; Homo sapiens (Human); CVCL_1272
• Experiment for Molecule Alteration: RT-PCR; Immunoprecipitation assay; Western blot analysis; Immunostaining assay
• Experiment for Drug Resistance: Trypan blue exclusion test assay
• Mechanism Description: Taken together immunolocalization on human cornea, in vitro efflux in human, rabbit corneal and MRP5 over expressing cells, ex vivo and in vivo studies in intact rabbit cornea suggest that MRP5 on cornea can significantly lower the permeability of antiviral and glaucoma drugs.

Azathioprine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Rheumatoid arthritis [2]

• Resistant Disease: Rheumatoid arthritis [ICD-11: FA20.0]
• Resistant Drug: Azathioprine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: MTX is a substrate for eight ABC transporters. In vitro studies demonstrated that RAFLS treated with MTX had higher ABCB1 expression levels than controls, with a positive correlation between ABCB1 expression levels and RA treatment duration. In addition to MTX, other DMARDs (e.g. sulfasalazine, leflunomide, bucillamine, azathioprine), glucocorticoids (e.g. betamethasone, dexamethasone), and NSAIDs (e.g. celecoxib and indomethacin) are also substrates of ABC transporters.

Bimatoprost

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glaucoma [1]

• Resistant Disease: Glaucoma [ICD-11: 9C61.0]
• Resistant Drug: Bimatoprost
• Molecule Alteration: Expression; Regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SIRC cells; Colon; Homo sapiens (Human); CVCL_2724
• In Vitro Model: SV40-HCEC cells; Kidney; Homo sapiens (Human); CVCL_1272
• Experiment for Molecule Alteration: RT-PCR; Immunoprecipitation assay; Western blot analysis; Immunostaining assay
• Experiment for Drug Resistance: Trypan blue exclusion test assay
• Mechanism Description: Taken together immunolocalization on human cornea, in vitro efflux in human, rabbit corneal and MRP5 over expressing cells, ex vivo and in vivo studies in intact rabbit cornea suggest that MRP5 on cornea can significantly lower the permeability of antiviral and glaucoma drugs.

Disease Class: Glaucoma [1]

• Resistant Disease: Glaucoma [ICD-11: 9C61.0]
• Resistant Drug: Bimatoprost
• Molecule Alteration: Expression; Regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SIRC cells; Colon; Homo sapiens (Human); CVCL_2724
• In Vitro Model: SV40-HCEC cells; Kidney; Homo sapiens (Human); CVCL_1272
• Experiment for Molecule Alteration: RT-PCR; Immunoprecipitation assay; Western blot analysis; Immunostaining assay
• Experiment for Drug Resistance: Trypan blue exclusion test assay
• Mechanism Description: Taken together immunolocalization on human cornea, in vitro efflux in human, rabbit corneal and MRP5 over expressing cells, ex vivo and in vivo studies in intact rabbit cornea suggest that MRP5 on cornea can significantly lower the permeability of antiviral and glaucoma drugs.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Ovarian cancer [3]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vitro Model: PEO14 cells; Ovary; Homo sapiens (Human); CVCL_2687
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overexpression of miR-128 resensitized SkOV3/CP cells to cisplatin and reduced the expression of cisplatin-resistant-related proteins ABCC5 and Bmi-1.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Breast cancer [4]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Reduction of miR-128 in BT-ICs leads to overexpression of Bmi-1 and ABCC5, two independent targets of miR-128. Ectopic expression of miR-128 decreases cell viability and increases apoptosis and DNA damage in the presence of doxorubicin, hence sensitizes BT-ICs to chemotherapy.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Gastric cancer [5]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Gemcitabine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Pancreatic cancer [6]

• Sensitive Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Sensitive Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: AsPC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0152
• In Vivo Model: Chick egg xenograft model; Gallus gallus
• Experiment for Molecule Alteration: Dual luciferase assay; qRT-PCR; Immunofluorescence and immunohistochemistry assay
• Experiment for Drug Resistance: RealTime-Glo MT Cell Viability Assay; Caspase-3/7 substrate assay; Colony formation assay
• Mechanism Description: microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer, miR210 is a direct suppressor of the multidrug efflux transporter ABCC5.

