Peptide name : ATP-binding cassette sub-family C member 5

Source/Organism : Human

Linear/Cyclic : Not found

Chirality : Not found

Peptide length: 1436

C-terminal modification: Not found

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : Not found

Cancer type : Not found

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 161123.083 Dalton

Aliphatic index : 1.001

Instability index : 40.1236

Hydrophobicity (GRAVY) : -0.001

Isoelectric point : 8.8045

Charge (pH 7) : 17.5774

Aromaticity : 0.084

Molar extinction coefficient (cysteine, cystine): (152640, 153765)

Hydrophobic/hydrophilic ratio : 1.11487481

hydrophobic moment : -0.031

Missing amino acid : None

Most occurring amino acid : L

Most occurring amino acid frequency : 168

Least occurring amino acid : C

Least occurring amino acid frequency : 18

Secondary structure fraction (Helix, Turn, Sheet): (0.3, 0.2, 0.3)

SMILES Notation: 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1 : Huttlin EL, et al. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010; 143:1174-89. doi: 10.1016/j.cell.2010.12.001

2 : de Wolf CJ, et al. cGMP transport by vesicles from human and mouse erythrocytes. FEBS J. 2007; 274:439-50. doi: 10.1111/j.1742-4658.2006.05591.x

3 : Cyranka M, et al. Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1. Obesity (Silver Spring). 2019; 27:1292-1304. doi: 10.1002/oby.22521

4 : Suzuki T, et al. Detailed structural analysis on both human MRP5 and mouse mrp5 transcripts. Gene. 2000; 242:167-73. doi: 10.1016/s0378-1119(99)00529-6

5 : Gerhard DS, et al. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004; 14:2121-7. doi: 10.1101/gr.2596504

6 : Korolnek T, et al. Control of metazoan heme homeostasis by a conserved multidrug resistance protein. Cell Metab. 2014; 19:1008-19. doi: 10.1016/j.cmet.2014.03.030

7 : Soontornmalai A, et al. Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood-brain barrier. Neuroscience. 2006; 138:159-69. doi: 10.1016/j.neuroscience.2005.11.011

8 : Trost M, et al. The phagosomal proteome in interferon-gamma-activated macrophages. Immunity. 2009; 30:143-54. doi: 10.1016/j.immuni.2008.11.006

9 : Jansen RS, et al. ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs. J Biol Chem. 2015; 290:30429-40. doi: 10.1074/jbc.M115.692103

Paper title : A tissue-specific atlas of mouse protein phosphorylation and expression.

Doi : https://doi.org/10.1016/j.cell.2010.12.001

Abstract : Although most tissues in an organism are genetically identical, the biochemistry of each is optimized to fulfill its unique physiological roles, with important consequences for human health and disease. Each tissue's unique physiology requires tightly regulated gene and protein expression coordinated by specialized, phosphorylation-dependent intracellular signaling. To better understand the role of phosphorylation in maintenance of physiological differences among tissues, we performed proteomic and phosphoproteomic characterizations of nine mouse tissues. We identified 12,039 proteins, including 6296 phosphoproteins harboring nearly 36,000 phosphorylation sites. Comparing protein abundances and phosphorylation levels revealed specialized, interconnected phosphorylation networks within each tissue while suggesting that many proteins are regulated by phosphorylation independently of their expression. Our data suggest that the "typical" phosphoprotein is widely expressed yet displays variable, often tissue-specific phosphorylation that tunes protein activity to the specific needs of each tissue. We offer this dataset as an online resource for the biological research community.

Paper title : cGMP transport by vesicles from human and mouse erythrocytes.

Doi : https://doi.org/10.1111/j.1742-4658.2006.05591.x

Abstract : cGMP secretion from cells can be mediated by ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCC11. Indirect evidence suggests that ABCC4 and ABCC5 contribute to cGMP transport by erythrocytes. We have re-investigated the issue using erythrocytes from wild-type and transporter knockout mice. Murine wild-type erythrocyte vesicles transported cGMP with an apparent Km that was 100-fold higher than their human counterparts, the apparent Vmax being similar. Whereas cGMP transport into human vesicles was efficiently inhibited by the ABCC4-specific substrate prostaglandin E1, cGMP transport into mouse vesicles was inhibited equally by Abcg2 and Abcc4 inhibitors/substrates. Similarly, cGMP transport into vesicles from Abcc4-/- and Abcg2-/- mice was 42% and 51% of that into wild-type mouse vesicles, respectively, whereas cGMP transport into vesicles from Abcc4(-/-)/Abcg2(-/-) mice was near background. The knockout mice were used to show that Abcg2-mediated cGMP transport occurred with lower affinity but higher Vmax than Abcc4-mediated transport. Involvement of Abcg2 in cGMP transport by Abcc4-/- erythrocyte vesicles was supported by higher transport at pH 5.5 than at pH 7.4, a characteristic of Abcg2-mediated transport. The relative contribution of ABCC4/Abcc4 and ABCG2/Abcg2 in cGMP transport was confirmed with a new inhibitor of ABCC4 transport, the protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride.

