ID S22A5_HUMAN Reviewed; 557 AA. AC O76082; A2Q0V1; B2R844; D3DQ87; Q6ZQZ8; Q96EH6; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 27-MAR-2024, entry version 208. DE RecName: Full=Organic cation/carnitine transporter 2 {ECO:0000305}; DE AltName: Full=High-affinity sodium-dependent carnitine cotransporter; DE AltName: Full=Solute carrier family 22 member 5; GN Name=SLC22A5 {ECO:0000312|HGNC:HGNC:10969}; GN Synonyms=OCTN2 {ECO:0000303|PubMed:10454528, GN ECO:0000303|PubMed:10525100}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9618255; DOI=10.1006/bbrc.1998.8669; RA Wu X., Prasad P.D., Leibach F.H., Ganapathy V.; RT "cDNA sequence, transport function, and genomic organization of human RT OCTN2, a new member of the organic cation transporter family."; RL Biochem. Biophys. Res. Commun. 246:589-595(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=9685390; DOI=10.1074/jbc.273.32.20378; RA Tamai I., Ohashi R., Nezu J., Yabuuchi H., Oku A., Shimane M., Sai Y., RA Tsuji A.; RT "Molecular and functional identification of sodium ion-dependent, high RT affinity human carnitine transporter OCTN2."; RL J. Biol. Chem. 273:20378-20382(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=9916797; DOI=10.1038/5030; RA Nezu J., Tamai I., Oku A., Ohashi R., Yabuuchi H., Hashimoto N., RA Nikaido H., Sai Y., Koizumi A., Shoji Y., Takada G., Matsuishi T., RA Yashino M., Kato H., Ohura T., Tsujimoto G., Hayakawa J., Shimane M., RA Tsuji A.; RT "Primary systemic carnitine deficiency is caused by mutations in a gene RT encoding sodium ion-dependent carnitine transporter."; RL Nat. Genet. 21:91-94(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION (ISOFORM 3), SUBCELLULAR RP LOCATION (ISOFORM 3), SUBCELLULAR LOCATION, TRANSORTER ACTIVITY, RP GLYCOSYLATION AT GLUT-91, AND MUTAGENESIS OF ASN-91. RX PubMed=17509700; DOI=10.1016/j.bbamcr.2007.04.005; RA Maekawa S., Mori D., Nishiya T., Takikawa O., Horinouchi T., Nishimoto A., RA Kajita E., Miwa S.; RT "OCTN2VT, a splice variant of OCTN2, does not transport carnitine because RT of the retention in the endoplasmic reticulum caused by insertion of 24 RT amino acids in the first extracellular loop of OCTN2."; RL Biochim. Biophys. Acta 1773:1000-1006(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND TRANSPORTER ACTIVITY. RX PubMed=10525100; RA Ohashi R., Tamai I., Yabuuchi H., Nezu J.I., Oku A., Sai Y., Shimane M., RA Tsuji A.; RT "Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): RT its pharmacological and toxicological relevance."; RL J. Pharmacol. Exp. Ther. 291:778-784(1999). RN [10] RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TRANSPORTER ACTIVITY, AND ACTIVITY RP REGULATION. RX PubMed=10966938; DOI=10.1152/ajprenal.2000.279.3.f584; RA Wagner C.A., Luekewille U., Kaltenbach S., Moschen I., Broeer A., RA Risler T., Broeer S., Lang F.; RT "Functional and pharmacological characterization of human Na(+)-carnitine RT cotransporter hOCTN2."; RL Am. J. Physiol. 279:F584-F591(2000). RN [11] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=17855766; DOI=10.1152/ajpgi.00233.2007; RA Srinivas S.R., Prasad P.D., Umapathy N.S., Ganapathy V., Shekhawat P.S.; RT "Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine RT transporter OCTN2 and the amino acid transporter ATB(0,+)."; RL Am. J. Physiol. 293:G1046-G1053(2007). RN [12] RP FUNCTION, TRANSPORTER ACTIVITY, TISSUE SPECIFICITY, AND SUBCELLULAR RP LOCATION. RX PubMed=18005709; DOI=10.1016/j.chom.2007.05.004; RA Fujiya M., Musch M.W., Nakagawa Y., Hu S., Alverdy J., Kohgo Y., RA Schneewind O., Jabri B., Chang E.B.; RT "The Bacillus subtilis quorum-sensing molecule CSF contributes to RT intestinal homeostasis via OCTN2, a host cell membrane transporter."; RL Cell Host Microbe 1:299-308(2007). RN [13] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57 AND ASN-91. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-486, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION BY CYTOKINES, RP TRANSPORTER ACTIVITY, AND INVOLVEMENT IN DISEASE. RX PubMed=20722056; DOI=10.1002/ibd.21444; RA Fujiya M., Inaba Y., Musch M.W., Hu S., Kohgo Y., Chang E.B.; RT "Cytokine regulation of OCTN2 expression and activity in small and large RT intestine."; RL Inflamm. Bowel Dis. 17:907-916(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-550, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=33124720; DOI=10.1096/fj.202001497r; RA Yee S.W., Buitrago D., Stecula A., Ngo H.X., Chien H.C., Zou L., RA Koleske M.L., Giacomini K.M.; RT "Deorphaning a solute carrier 22 family member, SLC22A15, through RT functional genomic studies."; RL FASEB J. 34:15734-15752(2020). RN [18] RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, RP TRANSPORTER ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=33334877; DOI=10.1074/jbc.ra120.015175; RA Zhang L., Gui T., Console L., Scalise M., Indiveri C., Hausler S., RA Kullak-Ublick G.A., Gai Z., Visentin M.; RT "Cholesterol stimulates the cellular uptake of L-carnitine by the RT carnitine/organic cation transporter novel 2 (OCTN2)."; RL J. Biol. Chem. 296:100204-100204(2021). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=35307651; DOI=10.1124/dmd.121.000748; RA Hau R.K., Klein R.R., Wright S.H., Cherrington N.J.; RT "Localization of Xenobiotic Transporters Expressed at the Human Blood- RT Testis Barrier."; RL Drug Metab. Dispos. 50:770-780(2022). RN [20] RP VARIANT CDSP GLN-169. RX PubMed=10425211; DOI=10.1006/bbrc.1999.1060; RA Burwinkel B., Kreuder J., Schweitzer S., Vorgerd M., Gempel K., RA Gerbitz K.-D., Kilimann M.W.; RT "Carnitine transporter OCTN2 mutations in systemic primary carnitine RT deficiency: a novel Arg169Gln mutation and a recurrent Arg282ter mutation RT associated with an unconventional splicing abnormality."; RL Biochem. Biophys. Res. Commun. 261:484-487(1999). RN [21] RP VARIANT CDSP CYS-211. RX PubMed=10480371; DOI=10.1007/s004399900105; RA Vaz F.M., Scholte H.R., Ruiter J., Hussaarts-Odijk L.M., RA Rodrigues Pereira R., Schweitzer S., de Klerk J.B.C., Waterham H.R., RA Wanders R.J.A.; RT "Identification of two novel mutations in OCTN2 of three patients with RT systemic carnitine deficiency."; RL Hum. Genet. 105:157-161(1999). RN [22] RP VARIANT CDSP LEU-478. RX PubMed=10072434; DOI=10.1093/hmg/8.4.655; RA Tang N.L., Ganapathy V., Wu X., Hui J., Seth P., Yuen P.M., Wanders R.J., RA Fok T.F., Hjelm N.M.; RT "Mutations of OCTN2, an organic cation/carnitine transporter, lead to RT deficient cellular carnitine uptake in primary carnitine deficiency."; RL Hum. Mol. Genet. 8:655-660(1999). RN [23] RP VARIANTS CDSP LEU-179; CYS-283 AND CYS-467, AND CHARACTERIZATION OF RP VARIANTS CDSP LEU-179; CYS-283 AND CYS-467. RX PubMed=10545605; DOI=10.1093/hmg/8.12.2247; RA Koizumi A., Nozaki J., Ohura T., Kayo T., Wada Y., Nezu J., Ohashi R., RA Tamai I., Shoji Y., Takada G., Kibira S., Matsuishi T., Tsuji A.; RT "Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese RT population and phenotypic characterization in Japanese pedigrees with RT primary systemic carnitine deficiency."; RL Hum. Mol. Genet. 