TheSLC22A5 gene, containing 10 exons,[7] is located on the q arm ofchromosome 5 in position 31.1 and spans 25,910 base pair.[5] The gene produces a 63 kDa protein composed of 557amino acids.[8][9] The protein has 12 putativetransmembrane domains, with a long extracellular loop of 107 amino acids between the first two transmembrane domains and an intracellular loop between the fourth and fifth transmembrane domains. This long extracellular loop has three potential sites forN-glycosylation, and the intracellular loop has anATP/GTP binding motif. In putative intracellular domains, there are five potential sites forprotein-kinase C-dependent phosphorylation and one forprotein-kinase A-dependent phosphorylation.[10]
TheSLC22A5 gene codes for a plasmaintegral membrane protein which functions as both anorganic cation transporter and a sodium-dependent high affinitycarnitine transporter.[5] The encoded protein is involved in the active cellular uptake of carnitine, transporting onesodium ion with one molecule of carnitine. Organic cations transported by this protein includetetraethylammonium (TEA) without involvement of sodium. The relative uptake activity ratio of carnitine to TEA is 11.3.[11]
^Wu X, Prasad PD, Leibach FH, Ganapathy V (May 1998). "cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family".Biochemical and Biophysical Research Communications.246 (3):589–95.doi:10.1006/bbrc.1998.8669.PMID9618255.
^Yilmaz TF, Atay M, Toprak H, Guler S, Aralasmak A, Alkan A (2014-03-10). "MRI findings in encephalopathy with primary carnitine deficiency: a case report".Journal of Neuroimaging.25 (2):325–328.doi:10.1111/jon.12102.PMID24612242.S2CID35640542.
^Mazzini M, Tadros T, Siwik D, Joseph L, Bristow M, Qin F, Cohen R, Monahan K, Klein M, Colucci W (2011). "Primary carnitine deficiency and sudden death: in vivo evidence of myocardial lipid peroxidation and sulfonylation of sarcoendoplasmic reticulum calcium ATPase 2".Cardiology.120 (1):52–8.doi:10.1159/000333127.PMID22116472.S2CID207687571.
^Yoon YA, Lee DH, Ki CS, Lee SY, Kim JW, Lee YW, Park HD (2012). "SLC22A5 mutations in a patient with systemic primary carnitine deficiency: the first Korean case confirmed by biochemical and molecular investigation".Annals of Clinical and Laboratory Science.42 (4):424–8.PMID23090741.
^Agnetti A, Bitton L, Tchana B, Raymond A, Carano N (January 2013). "Primary carnitine deficiency dilated cardiomyopathy: 28 years follow-up".International Journal of Cardiology.162 (2): e34–5.doi:10.1016/j.ijcard.2012.05.038.PMID22658351.
Erguven M, Yilmaz O, Koc S, Caki S, Ayhan Y, Donmez M, Dolunay G (2007). "A case of early diagnosed carnitine deficiency presenting with respiratory symptoms".Annals of Nutrition & Metabolism.51 (4):331–4.doi:10.1159/000107675.PMID17726310.S2CID40574037.
Hwu WL, Chien YH, Tang NL, Law LK, Lin CY, Lee NC (October 2007). "Deficiency of the carnitine transporter (OCTN2) with partial N-acetylglutamate synthase (NAGS) deficiency".Journal of Inherited Metabolic Disease.30 (5): 816.doi:10.1007/s10545-007-0594-y.PMID17703373.S2CID2764651.
Makhseed N, Vallance HD, Potter M, Waters PJ, Wong LT, Lillquist Y, Pasquali M, Amat di San Filippo C, Longo N (2004). "Carnitine transporter defect due to a novel mutation in the SLC22A5 gene presenting with peripheral neuropathy".Journal of Inherited Metabolic Disease.27 (6):778–80.doi:10.1023/B:BOLI.0000045837.23328.f4.PMID15617188.S2CID24144621.
