Plasma membrane monoamine transporter

SLC29A4
Identifiers
Aliases	SLC29A4, ENT4, PMAT, solute carrier family 29 member 4, Plasma membrane monoamine transporter
External IDs	OMIM: 609149 MGI: 2385330 HomoloGene: 71345 GeneCards: SLC29A4
Gene location (Human)
Chr.	Chromosome 7 (human)
End	5,306,912 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	142,722,490 bp
RNA expression pattern
	Top expressed in
	islet of Langerhans; ; prosencephalon; ; dorsolateral prefrontal cortex; ; hypothalamus; ; internal globus pallidus; ; adipose tissue; ; prefrontal cortex;
	More reference expression data
	n/a
Gene ontology
Molecular function	monoamine transmembrane transporter activity; nucleoside transmembrane transporter activity;
Cellular component	integral component of membrane; plasma membrane; apical plasma membrane; membrane;
Biological process	nucleoside transmembrane transport; monoamine transport; transmembrane transport;
	Sources:Amigo / QuickGO
Orthologs
	222962
	243328
	ENSG00000164638
	ENSMUSG00000050822
	Q7RTT9
	Q8R139
	NM_001040661; NM_001300847; NM_153247
	NM_146257
	NP_001035751; NP_001287776; NP_694979
	NP_666369
	Wikidata
View/Edit Human	View/Edit Mouse

The plasma membrane monoamine transporter (PMAT) is a low-affinity monoamine transporter protein which in humans is encoded by the SLC29A4 gene.^[5] It is known alternatively as the human equilibrative nucleoside transporter-4 (hENT4). Unlike other members of the ENT family, it is impermeable to most nucleosides, with the exception of the inhibitory neurotransmitter and ribonucleoside adenosine, which it is permeable to in a highly pH-dependent manner.

This protein is an integral membrane protein that transports the monoamine neurotransmitters (serotonin, dopamine, norepinephrine) as well as adenosine,^[6] from synaptic spaces into presynaptic neurons or neighboring glial cells. It is abundantly expressed in the human brain,^[7] heart tissue, and skeletal muscle, as well as in the kidneys. It is relatively insensitive to the high affinity inhibitors (such as SSRIs) of the SLC6A monoamine transporters (SERT, DAT, NET), as well being only weakly sensitive to the adenosine transport inhibitor, dipyridamole. Its transport of monoamines, unlike for adenosine, is pH-insensitive. At low pH, (5.5-6.5 range, as occurs under ischemic conditions) however, its transport efficiency for adenosine becomes greater than for serotonin.

It has 530 amino acid residues with 10–12 transmembrane segments, and is not homologous to other known monoamine transporters, such as the high-affinity SERT, DAT, and NET, or the low-affinity SLC22A OCT family. It was initially identified by a search of the draft human genome database by its sequence homology to ENTs (equilibrative nucleoside transporters).^[8]

Ligands[]

Inhibitors[]

No highly selective PMAT inhibitors are yet available, but a number of existing compounds have been found to act as weak inhibitors of this transporter, with the exception of decynium-22, which is more potent. These compounds include:^[9]

Luteolin^[10]
Cimetidine
Decynium-22
Dipyridamole
Quinidine
Quinine
Tryptamine
Verapamil

Substrates[]

Acetylcholine (poor)
Adenosine (at low pH)
Dopamine
Epinephrine
Histamine (poor)
Metformin (poor, pH-dependent)
MPP⁺
Norepinephrine
Serotonin

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000164638 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000050822 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (Feb 2004). "The equilibrative nucleoside transporter family, SLC29". Pflügers Archiv. 447 (5): 735–43. doi:10.1007/s00424-003-1103-2. PMID 12838422. S2CID 8817821.
^ Xia L, Zhou M, Kalhorn TF, Ho HT, Wang J (Jun 2009). "Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity". American Journal of Physiology. Renal Physiology. 296 (6): F1307-13. doi:10.1152/ajprenal.00046.2009. PMC 2692440. PMID 19357181.
^ Dahlin A, Xia L, Kong W, Hevner R, Wang J (May 2007). "Expression and immunolocalization of the plasma membrane monoamine transporter in the brain". Neuroscience. 146 (3): 1193–211. doi:10.1016/j.neuroscience.2007.01.072. PMC 2683847. PMID 17408864.
^ Engel K, Zhou M, Wang J (Nov 2004). "Identification and characterization of a novel monoamine transporter in the human brain". The Journal of Biological Chemistry. 279 (48): 50042–9. doi:10.1074/jbc.M407913200. PMID 15448143.
^ Engel K, Wang J (Nov 2005). "Interaction of organic cations with a newly identified plasma membrane monoamine transporter". Molecular Pharmacology. 68 (5): 1397–407. doi:10.1124/mol.105.016832. PMID 16099839. S2CID 26542965.
^ Zhu, Shujie; Lei, Shaowei; Zhou, Sisi; Jin, Lisha; Zeng, Su; Jiang, Huidi; Zhou, Hui (March 2019). "Luteolin shows antidepressant-like effect by inhibiting and downregulating plasma membrane monoamine transporter (PMAT, Slc29a4)". Journal of Functional Foods. 54: 440–448. doi:10.1016/j.jff.2019.01.048.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000164638 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000050822 - Ensembl, 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.

[pmid12838422-5] Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD (Feb 2004). "The equilibrative nucleoside transporter family, SLC29". Pflügers Archiv. 447 (5): 735–43. doi:10.1007/s00424-003-1103-2. PMID 12838422. S2CID 8817821.

[6] Xia L, Zhou M, Kalhorn TF, Ho HT, Wang J (Jun 2009). "Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity". American Journal of Physiology. Renal Physiology. 296 (6): F1307-13. doi:10.1152/ajprenal.00046.2009. PMC 2692440. PMID 19357181.

[7] Dahlin A, Xia L, Kong W, Hevner R, Wang J (May 2007). "Expression and immunolocalization of the plasma membrane monoamine transporter in the brain". Neuroscience. 146 (3): 1193–211. doi:10.1016/j.neuroscience.2007.01.072. PMC 2683847. PMID 17408864.

[8] Engel K, Zhou M, Wang J (Nov 2004). "Identification and characterization of a novel monoamine transporter in the human brain". The Journal of Biological Chemistry. 279 (48): 50042–9. doi:10.1074/jbc.M407913200. PMID 15448143.

[9] Engel K, Wang J (Nov 2005). "Interaction of organic cations with a newly identified plasma membrane monoamine transporter". Molecular Pharmacology. 68 (5): 1397–407. doi:10.1124/mol.105.016832. PMID 16099839. S2CID 26542965.

[10] Zhu, Shujie; Lei, Shaowei; Zhou, Sisi; Jin, Lisha; Zeng, Su; Jiang, Huidi; Zhou, Hui (March 2019). "Luteolin shows antidepressant-like effect by inhibiting and downregulating plasma membrane monoamine transporter (PMAT, Slc29a4)". Journal of Functional Foods. 54: 440–448. doi:10.1016/j.jff.2019.01.048.

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v t Membrane transport protein: neurotransmitter transporters (TC 2.A.1.2)
Vesicular	Vesicular monoamine VMAT1 VMAT2 Vesicular acetylcholine Vesicular glutamate Vesicular GABA
Other	Monoamine DAT NET SERT PMAT Excitatory amino-acid transporter GABA transporter

Plasma membrane monoamine transporter

Contents

Ligands[]

Inhibitors[]

Substrates[]

See also[]

References[]