title: The SLC37 family of sugar-phosphate/phosphate exchangers.
abstract: The SLC37 family members are endoplasmic reticulum (ER)-associated sugar-phosphate/phosphate (P(i)) exchangers. Three of the four members, SLC37A1, SLC37A2, and SLC37A4, function as Pi-linked glucose-6-phosphate (G6P) antiporters catalyzing G6P:P(i) and P(i):P(i) exchanges. The activity of SLC37A3 is unknown. SLC37A4, better known as the G6P transporter (G6PT), has been extensively characterized, functionally and structurally, and is the best characterized family member. G6PT contains 10 transmembrane helices with both N and C termini facing the cytoplasm. The primary in vivo function of the G6PT protein is to translocate G6P from the cytoplasm into the ER lumen where it couples with either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α or G6PC) or the ubiquitously expressed G6Pase-β (or G6PC3) to hydrolyze G6P to glucose and P(i). The G6PT/G6Pase-α complex maintains interprandial glucose homeostasis, and the G6PT/G6Pase-β complex maintains neutrophil energy homeostasis and functionality. G6PT is highly selective for G6P and is competitively inhibited by cholorogenic acid and its derivatives. Neither SLC37A1 nor SLC37A2 can couple functionally with G6Pase-α or G6Pase-β, and the antiporter activities of SLC37A1 or SLC37A2 are not inhibited by cholorogenic acid. Deficiencies in G6PT cause glycogen storage disease type Ib (GSD-Ib), a metabolic and immune disorder. To date, 91 separate SLC37A4 mutations, including 39 missense mutations, have been identified in GSD-Ib patients. Characterization of missense mutations has yielded valuable information on functionally important residues in the G6PT protein. The biological roles of the other SLC37 proteins remain to be determined and deficiencies have not yet been correlated to diseases.
authors.affiliation: Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: chouja@mail.nih.gov.
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Chou
authors.affiliation: Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA; Foundation Fighting Blindness, Columbia, Maryland, USA.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Mansfield
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010710:Phosphates / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D026901:Membrane Transport Proteins; D010710:Phosphates
keywords: Chlorogenic acid; Endoplasmic reticulum; Glucose-6-phosphate transporter; Glycogen storage disease type Ib; P(i)-linked G6P antiporters
references.citation: Science. 2003 Aug 1;301(5633):616-20
references.pmid: 12893936
references.citation: J Biol Chem. 1999 Mar 5;274(10):6148-53
references.pmid: 10037698
references.citation: J Biol Chem. 2000 Nov 3;275(44):34280-6
references.pmid: 10940311
references.citation: Eur J Pharmacol. 1999 Dec 10;386(1):75-82
references.pmid: 10611466
references.citation: J Med Chem. 1997 Jan 17;40(2):137-45
references.pmid: 9003513
references.citation: J Mol Genet Med. 2011;5:262-3
references.pmid: 21629566
references.citation: J Biol Chem. 2003 Nov 21;278(47):47098-103
references.pmid: 13129915
references.citation: Curr Mol Med. 2002 Mar;2(2):121-43
references.pmid: 11949931
references.citation: FEBS J. 2012 Jun;279(11):2022-35
references.pmid: 22458847
references.citation: PLoS One. 2011;6(9):e23157
references.pmid: 21949678
references.citation: Biochem J. 1994 Aug 15;302 ( Pt 1):253-60
references.pmid: 8068013
references.citation: Nucleic Acids Res. 1988 Nov 25;16(22):10881-90
references.pmid: 2849754
references.citation: Biochim Biophys Acta. 2000 Jul 24;1492(2-3):385-94
references.pmid: 11004510
references.citation: Science. 1993 Oct 22;262(5133):580-3
references.pmid: 8211187
references.citation: Nat Genet. 1996 Jun;13(2):203-9
references.pmid: 8640227
references.citation: Diabetes. 2001 Nov;50(11):2591-7
references.pmid: 11679439
references.citation: Semin Cell Dev Biol. 2007 Dec;18(6):732-42
references.pmid: 17997334
references.citation: Genomics. 2000 Dec 1;70(2):190-200
references.pmid: 11112347
references.citation: J Biol Chem. 1983 Aug 25;258(16):9739-44