Kinali M, Olpin SE, Clayton PT, Daubeney PE, Mercuri E, Manzur AY, Tein I, Leonard J, Muntoni F (2004). "Diagnostic difficulties in a case of primary systemic carnitine deficiency with idiopathic dilated cardiomyopathy".European Journal of Paediatric Neurology.8 (4):217–9.doi:10.1016/j.ejpn.2004.03.007.PMID15261886.
Kinali M, Olpin SE, Clayton PT, Daubeney PE, Mercuri E, Manzur AY, Tein I, Leonard J, Muntoni F (2004). "Diagnostic difficulties in a case of primary systemic carnitine deficiency with idiopathic dilated cardiomyopathy".European Journal of Paediatric Neurology.8 (4):217–9.doi:10.1016/j.ejpn.2004.03.007.PMID15261886.
Matsuishi T, Hirata K, Terasawa K, Kato H, Yoshino M, Ohtaki E, Hirose F, Nonaka I, Sugiyama N, Ohta K (February 1985). "Successful carnitine treatment in two siblings having lipid storage myopathy with hypertrophic cardiomyopathy".Neuropediatrics.16 (1):6–12.doi:10.1055/s-2008-1052536.PMID3974805.S2CID260240244.
Wu X, Prasad PD, Leibach FH, Ganapathy V (May 1998). "cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family".Biochemical and Biophysical Research Communications.246 (3):589–95.doi:10.1006/bbrc.1998.8669.PMID9618255.
Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, Nikaido H, Sai Y, Koizumi A, Shoji Y, Takada G, Matsuishi T, Yoshino M, Kato H, Ohura T, Tsujimoto G, Hayakawa J, Shimane M, Tsuji A (January 1999). "Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter".Nature Genetics.21 (1):91–4.doi:10.1038/5030.PMID9916797.S2CID20723174.
Burwinkel B, Kreuder J, Schweitzer S, Vorgerd M, Gempel K, Gerbitz KD, Kilimann MW (August 1999). "Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality".Biochemical and Biophysical Research Communications.261 (2):484–7.doi:10.1006/bbrc.1999.1060.PMID10425211.
Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V (September 1999). "Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter".The Journal of Pharmacology and Experimental Therapeutics.290 (3):1482–92.PMID10454528.
Vaz FM, Scholte HR, Ruiter J, Hussaarts-Odijk LM, Pereira RR, Schweitzer S, de Klerk JB, Waterham HR, Wanders RJ (1999). "Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency".Human Genetics.105 (1–2):157–61.doi:10.1007/s004390051079.PMID10480371.
Ohashi R, Tamai I, Inano A, Katsura M, Sai Y, Nezu J, Tsuji A (September 2002). "Studies on functional sites of organic cation/carnitine transporter OCTN2 (SLC22A5) using a Ser467Cys mutant protein".The Journal of Pharmacology and Experimental Therapeutics.302 (3):1286–94.doi:10.1124/jpet.102.036004.PMID12183691.S2CID1944987.
Rahbeeni Z, Vaz FM, Al-Hussein K, Bucknall MP, Ruiter J, Wanders RJ, Rashed MS (September 2002). "Identification of two novel mutations in OCTN2 from two Saudi patients with systemic carnitine deficiency".Journal of Inherited Metabolic Disease.25 (5):363–9.doi:10.1023/A:1020143632011.PMID12408185.S2CID25824831.
Elimrani I, Lahjouji K, Seidman E, Roy MJ, Mitchell GA, Qureshi I (May 2003). "Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells".American Journal of Physiology. Gastrointestinal and Liver Physiology.284 (5): G863–71.doi:10.1152/ajpgi.00220.2002.PMID12684216.
Karlic H, Lohninger A, Laschan C, Lapin A, Böhmer F, Huemer M, Guthann E, Rappold E, Pfeilstöcker M (July 2003). "Downregulation of carnitine acyltransferases and organic cation transporter OCTN2 in mononuclear cells in healthy elderly and patients with myelodysplastic syndromes".Journal of Molecular Medicine.81 (7):435–42.doi:10.1007/s00109-003-0447-6.PMID12802501.S2CID10992930.