Paper title : Abcc5 Knockout Mice Have Lower Fat Mass and Increased Levels of Circulating GLP-1.

Doi : https://doi.org/10.1002/oby.22521

Abstract : OBJECTIVE: A previous genome-wide association study linked overexpression of an ATP-binding cassette transporter, ABCC5, in humans with a susceptibility to developing type 2 diabetes with age. Specifically, ABCC5 gene overexpression was shown to be strongly associated with increased visceral fat mass and reduced peripheral insulin sensitivity. Currently, the role of ABCC5 in diabetes and obesity is unknown. This study reports the metabolic phenotyping of a global Abcc5 knockout mouse. METHODS: A global Abcc5-/- mouse was generated by CRISPR/Cas9. Fat mass was determined by weekly EchoMRI and fat pads were dissected and weighed at week 18. Glucose homeostasis was ascertained by an oral glucose tolerance test, intraperitoneal glucose tolerance test, and intraperitoneal insulin tolerance test. Energy expenditure and locomotor activity were measured using PhenoMaster cages. Glucagon-like peptide 1 (GLP-1) levels in plasma, primary gut cell cultures, and GLUTag cells were determined by enzyme-linked immunosorbent assay. RESULTS: Abcc5-/- mice had decreased fat mass and increased plasma levels of GLP-1, and they were more insulin sensitive and more active. Recombinant overexpression of ABCC5 protein in GLUTag cells decreased GLP-1 release. CONCLUSIONS: ABCC5 protein expression levels are inversely related to fat mass and appear to play a role in the regulation of GLP-1 secretion from enteroendocrine cells.

Paper title : Detailed structural analysis on both human MRP5 and mouse mrp5 transcripts.

Doi : https://doi.org/10.1016/s0378-1119(99)00529-6

Abstract : The multidrug-resistant phenotype in tumor cells is attributed in part to anti-cancer drug efflux transporters such as the MRP family. The amino-terminal structure of MRP5 has not been refined. To determine the amino-terminal structure of a major transcript of the MRP5 gene, we performed primer extension analysis to determine a major transcriptional start site of this gene and compared the structure of human MRP5 and that of mouse mrp5. We successfully determined the structures of human MRP5 and mouse mrp5. Estimated amino acid sequences are 1437 and 1436 amino acids for human MRP5 and mouse mrp5 respectively, and were highly conserved (94.1%). We further showed that our previously identified SMRP mRNA was a splicing variant of the MRP5 gene, which was expressed in various human tissues, suggesting that a short form of MRP5 protein encoded by the SMRP mRNA may have a physiological role.

Paper title : The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

Doi : https://doi.org/10.1101/gr.2596504

Abstract : The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

Paper title : Control of metazoan heme homeostasis by a conserved multidrug resistance protein.

Doi : https://doi.org/10.1016/j.cmet.2014.03.030

Abstract : Several lines of evidence predict that specific pathways must exist in metazoans for the escorted movement of heme, an essential but cytotoxic iron-containing organic ring, within and between cells and tissues, but these pathways remain obscure. In Caenorhabditis elegans, embryonic development is inextricably dependent on both maternally derived heme and environmentally acquired heme. Here, we show that the multidrug resistance protein MRP-5/ABCC5 likely acts as a heme exporter, and targeted depletion of mrp-5 in the intestine causes embryonic lethality. Transient knockdown of mrp5 in zebrafish leads to morphological defects and failure to hemoglobinize red blood cells. MRP5 resides on the plasma membrane and endosomal compartments and regulates export of cytosolic heme. Together, our genetic studies in worms, yeast, zebrafish, and mammalian cells identify a conserved, physiological role for a multidrug resistance protein in regulating systemic heme homeostasis. We envision other MRP family members may play similar unanticipated physiological roles in animal development.

