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ABCC2 Membrane Protein Introduction

Introduction of ABCC2

ABCC2, also known as MRP2, CMOAT, CMRP, CMOAT1, ABC30, or DJS, is an integral membrane glycoprotein of about 174 kDa, mainly expressed in the apical membrane of liver cells. It consists of 1545 amino acids and in humans, encoded by the ABCC2 gene mapping at the chromosome 10q24.2. This membrane transport protein belongs to the ATP-binding cassette (ABC) transporter superfamily. ABCC2 comprises two nucleotide-binding domains (NBDs) and up to 17 transmembrane helixes distributed within transmembrane domains 1, 2, and 3 (TMD1, 2, 3). In the same multi-drug resistance protein (MRP) family, human ABCC2, compared with ABCC1, shares 48% sequence identity and a similar membrane topology, which implies their structural and functional similarity. It has been testified that amino-terminal TMD1 of ABCC1 is not necessary for the substrate transport.

Basic Information of ABCC2
Protein Name Canalicular multispecific organic anion transporter 1
Gene Name ABCC2
Aliases ATP-binding cassette sub-family C member 2, Canalicular multidrug resistance protein, Multidrug resistance-associated protein 2
Organism Homo sapiens (Human)
UniProt ID Q92887
Transmembrane Times 17
Length (aa) 1545
Sequence MLEKFCNSTFWNSSFLDSPEADLPLCFEQTVLVWIPLGYLWLLAPWQLLHVYKSRTKRSSTTKLYLAKQVFVGFLLILAAIELALVLTEDSGQATVPAVRYTNPSLYLGTWLLVLLIQYSRQWCVQKNSWFLSLFWILSILCGTFQFQTLIRTLLQGDNSNLAYSCLFFISYGFQILILIFSAFSENNESSNNPSSIASFLSSITYSWYDSIILKGYKRPLTLEDVWEVDEEMKTKTLVSKFETHMKRELQKARRALQRRQEKSSQQNSGARLPGLNKNQSQSQDALVLEDVEKKKKKSGTKKDVPKSWLMKALFKTFYMVLLKSFLLKLVNDIFTFVSPQLLKLLISFASDRDTYLWIGYLCAILLFTAALIQSFCLQCYFQLCFKLGVKVRTAIMASVYKKALTLSNLARKEYTVGETVNLMSVDAQKLMDVTNFMHMLWSSVLQIVLSIFFLWRELGPSVLAGVGVMVLVIPINAILSTKSKTIQVKNMKNKDKRLKIMNEILSGIKILKYFAWEPSFRDQVQNLRKKELKNLLAFSQLQCVVIFVFQLTPVLVSVVTFSVYVLVDSNNILDAQKAFTSITLFNILRFPLSMLPMMISSMLQASVSTERLEKYLGGDDLDTSAIRHDCNFDKAMQFSEASFTWEHDSEATVRDVNLDIMAGQLVAVIGPVGSGKSSLISAMLGEMENVHGHITIKGTTAYVPQQSWIQNGTIKDNILFGTEFNEKRYQQVLEACALLPDLEMLPGGDLAEIGEKGINLSGGQKQRISLARATYQNLDIYLLDDPLSAVDAHVGKHIFNKVLGPNGLLKGKTRLLVTHSMHFLPQVDEIVVLGNGTIVEKGSYSALLAKKGEFAKNLKTFLRHTGPEEEATVHDGSEEEDDDYGLISSVEEIPEDAASITMRRENSFRRTLSRSSRSNGRHLKSLRNSLKTRNVNSLKEDEELVKGQKLIKKEFIETGKVKFSIYLEYLQAIGLFSIFFIILAFVMNSVAFIGSNLWLSAWTSDSKIFNSTDYPASQRDMRVGVYGALGLAQGIFVFIAHFWSAFGFVHASNILHKQLLNNILRAPMRFFDTTPTGRIVNRFAGDISTVDDTLPQSLRSWITCFLGIISTLVMICMATPVFTIIVIPLGIIYVSVQMFYVSTSRQLRRLDSVTRSPIYSHFSETVSGLPVIRAFEHQQRFLKHNEVRIDTNQKCVFSWITSNRWLAIRLELVGNLTVFFSALMMVIYRDTLSGDTVGFVLSNALNITQTLNWLVRMTSEIETNIVAVERITEYTKVENEAPWVTDKRPPPDWPSKGKIQFNNYQVRYRPELDLVLRGITCDIGSMEKIGVVGRTGAGKSSLTNCLFRILEAAGGQIIIDGVDIASIGLHDLREKLTIIPQDPILFSGSLRMNLDPFNNYSDEEIWKALELAHLKSFVASLQLGLSHEVTEAGGNLSIGQRQLLCLGRALLRKSKILVLDEATAAVDLETDNLIQTTIQNEFAHCTVITIAHRLHTIMDSDKVMVLDNGKIIECGSPEELLQIPGPFYFMAKEAGIENVNSTKF

