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{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
{{Infobox_gene}}
'''Solute carrier family 22, member 4''', also known as '''SLC22A4''', is a human [[gene]]; the encoded protein is known as the '''[[ergothioneine]] transporter'''.<ref name="entrez">{{cite web | title = Entrez Gene: SLC22A4 solute carrier family 22 (ergothioneine transporter), member 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6583| accessdate = }}</ref>
'''Solute carrier family 22, member 4''', also known as '''SLC22A4''', is a human [[gene]]; the encoded protein is known as the '''[[ergothioneine]] transporter'''.<ref name="review2022">{{cite journal |last1=Gründemann |first1=Dirk |last2=Hartmann |first2=Lea |last3=Flögel |first3=Svenja |title=The ergothioneine transporter (ETT): substrates and locations, an inventory |journal=FEBS Letters |date=May 2022 |volume=596 |issue=10 |pages=1252–1269 |doi=10.1002/1873-3468.14269 |pmid=34958679|s2cid=245535600 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC22A4 solute carrier family 22 (ergothioneine transporter), member 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6583}}</ref>


== Function ==
== 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.<ref>{{cite journal | vauthors = Gründemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels R, Jung N, Rubbert A, Schömig E | title = Discovery of the ergothioneine transporter | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 14 | pages = 5256–61 | date = Apr 2005 | pmid = 15795384 | pmc = 555966 | doi = 10.1073/pnas.0408624102 | bibcode = 2005PNAS..102.5256G | doi-access = free }}</ref> Thus, a more appropriate functional designation is ETT ("ergothioneine transporter").<ref name="review2022" />

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.<ref>{{cite journal | vauthors = Grigat S, Harlfinger S, Pal S, Striebinger R, Golz S, Geerts A, Lazar A, Schömig E, Gründemann D | title = Probing the substrate specificity of the ergothioneine transporter with methimazole, hercynine, and organic cations | journal = Biochemical Pharmacology | volume = 74 | issue = 2 | pages = 309–16 | date = Jul 2007 | pmid = 17532304 | doi = 10.1016/j.bcp.2007.04.015 }}</ref> 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.<ref>{{cite journal | vauthors = Gründemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels R, Jung N, Rubbert A, Schömig E | title = Discovery of the ergothioneine transporter | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 14 | pages = 5256–61 | date = Apr 2005 | pmid = 15795384 | pmc = 555966 | doi = 10.1073/pnas.0408624102 }}</ref> Thus, a more appropriate functional designation is ETT ("ergothioneine transporter").


== Interactions ==
== Interactions ==
SLC22A4 has been shown to [[Protein-protein interaction|interact]] with [[PDZK1]].<ref name=pmid14531806>{{cite journal | vauthors = Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H | title = PDZK1: I. a major scaffolder in brush borders of proximal tubular cells | journal = Kidney International | volume = 64 | issue = 5 | pages = 1733–45 | date = Nov 2003 | pmid = 14531806 | doi = 10.1046/j.1523-1755.2003.00266.x }}</ref>
SLC22A4 has been shown to [[Protein-protein interaction|interact]] with [[PDZK1]].<ref name=pmid14531806>{{cite journal | vauthors = Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H | title = PDZK1: I. a major scaffolder in brush borders of proximal tubular cells | journal = Kidney International | volume = 64 | issue = 5 | pages = 1733–45 | date = Nov 2003 | pmid = 14531806 | doi = 10.1046/j.1523-1755.2003.00266.x | doi-access = free }}</ref>