8:2247-2254(1999). RN [24] RP CHARACTERIZATION OF VARIANT CDSP LEU-478, AND MUTAGENESIS OF MET-352. RX PubMed=10559218; DOI=10.1074/jbc.274.47.33388; RA Seth P., Wu X., Huang W., Leibach F.H., Ganapathy V.; RT "Mutations in novel organic cation transporter (OCTN2), an organic RT cation/carnitine transporter, with differential effects on the organic RT cation transport function and the carnitine transport function."; RL J. Biol. Chem. 274:33388-33392(1999). RN [25] RP FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT CDSP LEU-478, RP MUTAGENESIS OF MET-352, AND TRANSPORTER ACTIVITY. RX PubMed=10454528; RA Wu X., Huang W., Prasad P.D., Seth P., Rajan D.P., Leibach F.H., Chen J., RA Conway S.J., Ganapathy V.; RT "Functional characteristics and tissue distribution pattern of organic RT cation transporter 2 (OCTN2), an organic cation/carnitine transporter."; RL J. Pharmacol. Exp. Ther. 290:1482-1492(1999). RN [26] RP VARIANTS CDSP ARG-283 AND PHE-446. RX PubMed=10612840; RX DOI=10.1002/(sici)1098-1004(200001)15:1<118::aid-humu28>3.0.co;2-8; RA Mayatepek E., Nezu J., Tamai I., Oku A., Katsura M., Shimane M., Tsuji A.; RT "Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a RT patient with primary systemic carnitine deficiency."; RL Hum. Mutat. 15:118-118(2000). RN [27] RP SUBCELLULAR LOCATION, AND VARIANT CDSP LYS-452. RX PubMed=10679939; RX DOI=10.1002/(sici)1098-1004(200003)15:3<238::aid-humu4>3.0.co;2-3; RA Wang Y., Kelly M.A., Cowan T.M., Longo N.; RT "A missense mutation in the OCTN2 gene associated with residual carnitine RT transport activity."; RL Hum. Mutat. 15:238-245(2000). RN [28] RP VARIANTS CDSP TRP-169; VAL-242; ASP-301 AND ARG-351, AND CHARACTERIZATION RP OF VARIANTS CDSP TRP-169; VAL-242; ASP-301 AND ARG-351. RX PubMed=11058897; RX DOI=10.1002/1098-1004(200011)16:5<401::aid-humu4>3.0.co;2-j; RA Wang Y., Taroni F., Garavaglia B., Longo N.; RT "Functional analysis of mutations in the OCTN2 transporter causing primary RT carnitine deficiency: lack of genotype-phenotype correlation."; RL Hum. Mutat. 16:401-407(2000). RN [29] RP VARIANTS CDSP PRO-19 AND GLN-399, AND CHARACTERIZATION OF VARIANTS CDSP RP PRO-19 AND GLN-399. RX PubMed=11715001; DOI=10.1097/00125817-200111000-00002; RA Wang Y., Korman S.H., Ye J., Gargus J.J., Gutman A., Taroni F., RA Garavaglia B., Longo N.; RT "Phenotype and genotype variation in primary carnitine deficiency."; RL Genet. Med. 3:387-392(2001). RN [30] RP VARIANT CDSP LEU-83. RX PubMed=15617188; DOI=10.1023/b:boli.0000045837.23328.f4; RA Makhseed N., Vallance H.D., Potter M., Waters P.J., Wong L.T.K., RA Lillquist Y., Pasquali M., Amat di San Filippo C., Longo N.; RT "Carnitine transporter defect due to a novel mutation in the SLC22A5 gene RT presenting with peripheral neuropathy."; RL J. Inherit. Metab. Dis. 27:778-780(2004). RN [31] RP VARIANTS CDSP PRO-19; LEU-83; TRP-169; MET-232; VAL-242; ASP-301; ARG-351; RP GLN-399; CYS-447; ASP-449; LYS-452 AND ARG-468, AND CHARACTERIZATION OF RP VARIANTS MET-232 AND ARG-468. RX PubMed=15714519; DOI=10.1002/humu.20137; RA Dobrowolski S.F., McKinney J.T., Amat di San Filippo C., Giak Sim K., RA Wilcken B., Longo N.; RT "Validation of dye-binding/high-resolution thermal denaturation for the RT identification of mutations in the SLC22A5 gene."; RL Hum. Mutat. 25:306-313(2005). RN [32] RP VARIANTS PHE-144; ILE-481; PHE-481; LEU-508; VAL-530 AND SER-549, AND RP VARIANTS CDSP LEU-17 AND ASP-449. RX PubMed=16931768; DOI=10.1124/mol.106.028126; RA Urban T.J., Gallagher R.C., Brown C., Castro R.A., Lagpacan L.L., RA Brett C.M., Taylor T.R., Carlson E.J., Ferrin T.E., Burchard E.G., RA Packman S., Giacomini K.M.; RT "Functional genetic diversity in the high-affinity carnitine transporter RT OCTN2 (SLC22A5)."; RL Mol. Pharmacol. 70:1602-1611(2006). RN [33] RP VARIANTS CDSP SER-32; SER-46; CYS-467 AND CYS-488, AND CHARACTERIZATION OF RP VARIANT CDSP SER-46. RX PubMed=17126586; DOI=10.1016/j.ymgme.2006.10.003; RA Schimmenti L.A., Crombez E.A., Schwahn B.C., Heese B.A., Wood T.C., RA Schroer R.J., Bentler K., Cederbaum S., Sarafoglou K., McCann M., RA Rinaldo P., Matern D., di San Filippo C.A., Pasquali M., Berry S.A., RA Longo N.; RT "Expanded newborn screening identifies maternal primary carnitine RT deficiency."; RL Mol. Genet. Metab. 90:441-445(2007). RN [34] RP VARIANTS CDSP TRP-15; SER-46; LEU-83; SER-142; VAL-214; MET-232; TRP-399 RP AND ILE-442. RX PubMed=20027113; DOI=10.1097/gim.0b013e3181c5e6f7; RA El-Hattab A.W., Li F.-Y., Shen J., Powell B.R., Bawle E.V., Adams D.J., RA Wahl E., Kobori J.A., Graham B., Scaglia F., Wong L.-J.; RT "Maternal systemic primary carnitine deficiency uncovered by newborn RT screening: clinical, biochemical, and molecular aspects."; RL Genet. Med. 12:19-24(2010). RN [35] RP VARIANTS CDSP SER-12; TRP-15; LEU-17; SER-32; SER-46; LEU-83; TYR-122; RP SER-142; TRP-169; GLN-169; PRO-186; VAL-214; HIS-227; MET-232; TRP-257; RP ARG-264; GLN-282; LEU-355; LEU-398; TRP-399; MET-440; ILE-442; VAL-443; RP ASP-449; LYS-452; ARG-455; CYS-467; CYS-488 AND SER-507, AND VARIANTS RP PRO-66; PRO-75; ALA-96; GLY-123; LEU-143; VAL-177; LEU-230; THR-240; RP VAL-312; ASN-358 AND SER-549. RX PubMed=20574985; DOI=10.1002/humu.21311; RA Li F.-Y., El-Hattab A.W., Bawle E.V., Boles R.G., Schmitt E.S., Scaglia F., RA Wong L.-J.; RT "Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 RT subjects evaluated for systemic carnitine deficiency."; RL Hum. Mutat. 31:E1632-E1651(2010). RN [36] RP VARIANTS CDSP LEU-17; ARG-234; GLN-282; LEU-362; CYS-467 AND CYS-471, AND RP VARIANT LEU-143. RX PubMed=20074989; DOI=10.1016/j.ymgme.2009.12.015; RA Lee N.-C., Tang N.-L., Chien Y.-H., Chen C.-A., Lin S.-J., Chiu P.-C., RA Huang A.-C., Hwu W.-L.; RT "Diagnoses of newborns and mothers with carnitine uptake defects through RT newborn screening."; RL Mol. Genet. Metab. 100:46-50(2010). RN [37] RP VARIANTS CDSP TRP-15; PRO-19; PHE-22 DEL; ASN-26; SER-32; SER-46; LEU-83; RP SER-142; GLN-169; TRP-169; VAL-214; MET-232; PHE-280; GLN-282; ARG-283; RP ARG-351; MET-440; ILE-442; PHE-446; CYS-447; CYS-467; PRO-471 AND HIS-488, RP AND CHARACTERIZATION OF VARIANTS CDSP TRP-15; PRO-19; PHE-22 DEL; ASN-26; RP SER-32; SER-46; LEU-83; GLN-169; TRP-169; VAL-214; MET-232; PHE-280; RP GLN-282; ARG-283; ARG-351; MET-440; ILE-442; PHE-446; CYS-447; CYS-467 AND RP PRO-471. RX PubMed=21922592; DOI=10.1002/humu.21607; RA Rose E.C., di San Filippo C.A., Ndukwe Erlingsson U.C., Ardon O., RA Pasquali M., Longo N.; RT "Genotype-phenotype correlation in primary carnitine deficiency."; RL Hum. Mutat. 