NameSolute carrier family 22 member 5
Synonyms
  • High-affinity sodium-dependent carnitine cotransporter
  • OCTN2
  • Organic cation/carnitine transporter 2
Gene NameSLC22A5
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000212|Solute carrier family 22 member 5
MRDYDEVTAFLGEWGPFQRLIFFLLSASIIPNGFTGLSSVFLIATPEHRCRVPDAANLSS
AWRNHTVPLRLRDGREVPHSCRRYRLATIANFSALGLEPGRDVDLGQLEQESCLDGWEFS
QDVYLSTIVTEWNLVCEDDWKAPLTISLFFVGVLLGSFISGQLSDRFGRKNVLFVTMGMQ
TGFSFLQIFSKNFEMFVVLFVLVGMGQISNYVAAFVLGTEILGKSVRIIFSTLGVCIFYA
FGYMVLPLFAYFIRDWRMLLVALTMPGVLCVALWWFIPESPRWLISQGRFEEAEVIIRKA
AKANGIVVPSTIFDPSELQDLSSKKQQSHNILDLLRTWNIRMVTIMSIMLWMTISVGYFG
LSLDTPNLHGDIFVNCFLSAMVEVPAYVLAWLLLQYLPRRYSMATALFLGGSVLLFMQLV
PPDLYYLATVLVMVGKFGVTAAFSMVYVYTAELYPTVVRNMGVGVSSTASRLGSILSPYF
VYLGAYDRFLPYILMGSLTILTAILTLFLPESFGTPLPDTIDQMLRVKGMKHRKTPSHTR
MLKDGQERPTILKSTAF
Number of residues557
Molecular Weight62751.08
Theoretical pI8.04
GO Classification
Functions
  • carnitine transmembrane transporter activity
  • cation
  • drug transmembrane transporter activity
  • PDZ domain binding
  • quaternary ammonium group transmembrane transporter activity
  • symporter activity
  • ATP binding
Processes
  • positive regulation of intestinal epithelial structure maintenance
  • quaternary ammonium group transport
  • transmembrane transport
  • quorum sensing involved in interaction with host
  • sodium-dependent organic cation transport
  • carnitine metabolic process
  • carnitine transmembrane transport
  • sodium ion transport
  • carnitine transport
  • drug transmembrane transport
  • drug transport
  • modified amino acid transport
Components
  • extracellular exosome
  • integral component of plasma membrane
  • apical plasma membrane
  • brush border membrane
  • plasma membrane
General FunctionSymporter activity
Specific FunctionSodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3.
Pfam Domain Function
Transmembrane Regions21-41 143-163 173-193 198-218 233-253 258-278 342-362 374-394 407-427 431-451 463-483 489-509
GenBank Protein ID3273741
UniProtKB IDO76082
UniProtKB Entry NameS22A5_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0009938|Solute carrier family 22 member 5 (SLC22A5)
ATGCGGGACTACGACGAGGTGACCGCCTTCCTGGGCGAGTGGGGGCCCTTCCAGCGCCTC
ATCTTCTTCCTGCTCAGCGCCAGCATCATCCCCAATGGCTTCACCGGCCTGTCCTCCGTG
TTCCTGATAGCGACCCCGGAGCACCGCTGCCGGGTGCCGGACGCCGCGAACCTGAGCAGC
GCCTGGCGCAACCACACTGTCCCACTGCGGCTGCGGGACGGCCGCGAGGTGCCCCACAGC
TGCCGCCGCTACCGGCTCGCCACCATCGCCAACTTCTCGGCGCTTGGGCTGGAGCCGGGG
CGCGACGTGGACCTGGGGCAGCTGGAGCAGGAGAGCTGTCTGGATGGCTGGGAGTTCAGT
CAGGACGTCTACCTGTCCACCATTGTGACCGAGCAAGACAGTGGGGCCTACAATGCTATG
AAAAACAGGATGGGAAAGAAGCCTGCTCTCTGCCTTCCTGCCCAGTGGAACCTGGTGTGT
GAGGACGACTGGAAGGCCCCACTCACAATCTCCTTGTTCTTCGTGGGTGTGCTGTTGGGC
TCCTTCATTTCAGGGCAGCTGTCAGACAGGTTTGGCCGGAAGAATGTGCTGTTCGTGACC
ATGGGCATGCAGACAGGCTTCAGCTTCCTGCAGATCTTCTCGAAGAATTTTGAGATGTTT
GTCGTGCTGTTTGTCCTTGTAGGCATGGGCCAGATCTCCAACTATGTGGCAGCATTTGTC
CTGGGGACAGAAATTCTTGGCAAGTCAGTTCGTATAATATTCTCTACGTTAGGAGTGTGC
ATATTTTATGCATTTGGCTACATGGTGCTGCCACTGTTTGCTTACTTCATCCGAGACTGG
CGGATGCTGCTGGTGGCGCTGACGATGCCGGGGGTGCTATGCGTGGCACTCTGGTGGTTC