references.pmid: 6309784
references.citation: Hum Genet. 2000 Nov;107(5):526-9
references.pmid: 11140953
references.citation: Arch Biochem Biophys. 1998 Mar 15;351(2):279-85
references.pmid: 9514661
references.citation: Hum Mol Genet. 2003 Oct 1;12(19):2547-58
references.pmid: 12925567
references.citation: FASEB J. 2008 Jul;22(7):2206-13
references.pmid: 18337460
references.citation: J Biol Chem. 2004 Mar 26;279(13):12479-83
references.pmid: 14718531
references.citation: Mol Genet Metab. 2008 Dec;95(4):220-3
references.pmid: 18835800
references.citation: Blood. 2012 Apr 26;119(17):4047-55
references.pmid: 22246029
references.citation: Annu Rev Biochem. 2000;69:69-93
references.pmid: 10966453
references.citation: J Biol Chem. 2002 Sep 6;277(36):32837-42
references.pmid: 12093795
references.citation: FEBS Lett. 1997 Dec 15;419(2-3):235-8
references.pmid: 9428641
references.citation: J Bacteriol. 1990 Apr;172(4):1688-93
references.pmid: 2156798
references.citation: Zhonghua Er Ke Za Zhi. 2011 Mar;49(3):203-8
references.pmid: 21575371
references.citation: Hum Genet. 2000 Sep;107(3):285-9
references.pmid: 11071391
references.citation: J Biol Chem. 1999 May 14;274(20):13865-9
references.pmid: 10318794
references.citation: Mol Aspects Med. 2013 Apr-Jun;34(2-3):601-11
references.pmid: 23506893
references.citation: Hum Genet. 2003 Apr;112(4):430-3
references.pmid: 12560945
references.citation: Biochem J. 2010 Dec 1;432(2):249-54
references.pmid: 20854262
references.citation: Biochem J. 2001 Jul 15;357(Pt 2):557-62
references.pmid: 11439108
references.citation: Breast Cancer Res Treat. 2010 Aug;122(3):755-64
references.pmid: 19894109
references.citation: Biochemistry. 2004 Jul 27;43(29):9289-97
references.pmid: 15260472
references.citation: J Biol Chem. 1998 Nov 27;273(48):31656-60
references.pmid: 9822626
references.citation: Nat Chem Biol. 2007 Jun;3(6):313-20
references.pmid: 17510649
references.citation: Hum Mol Genet. 2002 Dec 1;11(25):3199-207
references.pmid: 12444104
references.citation: Pflugers Arch. 2004 Feb;447(5):780-3
references.pmid: 12811562
references.citation: J Membr Biol. 1998 Jul 15;164(2):187-95
references.pmid: 9662562
references.citation: FEBS Lett. 2001 Aug 31;504(3):87-93
references.pmid: 11532438
references.citation: J Clin Invest. 2007 Mar;117(3):784-93
references.pmid: 17318259
references.citation: Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E110-20
references.pmid: 17356011
references.citation: Eur J Hum Genet. 1999 Sep;7(6):717-23
references.pmid: 10482962
references.citation: Microbiol Mol Biol Rev. 1998 Mar;62(1):1-34
references.pmid: 9529885
references.citation: Blood. 2010 Oct 14;116(15):2783-92
references.pmid: 20498302
references.citation: J Cell Biol. 1993 Apr;121(2):317-33
references.pmid: 8468349
references.citation: Gene. 1999 Feb 18;227(2):189-95
references.pmid: 10023055
references.citation: J Biol Chem. 1972 Apr 25;247(8):2558-65
references.pmid: 4336378
references.citation: Nat Rev Endocrinol. 2010 Dec;6(12):676-88
references.pmid: 20975743
references.citation: Mol Genet Metab. 2009 Jan;96(1):32-7
references.pmid: 19008136
references.citation: J Biol Chem. 1993 Mar 15;268(8):5798-801
references.pmid: 8449946
references.citation: Am J Hum Genet. 1998 Oct;63(4):976-83
references.pmid: 9758626
references.citation: Am J Hum Genet. 1998 Feb;62(2):400-5
references.pmid: 9463334
references.citation: J Biol Chem. 1999 Feb 26;274(9):5532-6
references.pmid: 10026167
references.citation: Hum Genomics. 2009 Jan;3(2):195-206
references.pmid: 19164095
references.citation: EMBO J. 1990 Oct;9(10):3153-62
references.pmid: 2120038
references.citation: Curr Opin Hematol. 2010 Jan;17(1):36-42
references.pmid: 19741523
references.citation: N Engl J Med. 2009 Jan 1;360(1):32-43
references.pmid: 19118303
references.citation: FEBS Lett. 1999 Oct 8;459(2):255-8
references.pmid: 10518030
references.citation: J Biol Chem. 1976 Nov 10;251(21):6784-90
references.pmid: 10305
references.citation: J Biol Chem. 2000 Jan 14;275(2):828-32
references.pmid: 10625614