33:118-123(2012). RN [38] RP VARIANTS CDSP 4-TYR--PHE-557 DEL; SER-12; TRP-15; LEU-16; LEU-17; PRO-19; RP HIS-20; PHE-22 DEL; ASN-26; ILE-28; SER-32; VAL-44; LEU-46; SER-46; TYR-50; RP PRO-66; PRO-75; LEU-83; TRP-93; VAL-95; ALA-96; GLY-115; 117-TRP--PHE-557 RP DEL; GLY-123; ASP-131; 132-TRP--PHE-557 DEL; 140-TRP--PHE-557 DEL; SER-142; RP LEU-143; MET-151; GLN-169; PRO-169; TRP-169; MET-175; VAL-177; LEU-179; RP PRO-186; ARG-205; SER-210; CYS-211; VAL-214; LYS-219; LEU-225; HIS-227; RP LEU-230; PHE-231; MET-232; THR-240; VAL-242; ARG-247; 254-ARG--PHE-557 DEL; RP GLN-254; 256-TRP--PHE-557 DEL; TRP-257; ARG-264; MET-264; PRO-269; RP 275-TRP--PHE-557 DEL; PHE-280; 282-ARG--PHE-557 DEL; GLN-282; ARG-283; RP CYS-283; 289-ARG--PHE-557 DEL; 295-VAL--PHE-557 DEL; ASP-301; VAL-312; RP LYS-317; 319-GLN--PHE-557 DEL; THR-348; ARG-351; LEU-355; ASN-358; PRO-363; RP 387-TYR--PHE-557 DEL; LEU-394 DEL; LEU-398; GLN-399; TRP-399; GLY-412; RP GLY-439; MET-440; ILE-442; VAL-443; PHE-446; CYS-447; LEU-448; ASP-449; RP LYS-452; ARG-455; VAL-462; CYS-467; ARG-468; PHE-470; HIS-471; PRO-471; RP ARG-476; LEU-478; CYS-488; HIS-488 AND SER-507, VARIANTS PHE-481 AND RP SER-549, CHARACTERIZATION OF VARIANTS CDSP SER-12; TRP-15; LEU-16; LEU-17; RP PRO-19; HIS-20; PHE-23 DEL; ASN-26; ILE-28; SER-32; VAL-44; LEU-46; SER-46; RP TYR-50; PRO-66; PRO-75; LEU-83; TRP-93; VAL-95; ALA-96; GLY-115; GLY-123; RP ASP-131; SER-142; LEU-143; MET-151; GLN-169; PRO-169; TRP-169; MET-175; RP VAL-177; LEU-179; PRO-186; ARG-205; SER-210; CYS-211; VAL-214; LYS-219; RP LEU-225; HIS-227; LEU-230; PHE-231; MET-232; THR-240; VAL-242; ARG-247; RP GLN-254; TRP-257; ARG-264; MET-264; PRO-269; PHE-280; GLN-282; ARG-283; RP CYS-283; ASP-301; VAL-312; LYS-317; THR-348; ARG-351; LEU-355; ASN-358; RP PRO-363; LEU-394 DEL; LEU-398; GLN-399; TRP-399; GLY-412; GLY-439; MET-440; RP ILE-442; VAL-443; PHE-446; CYS-447; LEU-448; ASP-449; LYS-452; ARG-455; RP VAL-462; CYS-467; ARG-468; PHE-470; HIS-471; PRO-471; ARG-476; LEU-478; RP CYS-488; HIS-488 AND SER-507, AND CHARACTERIZATION OF VARIANTS PHE-481 AND RP SER-549. RX PubMed=28841266; DOI=10.1002/humu.23315; RA Frigeni M., Balakrishnan B., Yin X., Calderon F.R.O., Mao R., Pasquali M., RA Longo N.; RT "Functional and molecular studies in primary carnitine deficiency."; RL Hum. Mutat. 38:1684-1699(2017). CC -!- FUNCTION: Sodium-ion dependent, high affinity carnitine transporter. CC Involved in the active cellular uptake of carnitine. Transports one CC sodium ion with one molecule of carnitine (PubMed:10454528, CC PubMed:10525100, PubMed:10966938, PubMed:17509700, PubMed:20722056, CC PubMed:33124720). Also transports organic cations such as CC tetraethylammonium (TEA) without the involvement of sodium. Relative CC uptake activity ratio of carnitine to TEA is 11.3 (PubMed:10454528, CC PubMed:10525100, PubMed:10966938). In intestinal epithelia, transports CC the quorum-sensing pentapeptide CSF (competence and sporulation factor) CC from Bacillus Subtilis wich induces cytoprotective heat shock proteins CC contributing to intestinal homeostasis (PubMed:18005709). May also CC contribute to regulate the transport of organic compounds in testis CC across the blood-testis-barrier (Probable). CC {ECO:0000269|PubMed:10454528, ECO:0000269|PubMed:10525100, CC ECO:0000269|PubMed:10966938, ECO:0000269|PubMed:17509700, CC ECO:0000269|PubMed:18005709, ECO:0000269|PubMed:20722056, CC ECO:0000305|PubMed:35307651}. CC -!- FUNCTION: [Isoform 3]: Retained in the ER, unable to perform carnitine CC uptake. {ECO:0000269|PubMed:17509700}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(out) + Na(+)(out) = (R)-carnitine(in) + CC Na(+)(in); Xref=Rhea:RHEA:72091, ChEBI:CHEBI:16347, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:10454528, CC ECO:0000269|PubMed:10525100, ECO:0000269|PubMed:17509700, CC ECO:0000269|PubMed:17855766, ECO:0000269|PubMed:20722056, CC ECO:0000269|PubMed:33124720}; CC -!- CATALYTIC ACTIVITY: CC Reaction=glycine betaine(out) + Na(+)(out) = glycine betaine(in) + CC Na(+)(in); Xref=Rhea:RHEA:72115, ChEBI:CHEBI:17750, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:10966938, CC ECO:0000269|PubMed:33124720}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-carnitine(in) + glycine betaine(out) = (R)-carnitine(out) CC + glycine betaine(in); Xref=Rhea:RHEA:72119, ChEBI:CHEBI:16347, CC ChEBI:CHEBI:17750; Evidence={ECO:0000269|PubMed:10966938}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(out) + O-butanoyl-(R)-carnitine(out) = Na(+)(in) + O- CC butanoyl-(R)-carnitine(in); Xref=Rhea:RHEA:72123, ChEBI:CHEBI:21949, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:17855766}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(out) + O-acetyl-(R)-carnitine(out) = Na(+)(in) + O- CC acetyl-(R)-carnitine(in); Xref=Rhea:RHEA:72099, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:57589; Evidence={ECO:0000269|PubMed:10454528, CC ECO:0000269|PubMed:10525100}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(out) + O-propanoyl-(R)-carnitine(out) = Na(+)(in) + O- CC propanoyl-(R)-carnitine(in); Xref=Rhea:RHEA:72103, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:53210; Evidence={ECO:0000269|PubMed:10454528}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(S)-carnitine(out) + Na(+)(out) = (S)-carnitine(in) + CC Na(+)(in); Xref=Rhea:RHEA:72095, ChEBI:CHEBI:11060, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:10525100}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(out) + O-acyl-(R)-carnitine(out) = Na(+)(in) + O-acyl- CC (R)-carnitine(in); Xref=Rhea:RHEA:72107, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:75659; Evidence={ECO:0000305|PubMed:10525100}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-glutamyl-L-arginyl-glycyl-L-methionyl-L-threonine(out) + CC Na(+)(out) = L-glutamyl-L-arginyl-glycyl-L-methionyl-L-threonine(in) CC + Na(+)(in); Xref=Rhea:RHEA:72111, ChEBI:CHEBI:29101, CC ChEBI:CHEBI:191852; Evidence={ECO:0000269|PubMed:18005709}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N,N-dimethylglycine(out) + Na(+)(out) = N,N- CC dimethylglycine(in) + Na(+)(in); Xref=Rhea:RHEA:76591, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:58251; CC Evidence={ECO:0000269|PubMed:33124720}; CC -!- ACTIVITY REGULATION: Inhibited by emetine, quinidine and verapamil. The CC IC(50) of emetine is 4.2 uM. Not inhibited by valproic acid CC (PubMed:10966938). Transport of (R)-carnitine is stimulated by CC cholesterol in the plasma membrane (PubMed:33334877). CC {ECO:0000269|PubMed:10966938, ECO:0000269|PubMed:33334877}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=4.3 uM for (R)-carnitine {ECO:0000269|PubMed:10525100}; CC KM=4.8 uM for (R)-carnitine (at -60 mV holding potential) CC {ECO:0000269|PubMed:10966938}; CC KM=2.58 uM for (R)-carnitine (at -90 mV holding potential) CC {ECO:0000269|PubMed:10966938}; CC KM=19.9 uM for (R)-carnitine {ECO:0000269|PubMed:33334877}; CC KM=8.5 uM for O-acetyl-(R)-carnitine {ECO:0000269|PubMed:10525100}; CC KM=10.9 uM for (S)-carnitine {ECO:0000269|PubMed:10525100}; CC KM=98.3 uM for (S)-carnitine {ECO:0000269|PubMed:10966938}; CC KM=18.5 uM for Na(+) {ECO:0000269|PubMed:10525100}; CC Vmax=0.63 pmol/min/ug enzyme {ECO:0000269|PubMed:33334877}; CC pH dependence: CC Optimum pH is from 7 to 8.5. {ECO:0000269|PubMed:10525100, CC ECO:0000269|PubMed:10966938}; CC -!- SUBUNIT: Interacts with PDZK1. {ECO:0000250|UniProtKB:Q9Z0E8}. CC -!