Latanoprost

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Glaucoma [1]

• Resistant Disease: Glaucoma [ICD-11: 9C61.0]
• Resistant Drug: Latanoprost
• Molecule Alteration: Expression; Regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SIRC cells; Colon; Homo sapiens (Human); CVCL_2724
• In Vitro Model: SV40-HCEC cells; Kidney; Homo sapiens (Human); CVCL_1272
• Experiment for Molecule Alteration: RT-PCR; Immunoprecipitation assay; Western blot analysis; Immunostaining assay
• Experiment for Drug Resistance: Trypan blue exclusion test assay
• Mechanism Description: Taken together immunolocalization on human cornea, in vitro efflux in human, rabbit corneal and MRP5 over expressing cells, ex vivo and in vivo studies in intact rabbit cornea suggest that MRP5 on cornea can significantly lower the permeability of antiviral and glaucoma drugs.

Disease Class: Glaucoma [1]

• Resistant Disease: Glaucoma [ICD-11: 9C61.0]
• Resistant Drug: Latanoprost
• Molecule Alteration: Expression; Regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: SIRC cells; Colon; Homo sapiens (Human); CVCL_2724
• In Vitro Model: SV40-HCEC cells; Kidney; Homo sapiens (Human); CVCL_1272
• Experiment for Molecule Alteration: RT-PCR; Immunoprecipitation assay; Western blot analysis; Immunostaining assay
• Experiment for Drug Resistance: Trypan blue exclusion test assay
• Mechanism Description: Taken together immunolocalization on human cornea, in vitro efflux in human, rabbit corneal and MRP5 over expressing cells, ex vivo and in vivo studies in intact rabbit cornea suggest that MRP5 on cornea can significantly lower the permeability of antiviral and glaucoma drugs.

Vincristine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Gastric cancer [5]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.22E-01; Fold-change: -1.88E+00; Z-score: -1.52E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.65E-07; Fold-change: -1.97E+00; Z-score: -2.18E+00

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.28E-03; Fold-change: 6.40E-01; Z-score: 7.46E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.65E-08; Fold-change: 7.93E-01; Z-score: 9.67E-01

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.09E-71; Fold-change: 9.28E-01; Z-score: 1.48E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.34E-07; Fold-change: 4.85E-01; Z-score: 7.87E-01

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.17E-02; Fold-change: 6.11E-01; Z-score: 7.54E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.38E-03; Fold-change: 5.70E-01; Z-score: 8.66E-01

ICD Disease Classification 15

Rheumatoid arthritis [ICD-11: FA20]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Peripheral blood
• The Specified Disease: Rheumatoid arthritis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.22E-01; Fold-change: -1.77E-02; Z-score: -5.99E-02
• The Studied Tissue: Synovial tissue
• The Specified Disease: Rheumatoid arthritis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.38E-02; Fold-change: -3.21E-01; Z-score: -6.75E-01

References

• Ref 1: Expression of multidrug resistance associated protein 5 (MRP5) on cornea and its role in drug efflux .J Ocul Pharmacol Ther. 2009 Apr;25(2):121-32. doi: 10.1089/jop.2008.0084. 10.1089/jop.2008.0084
• Ref 2: Drug-resistance in rheumatoid arthritis: the role of p53 gene mutations, ABC family transporters and personal factors .Curr Opin Pharmacol. 2020 Oct;54:59-71. doi: 10.1016/j.coph.2020.08.002. Epub 2020 Sep 14. 10.1016/j.coph.2020.08.002
• Ref 3: Deregulation of miR-128 in ovarian cancer promotes cisplatin resistance. Int J Gynecol Cancer. 2014 Oct;24(8):1381-8. doi: 10.1097/IGC.0000000000000252.
• Ref 4: Reduced miR-128 in breast tumor-initiating cells induces chemotherapeutic resistance via Bmi-1 and ABCC5. Clin Cancer Res. 2011 Nov 15;17(22):7105-15. doi: 10.1158/1078-0432.CCR-11-0071. Epub 2011 Sep 27.
• Ref 5: Methylation of miR-129-5p CpG island modulates multi-drug resistance in gastric cancer by targeting ABC transporters. Oncotarget. 2014 Nov 30;5(22):11552-63. doi: 10.18632/oncotarget.2594.
• Ref 6: microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer. Cancer Lett. 2017 Mar 1;388:107-117. doi: 10.1016/j.canlet.2016.11.035. Epub 2016 Dec 7.