Equilibrative nucleoside transporter 4

Details

Name
Equilibrative nucleoside transporter 4
Synonyms
  • ENT4
  • hENT4
  • Plasma membrane monoamine transporter
  • PMAT
  • Solute carrier family 29 member 4
Gene Name
SLC29A4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008624|Equilibrative nucleoside transporter 4
MGSVGSQRLEEPSVAGTPDPGVVMSFTFDSHQLEEAAEAAQGQGLRARGVPAFTDTTLDE
PVPDDRYHAIYFAMLLAGVGFLLPYNSFITDVDYLHHKYPGTSIVFDMSLTYILVALAAV
LLNNVLVERLTLHTRITAGYLLALGPLLFISICDVWLQLFSRDQAYAINLAAVGTVAFGC
TVQQSSFYGYTGMLPKRYTQGVMTGESTAGVMISLSRILTKLLLPDERASTLIFFLVSVA
LELLCFLLHLLVRRSRFVLFYTTRPRDSHRGRPGLGRGYGYRVHHDVVAGDVHFEHPAPA
LAPNESPKDSPAHEVTGSGGAYMRFDVPRPRVQRSWPTFRALLLHRYVVARVIWADMLSI
AVTYFITLCLFPGLESEIRHCILGEWLPILIMAVFNLSDFVGKILAALPVDWRGTHLLAC
SCLRVVFIPLFILCVYPSGMPALRHPAWPCIFSLLMGISNGYFGSVPMILAAGKVSPKQR
ELAGNTMTVSYMSGLTLGSAVAYCTYSLTRDAHGSCLHASTANGSILAGL
Number of residues
530
Molecular Weight
58058.005
Theoretical pI
Not Available
GO Classification
Functions
monoamine transmembrane transporter activity / nucleoside transmembrane transporter activity
Processes
transmembrane transport
Components
apical plasma membrane / integral component of membrane / plasma membrane
General Function
Nucleoside transmembrane transporter activity
Specific Function
Functions as a polyspecific organic cation transporter, efficiently transporting many organic cations such as monoamine neurotransmitters 1-methyl-4-phenylpyridinium and biogenic amines including serotonin, dopamine, norepinephrine and epinephrine. May play a role in regulating central nervous system homeostasis of monoamine neurotransmitters. May be involved in luminal transport of organic cations in the kidney and seems to use luminal proton gradient to drive organic cation reabsorption. Does not seem to transport nucleoside and nucleoside analogs such as uridine, cytidine, thymidine, adenosine, inosine, guanosine, and azidothymidine. In (PubMed:16873718) adenosine is efficiently transported but in a fashion highly sensitive to extracellular pH, with maximal activity in the pH range 5.5 to 6.5. Glu-206 is essential for the cation selectivity and may function as the charge sensor for cationic substrates. Transport is chloride and sodium-independent but appears to be sensitive to changes in membrane potential. Weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine. May play a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia.
Pfam Domain Function
Transmembrane Regions
69-89 102-122 140-160 167-187 232-252 352-372 382-402 417-437 451-471 487-509
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0013311|Equilibrative nucleoside transporter 4 (SLC29A4)
ATGGGCTCCGTGGGGAGCCAGCGCCTTGAGGAGCCCAGCGTGGCAGGCACACCAGACCCG
GGCGTAGTGATGAGCTTCACCTTCGACAGTCACCAGCTGGAGGAGGCGGCGGAGGCGGCT
CAGGGCCAGGGCCTTAGGGCCAGGGGCGTCCCAGCTTTCACGGATACTACATTGGACGAG
CCAGTGCCCGATGACCGTTATCACGCCATCTACTTTGCGATGCTGCTGGCTGGCGTGGGC
TTCCTGCTGCCATACAACAGCTTCATCACGGACGTGGACTACCTGCATCACAAGTACCCA
