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Regular Article Tissue-Specific Mrna Expression Profiles of Human Solute Carrier Transporter Superfamilies

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Drug Metab. Pharmacokinet. 23 (1): 22–44 (2008). Regular Article Tissue-specific mRNA Expression Profiles of Human Solute Carrier Transporter Superfamilies Masuhiro NISHIMURA and Shinsaku NAITO* Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan Full text of this paper is available at http://www.jstage.jst.go.jp/browse/dmpk Summary: Pairs of forward and reverse primers and TaqMan probes specific to each of 173 human solute carrier (SLC) transporters were prepared. The mRNA expression level of each target transporter was ana- lyzed in total RNA from single and pooled specimens of various human tissues (adrenal gland, bladder, bone marrow, brain, colon, heart, kidney, liver, lung, mammary gland, ovary, pancreas, peripheral leukocytes, placenta, prostate, retina, salivary gland, skeletal muscle, small intestine, smooth muscle, spinal cord, spleen, stomach, testis, thymus, thyroid gland, trachea, and uterus) by real-time reverse transcription PCR using an Applied Biosystems 7500 Fast Real-Time PCR System. Individual differences in the mRNA expression of hu- man SLC transporters in the liver were also evaluated. These newly determined expression profiles were used to study the gene expression in the 28 different human tissues listed above, and tissues with high transcrip- tional activity for human SLC transporters were identified. These results are expected to be valuable for research concerning the clinical diagnosis of disease. Keywords: SLC transporter; mRNA expression; tissue distribution; quantification; human SLC28As, SLC29As, SLC36As, and SLC38As.9) However, the Introduction tissue distribution of the mRNA expression of many other hu- Solute carrier (SLC) transporters transport a variety of sub- man SLC transporters such as SLC8As, SLC9As, SLC11As, strates, including amino acids, lipids, inorganic ions, peptides, SLC12As, SLC13As, SLC14As, SLC16As, SLC17As, SLC18As, saccharides, metals, drugs, toxic xenobiotics, chemical com- SLC19AS, SLC20As, SLC23As, SLC24As, SLC25As, SLC26As, pounds, and proteins.1–8) Assessment of the protein levels SLC27As, SLC30As, SLC31As, SLC32A1, SLC33A1, SLC34As, and/or transport capacity of each SLC transporter is important SLC37As, SLC39As, SLC40A1, and SLC41As has not been in identifying the transporters that may be involved in the in- evaluated under the same experimental conditions. These im- flux and efflux of many substrates. However, such assessment portant transporters transport a variety of substrates such as of these SLC transporters in the same sample is difficult be- monocarboxylate, folate/thiamine, inorganic ions, metals, ami- causealargeamountofsampleisrequiredformeasurement. no acids, drugs, and other chemical compounds.4–8,10,11) For ex- Thus, we considered that rapid estimation should be possible ample, it is known that SLC16As are transporters for monocar- by the detailed evaluation of the mRNA expression levels of boxylate,4) SLC19As are transporters for folate/thiamine,5) each transporter in target tissues based on the findings of SLC11As, SLC30As, SLC39As, and SLC41As are transporters