ATCCCTGAGTCCCCCCGATGGCTCATCTCTCAGGGACGATTTGAAGAGGCAGAGGTGATC
ATCCGCAAGGCTGCCAAAGCCAATGGGATTGTTGTGCCTTCCACTATCTTTGACCCGAGT
GAGTTACAAGACCTAAGTTCCAAGAAGCAGCAGTCCCACAACATTCTGGATCTGCTTCGA
ACCTGGAATATCCGGATGGTCACCATCATGTCCATAATGCTGTGGATGACCATATCAGTG
GGCTATTTTGGGCTTTCGCTTGATACTCCTAACTTGCATGGGGACATCTTTGTGAACTGC
TTCCTTTCAGCGATGGTTGAAGTCCCAGCATATGTGTTGGCCTGGCTGCTGCTGCAATAT
TTGCCCCGGCGCTATTCCATGGCCACTGCCCTCTTCCTGGGTGGCAGTGTCCTTCTCTTC
ATGCAGCTGGTACCCCCAGACTTGTATTATTTGGCTACAGTCCTGGTGATGGTGGGCAAG
TTTGGAGTCACGGCTGCCTTTTCCATGGTCTACGTGTACACAGCCGAGCTGTATCCCACA
GTGGTGAGAAACATGGGTGTGGGAGTCAGCTCCACAGCATCCCGCCTGGGCAGCATCCTG
TCTCCCTACTTCGTTTACCTTGGTGCCTACGACCGCTTCCTGCCCTACATTCTCATGGGA
AGTCTGACCATCCTGACAGCCATCCTCACCTTGTTTCTCCCAGAGAGCTTCGGTACCCCA
CTCCCAGACACCATTGACCAGATGCTAAGAGTCAAAGGAATGAAACACAGAAAAACTCCA
AGTCACACAAGGATGTTAAAAGATGGTCAAGAAAGGCCCACAATCCTTAAAAGCACAGCC
TTCTAA
GenBank Gene IDAF057164
GeneCard IDNot Available
GenAtlas IDSLC22A5
HGNC IDHGNC:10969
Chromosome Location5
Locus5q31
References
  1. Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. 9618255
  2. Tamai I, Ohashi R, Nezu J, Yabuuchi H, Oku A, Shimane M, Sai Y, Tsuji A: Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem. 1998 Aug 7;273(32):20378-82. 9685390
  3. 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: Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet. 1999 Jan;21(1):91-4. 9916797
  4. Maekawa S, Mori D, Nishiya T, Takikawa O, Horinouchi T, Nishimoto A, Kajita E, Miwa S: OCTN2VT, a splice variant of OCTN2, does not transport carnitine because of the retention in the endoplasmic reticulum caused by insertion of 24 amino acids in the first extracellular loop of OCTN2. Biochim Biophys Acta. 2007 Jun;1773(6):1000-6. Epub 2007 Apr 19. 17509700
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  6. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. 15372022
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. 10454528
  9. Wollscheid B, Bausch-Fluck D, Henderson C, O'Brien R, Bibel M, Schiess R, Aebersold R, Watts JD: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol. 2009 Apr;27(4):378-86. doi: 10.1038/nbt.1532. Epub 2009 Apr 6. 19349973
  10. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  11. Burwinkel B, Kreuder J, Schweitzer S, Vorgerd M, Gempel K, Gerbitz KD, Kilimann MW: Carnitine transporter OCTN2 mutations in systemic primary carnitine deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation associated with an unconventional splicing abnormality. Biochem Biophys Res Commun. 1999 Aug 2;261(2):484-7. 10425211
  12. Vaz FM, Scholte HR, Ruiter J, Hussaarts-Odijk LM, Pereira RR, Schweitzer S, de Klerk JB, Waterham HR, Wanders RJ: Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency. Hum Genet. 1999 Jul-Aug;105(1-2):157-61. 10480371
  13. Tang NL, Ganapathy V, Wu X, Hui J, Seth P, Yuen PM, Wanders RJ, Fok TF, Hjelm NM: Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Hum Mol Genet. 1999 Apr;8(4):655-60. 10072434
  14. 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: Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum Mol Genet. 1999 Nov;8(12):2247-54. 10545605
