Organic cation/carnitine transporter 2

Details

Name
Organic cation/carnitine transporter 2
Kind
protein
Synonyms
  • High-affinity sodium-dependent carnitine cotransporter
  • OCTN2
  • Solute carrier family 22 member 5
Gene Name
SLC22A5
UniProtKB Entry
O76082Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000212|Organic cation/carnitine transporter 2
MRDYDEVTAFLGEWGPFQRLIFFLLSASIIPNGFTGLSSVFLIATPEHRCRVPDAANLSS
AWRNHTVPLRLRDGREVPHSCRRYRLATIANFSALGLEPGRDVDLGQLEQESCLDGWEFS
QDVYLSTIVTEWNLVCEDDWKAPLTISLFFVGVLLGSFISGQLSDRFGRKNVLFVTMGMQ
TGFSFLQIFSKNFEMFVVLFVLVGMGQISNYVAAFVLGTEILGKSVRIIFSTLGVCIFYA
FGYMVLPLFAYFIRDWRMLLVALTMPGVLCVALWWFIPESPRWLISQGRFEEAEVIIRKA
AKANGIVVPSTIFDPSELQDLSSKKQQSHNILDLLRTWNIRMVTIMSIMLWMTISVGYFG
LSLDTPNLHGDIFVNCFLSAMVEVPAYVLAWLLLQYLPRRYSMATALFLGGSVLLFMQLV
PPDLYYLATVLVMVGKFGVTAAFSMVYVYTAELYPTVVRNMGVGVSSTASRLGSILSPYF
VYLGAYDRFLPYILMGSLTILTAILTLFLPESFGTPLPDTIDQMLRVKGMKHRKTPSHTR
MLKDGQERPTILKSTAF
Number of residues
557
Molecular Weight
62751.08
Theoretical pI
8.04
GO Classification
Functions
(R)-carnitine transmembrane transporter activity / amino-acid betaine transmembrane transporter activity / xenobiotic transmembrane transporter activity
Processes
(R)-carnitine transmembrane transport / (R)-carnitine transport / response to symbiotic bacterium / response to tumor necrosis factor / response to type II interferon / transport across blood-brain barrier / xenobiotic detoxification by transmembrane export across the plasma membrane
Components
basal plasma membrane / cytoplasm / cytosol / endoplasmic reticulum
General Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine (PubMed:10454528, PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, PubMed:33124720). Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from Bacillus Subtilis wich induces cytoprotective heat shock proteins contributing to intestinal homeostasis (PubMed:18005709). May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
(r)-carnitine transmembrane transporter activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
21-41 143-163 173-193 198-218 233-253 258-278 342-362 374-394 407-427 431-451 463-483 489-509
Cellular Location
Cell membrane
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
Chromosome Location
5
Locus
5q31.1
External Identifiers
ResourceLink
UniProtKB IDO76082
UniProtKB Entry NameS22A5_HUMAN
GenBank Protein ID3273741
GenBank Gene IDAF057164
GeneCard IDSLC22A5
GenAtlas IDSLC22A5
HGNC IDHGNC:10969
KEGG IDhsa:6584
NCBI Gene ID6584
General 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
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  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Levocarnitineapproved, investigationalunknowntargetDetails
ProcainamideapprovedunknowntransporterinhibitorDetails
NicotineapprovedunknowntransporterinhibitorDetails
Metamfetamineapproved, illicit, withdrawnunknowntransporterinhibitorDetails
GuanidineapprovedunknowntransporterinhibitorDetails
Cimetidineapproved, investigationalunknowntransporterinhibitorDetails
Cholineapproved, nutraceuticalunknowntransporterinhibitorDetails
Amphetamineapproved, illicit, investigationalunknowntransportersubstrateDetails
Desipramineapproved, investigationalunknowntransporterinhibitorDetails
VerapamilapprovedunknowntransporterinhibitorDetails
Valproic acidapproved, investigationalunknowntransporterinhibitorDetails
Sparfloxacinapproved, investigational, withdrawnunknowntransporterinhibitorDetails
QuinineapprovedunknowntransporterinhibitorDetails
Quinidineapproved, investigationalunknowntransporterinhibitorDetails
Probenecidapproved, investigationalunknowntransporterinhibitorDetails
Aminohippuric acidapproved, investigationalunknowntransporterinhibitorDetails
OfloxacinapprovedunknowntransporterinhibitorDetails
NorfloxacinapprovedunknowntransporterinhibitorDetails
Niacinapproved, investigational, nutraceuticalunknowntransporterinhibitorDetails
Lomefloxacinapproved, investigationalunknowntransporterinhibitorDetails
Grepafloxacinapproved, investigational, withdrawnunknowntransporterinhibitorDetails
Furosemideapproved, vet_approvedunknowntransporterinhibitorDetails
Creatineapproved, investigational, nutraceuticalunknowntransporterinhibitorDetails
ClonidineapprovedunknowntransporterinhibitorDetails
Cefalotinapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
CephaloglycinapprovedunknowntransporterinhibitorDetails
Arginineinvestigational, nutraceuticalunknowntransporterinhibitorDetails
Aldosteroneexperimental, investigationalunknowntransporterinhibitorDetails
Dactinomycinapproved, investigationalunknowntransporterinhibitorDetails
Benzylpenicillinapproved, vet_approvedunknowntransporterinhibitorDetails
CyclacillinapprovedunknowntransporterinhibitorDetails
CefradineapprovedunknowntransporterinhibitorDetails
Cephalexinapproved, investigational, vet_approvedunknowntransporterinhibitorDetails
Cefepimeapproved, investigationalunknowntransporterinhibitorDetails
CefdinirapprovedunknowntransporterinhibitorDetails
Cefadroxilapproved, vet_approved, withdrawnunknowntransporterinhibitorDetails
Ampicillinapproved, vet_approvedunknowntransporterinhibitorDetails
Thiamineapproved, investigational, nutraceutical, vet_approvedunknowntransporterinhibitorDetails
NorepinephrineapprovedunknowntransporterinhibitorDetails
Lidocaineapproved, vet_approvedunknowntransporterinhibitorDetails
Histamineapproved, investigationalunknowntransporterinhibitorDetails
DopamineapprovedunknowntransporterinhibitorDetails
Diphenhydramineapproved, investigationalunknowntransporterinhibitorDetails
Acetylcholineapproved, investigationalunknowntransporterinhibitorDetails
Levocarnitineapproved, investigationalunknowntransportersubstrateDetails
Ipratropiumapproved, experimentalunknowntransportersubstrateDetails
TiotropiumapprovedunknowntransportersubstrateDetails
AzidocillinexperimentalunknowntransporterinhibitorDetails
Tetraethylammoniumexperimental, investigationalunknowntransporterDetails
Mepyramineapproved, vet_approvedunknowntransporterDetails
Acetylcarnitineapproved, investigationalunknowntransporterDetails
Degraded CephaloridineexperimentalunknowntransporterDetails
Choline salicylateapproved, nutraceuticalunknowntransporterinhibitorDetails
SolriamfetolapprovedunknowntransporterDetails
Levamlodipineapproved, investigationalunknowntransporterinhibitorDetails
Formoterolapproved, investigationalunknowntransportersubstrateDetails
Methacholineapproved, investigationalnotransporterinhibitorDetails
TerbutalineapprovedunknowntransportersubstrateDetails
ImatinibapprovednotransportersubstrateDetails
HydroxyureaapprovednotransportersubstrateDetails