previous studies, followed by the evaluation of protein levels for metals,6,8) and SLC25As are transporters for a variety of and transport capacities. Investigation of the tissue-specific substrates such as ATP/ADP, amino acids, malate, ornithine, mRNA expression profiles of SLC transporters could therefore and citruline.10) The present study was therefore undertaken to provide important information concerning the mechanisms of investigate the mRNA expression levels of these 173 human the influx and efflux of endogenous and exogenous substrates. SLC transporters in total RNA from single and pooled speci- We have previously reported the tissue distribution of the mens of 28 adult human tissues using high-sensitivity real-time mRNA expression of large numbers of human SLC transport- reverse transcription PCR (RT-PCR). The nomenclature of the ers such as SLC1As, SLC2As, SLC3As, SLC4As, SLC5As, transporters that were evaluated in the present study is sum- SLC6As, SLC7As, SLC10As, SLC15As, SLC21As, SLC22As, marized in Table 1. Received; August 20, 2007, Accepted; November 2, 2007 *To whom correspondence should be addressed: Shinsaku NAITO,Ph.D.,Division of Pharmacology, Drug Safety and Metabolism, Otsuka Phar- maceutical Factory, Inc., Naruto, Tokushima 772-8601, Japan. Tel. ＋81-88-685-1151, Fax. ＋81-88-686-8176, E-mail: naitousn＠otsukakj.co.jp 22 mRNA Expression Profiles of Human SLC Transporters 23 Table 1. Nomenclature of Target Genes Table 1. (continued) Abbreviation Trivial Name(s)/Synonym(s) Abbreviation Trivial Name(s)/Synonym(s) SLC8A1 NCX1, MGC119581, DKFZp779F0871 SLC24A4 NCKX4, SLC24A2, FLJ38852 SLC8A2 NCX2 SLC24A5 JSX, NCKX5 SLC8A3 NCX3 SLC24A6 NCLX, NCKX6, FLJ22233 SLC9A1 APNH, NHE1, FLJ42224 SLC25A1 CTP, SLC20A3 SLC9A2 NHE2 SLC25A2 ORC2, ORNT2, MGC119151, MGC119153 SLC9A3 NHE3, MGC126718, MGC126720 SLC25A3 PHC, OK/SW-cl.48 SLC9A4 NHE4, DKFZp313B031 SLC25A4 T1, ANT, ANT1, PEO2, PEO3 SLC9A5 NHE5 SLC25A5 T2, T3, 2F1, ANT2 SLC9A6 NHE6, KIAA0267 SLC25A6 ANT3, ANT3Y, MGC17525 SLC9A7 NHE7 SLC25A7 UCP1, UCP SLC9A8 NHE8, FLJ42500, KIAA0939, MGC138418, DKFZp686C03237 SLC25A8 UCP2, UCPH SLC9A9 NHE9, FLJ35613, Nbla00118 SLC25A9 UCP3 SLC9A10 SLC25A10 DIC SLC9A11 MGC43026, RP3-436N22.2 SLC25A11 OGC, SLC20A4 SLC11A1 LSH, NRAMP, NRAMP1 SLC25A12 ARALAR, ARALAR1 SLC11A2 DCT1, DMT1, NRAMP2, FLJ37416 SLC25A13 CTLN2, CITRIN, ARALAR2 SLC12A1 BSC1, NKCC2, MGC48843 SLC25A14 UCP5, BMCP1, MGC149543 SLC12A2 BSC, BSC2, NKCC1, MGC104233 SLC25A15 HHH, ORC1, ORNT1, D13S327 SLC12A3 TSC, NCCT SLC25A16 GDA, GDC, ML7, hML7, HGT.1, D10S105E, MGC39851 SLC12A4 KCC1, FLJ40489 SLC25A17 PMP34 SLC12A5 KCC2, KIAA1176 SLC25A18 GC2 SLC12A6 KCC3, ACCPN, KCC3A, KCC3B, DKFZP434D2135 SLC25A19 DNC, TPC, MUP1, MCPHA SLC12A7 KCC4, DKFZP434F076 SLC25A20 CAC, CACT SLC12A8 CCC9, FLJ23188, DKFZp686L18248 SLC25A21 ODC, ODC1, MGC126570 SLC12A9 CIP1, FLJ46905 SLC25A22 GC1, FLJ13044 SLC13A1 NAS1, NaSi-1 SLC25A23 APC2, MCSC2, MGC2615, SCaMC-3 SLC13A2 NADC1, NaDC-1 SLC25A24 APC1, SCAMC-1, DKFZp586G0123 SLC13A3 NADC3, SDCT2 SLC25A25 MCSC, PCSCL, SCAMC-2, KIAA1896, MGC105138, MGC119514, SLC13A4 SUT1, SUT-1 MGC119515, MGC119516, MGC119517, RP11-395P17.4 SLC13A5 NACT, MGC138356, DKFZp686E17257 SLC25A26 SAMC, DKFZp434E079 SLC14A1 JK, UT1, UTE, HUT11, RACH1, UT-B1, HsT1341, FLJ33745, FLJ41687 SLC25A27 