We have recently reported on two novel human ABC transporters, ABCC11 and ABCC12, the genes of which are tandemly located on human chromosome 16q12.1 [Biochem. Biophys. Res. Commun. 288 (2001) 933]. The present study addresses the cloning and characterization of Abcc12, a mouse orthologue of human ABCC12. The cloned Abcc12 cDNA was 4511 bp long, comprising a 4101 bp open reading frame. The deduced peptide consists of 1367 amino acids and exhibits high sequence identity (84.5%) with human ABCC12. The mouse Abcc12 gene consists of at least 29 exons and is located on the mouse chromosome 8D3 locus where conserved linkage homologies have hitherto been identified with human chromosome 16q12.1. The mouse Abcc12 gene was expressed at high levels exclusively in the seminiferous tubules in the testis. In addition to the Abcc12 transcript, two splicing variants encoding short peptides (775 and 687 amino acid residues) were detected. In spite of the genes coding for both ABCC11 and ABCC12 being tandemly located on human chromosome 16q12.1, no putative mouse orthologous gene corresponding to the human ABCC11 was detected at the mouse chromosome 8D3 locus.
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http://dx.doi.org/10.1016/s0378-1119(03)00504-3 | DOI Listing |
Proc Natl Acad Sci U S A
February 2022
Department of Animal and Avian Sciences and Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742;
Multidrug Resistance Proteins (MRPs) are transporters that play critical roles in cancer even though the physiological substrates of these enigmatic transporters are poorly elucidated. In , MRP5/ABCC5 is an essential heme exporter because mutants are unviable due to their inability to export heme from the intestine to extraintestinal tissues. Heme supplementation restores viability of these mutants but fails to restore male reproductive deficits.
View Article and Find Full Text PDFGastroenterology
July 2021
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address:
Background & Aims: The etiology of cholestasis remains unknown in many children. We surveyed the genome of children with chronic cholestasis for variants in genes not previously associated with liver disease and validated their biological relevance in zebrafish and murine models.
Method: Whole-exome (n = 4) and candidate gene sequencing (n = 89) was completed on 93 children with cholestasis and normal serum γ-glutamyl transferase (GGT) levels without pathogenic variants in genes known to cause low GGT cholestasis such as ABCB11 or ATP8B1.
Essays Biochem
September 2011
Division of Cancer Biology and Genetics, Queen's University Cancer Research Institute, Kingston, ON, Canada, K7L 3N6.
Subfamily C of the human ABC (ATP-binding cassette) superfamily contains nine proteins that are often referred to as the MRPs (multidrug-resistance proteins). The 'short' MRP/ABCC transporters (MRP4, MRP5, MRP8 and ABCC12) have a typical ABC structure with four domains comprising two membrane-spanning domains (MSD1 and MSD2) each followed by a nucleotide-binding domain (NBD1 and NBD2). The 'long' MRP/ABCCs (MRP1, MRP2, MRP3, ABCC6 and MRP7) have five domains with the extra domain, MSD0, at the N-terminus.
View Article and Find Full Text PDFBiochem J
August 2007
Division of Molecular Biology and Center of Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
The human and murine genes for MRP9 (multidrug resistance-associated protein 9; ABCC12) yield many alternatively spliced RNAs. Using a panel of monoclonal antibodies, we detected full-length Mrp9 only in testicular germ cells and mouse sperm; we obtained no evidence for the existence of the truncated 100 kDa MRP9 protein reported previously. In contrast with other MRPs, neither murine Mrp9 nor the human MRP9 produced in MRP9-transfected HEK-293 cells (human embryonic kidney cells) appears to contain N-linked carbohydrates.
View Article and Find Full Text PDFGene
May 2003
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, 226-8501, Yokohama, Japan.
We have recently reported on two novel human ABC transporters, ABCC11 and ABCC12, the genes of which are tandemly located on human chromosome 16q12.1 [Biochem. Biophys.
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