- INTERACTION: CC O76082; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-9846338, EBI-3044087; CC O76082; O76011: KRT34; NbExp=3; IntAct=EBI-9846338, EBI-1047093; CC O76082; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-9846338, EBI-11522433; CC O76082; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-9846338, EBI-22310682; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10679939, CC ECO:0000269|PubMed:17509700, ECO:0000269|PubMed:33334877}; Multi-pass CC membrane protein {ECO:0000269|PubMed:10679939}. Apical cell membrane CC {ECO:0000269|PubMed:10966938, ECO:0000269|PubMed:20722056}; Multi-pass CC membrane protein {ECO:0000255}. Basal cell membrane CC {ECO:0000269|PubMed:35307651}; Multi-pass membrane protein CC {ECO:0000255}. Note=In intestinal cells, apical expression is induced CC by TNF. Localized to the basal membrane of Sertoli cells CC (PubMed:35307651). {ECO:0000269|PubMed:20722056, CC ECO:0000269|PubMed:35307651}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Endoplasmic reticulum CC {ECO:0000269|PubMed:17509700}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O76082-1; Sequence=Displayed; CC Name=2; CC IsoId=O76082-2; Sequence=VSP_011120, VSP_011121; CC Name=3; Synonyms=OCTN2VT {ECO:0000303|PubMed:17509700}; CC IsoId=O76082-3; Sequence=VSP_043904; CC -!- TISSUE SPECIFICITY: Strongly expressed in kidney, skeletal muscle, CC heart and placenta (PubMed:10454528). Primarily expressed by surface CC epithelial cells of the colon (at protein level) (PubMed:18005709). CC Expressed in CD68 macrophage and CD43 T-cells but not in CD20 B-cells CC (PubMed:10454528). In testis, localized to Sertoli cell basal CC membranes, peritubular myoid cells and Leydig cells (PubMed:35307651). CC {ECO:0000269|PubMed:10454528, ECO:0000269|PubMed:18005709, CC ECO:0000269|PubMed:35307651}. CC -!- INDUCTION: Intestinal expression is induced by IFNG. CC {ECO:0000269|PubMed:20722056}. CC -!- PTM: Glycosylated. Glycosylation affects the expression levels. CC {ECO:0000269|PubMed:17509700}. CC -!- PTM: [Isoform 3]: Not glycosylated. {ECO:0000269|PubMed:17509700}. CC -!- DISEASE: Systemic primary carnitine deficiency (CDSP) [MIM:212140]: CC Autosomal recessive disorder of fatty acid oxidation caused by CC defective carnitine transport. Present early in life with hypoketotic CC hypoglycemia and acute metabolic decompensation, or later in life with CC skeletal myopathy or cardiomyopathy. {ECO:0000269|PubMed:10072434, CC ECO:0000269|PubMed:10425211, ECO:0000269|PubMed:10454528, CC ECO:0000269|PubMed:10480371, ECO:0000269|PubMed:10545605, CC ECO:0000269|PubMed:10559218, ECO:0000269|PubMed:10612840, CC ECO:0000269|PubMed:10679939, ECO:0000269|PubMed:11058897, CC ECO:0000269|PubMed:11715001, ECO:0000269|PubMed:15617188, CC ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:16931768, CC ECO:0000269|PubMed:17126586, ECO:0000269|PubMed:20027113, CC ECO:0000269|PubMed:20074989, ECO:0000269|PubMed:20574985, CC ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Note=Expression in colon is increased in Crohn's disease and CC human ulcerative colitis (at protein level). CC {ECO:0000269|PubMed:20722056}. CC -!- SIMILARITY: Belongs to the major facilitator (TC 2.A.1) superfamily. CC Organic cation transporter (TC 2.A.1.19) family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=The SLC22A5 database; CC URL="http://www.arup.utah.edu/database/OCTN2/OCTN2_welcome.php"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF057164; AAC24828.1; -; mRNA. DR EMBL; AB015050; BAA29023.1; -; mRNA. DR EMBL; AB016625; BAA36712.1; -; Genomic_DNA. DR EMBL; AB291606; BAF45812.1; -; mRNA. DR EMBL; AK128610; BAC87527.1; -; mRNA. DR EMBL; AK313230; BAG36041.1; -; mRNA. DR EMBL; AC118464; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW62337.1; -; Genomic_DNA. DR EMBL; CH471062; EAW62338.1; -; Genomic_DNA. DR EMBL; BC012325; AAH12325.1; -; mRNA. DR CCDS; CCDS4154.1; -. [O76082-1] DR CCDS; CCDS78058.1; -. [O76082-3] DR PIR; JW0089; JW0089. DR RefSeq; NP_001295051.1; NM_001308122.1. [O76082-3] DR RefSeq; NP_003051.1; NM_003060.3. [O76082-1] DR AlphaFoldDB; O76082; -. DR SMR; O76082; -. DR BioGRID; 112471; 27. DR IntAct; O76082; 11. DR MINT; O76082; -. DR STRING; 9606.ENSP00000402760; -. DR BindingDB; O76082; -. DR ChEMBL; CHEMBL2073693; -. DR DrugBank; DB08842; Acetylcarnitine. DR DrugBank; DB03128; Acetylcholine. DR DrugBank; DB04630; Aldosterone. DR DrugBank; DB00345; Aminohippuric acid. DR DrugBank; DB00182; Amphetamine. DR DrugBank; DB00415; Ampicillin. DR DrugBank; DB00125; Arginine. DR DrugBank; DB08795; Azidocillin. DR DrugBank; DB01053; Benzylpenicillin. DR DrugBank; DB01140; Cefadroxil. DR DrugBank; DB00456; Cefalotin. DR DrugBank; DB00535; Cefdinir. DR DrugBank; DB01413; Cefepime. DR DrugBank; DB00671; Cefixime. DR DrugBank; DB01333; Cefradine. DR DrugBank; DB00567; Cephalexin. DR DrugBank; DB00689; Cephaloglycin. DR DrugBank; DB00122; Choline. DR DrugBank; DB14006; Choline salicylate. DR DrugBank; DB00501; Cimetidine. DR DrugBank; DB00575; Clonidine. DR DrugBank; DB00148; Creatine. DR DrugBank; DB01000; Cyclacillin. DR DrugBank; DB00970; Dactinomycin. DR DrugBank; DB04133; Degraded Cephaloridine. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB01075; Diphenhydramine. DR DrugBank; DB00988; Dopamine. DR DrugBank; DB00983; Formoterol. DR DrugBank; DB00695; Furosemide. DR DrugBank; DB00365; Grepafloxacin. DR DrugBank; DB00536; Guanidine. DR DrugBank; DB05381; Histamine. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB00332; Ipratropium. DR DrugBank; DB09237; Levamlodipine. DR DrugBank; DB00583; Levocarnitine. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB00978; Lomefloxacin. DR DrugBank; DB06691; Mepyramine. DR DrugBank; DB01577; Metamfetamine. DR DrugBank; DB06709; Methacholine. DR DrugBank; DB00627; Niacin. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB01059; Norfloxacin. DR DrugBank; DB01165; Ofloxacin. DR DrugBank; DB01032; Probenecid. DR DrugBank; DB01035; Procainamide. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB00468; Quinine. DR DrugBank; DB14754; Solriamfetol. DR DrugBank; DB01208; Sparfloxacin. DR DrugBank; DB00871; Terbutaline. DR DrugBank; DB08837; Tetraethylammonium. DR DrugBank; DB00152; Thiamine. DR DrugBank; DB01409; Tiotropium. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB00661; Verapamil. DR TCDB; 2.A.1.19.3; the major facilitator superfamily (mfs). DR GlyCosmos; O76082; 3 sites, No reported glycans. DR GlyGen; O76082; 3 sites. DR iPTMnet; O76082; -. DR PhosphoSitePlus; O76082; -. DR BioMuta; SLC22A5; -. DR EPD; O76082; -. DR MassIVE; O76082; -. DR MaxQB; O76082; -. DR PaxDb; 9606-ENSP00000245407; -. DR PeptideAtlas; O76082; -. DR ProteomicsDB; 50388; -. [O76082-1] DR ProteomicsDB; 50389; -. [O76082-2] DR ProteomicsDB; 50390; -. [O76082-3] DR Pumba; O76082; -. DR Antibodypedia; 45160; 214 antibodies from 30 providers. DR DNASU; 6584; -. DR Ensembl; ENST00000245407.8; ENSP00000245407.3; ENSG00000197375.14. [O76082-1] DR Ensembl; ENST00000435065.7; ENSP00000402760.2; ENSG00000197375.14. [O76082-3] DR GeneID; 6584; -. DR KEGG; hsa:6584; -. DR MANE-Select; ENST00000245407.8; ENSP00000245407.3; NM_003060.4; NP_003051.1. DR UCSC; uc003kww.5; human. [O76082-1] DR AGR; HGNC:10969; -. DR CTD; 6584; -. DR DisGeNET; 6584; -. DR GeneCards; SLC22A5; -. DR GeneReviews; SLC22A5; -. DR HGNC; HGNC:10969; SLC22A5. DR HPA; ENSG00000197375; Tissue enhanced (skeletal). DR MalaCards; SLC22A5; -. DR MIM; 212140; phenotype. DR MIM; 603377; gene. DR neXtProt; NX_O76082; -. DR OpenTargets; ENSG00000197375; -. DR Orphanet; 158; Systemic primary carnitine deficiency. DR PharmGKB; PA333; -. DR VEuPathDB; HostDB:ENSG00000197375; -. DR eggNOG; KOG0255; Eukaryota. DR GeneTree; ENSGT00940000154155; -. DR HOGENOM; CLU_001265_33_4_1; -. DR InParanoid; O76082; -. DR OMA; WRLVFVW; -. DR OrthoDB; 1448128at2759; -. DR PhylomeDB; O76082; -. DR TreeFam; TF315847; -. DR PathwayCommons; O76082; -. DR Reactome; R-HSA-200425; Carnitine metabolism. DR Reactome; R-HSA-549127; Organic cation transport. DR Reactome; R-HSA-5619053; Defective SLC22A5 causes systemic primary carnitine deficiency (CDSP). DR SignaLink; O76082; -. DR BioGRID-ORCS; 6584; 13 hits in 1158 CRISPR screens. DR ChiTaRS; SLC22A5; human. DR GeneWiki; SLC22A5; -. DR GenomeRNAi; 6584; -. DR Pharos; O76082; Tbio. DR PRO; PR:O76082; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O76082; Protein. DR Bgee; ENSG00000197375; Expressed in gastrocnemius and 147 other cell types or tissues. DR ExpressionAtlas; O76082; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB. DR GO; GO:0031526; C:brush border membrane; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; ISS:ARUK-UCL. DR GO; GO:0005829; C:cytosol; ISS:ARUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:1901235; F:(R)-carnitine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015199; F:amino-acid betaine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0015226; F:carnitine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL. DR GO; GO:0015651; F:quaternary ammonium group transmembrane transporter activity; IDA:ARUK-UCL. DR GO; GO:0015293; F:symporter activity; IEA:UniProtKB-KW. DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; IC:BHF-UCL. DR GO; GO:1902270; P:(R)-carnitine transmembrane transport; IDA:UniProtKB. DR GO; GO:1900749; P:(R)-carnitine transport; IDA:UniProtKB. DR GO; GO:1902603; P:carnitine transmembrane transport; TAS:Reactome. DR GO; GO:0015879; P:carnitine transport; IDA:BHF-UCL. DR GO; GO:0060731; P:positive regulation of intestinal epithelial structure maintenance; IMP:BHF-UCL. DR GO; GO:0015697; P:quaternary ammonium group transport; IDA:ARUK-UCL. DR GO; GO:0009609; P:response to symbiotic bacterium; IMP:BHF-UCL. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:UniProtKB. DR GO; GO:0034341; P:response to type II interferon; IDA:UniProtKB. DR GO; GO:0006814; P:sodium ion transport; IEA:UniProtKB-KW. DR GO; GO:0070715; P:sodium-dependent organic cation transport; IDA:BHF-UCL. DR GO; GO:0150104; P:transport across blood-brain barrier; ISS:ARUK-UCL. DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; IC:BHF-UCL. DR CDD; cd17376; MFS_SLC22A4_5_OCTN1_2; 1. DR Gene3D; 1.20.1250.20; MFS general substrate transporter like domains; 1. DR InterPro; IPR020846; MFS_dom. DR InterPro; IPR005828; MFS_sugar_transport-like. DR InterPro; IPR036259; MFS_trans_sf. DR InterPro; IPR004749; Orgcat_transp/SVOP. DR InterPro; IPR045915; S22A4/5. DR InterPro; IPR005829; Sugar_transporter_CS. DR NCBIfam; TIGR00898; 2A0119; 1. DR PANTHER; PTHR24064; SOLUTE CARRIER FAMILY 22 MEMBER; 1. DR PANTHER; PTHR24064:SF283; SOLUTE CARRIER FAMILY 22 MEMBER 5; 1. DR Pfam; PF00083; Sugar_tr; 1. DR SUPFAM; SSF103473; MFS general substrate transporter; 1. DR PROSITE; PS50850; MFS; 1. DR PROSITE; PS00216; SUGAR_TRANSPORT_1; 1. DR Genevisible; O76082; HS. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cell membrane; Disease variant; KW Endoplasmic reticulum; Glycoprotein; Ion transport; Membrane; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Sodium; KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..557 FT /note="Organic cation/carnitine transporter 2" FT /id="PRO_0000220500" FT TOPO_DOM 1..20 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 21..41 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 42..142 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 143..163 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 164..172 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 173..193 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 194..197 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 198..218 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 219..232 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 233..253 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 254..257 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 258..278 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 279..341 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 342..362 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 363..373 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 374..394 FT /note="Helical; Name=8" FT /evidence="ECO:0000255" FT TOPO_DOM 395..406 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 407..427 FT /note="Helical; Name=9" FT /evidence="ECO:0000255" FT TOPO_DOM 428..430 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 431..451 FT /note="Helical; Name=10" FT /evidence="ECO:0000255" FT TOPO_DOM 452..462 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 463..483 FT /note="Helical; Name=11" FT /evidence="ECO:0000255" FT TOPO_DOM 484..488 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 489..509 FT /note="Helical; Name=12" FT /evidence="ECO:0000255" FT REGION 535..557 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 218..225 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT MOD_RES 486 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 550 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 57 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT CARBOHYD 64 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 91 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17509700, FT ECO:0000269|PubMed:19349973" FT VAR_SEQ 1..336 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_011120" FT VAR_SEQ 131 FT /note="E -> EQDSGAYNAMKNRMGKKPALCLPAQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17509700" FT /id="VSP_043904" FT VAR_SEQ 337..351 FT /note="TWNIRMVTIMSIMLW -> MWILLFQLSSALCFR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_011121" FT VARIANT 4..