== See also ==
== See also ==
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{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal | vauthors = Xuan W, Lamhonwah AM, Librach C, Jarvi K, Tein I | title = Characterization of organic cation/carnitine transporter family in human sperm | journal = Biochemical and Biophysical Research Communications | volume = 306 | issue = 1 | pages = 121–8 | date = Jun 2003 | pmid = 12788076 | doi = 10.1016/S0006-291X(03)00930-6 }}
* {{cite journal | vauthors = Xuan W, Lamhonwah AM, Librach C, Jarvi K, Tein I | title = Characterization of organic cation/carnitine transporter family in human sperm | journal = Biochemical and Biophysical Research Communications | volume = 306 | issue = 1 | pages = 121–8 | date = Jun 2003 | pmid = 12788076 | doi = 10.1016/S0006-291X(03)00930-6 }}
* {{cite journal | vauthors = Yamada R, Tokuhiro S, Chang X, Yamamoto K | title = SLC22A4 and RUNX1: identification of RA susceptible genes | journal = Journal of Molecular Medicine | volume = 82 | issue = 9 | pages = 558–64 | date = Sep 2004 | pmid = 15184985 | doi = 10.1007/s00109-004-0547-y }}
* {{cite journal | vauthors = Yamada R, Tokuhiro S, Chang X, Yamamoto K | title = SLC22A4 and RUNX1: identification of RA susceptible genes | journal = Journal of Molecular Medicine | volume = 82 | issue = 9 | pages = 558–64 | date = Sep 2004 | pmid = 15184985 | doi = 10.1007/s00109-004-0547-y | s2cid = 9156168 }}
* {{cite journal | vauthors = Silverberg MS | title = OCTNs: will the real IBD5 gene please stand up? | journal = World Journal of Gastroenterology | volume = 12 | issue = 23 | pages = 3678–81 | date = Jun 2006 | pmid = 16773684 | pmc = 4087460 | doi = 10.3748/wjg.v12.i23.36 | doi-broken-date = 2019-02-21 }}
* {{cite journal | vauthors = Silverberg MS | title = OCTNs: will the real IBD5 gene please stand up? | journal = World Journal of Gastroenterology | volume = 12 | issue = 23 | pages = 3678–81 | date = Jun 2006 | pmid = 16773684 | pmc = 4087460 | doi = 10.3748/wjg.v12.i23.3678 | doi-access = free }}
* {{cite journal | vauthors = Tamai I, Yabuuchi H, Nezu J, Sai Y, Oku A, Shimane M, Tsuji A | title = Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1 | journal = FEBS Letters | volume = 419 | issue = 1 | pages = 107–11 | date = Dec 1997 | pmid = 9426230 | doi = 10.1016/S0014-5793(97)01441-5 }}
* {{cite journal | vauthors = Tamai I, Yabuuchi H, Nezu J, Sai Y, Oku A, Shimane M, Tsuji A | title = Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1 | journal = FEBS Letters | volume = 419 | issue = 1 | pages = 107–11 | date = Dec 1997 | pmid = 9426230 | doi = 10.1016/S0014-5793(97)01441-5 | s2cid = 35546307 }}
* {{cite journal | vauthors = Meyer-Wentrup F, Karbach U, Gorboulev V, Arndt P, Koepsell H | title = Membrane localization of the electrogenic cation transporter rOCT1 in rat liver | journal = Biochemical and Biophysical Research Communications | volume = 248 | issue = 3 | pages = 673–8 | date = Jul 1998 | pmid = 9703985 | doi = 10.1006/bbrc.1998.9034 }}
* {{cite journal | vauthors = Meyer-Wentrup F, Karbach U, Gorboulev V, Arndt P, Koepsell H | title = Membrane localization of the electrogenic cation transporter rOCT1 in rat liver | journal = Biochemical and Biophysical Research Communications | volume = 248 | issue = 3 | pages = 673–8 | date = Jul 1998 | pmid = 9703985 | doi = 10.1006/bbrc.1998.9034 }}
* {{cite journal | vauthors = Urakami Y, Okuda M, Masuda S, Saito H, Inui KI | title = Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 287 | issue = 2 | pages = 800–5 | date = Nov 1998 | pmid = 9808712 | doi = }}
* {{cite journal | vauthors = Urakami Y, Okuda M, Masuda S, Saito H, Inui KI | title = Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 287 | issue = 2 | pages = 800–5 | date = Nov 1998 | pmid = 9808712 }}
* {{cite journal | vauthors = Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A | title = Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 289 | issue = 2 | pages = 768–73 | date = May 1999 | pmid = 10215651 | doi = }}
* {{cite journal | vauthors = Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A | title = Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 289 | issue = 2 | pages = 768–73 | date = May 1999 | pmid = 10215651 }}
* {{cite journal | vauthors = Alcorn J, Lu X, Moscow JA, McNamara PJ | title = Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 303 | issue = 2 | pages = 487–96 | date = Nov 2002 | pmid = 12388627 | doi = 10.1124/jpet.102.038315 }}
* {{cite journal | vauthors = Alcorn J, Lu X, Moscow JA, McNamara PJ | title = Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 303 | issue = 2 | pages = 487–96 | date = Nov 2002 | pmid = 12388627 | doi = 10.1124/jpet.102.038315 | s2cid = 16195525 }}
