SLC22A5
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 5: 132.37 – 132.4 Mb | Chr 11: 53.76 – 53.78 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
SLC22A5 is a
organic cation transporters in the liver, kidney, intestine, and other organs are critical for the elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins.[5] Mutations in the SLC22A5 gene cause systemic primary carnitine deficiency, which can lead to heart failure.[6]
Structure
The SLC22A5 gene, containing 10 exons,transmembrane 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 for N-glycosylation, and the intracellular loop has an ATP/GTP binding motif. In putative intracellular domains, there are five potential sites for protein-kinase C-dependent phosphorylation and one for protein-kinase A-dependent phosphorylation.[10]
Function
The SLC22A5 gene codes for a plasma
organic cation transporter and a sodium-dependent high affinity carnitine transporter.[5] The encoded protein is involved in the active cellular uptake of carnitine, transporting one sodium ion with one molecule of carnitine. Organic cations transported by this protein include tetraethylammonium (TEA) without involvement of sodium. The relative uptake activity ratio of carnitine to TEA is 11.3.[11]
Clinical Significance
The main
arrhythmias, muscle weakness, and heart failure in early childhood.[6][12][13] Patients may be asymptomatic, with about 70% of asymptomatic patients having a missense mutation or in-frame deletion; nonsense mutation frequency is increased in symptomatic patients.[14] The symptoms and outcome of the disease can be drastically improved by replacement therapy with L-carnitine.[15] The estimated incidence of primary carnitine deficiency in newborns is about 1 in 40,000.[16]
Interactions
SLC22A5 interacts with PDZK1.[11]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000197375 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018900 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c "Entrez Gene: SLC22A5 solute carrier family 22 (organic cation transporter), member 5". Retrieved 2018-07-25.
- ^ PMID 28295041.
- ^ a b Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {603377}: {04/29/2015}: . World Wide Web URL: https://omim.org/
- PMID 23965338.
- ^ "SLC22A5 - Solute carrier family 22 member 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-07-26. Retrieved 2018-07-25.
- PMID 9618255.
- ^ a b "SLC22A5 - Solute carrier family 22 member 5 - Homo sapiens (Human) - SLC22A5 gene & protein". www.uniprot.org. Retrieved 2018-07-25.
- S2CID 35640542.
- S2CID 207687571.
- PMID 23090741.
- PMID 22658351.
- PMID 10545605.
Further reading
- Ascunce RR, Nayar AC, Phoon CK, Srichai MB (2013). "Cardiac magnetic resonance findings in a case of carnitine deficiency". Texas Heart Institute Journal. 40 (1): 104–5. PMID 23468586.
- 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. S2CID 40574037.
- 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. S2CID 2764651.
- 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. S2CID 24144621.
- 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. PMID 15261886.
- 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. PMID 15261886.
- Silverberg MS (June 2006). "OCTNs: will the real IBD5 gene please stand up?". World Journal of Gastroenterology. 12 (23): 3678–81. PMID 16773684.
- 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. S2CID 260240244.
- 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. PMID 9618255.
- Shoji Y, Koizumi A, Kayo T, Ohata T, Takahashi T, Harada K, Takada G (July 1998). "Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q". American Journal of Human Genetics. 63 (1): 101–8. PMID 9634512.
- Tamai I, Ohashi R, Nezu J, Yabuuchi H, Oku A, Shimane M, Sai Y, Tsuji A (August 1998). "Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2". The Journal of Biological Chemistry. 273 (32): 20378–82. PMID 9685390.
- 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. S2CID 20723174.
- Tang NL, Ganapathy V, Wu X, Hui J, Seth P, Yuen PM, Wanders RJ, Fok TF, Hjelm NM (April 1999). "Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency". Human Molecular Genetics. 8 (4): 655–60. PMID 10072434.
- 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. PMID 10425211.
- 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. PMID 10454528.
- 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. PMID 10480371.
- Koizumi A, Nozaki J, Ohura T, Kayo T, Wada Y, Nezu J, Ohashi R, Tamai I, Shoji Y, Takada G, Kibira S, Matsuishi T, Tsuji A (November 1999). "Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency". Human Molecular Genetics. 8 (12): 2247–54. PMID 10545605.
- Seth P, Wu X, Huang W, Leibach FH, Ganapathy V (November 1999). "Mutations in novel organic cation transporter (OCTN2), an organic cation/carnitine transporter, with differential effects on the organic cation transport function and the carnitine transport function". The Journal of Biological Chemistry. 274 (47): 33388–92. PMID 10559218.
- Mayatepek E, Nezu J, Tamai I, Oku A, Katsura M, Shimane M, Tsuji A (January 2000). "Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency". Human Mutation. 15 (1): 118. PMID 10612840.
- Wang Y, Kelly MA, Cowan TM, Longo N (2000). "A missense mutation in the OCTN2 gene associated with residual carnitine transport activity". Human Mutation. 15 (3): 238–45. S2CID 34117262.
- 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. S2CID 1944987.
- 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. S2CID 25824831.
- 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. PMID 12684216.
- 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. S2CID 10992930.
- Amat di San Filippo C, Wang Y, Longo N (November 2003). "Functional domains in the carnitine transporter OCTN2, defective in primary carnitine deficiency". The Journal of Biological Chemistry. 278 (48): 47776–84. PMID 14506273.
External links
- SLC22A5+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Primary Carnitine Deficiency (OCTN2 database)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.