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079640" FT VARIANT 12 FT /note="G -> S (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains 50% of wild-type FT activity; dbSNP:rs139203363)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064109" FT VARIANT 15 FT /note="G -> W (in CDSP; carnitine transport reduced to less FT than 20% of wild-type; dbSNP:rs267607052)" FT /evidence="ECO:0000269|PubMed:20027113, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064110" FT VARIANT 16 FT /note="P -> L (in CDSP; loss of carnitine transport)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079641" FT VARIANT 17 FT /note="F -> L (in CDSP; carnitine transport reduced to less FT than 20% of wild-type; dbSNP:rs11568520)" FT /evidence="ECO:0000269|PubMed:16931768, FT ECO:0000269|PubMed:20074989, ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_020347" FT VARIANT 19 FT /note="R -> P (in CDSP; carnitine transport is reduced to FT less than 5% of normal; dbSNP:rs72552723)" FT /evidence="ECO:0000269|PubMed:11715001, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064111" FT VARIANT 20 FT /note="L -> H (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains 50% of wild-type FT activity; dbSNP:rs144020613)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079642" FT VARIANT 22 FT /note="Missing (in CDSP; reduces carnitine transport to FT less than 1% of normal)" FT /evidence="ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_066842" FT VARIANT 26 FT /note="S -> N (in CDSP; carnitine transport reduced to less FT than 6% of wild-type; dbSNP:rs772578415)" FT /evidence="ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_066843" FT VARIANT 28 FT /note="S -> I (in CDSP; carnitine transport reduced to 1% FT of wild-type; dbSNP:rs72552724)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079643" FT VARIANT 32 FT /note="N -> S (in CDSP; carnitine transport reduced to less FT than 1% of wild-type; dbSNP:rs72552725)" FT /evidence="ECO:0000269|PubMed:17126586, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064112" FT VARIANT 44 FT /note="A -> V (in CDSP; carnitine transport reduced to less FT than 10% of wild-type; dbSNP:rs199689597)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079644" FT VARIANT 46 FT /note="P -> L (in CDSP; carnitine transport reduced to less FT than 5% of wild-type; dbSNP:rs377767445)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079645" FT VARIANT 46 FT /note="P -> S (in CDSP; carnitine transport is reduced to FT less than 5% of normal; dbSNP:rs202088921)" FT /evidence="ECO:0000269|PubMed:17126586, FT ECO:0000269|PubMed:20027113, ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266" FT /id="VAR_064113" FT VARIANT 50 FT /note="C -> Y (in CDSP; loss of carnitine transport)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079646" FT VARIANT 66 FT /note="T -> P (in CDSP; carnitine transport reduced to 2% FT of wild-type)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064114" FT VARIANT 75 FT /note="R -> P (in CDSP; carnitine transport reduced to 2% FT of wild-type; dbSNP:rs757711838)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064115" FT VARIANT 83 FT /note="R -> L (in CDSP; loss of carnitine transport; FT dbSNP:rs72552726)" FT /evidence="ECO:0000269|PubMed:15617188, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:20027113, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064116" FT VARIANT 93 FT /note="S -> W (in CDSP; loss of carnitine transport; FT dbSNP:rs386134190)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079647" FT VARIANT 95 FT /note="L -> V (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains 30% of wild-type FT activity; dbSNP:rs386134191)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079648" FT VARIANT 96 FT /note="G -> A (in CDSP; carnitine transport reduced to 20% FT of wild-type; dbSNP:rs377767450)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064117" FT VARIANT 115 FT /note="D -> G (in CDSP; carnitine transport reduced to less FT than 5% of wild-type; dbSNP:rs386134192)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079649" FT VARIANT 117..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079650" FT VARIANT 122 FT /note="D -> Y (in CDSP; dbSNP:rs201082652)" FT /evidence="ECO:0000269|PubMed:20574985" FT /id="VAR_064118" FT VARIANT 123 FT /note="V -> G (in CDSP; carnitine transport reduced to less FT than 20% of wild-type; dbSNP:rs748605096)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064119" FT VARIANT 131 FT /note="E -> D (in CDSP; uncertain significance; may affect FT splicing; reduces carnitine transport but the mutant FT retains 30% of wild-type activity)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079651" FT VARIANT 132..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079652" FT VARIANT 140..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079653" FT VARIANT 142 FT /note="A -> S (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains more than 25% of FT wild-type activity; dbSNP:rs151231558)" FT /evidence="ECO:0000269|PubMed:20027113, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064120" FT VARIANT 143 FT /note="P -> L (in CDSP; carnitine transport reduced to less FT than 2% of wild-type; dbSNP:rs1178584184)" FT /evidence="ECO:0000269|PubMed:20074989, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:28841266" FT /id="VAR_064121" FT VARIANT 144 FT /note="L -> F (in dbSNP:rs10040427)" FT /evidence="ECO:0000269|PubMed:16931768" FT /id="VAR_020348" FT VARIANT 151 FT /note="V -> M (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains more than 60% of FT wild-type activity; dbSNP:rs386134193)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079654" FT VARIANT 169 FT /note="R -> P (in CDSP; loss of carnitine transport)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079655" FT VARIANT 169 FT /note="R -> Q (in CDSP; loss of carnitine transport; FT dbSNP:rs121908889)" FT /evidence="ECO:0000269|PubMed:10425211, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_009252" FT VARIANT 169 FT /note="R -> W (in CDSP; loss of carnitine transport; FT dbSNP:rs121908890)" FT /evidence="ECO:0000269|PubMed:11058897, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266" FT /id="VAR_064122" FT VARIANT 175 FT /note="V -> M (in CDSP; carnitine transport reduced to less FT than 10% of wild-type; dbSNP:rs781721860)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079656" FT VARIANT 177 FT /note="M -> V (in CDSP; carnitine transport reduced to less FT than 20% of wild-type; dbSNP:rs145068530)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064123" FT VARIANT 179 FT /note="M -> L (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains more than 40% of FT wild-type activity; dbSNP:rs386134196)" FT /evidence="ECO:0000269|PubMed:10545605, FT ECO:0000269|PubMed:28841266" FT /id="VAR_022564" FT VARIANT 186 FT /note="L -> P (in CDSP; loss of carnitine transport; FT dbSNP:rs386134197)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064124" FT VARIANT 205 FT /note="M -> R (in CDSP; loss of carnitine transport; FT dbSNP:rs796052033)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079657" FT VARIANT 210 FT /note="N -> S (in CDSP; loss of carnitine transport; FT dbSNP:rs386134198)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079658" FT VARIANT 211 FT /note="Y -> C (in CDSP; loss of carnitine transport; FT dbSNP:rs121908888)" FT /evidence="ECO:0000269|PubMed:10480371, FT ECO:0000269|PubMed:28841266" FT /id="VAR_009253" FT VARIANT 214 FT /note="A -> V (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains 30% of wild-type FT activity; dbSNP:rs386134199)" FT /evidence="ECO:0000269|PubMed:20027113, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064125" FT VARIANT 219 FT /note="T -> K (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains 30% of wild-type FT activity)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079659" FT VARIANT 225 FT /note="S -> L (in CDSP; reduces carnitine transport to less FT than 20% of wild-type activity; dbSNP:rs386134205)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079660" FT VARIANT 227 FT /note="R -> H (in CDSP; reduces carnitine transport to less FT than 10% of wild-type activity; dbSNP:rs185551386)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064126" FT VARIANT 230 FT /note="F -> L (in CDSP; reduces carnitine transport to less FT than 1% of wild-type activity; dbSNP:rs756650860)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064127" FT VARIANT 231 FT /note="S -> F (in CDSP; loss of carnitine transport; FT dbSNP:rs386134206)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079661" FT VARIANT 232 FT /note="T -> M (in CDSP; reduces carnitine transport to less FT than 20% of wild-type activity; dbSNP:rs114269482)" FT /evidence="ECO:0000269|PubMed:15714519, FT ECO:0000269|PubMed:20027113, ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266" FT /id="VAR_064128" FT VARIANT 234 FT /note="G -> R (in CDSP; dbSNP:rs1457258524)" FT /evidence="ECO:0000269|PubMed:20074989" FT /id="VAR_064129" FT VARIANT 240 FT /note="A -> T (in CDSP; reduces carnitine transport to less FT than 2% of wild-type activity)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064130" FT VARIANT 242 FT /note="G -> V (in CDSP; loss of carnitine transport; FT dbSNP:rs72552728)" FT /evidence="ECO:0000269|PubMed:11058897, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:28841266" FT /id="VAR_064131" FT VARIANT 247 FT /note="P -> R (in CDSP; loss of carnitine transport)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079662" FT VARIANT 254..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079663" FT VARIANT 254 FT /note="R -> Q (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains more than 30% of FT wild-type activity; dbSNP:rs200699819)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079664" FT VARIANT 256..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079665" FT VARIANT 257 FT /note="R -> W (in CDSP; reduces carnitine transport to less FT than 10% of wild-type activity; dbSNP:rs386134203)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064132" FT VARIANT 264 FT /note="T -> M (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains more than 40% of FT wild-type activity; dbSNP:rs201262157)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079666" FT VARIANT 264 FT /note="T -> R (in CDSP; reduces carnitine transport to less FT than 5% of wild-type activity; dbSNP:rs201262157)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064133" FT VARIANT 269 FT /note="L -> P (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains more than 40% of FT wild-type activity)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079667" FT VARIANT 275..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079668" FT VARIANT 280 FT /note="S -> F (in CDSP; reduces carnitine transport to less FT than 1% of wild-type activity; dbSNP:rs386134208)" FT /evidence="ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_066844" FT VARIANT 282..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079669" FT VARIANT 282 FT /note="R -> Q (in CDSP; reduces carnitine transport to 5% FT of wild-type activity; dbSNP:rs386134210)" FT /evidence="ECO:0000269|PubMed:20074989, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064134" FT VARIANT 283 FT /note="W -> C (in CDSP; loss of carnitine transport; FT dbSNP:rs386134211)" FT /evidence="ECO:0000269|PubMed:10545605, FT ECO:0000269|PubMed:28841266" FT /id="VAR_022565" FT VARIANT 283 FT /note="W -> R (in CDSP; reduces carnitine transport to less FT than 1% of wild-type activity; dbSNP:rs72552729)" FT /evidence="ECO:0000269|PubMed:10612840, FT ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266" FT /id="VAR_009254" FT VARIANT 289..557 FT /note="Missing (in CDSP; dbSNP:rs1554087707)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079670" FT VARIANT 295..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079671" FT VARIANT 301 FT /note="A -> D (in CDSP; reduces carnitine transport to FT less-than-1% to 3% of wild-type activity; FT dbSNP:rs72552730)" FT /evidence="ECO:0000269|PubMed:11058897, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:28841266" FT /id="VAR_064135" FT VARIANT 312 FT /note="I -> V (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains 70% of wild-type FT activity; dbSNP:rs77300588)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064136" FT VARIANT 317 FT /note="E -> K (in CDSP; uncertain significance; no effect FT on carnitine transport; dbSNP:rs774792831)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079672" FT VARIANT 319..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079673" FT VARIANT 348 FT /note="I -> T (in CDSP; uncertain significance; reduces FT carnitine transport but the mutant retains 60% of wild-type FT activity; dbSNP:rs150544263)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079674" FT VARIANT 351 FT /note="W -> R (in CDSP; loss of carnitine transport; FT dbSNP:rs68018207)" FT /evidence="ECO:0000269|PubMed:11058897, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064137" FT VARIANT 355 FT /note="S -> L (in CDSP; reduces carnitine transport to less FT than 2% of wild-type activity; dbSNP:rs1385634398)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064138" FT VARIANT 358 FT /note="Y -> N (in CDSP; loss of carnitine transport; FT dbSNP:rs61731073)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064139" FT VARIANT 362 FT /note="S -> L (in CDSP; dbSNP:rs886042092)" FT /evidence="ECO:0000269|PubMed:20074989" FT /id="VAR_064140" FT VARIANT 363 FT /note="L -> P (in CDSP; loss of carnitine transport; FT dbSNP:rs386134214)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079675" FT VARIANT 387..557 FT /note="Missing (in CDSP)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079676" FT VARIANT 394 FT /note="Missing (in CDSP; reduces carnitine transport to 5% FT of wild-type activity)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079677" FT VARIANT 398 FT /note="P -> L (in CDSP; reduces carnitine transport to less FT than 1% of wild-type activity; dbSNP:rs144547521)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064141" FT VARIANT 399 FT /note="R -> Q (in CDSP; carnitine transport is reduced to FT less than 1% of normal; dbSNP:rs121908891)" FT /evidence="ECO:0000269|PubMed:11715001, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:28841266" FT /id="VAR_064142" FT