UCP4, FLJ33552, RP11-446F17.2 SLC14A2 UT2, UTR, HUT2, UT-A2, hUT-A6, FLJ16167, MGC119566, MGC119567 SLC25A28 MRS4L, MRS3/4, NPD016, DKFZp547C109 SLC16A1 MCT, MCT1, FLJ36745, MGC44475 SLC25A29 CACL, C14orf69, FLJ38975 SLC16A2 AHDS, MCT7, MCT8, XPCT, DXS128, DXS128E SLC25A30 KMCP1 SLC16A3 MCT3, MCT4, MGC138472, MGC138474 SLC25A31 AAC4, ANT4, SFEC35kDa, DKFZp434N1235 SLC16A4 MCT4, MCT5 SLC25A32 MFT, MFTC, FLJ23872 SLC16A5 MCT5, MCT6 SLC25A33 MGC4399, BMSC-MCP SLC16A6 MCT6, MCT7 SLC25A34 RP11-169K16.2, DKFZp781A10161 SLC16A7 MCT2 SLC25A35 FLJ40217, MGC120446, MGC120448 SLC16A8 MCT3, REMP SLC25A36 FLJ10618 SLC16A9 MCT9, C10orf36, FLJ43803 SLC25A37 MSC, MFRN, MSCP, HT015, PRO1278, PRO1584, PRO2217 SLC16A10 TAT1, PRO0813 SLC25A38 FLJ20551, FLJ22703 SLC16A11 MCT11, FLJ90193 SLC25A39 CGI69, CGI-69, FLJ22407 SLC16A12 MCT12, DKFZp686E188 SLC25A40 MCFP SLC16A13 MCT13 SLC25A41 FLJ40442, MGC34725 SLC16A14 MCT14, FLJ30794 SLC25A42 MGC26694 SLC17A1 NPT1, NPT-1, NAPI-1, MGC126794, MGC126796 SLC25A43 SLC17A2 NPT3, MGC138238 SLC25A44 FLJ90431, KIAA0446, RP11-54H19.3 SLC17A3 HPRD:HPRD_10233 SLC25A45 SLC17A4 KAIA2138, KIAA2138, MGC129623 SLC25A46 SLC17A5 SD, AST, NSD, SLD, ISSD, SIASD, SIALIN, FLJ22227, FLJ23268 SLC26A1 EDM4, SAT1, SAT-1 SLC17A6 DNPI, VGLUT2 SLC26A2 DTD, EDM4, DTDST, MST153, D5S1708, MSTP157 SLC17A7 BNPI, VGLUT1 SLC26A3 CLD, DRA SLC17A8 VGLUT3 SLC26A4 PDS, DFNB4 SLC18A1 CGAT, VAT1, VMAT1 SLC26A5 PRES, DFNB61, MGC118886, MGC118887, MGC118888, MGC118889 SLC18A2 SVAT, SVMT, VAT2, VMAT2, MGC26538, MGC120477, MGC120478 SLC26A6 DKFZp586E1422 SLC18A3 VACHT, MGC12716 SLC26A7 SUT2, MGC126268 SLC19A1 CHMD, FOLT, IFC1, REFC, RFC1 SLC26A8 TAT1, FLJ32714 SLC19A2 TC1, THT1, TRMA, THTR1 SLC26A9 SLC19A3 SLC26A10 SLC20A1 PIT1, GLVR1, PiT-1, Glvr-1, FLJ41426, DKFZp686J2397 SLC26A11 MGC46523 SLC20A2 GLVR2,MLVAR,PIT-2,Glvr-2 SLC27A1 FATP, FATP1, ACSVL5, FLJ00336, MGC71751 SLC23A1 SVCT1, YSPL3, SLC23A2, MGC22361 SLC27A2 VLCS, FATP2, VLACS, ACSVL1, FACVL1, hFACVL1, HsT17226 SLC23A2 NBTL1, SVCT2, YSPL2, SLC23A1, KIAA0238 SLC27A3 FATP3, ACSVL3, VLCS-3, MGC4365 SLC23A3 E2BP3, SVCT3, Yspl1, FLJ31168 SLC27A4 FATP4, ACSVL4 SLC24A1 NCKX, RODX, NCKX1, HsT17412, KIAA0702 SLC27A5 ACSB, FATP5, ACSVL6, FACVL3, VLACSR, VLCSH2, VLCS-H2, FLJ22987 SLC24A2 NCKX2 SLC27A6 FATP6, ACSVL2, FACVL2, VLCS-H1, DKFZp779M0564 SLC24A3 NCKX3 SLC30A1 ZNT1, ZRC1 24 Masuhiro NISHIMURA and Shinsaku NAITO Table 1. (continued) Table 2. Total RNA Source Information for Various Tissues Abbreviation Trivial Name(s)/Synonym(s) Tissue Pool size Age Sex Race SLC30A2 ZNT2, ZnT-2, PP12488, FLJ36708, MGC11303 Total RNA source (purchased from CLONTECH Laboratories, Inc.) SLC30A3 ZNT3 Adrenal gland 62 15–61 years female, male Caucasian SLC30A4 ZNT4 Bladder 20 17–60 years female, male Caucasian SLC30A5 ZNT5, ZTL1, ZNTL1, ZnT-5, MGC5499, FLJ12496, FLJ12756 SLC30A6 ZNT6, FLJ31101, MGC45055 Bone marrow 10 35–60 years female, male Caucasian SLC30A7 ZNT7, ZnT-7, ZnTL2, DKFZp686M0368 Brain 2 47, 55 years male Caucasian SLC30A8 ZnT-8 Colon 1 23 years female Caucasian SLC30A9 HUEL,ZNT9,GAC63,C4orf1 Heart* 10 21–51 years female, male Caucasian SLC30A10 ZnT-10, DKFZp547M236
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    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
  • Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS

    Protein Identities in Evs Isolated from U87-MG GBM Cells As Determined by NG LC-MS/MS

    Protein identities in EVs isolated from U87-MG GBM cells as determined by NG LC-MS/MS. No. Accession Description Σ Coverage Σ# Proteins Σ# Unique Peptides Σ# Peptides Σ# PSMs # AAs MW [kDa] calc. pI 1 A8MS94 Putative golgin subfamily A member 2-like protein 5 OS=Homo sapiens PE=5 SV=2 - [GG2L5_HUMAN] 100 1 1 7 88 110 12,03704523 5,681152344 2 P60660 Myosin light polypeptide 6 OS=Homo sapiens GN=MYL6 PE=1 SV=2 - [MYL6_HUMAN] 100 3 5 17 173 151 16,91913397 4,652832031 3 Q6ZYL4 General transcription factor IIH subunit 5 OS=Homo sapiens GN=GTF2H5 PE=1 SV=1 - [TF2H5_HUMAN] 98,59 1 1 4 13 71 8,048185945 4,652832031 4 P60709 Actin, cytoplasmic 1 OS=Homo sapiens GN=ACTB PE=1 SV=1 - [ACTB_HUMAN] 97,6 5 5 35 917 375 41,70973209 5,478027344 5 P13489 Ribonuclease inhibitor OS=Homo sapiens GN=RNH1 PE=1 SV=2 - [RINI_HUMAN] 96,75 1 12 37 173 461 49,94108966 4,817871094 6 P09382 Galectin-1 OS=Homo sapiens GN=LGALS1 PE=1 SV=2 - [LEG1_HUMAN] 96,3 1 7 14 283 135 14,70620005 5,503417969 7 P60174 Triosephosphate isomerase OS=Homo sapiens GN=TPI1 PE=1 SV=3 - [TPIS_HUMAN] 95,1 3 16 25 375 286 30,77169764 5,922363281 8 P04406 Glyceraldehyde-3-phosphate dehydrogenase OS=Homo sapiens GN=GAPDH PE=1 SV=3 - [G3P_HUMAN] 94,63 2 13 31 509 335 36,03039959 8,455566406 9 Q15185 Prostaglandin E synthase 3 OS=Homo sapiens GN=PTGES3 PE=1 SV=1 - [TEBP_HUMAN] 93,13 1 5 12 74 160 18,68541938 4,538574219 10 P09417 Dihydropteridine reductase OS=Homo sapiens GN=QDPR PE=1 SV=2 - [DHPR_HUMAN] 93,03 1 1 17 69 244 25,77302971 7,371582031 11 P01911 HLA class II histocompatibility antigen,
  • Differential Expression of Hydroxyurea Transporters in Normal and Polycythemia Vera Hematopoietic Stem and Progenitor Cell Subpopulations

    Differential Expression of Hydroxyurea Transporters in Normal and Polycythemia Vera Hematopoietic Stem and Progenitor Cell Subpopulations