GGGACCTCCATCGTGTTTGACATGAGCCTCACCTACATCTTGGTGGCACTGGCAGCTGTC
CTCCTGAACAACGTCCTGGTGGAGAGACTGACCCTGCACACCAGGATCACCGCAGGCTAC
CTCTTAGCCTTGGGCCCTCTCCTTTTTATCAGCATCTGCGACGTGTGGCTGCAGCTCTTC
TCTCGGGACCAGGCCTACGCCATCAACCTGGCCGCTGTGGGCACCGTGGCCTTCGGCTGC
ACAGTGCAGCAATCCAGCTTCTACGGGTACACGGGGATGCTGCCCAAGCGGTACACGCAG
GGGGTGATGACCGGGGAGAGCACGGCGGGCGTGATGATCTCTCTGAGCCGCATCCTCACG
AAGCTGCTGCTGCCCGACGAGCGCGCCAGCACGCTCATCTTCTTCCTGGTGTCGGTGGCG
CTGGAGCTGCTGTGTTTCCTGCTGCACCTGTTAGTGCGGCGCAGCCGCTTCGTGCTCTTC
TATACCACACGGCCGCGTGACAGCCACCGGGGCAGGCCAGGCCTGGGCAGGGGCTATGGC
TACCGCGTGCACCACGACGTTGTCGCCGGGGACGTCCACTTCGAGCACCCAGCCCCGGCC
CTGGCCCCCAACGAGTCCCCAAAGGACAGCCCAGCCCACGAGGTGACCGGCAGCGGCGGG
GCCTACATGCGCTTTGATGTGCCGCGGCCAAGGGTCCAGCGCAGCTGGCCCACCTTCAGA
GCCCTGTTACTGCACCGCTACGTGGTGGCGCGGGTGATCTGGGCCGACATGCTCTCCATC
GCCGTGACCTACTTCATCACGCTGTGCCTGTTCCCCGGCCTCGAGTCTGAGATCCGCCAC
TGCATCCTGGGCGAGTGGCTGCCCATCCTCATCATGGCTGTGTTCAACCTGTCAGACTTC
GTGGGCAAGATCCTGGCAGCCCTGCCCGTGGACTGGCGGGGCACCCACCTGCTGGCCTGC
TCCTGCCTGCGTGTGGTCTTCATCCCCCTCTTCATCCTGTGCGTCTACCCCAGCGGCATG
CCCGCCCTCCGTCACCCCGCCTGGCCCTGCATCTTCTCACTGCTCATGGGCATCAGCAAC
GGCTACTTCGGCAGCGTGCCCATGATCCTGGCGGCAGGCAAAGTGAGCCCCAAGCAGCGG
GAGCTGGCAGGGAACACCATGACCGTGTCCTACATGTCAGGGCTGACGCTGGGGTCCGCC
GTGGCCTACTGCACCTACAGCCTCACCCGCGACGCTCACGGCAGCTGCCTGCACGCCTCC
ACCGCCAATGGTTCCATCCTCGCAGGCCTCTGA
Chromosome Location
7
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ7RTT9
UniProtKB Entry NameS29A4_HUMAN
HGNC IDHGNC:23097
General References
  1. Engel K, Zhou M, Wang J: Identification and characterization of a novel monoamine transporter in the human brain. J Biol Chem. 2004 Nov 26;279(48):50042-9. Epub 2004 Sep 23. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Acimovic Y, Coe IR: Molecular evolution of the equilibrative nucleoside transporter family: identification of novel family members in prokaryotes and eukaryotes. Mol Biol Evol. 2002 Dec;19(12):2199-210. [Article]
  5. Barnes K, Dobrzynski H, Foppolo S, Beal PR, Ismat F, Scullion ER, Sun L, Tellez J, Ritzel MW, Claycomb WC, Cass CE, Young JD, Billeter-Clark R, Boyett MR, Baldwin SA: Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ Res. 2006 Sep 1;99(5):510-9. Epub 2006 Jul 27. [Article]
  6. Xia L, Engel K, Zhou M, Wang J: Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells. Am J Physiol Renal Physiol. 2007 Feb;292(2):F682-90. Epub 2006 Oct 3. [Article]
  7. Zhou M, Xia L, Engel K, Wang J: Molecular determinants of substrate selectivity of a novel organic cation transporter (PMAT) in the SLC29 family. J Biol Chem. 2007 Feb 2;282(5):3188-95. Epub 2006 Nov 22. [Article]
  8. Bottalico B, Noskova V, Pilka R, Larsson I, Domanski H, Casslen B, Hansson SR: The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy decidua. Mol Reprod Dev. 2007 Oct;74(10):1303-11. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00331MetforminapprovedunknownsubstrateDetails
DB01104SertralineapprovedunknownDetails
DB00640Adenosineapproved, investigationalunknownsubstrateDetails