VARIANT 399 FT /note="R -> W (in CDSP; reduces carnitine transport to less FT than 5% of wild-type activity; dbSNP:rs267607054)" FT /evidence="ECO:0000269|PubMed:20027113, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:28841266" FT /id="VAR_064143" FT VARIANT 412 FT /note="S -> G (in CDSP; uncertain significance; no effect FT on carnitine transport)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079678" FT VARIANT 439 FT /note="V -> G (in CDSP; reduces carnitine transport to less FT than 1% of wild-type activity)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079679" FT VARIANT 440 FT /note="T -> M (in CDSP; loss of carnitine transport; FT dbSNP:rs72552732)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266" FT /id="VAR_064144" FT VARIANT 442 FT /note="A -> I (in CDSP; reduces carnitine transport to less FT than 20% of wild-type activity; requires 2 nucleotide FT substitutions; dbSNP:rs267607053)" FT /evidence="ECO:0000269|PubMed:20027113, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064145" FT VARIANT 443 FT /note="F -> V (in CDSP; reduces carnitine transport to less FT than 1% of wild-type)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064146" FT VARIANT 446 FT /note="V -> F (in CDSP; reduces carnitine transport to less FT than 1% of wild-type; dbSNP:rs72552733)" FT /evidence="ECO:0000269|PubMed:10612840, FT ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266" FT /id="VAR_009255" FT VARIANT 447 FT /note="Y -> C (in CDSP; loss of carnitine transport; FT dbSNP:rs386134218)" FT /evidence="ECO:0000269|PubMed:15714519, FT ECO:0000269|PubMed:21922592, ECO:0000269|PubMed:28841266" FT /id="VAR_064147" FT VARIANT 448 FT /note="V -> L (in CDSP; reduces carnitine transport to less FT than 20% of wild-type; dbSNP:rs386134219)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079680" FT VARIANT 449 FT /note="Y -> D (in CDSP; uncertain significance; reduces FT carnitine transport to less than 20% of wild-type; FT dbSNP:rs11568514)" FT /evidence="ECO:0000269|PubMed:15714519, FT ECO:0000269|PubMed:16931768, ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_029315" FT VARIANT 452 FT /note="E -> K (in CDSP; reduces carnitine transport to less FT than 5% of wild-type; dbSNP:rs72552734)" FT /evidence="ECO:0000269|PubMed:10679939, FT ECO:0000269|PubMed:15714519, ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_009256" FT VARIANT 455 FT /note="P -> R (in CDSP; loss of carnitine transport; FT dbSNP:rs1408166345)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064148" FT VARIANT 462 FT /note="G -> V (in CDSP; reduces carnitine transport to less FT than 5% of wild-type)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079681" FT VARIANT 467 FT /note="S -> C (in CDSP; reduces carnitine transport to less FT than 20% of wild-type activity; dbSNP:rs60376624)" FT /evidence="ECO:0000269|PubMed:10545605, FT ECO:0000269|PubMed:17126586, ECO:0000269|PubMed:20074989, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_022566" FT VARIANT 468 FT /note="T -> R (in CDSP; markedly reduced carnitine FT transport compared to the wild-type protein; less than 1% FT of wild-type activity; dbSNP:rs386134221)" FT /evidence="ECO:0000269|PubMed:15714519, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064149" FT VARIANT 470 FT /note="S -> F (in CDSP; loss of carnitine transport; FT dbSNP:rs386134222)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079682" FT VARIANT 471 FT /note="R -> C (in CDSP; dbSNP:rs749282641)" FT /evidence="ECO:0000269|PubMed:20074989" FT /id="VAR_064150" FT VARIANT 471 FT /note="R -> H (in CDSP; reduces carnitine transport to less FT than 2% of wild-type; dbSNP:rs386134223)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079683" FT VARIANT 471 FT /note="R -> P (in CDSP; loss of carnitine transport)" FT /evidence="ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_066845" FT VARIANT 476 FT /note="L -> R (in CDSP; loss of carnitine transport)" FT /evidence="ECO:0000269|PubMed:28841266" FT /id="VAR_079684" FT VARIANT 478 FT /note="P -> L (in CDSP; loss of carnitine transport but FT stimulated organic cation transport; no effect on protein FT expression; dbSNP:rs72552735)" FT /evidence="ECO:0000269|PubMed:10072434, FT ECO:0000269|PubMed:10454528, ECO:0000269|PubMed:10559218, FT ECO:0000269|PubMed:28841266" FT /id="VAR_009257" FT VARIANT 481 FT /note="V -> F (reduces carnitine transport but the mutant FT retains more than 60% of wild-type activity; FT dbSNP:rs11568513)" FT /evidence="ECO:0000269|PubMed:16931768, FT ECO:0000269|PubMed:28841266" FT /id="VAR_020349" FT VARIANT 481 FT /note="V -> I (in dbSNP:rs11568513)" FT /evidence="ECO:0000269|PubMed:16931768" FT /id="VAR_036816" FT VARIANT 488 FT /note="R -> C (in CDSP; reduces carnitine transport to less FT than 10% of wild-type; dbSNP:rs377216516)" FT /evidence="ECO:0000269|PubMed:17126586, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:28841266" FT /id="VAR_064151" FT VARIANT 488 FT /note="R -> H (in CDSP; uncertain significance; reduces FT carnitine transport to 40% of wild-type; dbSNP:rs28383481)" FT /evidence="ECO:0000269|PubMed:21922592, FT ECO:0000269|PubMed:28841266" FT /id="VAR_066846" FT VARIANT 507 FT /note="L -> S (in CDSP; reduces carnitine transport to 5% FT of wild-type; dbSNP:rs1157198543)" FT /evidence="ECO:0000269|PubMed:20574985, FT ECO:0000269|PubMed:28841266" FT /id="VAR_064152" FT VARIANT 508 FT /note="F -> L (in dbSNP:rs11568521)" FT /evidence="ECO:0000269|PubMed:16931768" FT /id="VAR_029316" FT VARIANT 530 FT /note="M -> V (in dbSNP:rs11568524)" FT /evidence="ECO:0000269|PubMed:16931768" FT /id="VAR_029317" FT VARIANT 549 FT /note="P -> S (reduces carnitine transport but the mutant FT retains more than 20% of wild-type activity; FT dbSNP:rs11568525)" FT /evidence="ECO:0000269|PubMed:16931768, FT ECO:0000269|PubMed:20574985, ECO:0000269|PubMed:28841266" FT /id="VAR_020350" FT MUTAGEN 91 FT /note="N->Q: Reduces expression to 50%. No effect on FT carnitine transporter activity." FT /evidence="ECO:0000269|PubMed:17509700" FT MUTAGEN 352 FT /note="M->R: Loss of both carnitine and organic cation FT transport functionalities. No effect on protein FT expression." FT /evidence="ECO:0000269|PubMed:10454528, FT ECO:0000269|PubMed:10559218" FT CONFLICT 114 FT /note="L -> P (in Ref. 8; AAH12325)" FT /evidence="ECO:0000305" SQ SEQUENCE 557 AA; 62752 MW; 928B1F6EFF63C48D CRC64; MRDYDEVTAF LGEWGPFQRL IFFLLSASII PNGFTGLSSV FLIATPEHRC RVPDAANLSS AWRNHTVPLR LRDGREVPHS CRRYRLATIA NFSALGLEPG RDVDLGQLEQ ESCLDGWEFS QDVYLSTIVT EWNLVCEDDW KAPLTISLFF VGVLLGSFIS GQLSDRFGRK NVLFVTMGMQ TGFSFLQIFS KNFEMFVVLF VLVGMGQISN YVAAFVLGTE ILGKSVRIIF STLGVCIFYA FGYMVLPLFA YFIRDWRMLL VALTMPGVLC VALWWFIPES PRWLISQGRF EEAEVIIRKA AKANGIVVPS TIFDPSELQD LSSKKQQSHN ILDLLRTWNI RMVTIMSIML WMTISVGYFG LSLDTPNLHG DIFVNCFLSA MVEVPAYVLA WLLLQYLPRR YSMATALFLG GSVLLFMQLV PPDLYYLATV LVMVGKFGVT AAFSMVYVYT AELYPTVVRN MGVGVSSTAS RLGSILSPYF VYLGAYDRFL PYILMGSLTI LTAILTLFLP ESFGTPLPDT IDQMLRVKGM KHRKTPSHTR MLKDGQERPT ILKSTAF //