SLC22A4 explained

Solute carrier family 22, member 4, also known as SLC22A4, is a human gene; the encoded protein is known as the ergothioneine transporter.^{[1] [2]}

Function

The encoded protein is an integral protein of the plasma membrane containing 12 transmembrane segments. The first functional designation of this protein was OCTN1 ("organic cation transporter, novel, type 1"), but efficiency of transport for organic cations (e.g., tetraethylammonium) is very low. The transport efficiency for carnitine is also negligible. Instead, the protein is responsible for the cotransport of sodium ions and ergothioneine, which is an antioxidant, into cells.^[3] Thus, a more appropriate functional designation is ETT ("ergothioneine transporter").

Interactions

SLC22A4 has been shown to interact with PDZK1.^[4]

See also

• Solute carrier family

Further reading

• Xuan W, Lamhonwah AM, Librach C, Jarvi K, Tein I . Characterization of organic cation/carnitine transporter family in human sperm . Biochemical and Biophysical Research Communications . 306 . 1 . 121–8 . Jun 2003 . 12788076 . 10.1016/S0006-291X(03)00930-6 .
• Yamada R, Tokuhiro S, Chang X, Yamamoto K . SLC22A4 and RUNX1: identification of RA susceptible genes . Journal of Molecular Medicine . 82 . 9 . 558–64 . Sep 2004 . 15184985 . 10.1007/s00109-004-0547-y . 9156168 .
• Silverberg MS . OCTNs: will the real IBD5 gene please stand up? . World Journal of Gastroenterology . 12 . 23 . 3678–81 . Jun 2006 . 16773684 . 4087460 . 10.3748/wjg.v12.i23.3678 . free .
• Tamai I, Yabuuchi H, Nezu J, Sai Y, Oku A, Shimane M, Tsuji A . Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1 . FEBS Letters . 419 . 1 . 107–11 . Dec 1997 . 9426230 . 10.1016/S0014-5793(97)01441-5 . 35546307 .
• Meyer-Wentrup F, Karbach U, Gorboulev V, Arndt P, Koepsell H . Membrane localization of the electrogenic cation transporter rOCT1 in rat liver . Biochemical and Biophysical Research Communications . 248 . 3 . 673–8 . Jul 1998 . 9703985 . 10.1006/bbrc.1998.9034 .
• Urakami Y, Okuda M, Masuda S, Saito H, Inui KI . Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs . The Journal of Pharmacology and Experimental Therapeutics . 287 . 2 . 800–5 . Nov 1998 . 9808712 .
• Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A . Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations . The Journal of Pharmacology and Experimental Therapeutics . 289 . 2 . 768–73 . May 1999 . 10215651 .
• Alcorn J, Lu X, Moscow JA, McNamara PJ . Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction . The Journal of Pharmacology and Experimental Therapeutics . 303 . 2 . 487–96 . Nov 2002 . 12388627 . 10.1124/jpet.102.038315 . 16195525 .
• Saito S, Iida A, Sekine A, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y . Catalog of 238 variations among six human genes encoding solute carriers (hSLCs) in the Japanese population . Journal of Human Genetics . 47 . 11 . 576–84 . 2003 . 12436193 . 10.1007/s100380200088 . free .
• Eraly SA, Hamilton BA, Nigam SK . Organic anion and cation transporters occur in pairs of similar and similarly expressed genes . Biochemical and Biophysical Research Communications . 300 . 2 . 333–42 . Jan 2003 . 12504088 . 10.1016/S0006-291X(02)02853-X .
• Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H . PDZK1: I. a major scaffolder in brush borders of proximal tubular cells . Kidney International . 64 . 5 . 1733–45 . Nov 2003 . 14531806 . 10.1046/j.1523-1755.2003.00266.x . free .
• Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, Furukawa H, Nagashima M, Yoshino S, Mabuchi A, Sekine A, Saito S, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K . An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis . Nature Genetics . 35 . 4 . 341–8 . Dec 2003 . 14608356 . 10.1038/ng1267 . 21564858 .
• Peltekova VD, Wintle RF, Rubin LA, Amos CI, Huang Q, Gu X, Newman B, Van Oene M, Cescon D, Greenberg G, Griffiths AM, St George-Hyslop PH, Siminovitch KA . Functional variants of OCTN cation transporter genes are associated with Crohn disease . Nature Genetics . 36 . 5 . 471–5 . May 2004 . 15107849 . 10.1038/ng1339 . free .
• Kawasaki Y, Kato Y, Sai Y, Tsuji A . Functional characterization of human organic cation transporter OCTN1 single nucleotide polymorphisms in the Japanese population . Journal of Pharmaceutical Sciences . 93 . 12 . 2920–6 . Dec 2004 . 15459889 . 10.1002/jps.20190 .
• Newman B, Gu X, Wintle R, Cescon D, Yazdanpanah M, Liu X, Peltekova V, Van Oene M, Amos CI, Siminovitch KA . A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease . Gastroenterology . 128 . 2 . 260–9 . Feb 2005 . 15685536 . 10.1053/j.gastro.2004.11.056 . free .

Notes and References

1. Gründemann . Dirk . Hartmann . Lea . Flögel . Svenja . The ergothioneine transporter (ETT): substrates and locations, an inventory . FEBS Letters . May 2022 . 596 . 10 . 1252–1269 . 10.1002/1873-3468.14269 . 34958679. 245535600 .
2. Web site: Entrez Gene: SLC22A4 solute carrier family 22 (ergothioneine transporter), member 4.
3. Gründemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels R, Jung N, Rubbert A, Schömig E . Discovery of the ergothioneine transporter . Proceedings of the National Academy of Sciences of the United States of America . 102 . 14 . 5256–61 . Apr 2005 . 15795384 . 555966 . 10.1073/pnas.0408624102 . 2005PNAS..102.5256G . free .
4. Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H . PDZK1: I. a major scaffolder in brush borders of proximal tubular cells . Kidney International . 64 . 5 . 1733–45 . Nov 2003 . 14531806 . 10.1046/j.1523-1755.2003.00266.x . free .