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SLC22A5

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(Redirected from OCTN2) Protein-coding gene in the species Homo sapiens
SLC22A5
Identifiers
AliasesSLC22A5, CDSP, OCTN2, solute carrier family 22 member 5
External IDsOMIM: 603377; MGI: 1329012; HomoloGene: 68295; GeneCards: SLC22A5; OMA:SLC22A5 - orthologs
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)
Chromosome 5 (human)Genomic location for SLC22A5Genomic location for SLC22A5
Band5q31.1Start132,369,710 bp
End132,395,613 bp
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)
Chromosome 11 (mouse)Genomic location for SLC22A5Genomic location for SLC22A5
Band11 B1.3|11 32.02 cMStart53,755,368 bp
End53,782,486 bp
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • gastrocnemius muscle

  • mucosa of transverse colon

  • mucosa of ileum

  • jejunal mucosa

  • muscle of thigh

  • right uterine tube

  • human kidney

  • right hemisphere of cerebellum

  • apex of heart

  • tibialis anterior muscle
Top expressed in
  • right kidney

  • human kidney

  • proximal tubule

  • duodenum

  • decidua

  • spermatocyte

  • choroid plexus of fourth ventricle

  • muscle of thigh

  • spermatid

  • blastocyst
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

6584

20520

Ensembl

ENSG00000197375

ENSMUSG00000018900

UniProt

O76082

Q9Z0E8

RefSeq (mRNA)

NM_001308122
NM_003060

NM_011396
NM_001362711
NM_001362712

RefSeq (protein)

NP_001295051
NP_003051

NP_035526
NP_001349640
NP_001349641

Location (UCSC)Chr 5: 132.37 – 132.4 MbChr 11: 53.76 – 53.78 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

SLC22A5 is a membrane transport protein associated with primary carnitine deficiency. This protein is involved in the active cellular uptake of carnitine. It acts a symporter, moving sodium ions and other organic cations across the membrane along with carnitine. Such polyspecific 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. Mutations in the SLC22A5 gene cause systemic primary carnitine deficiency, which can lead to heart failure.

Structure

The SLC22A5 gene, containing 10 exons, is located on the q arm of chromosome 5 in position 31.1 and spans 25,910 base pair. The gene produces a 63 kDa protein composed of 557 amino acids. The protein has 12 putative 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.

Function

The SLC22A5 gene codes for a plasma integral membrane protein which functions as both an organic cation transporter and a sodium-dependent high affinity carnitine transporter. 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.

Clinical Significance

The main phenotypical effect of autosomal recessive mutations, either compound heterozygous or homozygous, in the SLC22A5 gene is systemic primary carnitine deficiency, characterized by impaired carnitine transport, urinary carnitine wasting, low serum carnitine levels, reduced intracellular carnitine accumulation, impaired beta oxidation, and cytosolic fatty acid accumulation. Patients often display metabolic decompensation, hypoketotic hypoglycemia, hepatic encephalopathy, Reye syndrome, and sudden infant death in their first year, followed by the later onset of cardiomyopathy or skeletal myopathy, arrhythmias, muscle weakness, and heart failure in early childhood. 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. The symptoms and outcome of the disease can be drastically improved by replacement therapy with L-carnitine. The estimated incidence of primary carnitine deficiency in newborns is about 1 in 40,000.

Interactions

SLC22A5 interacts with PDZK1.

See also

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000197375 – Ensembl, May 2017
  2. ^ GRCm38: Ensembl release 89: ENSMUSG00000018900 – Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: SLC22A5 solute carrier family 22 (organic cation transporter), member 5". Retrieved 2018-07-25.
  6. ^ Lahrouchi N, Lodder EM, Mansouri M, Tadros R, Zniber L, Adadi N, Clur SB, van Spaendonck-Zwarts KY, Postma AV, Sefiani A, Ratbi I, Bezzina CR (June 2017). "Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death". European Journal of Human Genetics. 25 (6): 783–787. doi:10.1038/ejhg.2017.22. PMC 5477358. PMID 28295041.
  7. ^ Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: {603377}: {04/29/2015}: . World Wide Web URL: https://omim.org/
  8. Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  9. "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.
  10. 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. PMID 9618255.
  11. ^ "SLC22A5 - Solute carrier family 22 member 5 - Homo sapiens (Human) - SLC22A5 gene & protein". www.uniprot.org. Retrieved 2018-07-25.
  12. 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. PMID 24612242. S2CID 35640542.
  13. 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. PMID 22116472. S2CID 207687571.
  14. 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. PMID 23090741.
  15. 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. PMID 22658351.
  16. 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. doi:10.1093/hmg/8.12.2247. PMID 10545605.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane proteins, carrier proteins: membrane transport proteins solute carrier (TC 2A)
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SLC11–20
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SLC21–30
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SLC31–40
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SLC41–48
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SLCO1–4
Ion pumps
Symporter, Cotransporter
Antiporter (exchanger)
see also solute carrier disorders
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