Paper title : Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood-brain barrier.

Doi : https://doi.org/10.1016/j.neuroscience.2005.11.011

Abstract : Multidrug transporters of the ATP-binding cassette family play an important role in regulating drug distribution and efflux in the brain, owing to their selective distribution in microvessels and choroid plexus. Their expression pattern and cellular distribution remain controversial, in part due to technical difficulties in localizing these membrane proteins in closely associated cells, such as endothelial cells and astrocytic end-feet at the blood-brain barrier. Here, we used high-resolution immunofluorescence staining with cell-type specific markers to investigate the distribution of major ATP-binding cassette transporters in mouse brain. We report that four ATP-binding cassette transporters, Mdr1, Mrp1, Mrp2 and Mrp5 can be detected in brain endothelial cells, forming three distinct layers, with Mdr1 and Mrp5 being located on the luminal side, Mrp1 on the abluminal (basal) side, and Mrp2 in between. Mrp3 and Mdr3 were undetectable. In choroid plexus, only Mrp1, Mrp2 and Mrp3 were detected, again with a differential distribution. Mrp1 was targeted basolaterally in epithelial cells, Mrp2 was restricted to endothelial cells, and Mrp3 was co-localized with zonula occludens-1 at tight junctions. Analysis of Mdr1a(0/0) and Mrp1(0/0) mice, generated in the FVB strain, revealed no major alteration in expression of the remaining transporters. An unexpected strain difference was unraveled, with wildtype FVB mice selectively lacking Mrp2 protein in brain, but not liver. In conclusion, these results indicate that ATP-binding cassette transporters provide multiple penetration barriers in the blood-brain barrier and choroid plexus, with a selective cellular and subcellular distribution, emphasizing their potential role for drug resistance in neurological disorders, such as epilepsy.

Paper title : The phagosomal proteome in interferon-gamma-activated macrophages.

Doi : https://doi.org/10.1016/j.immuni.2008.11.006

Abstract : The ability of macrophages to clear pathogens and elicit a sustained immune response is regulated by various cytokines, including interferon-gamma (IFN-gamma). To investigate the molecular mechanisms by which IFN-gamma modulates phagosome functions, we profiled the changes in composition, abundance, and phosphorylation of phagosome proteins in resting and activated macrophages by using quantitative proteomics and bioinformatics approaches. We identified 2415 phagosome proteins together with 2975 unique phosphorylation sites with a high level of sensitivity. Using network analyses, we determined that IFN-gamma delays phagosomal acquisition of lysosomal hydrolases and peptidases for the gain of antigen presentation. Furthermore, this gain in antigen presentation is dependent on phagosomal networks of the actin cytoskeleton and vesicle-trafficking proteins, as well as Src kinases and calpain proteases. Major histocompatibility complex class I antigen-presentation assays validated the molecular participation of these networks in the enhanced capacity of IFN-gamma-activated macrophages to crosspresent exogenous antigens to CD8(+) T cells.

Paper title : ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs.

Doi : https://doi.org/10.1074/jbc.M115.692103

Abstract : The ubiquitous efflux transporter ABCC5 (ATP-binding cassette subfamily C member 5) is present at high levels in the blood-brain barrier, neurons, and glia, but its in vivo substrates and function are not known. Using untargeted metabolomic screens, we show that Abcc5(-/-) mice accumulate endogenous glutamate conjugates in several tissues, but brain in particular. The abundant neurotransmitter N-acetylaspartylglutamate was 2.4-fold higher in Abcc5(-/-) brain. The metabolites that accumulated in Abcc5(-/-) tissues were depleted in cultured cells that overexpressed human ABCC5. In a vesicular membrane transport assay, ABCC5 also transported exogenous glutamate analogs, like the classic excitotoxic neurotoxins kainic acid, domoic acid, and NMDA; the therapeutic glutamate analog ZJ43; and, as previously shown, the anti-cancer drug methotrexate. Glutamate conjugates and analogs are of physiological relevance because they can affect the function of glutamate, the principal excitatory neurotransmitter in the brain. After CO2 asphyxiation, several immediate early genes were expressed at lower levels in Abcc5(-/-) brains than in wild type brains, suggesting altered glutamate signaling. Our results show that ABCC5 is a general glutamate conjugate and analog transporter that affects the disposition of endogenous metabolites, toxins, and drugs.