Function of ABCC2 Membrane Protein

The exporter ABCC2, a membrane-bound protein, utilizes the energy of ATP hydrolysis to translocate its substrates across the biological membrane and transports a wide range of compounds, including many endobiotics and xenobiotics, glutathione, leukotriene C4, some conjugated bile salts, drugs, and phytonutrients. This transmembrane protein is primarily expressed in the liver, and with smaller amounts in the kidney, intestine, and placenta. It mediates the hepatobiliary excretion of various organic anions. For instance, ABCC2 clears several drugs from tissues and organs, playing a role in drug metabolism. Lacking ABCC2 in human results in an autosomal dominant hereditary disease, the Dubin-Johnson syndrome. This disease is revealed by chronic hyperbilirubinemia due to the decreased biliary secretion of bilirubin conjugates. Furthermore, ABCC2 is also a member of the MRP subfamily, which is implicated in multi-drug resistance. And this protein is reported to involve in the resistance of tumor cells to chemotherapeutic drugs.

ABCC2 Membrane Protein Introduction Fig.1 Structure of the ABCC2 transporter generated in silico. (Williamson, 2007)

Application of ABCC2 Membrane Protein in Literature

  1. Prado Y., et al. Gender-specific association between ABCC2 -24C>T SNP and reduction in triglycerides in chilean patients treated with atorvastatin. Basic Clin Pharmacol Toxicol. 2018, 122(5): 517-522. PubMed ID: 29178257

    It is known that Statin is the first-line medicine prescribed to lower the plasma cholesterol level. This paper indicates that the TG level and TG/HDL-C ratio are influenced by the rs717620 SNP in Chilean males but not in females after the atorvastatin treatment.

  2. Liu L., et al. A single amino acid polymorphism in ABCC2 loop 1 is responsible of differential toxicity of Bacillus thuringiensis Cry1Ac toxin in different Spodoptera (Noctuidae) species. Insect Biochem Mol Biol. 2018, 100: 59-65. PubMed ID: 29964167

    Bacillus thuringiensis Cry toxin exerts its toxicity by generating membrane pores after binding with the larval midgut membrane protein known as a receptor. The findings in this study confirm a single amino acid residue which is located in loop 1 of ABCC2 transporter, in charge of different degrees of susceptibility to Cry1Ac in various lepidopteran species.

  3. Chen J., et al. ABCC2 rs2273697 is associated with valproic acid concentrations in patients with epilepsy on valproic acid monotherapy. Pharmazie. 2018, 73(5): 279-282. PubMed ID: 29724294

    Valproic acid (VPA) is a widely used antiepileptic drug and featured by intensive inter-individual variability in concentration. The current study suggests that ABCC2 polymorphisms affect VPA concentrations in epilepsy patients with VPA monotherapy, which may influence final treatment outcomes.

  4. Flagel L., et al. Mutational disruption of the ABCC2 gene in fall armyworm, Spodoptera frugiperda, confers resistance to the Cry1Fa and Cry1A.105 insecticidal proteins. Sci Rep. 2018, 8(1): 7255. PubMed ID: 29740041

    This review validates that ABCC2 is indeed a receptor for both Cry1Fa and Cry1A.105 in S. frugiperda, and the results lay the basis for genetically ensured resistance management in this species, with a caution that there probably are a number of distinct ABCC2 resistances alleles in nature.

  5. Wissel G., et al. A structure-activity relationship study of ABCC2 inhibitors. Eur J Pharm Sci. 2017, 103: 60-69. PubMed ID: 28185990

    ABCC2/MRP2 as a membrane transport protein potentially affects the disposition of various substrate drugs and their metabolites. Authors recently studied the interaction of a library (containing 432 compounds) with ABCC2, and the SAR (structure-activity relationship) of a subset of 64 compounds classified into four groups.

ABCC2 Preparation Options

To harvest an intact target protein, we have established reconstitution formats and active forms for membrane proteins. Our powerful Magic™ membrane protein production platform offers clients varieties of flexible options and assists them finding an optimal match to satisfy their aims. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-ABCC2 antibody development services.


Here, Creative Biolabs works as a first-class producer in the biological market that has successfully achieved quantities of membrane protein preparations. We are proud to introduce our one-stop, self-identity services for specific proteins as clients’ requirements. Please feel free to contact us for more information.

Reference

  1. Williamson G, et al. (2007). Interaction of positional isomers of quercetin glucuronides with the transporter ABCC2 (cMOAT, MRP2). Drug Metab Dispos. 35(8), 1262-1268.

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