SLC22A4 cotransports ERGT, Na+ from extracellular region to cytosol

Stable Identifier
R-HSA-549241
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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The human gene SLC22A4 encodes the ergothioneine transporter (ETT). It was originally discovered as an organic cation/carnitine transporter (OCTN1) (Tamai et al. 1997) but its main substrate is not carnitine. It is widely expressed and transports ergothioneine more than 100 times more efficiently than tetraethylammonium and carnitine (Grundemann et al. 2005), leading to the name change from OCTN1 to ETT. Defects in SLC22A4 could be implicated in rheumatoid arthritis (RA; MIM:180300), an inflammatory disease with autoimmune features and a complex genetic component (Tokuhiro et al. 2003, Yamada et al. 2004). An intronic SNP (slc2F2) in intron 1, consists of a susceptible T allele and a nonsusceptible C allele. The runt-related transcription factor 1 (RUNX1) has a suppressive effect on SLC22A4 expression and this suppression appears to be stronger with the susceptible T allele of SLC22A4 than with the nonsusceptible C allele, leading to a lower expression of SLC22A4 (Tokuhiro et al. 2003).

Literature References
PubMed ID Title Journal Year
15795384 Discovery of the ergothioneine transporter

Gr√ľndemann, D, Harlfinger, S, Golz, S, Geerts, A, Lazar, A, Berkels, R, Jung, N, Rubbert, A, Sch√∂mig, E

Proc Natl Acad Sci U S A 2005
14608356 An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis

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

Nat. Genet. 2003
15184985 SLC22A4 and RUNX1: identification of RA susceptible genes

Yamada, R, Tokuhiro, S, Chang, X, Yamamoto, K

J. Mol. Med. 2004
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
secondary active organic cation transmembrane transporter activity of SLC22A4 [plasma membrane]
Physical Entity
Activity
This event is regulated
Negatively by
Orthologous Events
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