* {{cite journal | vauthors = Saito S, Iida A, Sekine A, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y | title = Catalog of 238 variations among six human genes encoding solute carriers ( hSLCs) in the Japanese population | journal = Journal of Human Genetics | volume = 47 | issue = 11 | pages = 576–84 | year = 2003 | pmid = 12436193 | doi = 10.1007/s100380200088 }}
* {{cite journal | vauthors = Saito S, Iida A, Sekine A, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y | title = Catalog of 238 variations among six human genes encoding solute carriers ( hSLCs) in the Japanese population | journal = Journal of Human Genetics | volume = 47 | issue = 11 | pages = 576–84 | year = 2003 | pmid = 12436193 | doi = 10.1007/s100380200088 | doi-access = free }}
* {{cite journal | vauthors = Eraly SA, Hamilton BA, Nigam SK | title = Organic anion and cation transporters occur in pairs of similar and similarly expressed genes | journal = Biochemical and Biophysical Research Communications | volume = 300 | issue = 2 | pages = 333–42 | date = Jan 2003 | pmid = 12504088 | doi = 10.1016/S0006-291X(02)02853-X }}
* {{cite journal | vauthors = Eraly SA, Hamilton BA, Nigam SK | title = Organic anion and cation transporters occur in pairs of similar and similarly expressed genes | journal = Biochemical and Biophysical Research Communications | volume = 300 | issue = 2 | pages = 333–42 | date = Jan 2003 | pmid = 12504088 | doi = 10.1016/S0006-291X(02)02853-X }}
* {{cite journal | vauthors = Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H | title = PDZK1: I. a major scaffolder in brush borders of proximal tubular cells | journal = Kidney International | volume = 64 | issue = 5 | pages = 1733–45 | date = Nov 2003 | pmid = 14531806 | doi = 10.1046/j.1523-1755.2003.00266.x }}
* {{cite journal | vauthors = Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H | title = PDZK1: I. a major scaffolder in brush borders of proximal tubular cells | journal = Kidney International | volume = 64 | issue = 5 | pages = 1733–45 | date = Nov 2003 | pmid = 14531806 | doi = 10.1046/j.1523-1755.2003.00266.x | doi-access = free }}
* {{cite journal | vauthors = 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 | title = An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis | journal = Nature Genetics | volume = 35 | issue = 4 | pages = 341–8 | date = Dec 2003 | pmid = 14608356 | doi = 10.1038/ng1267 }}
* {{cite journal | vauthors = 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 | title = An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis | journal = Nature Genetics | volume = 35 | issue = 4 | pages = 341–8 | date = Dec 2003 | pmid = 14608356 | doi = 10.1038/ng1267 | s2cid = 21564858 }}
* {{cite journal | vauthors = 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 | title = Functional variants of OCTN cation transporter genes are associated with Crohn disease | journal = Nature Genetics | volume = 36 | issue = 5 | pages = 471–5 | date = May 2004 | pmid = 15107849 | doi = 10.1038/ng1339 }}
* {{cite journal | vauthors = 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 | title = Functional variants of OCTN cation transporter genes are associated with Crohn disease | journal = Nature Genetics | volume = 36 | issue = 5 | pages = 471–5 | date = May 2004 | pmid = 15107849 | doi = 10.1038/ng1339 | doi-access = free }}
* {{cite journal | vauthors = Kawasaki Y, Kato Y, Sai Y, Tsuji A | title = Functional characterization of human organic cation transporter OCTN1 single nucleotide polymorphisms in the Japanese population | journal = Journal of Pharmaceutical Sciences | volume = 93 | issue = 12 | pages = 2920–6 | date = Dec 2004 | pmid = 15459889 | doi = 10.1002/jps.20190 }}
* {{cite journal | vauthors = Kawasaki Y, Kato Y, Sai Y, Tsuji A | title = Functional characterization of human organic cation transporter OCTN1 single nucleotide polymorphisms in the Japanese population | journal = Journal of Pharmaceutical Sciences | volume = 93 | issue = 12 | pages = 2920–6 | date = Dec 2004 | pmid = 15459889 | doi = 10.1002/jps.20190 }}
* {{cite journal | vauthors = Newman B, Gu X, Wintle R, Cescon D, Yazdanpanah M, Liu X, Peltekova V, Van Oene M, Amos CI, Siminovitch KA | title = A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease | journal = Gastroenterology | volume = 128 | issue = 2 | pages = 260–9 | date = Feb 2005 | pmid = 15685536 | doi = 10.1053/j.gastro.2004.11.056 }}
* {{cite journal | vauthors = Newman B, Gu X, Wintle R, Cescon D, Yazdanpanah M, Liu X, Peltekova V, Van Oene M, Amos CI, Siminovitch KA | title = A risk haplotype in the Solute Carrier Family 22A4/22A5 gene cluster influences phenotypic expression of Crohn's disease | journal = Gastroenterology | volume = 128 | issue = 2 | pages = 260–9 | date = Feb 2005 | pmid = 15685536 | doi = 10.1053/j.gastro.2004.11.056 | doi-access = free }}
{{refend}}
{{refend}}