  15. Seth P, Wu X, Huang W, Leibach FH, Ganapathy V: 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. J Biol Chem. 1999 Nov 19;274(47):33388-92. 10559218
  16. Mayatepek E, Nezu J, Tamai I, Oku A, Katsura M, Shimane M, Tsuji A: Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency. Hum Mutat. 2000 Jan;15(1):118. 10612840
  17. Wang Y, Kelly MA, Cowan TM, Longo N: A missense mutation in the OCTN2 gene associated with residual carnitine transport activity. Hum Mutat. 2000;15(3):238-45. 10679939
  18. Wang Y, Taroni F, Garavaglia B, Longo N: Functional analysis of mutations in the OCTN2 transporter causing primary carnitine deficiency: lack of genotype-phenotype correlation. Hum Mutat. 2000 Nov;16(5):401-7. 11058897
  19. Wang Y, Korman SH, Ye J, Gargus JJ, Gutman A, Taroni F, Garavaglia B, Longo N: Phenotype and genotype variation in primary carnitine deficiency. Genet Med. 2001 Nov-Dec;3(6):387-92. 11715001
  20. Makhseed N, Vallance HD, Potter M, Waters PJ, Wong LT, Lillquist Y, Pasquali M, Amat di San Filippo C, Longo N: Carnitine transporter defect due to a novel mutation in the SLC22A5 gene presenting with peripheral neuropathy. J Inherit Metab Dis. 2004;27(6):778-80. 15617188
  21. Dobrowolski SF, McKinney JT, Amat di San Filippo C, Giak Sim K, Wilcken B, Longo N: Validation of dye-binding/high-resolution thermal denaturation for the identification of mutations in the SLC22A5 gene. Hum Mutat. 2005 Mar;25(3):306-13. 15714519
  22. Urban TJ, Gallagher RC, Brown C, Castro RA, Lagpacan LL, Brett CM, Taylor TR, Carlson EJ, Ferrin TE, Burchard EG, Packman S, Giacomini KM: Functional genetic diversity in the high-affinity carnitine transporter OCTN2 (SLC22A5). Mol Pharmacol. 2006 Nov;70(5):1602-11. Epub 2006 Aug 24. 16931768
  23. Schimmenti LA, Crombez EA, Schwahn BC, Heese BA, Wood TC, Schroer RJ, Bentler K, Cederbaum S, Sarafoglou K, McCann M, Rinaldo P, Matern D, di San Filippo CA, Pasquali M, Berry SA, Longo N: Expanded newborn screening identifies maternal primary carnitine deficiency. Mol Genet Metab. 2007 Apr;90(4):441-5. Epub 2006 Nov 28. 17126586
  24. El-Hattab AW, Li FY, Shen J, Powell BR, Bawle EV, Adams DJ, Wahl E, Kobori JA, Graham B, Scaglia F, Wong LJ: Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects. Genet Med. 2010 Jan;12(1):19-24. doi: 10.1097/GIM.0b013e3181c5e6f7. 20027113
  25. Li FY, El-Hattab AW, Bawle EV, Boles RG, Schmitt ES, Scaglia F, Wong LJ: Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. Hum Mutat. 2010 Aug;31(8):E1632-51. doi: 10.1002/humu.21311. 20574985
  26. Lee NC, Tang NL, Chien YH, Chen CA, Lin SJ, Chiu PC, Huang AC, Hwu WL: Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening. Mol Genet Metab. 2010 May;100(1):46-50. doi: 10.1016/j.ymgme.2009.12.015. Epub 2009 Dec 28. 20074989
  27. Rose EC, di San Filippo CA, Ndukwe Erlingsson UC, Ardon O, Pasquali M, Longo N: Genotype-phenotype correlation in primary carnitine deficiency. Hum Mutat. 2012 Jan;33(1):118-23. doi: 10.1002/humu.21607. Epub 2011 Oct 11. 21922592