    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2021 Differential expression of hydroxyurea transporters in normal and polycythemia vera hematopoietic stem and progenitor cell subpopulations Tan, Ge ; Meier-Abt, Fabienne Abstract: Polycythemia vera (PV) is a myeloproliferative neoplasm marked by hyperproliferation of the myeloid lineages and the presence of an activating JAK2 mutation. Hydroxyurea (HU) is a standard treat- ment for high-risk patients with PV. Because disease-driving mechanisms are thought to arise in PV stem cells, effective treatments should target primarily the stem cell compartment. We tested for theantipro- liferative effect of patient treatment with HU in fluorescence-activated cell sorting-isolated hematopoietic stem/multipotent progenitor cells (HSC/MPPs) and more committed erythroid progenitors (common myeloid/megakaryocyte-erythrocyte progenitors [CMP/MEPs]) in PV using RNA-sequencing and gene set enrichment analysis. HU treatment led to significant downregulation of gene sets associated with cell proliferation in PV HSCs/MPPs, but not in PV CMP/MEPs. To explore the mechanism underlying this finding, we assessed for expression of solute carrier membrane transporters, which mediate trans- membrane movement of drugs such as HU into target cells. The active HU uptake transporter OCTN1 was upregulated in HSC/MPPs compared with CMP/MEPs of untreated patients with PV, and the HU diffusion facilitator urea transporter B (UTB) was downregulated in HSC/MPPs compared withCM- P/MEPs in all patient and control groups tested. These findings indicate a higher accumulation ofHU within PV HSC/MPPs compared with PV CMP/MEPs and provide an explanation for the differential effects of HU in HSC/MPPs and CMP/MEPs of patients with PV.
  • Anti-SLC22A13 (Aa 38-139) Polyclonal Antibody (DPAB-DC3801) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use

    Anti-SLC22A13 (Aa 38-139) Polyclonal Antibody (DPAB-DC3801) This Product Is for Research Use Only and Is Not Intended for Diagnostic Use

    Anti-SLC22A13 (aa 38-139) polyclonal antibody (DPAB-DC3801) This product is for research use only and is not intended for diagnostic use. PRODUCT INFORMATION Antigen Description This gene encodes a member of the organic-cation transporter family. It is located in a gene cluster with another member of the family, organic cation transporter like 4. The encoded protein is a transmembrane protein involved in the transport of small molecules. This protein can function to mediate urate uptake and is a high affinity nicotinate exchanger in the kidneys and the intestine. Immunogen SLC22A13 (NP_004247, 38 a.a. ~ 139 a.a) partial recombinant protein with GST tag. The sequence is AHVFMVLDEPHHCAVAWVKNHTFNLSAAEQLVLSVPLDTAGHPEPCLMFRPPPANASLQDILSH RFNETQPCDMGWEYPENRLPSLKNEFNLVCDRKHLKDT Source/Host Mouse Species Reactivity Human Conjugate Unconjugated Applications WB (Recombinant protein), ELISA, Size 50 μl Buffer 50 % glycerol Preservative None Storage Store at -20°C or lower. Aliquot to avoid repeated freezing and thawing. GENE INFORMATION Gene Name SLC22A13 solute carrier family 22 (organic anion/urate transporter), member 13 [ Homo sapiens (human) ] Official Symbol SLC22A13 Synonyms SLC22A13; solute carrier family 22 (organic anion/urate transporter), member 13; OAT10; 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 1 © Creative Diagnostics All Rights Reserved OCTL1; OCTL3; ORCTL3; ORCTL-3; solute carrier family 22 member 13; organic cation transporter-like 3; organic-cation transporter like 3; organic cationic transporter-like 3; solute carrier family 22, member 13; solute carrier family 22 (organic anion transporter), member 13; Entrez Gene ID 9390 Protein Refseq NP_004247 UniProt ID Q9Y226 Chromosome Location 3p21.3 Function nicotinate transporter activity; organic cation transmembrane transporter activity; 45-1 Ramsey Road, Shirley, NY 11967, USA Email: [email protected] Tel: 1-631-624-4882 Fax: 1-631-938-8221 2 © Creative Diagnostics All Rights Reserved.
  • The Concise Guide to Pharmacology 2019/20

    The Concise Guide to Pharmacology 2019/20

    Edinburgh Research Explorer THE CONCISE GUIDE TO PHARMACOLOGY 2019/20 Citation for published version: Cgtp Collaborators 2019, 'THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters', British Journal of Pharmacology, vol. 176 Suppl 1, pp. S397-S493. https://doi.org/10.1111/bph.14753 Digital Object Identifier (DOI): 10.1111/bph.14753 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: British Journal of Pharmacology General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 28. Sep. 2021 S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Transporters. British Journal of Pharmacology (2019) 176, S397–S493 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters Stephen PH Alexander1 , Eamonn Kelly2, Alistair Mathie3 ,JohnAPeters4 , Emma L Veale3 , Jane F Armstrong5 , Elena Faccenda5 ,SimonDHarding5 ,AdamJPawson5 , Joanna L