{{NLM content}}
{{NLM content}}
{{Membrane transport proteins}}
{{Membrane transport proteins}}



[[Category:Solute carrier family]]
[[Category:Solute carrier family]]

Latest revision as of 08:15, 17 April 2024

SLC22A4
Identifiers
AliasesSLC22A4, OCTN1, solute carrier family 22 member 4, DFNB60
External IDsOMIM: 604190; MGI: 1353479; HomoloGene: 81701; GeneCards: SLC22A4; OMA:SLC22A4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003059

NM_019687
NM_001330304

RefSeq (protein)

NP_003050

NP_001317233
NP_062661

Location (UCSC)Chr 5: 132.29 – 132.34 MbChr 11: 53.87 – 53.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Solute carrier family 22, member 4, also known as SLC22A4, is a human gene; the encoded protein is known as the ergothioneine transporter.[5][6]

Function[edit]

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.[7] Thus, a more appropriate functional designation is ETT ("ergothioneine transporter").[5]

Interactions[edit]

SLC22A4 has been shown to interact with PDZK1.[8]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000197208Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020334Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Gründemann, Dirk; Hartmann, Lea; Flögel, Svenja (May 2022). "The ergothioneine transporter (ETT): substrates and locations, an inventory". FEBS Letters. 596 (10): 1252–1269. doi:10.1002/1873-3468.14269. PMID 34958679. S2CID 245535600.
  6. ^ "Entrez Gene: SLC22A4 solute carrier family 22 (ergothioneine transporter), member 4".
  7. ^ Gründemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels R, Jung N, Rubbert A, Schömig E (Apr 2005). "Discovery of the ergothioneine transporter". Proceedings of the National Academy of Sciences of the United States of America. 102 (14): 5256–61. Bibcode:2005PNAS..102.5256G. doi:10.1073/pnas.0408624102. PMC 555966. PMID 15795384.
  8. ^ Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H (Nov 2003). "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells". Kidney International. 64 (5): 1733–45. doi:10.1046/j.1523-1755.2003.00266.x. PMID 14531806.

Further reading[edit]

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