SLC29A4 Identifiers Aliases SLC29A4 , ENT4, PMAT, solute carrier family 29 member 4, Plasma membrane monoamine transporterExternal IDs OMIM : 609149 MGI : 2385330 HomoloGene : 71345 GeneCards : SLC29A4 Gene location (Human ) Chr. Chromosome 7 (human) [1] Band 7p22.1 Start 5,274,369 bp [1] End 5,306,912 bp [1]
Gene location (Mouse ) Chr. Chromosome 5 (mouse)[2] Band 5|5 G2 Start 142,692,512 bp [2] End 142,722,490 bp [2]
Gene ontology Molecular function Cellular component Biological process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez Ensembl UniProt RefSeq (mRNA) RefSeq (protein) Location (UCSC) Chr 7: 5.27 – 5.31 Mb Chr 5: 142.69 – 142.72 Mb PubMed search[3] [4] Wikidata
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 [ ]
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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
See also [ ]
Extraneuronal monoamine transporter (EMT)
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 .
Vesicular
Vesicular monoamine
Vesicular acetylcholine
Vesicular glutamate
Vesicular GABA
Other
By group
SLC1–10
(1):
high affinity glutamate and neutral amino-acid transporter
(2): (3):
heavy subunits of heterodimeric amino-acid transporters
(4): (5):
sodium glucose cotransporter
(6):
sodium - and chloride - dependent sodium:neurotransmitter symporters
SLC6A1
SLC6A2
SLC6A3
SLC6A4
SLC6A5
SLC6A6
SLC6A8
SLC6A9
SLC6A11
SLC6A12
SLC6A13
SLC6A14
SLC6A15
SLC6A18
SLC6A19
SLC6A20
(7):
cationic amino-acid transporter/glycoprotein-associated
SLC7A1
SLC7A2
SLC7A3
SLC7A4
glycoprotein-associated/light or catalytic subunits of heterodimeric amino-acid transporters
SLC7A5
SLC7A6
SLC7A7
SLC7A8
SLC7A9
SLC7A10
SLC7A11
SLC7A14
(8): (9): (10):
SLC10A1
SLC10A2
SLC10A3
SLC10A7
10A1
10A2
10A3
10A7
SLC11–20
(11): (12): (13): (14): (15): (16): (17):
Vesicular glutamate transporter 1
SLC17A1
SLC17A3
SLC17A5
SLC17A7
SLC17A8
(18):
vesicular monoamine transporter
(19):
folate /thiamine transporter
(20):
SLC31–40
(31): (32):
Vesicular glutamate transporter 1
(33): (34): (35): (36): (37): (38): (39):
metal ion transporter
SLC39A1
SLC39A2
SLC39A3
SLC39A4
SLC39A6
SLC39A7
SLC39A8
SLC39A9
SLC39A10
SLC39A12
(40):
SLC41–48
(41): (42): (43): (44): (45): (46): (47): (48):
SLCO1–4
O1A2
O1B1
O1B3
O2B1
O431
O4A1
see also solute carrier disorders
Monoamine reuptake inhibitors
DAT (DRIs )
Piperazines: DBL-583
GBR-12783
GBR-12935
GBR-13069
GBR-13098
Nefazodone
Vanoxerine
Pyrrolidines: Diphenylprolinol
MDPV
Naphyrone
Prolintane
Pyrovalerone
NET (NRIs )
Tricyclic antidepressants: Amitriptyline
Butriptyline
Cianopramine
Clomipramine
Desipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Melitracen
Nortriptyline
Protriptyline
Trimipramine
Tetracyclic antidepressants: Amoxapine
Maprotiline
Mianserin
Oxaprotiline
Setiptiline
Others: Antihistamines (e.g., brompheniramine , chlorphenamine , pheniramine , tripelennamine )
Antipsychotics (e.g., loxapine , ziprasidone )
Arylcyclohexylamines (e.g., ketamine , phencyclidine )
Dopexamine
Ephenidine
Ginkgo biloba
Indeloxazine
Nefazodone
Opioids (e.g., desmetramadol , methadone , pethidine (meperidine) , tapentadol , tramadol , levorphanol )
SERT (SRIs )
Selective serotonin reuptake inhibitors and serotonin receptor modulators: Etoperidone
Litoxetine
Lubazodone
LY-393558
Quipazine
SB-649915
TGBA01AD
Trazodone
Vilazodone
Vortioxetine
Tricyclic antidepressants: Amitriptyline
Cianopramine
Clomipramine
Cyanodothiepin
Desipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Nortriptyline
Pipofezine
Protriptyline
Others:
Amoxapine
Antihistamines (e.g., brompheniramine , chlorphenamine , dimenhydrinate , diphenhydramine , mepyramine (pyrilamine) , pheniramine , tripelennamine )
Antipsychotics (e.g., loxapine , ziprasidone )
Arylcyclohexylamines (e.g., 3-MeO-PCP , esketamine , ketamine , methoxetamine , phencyclidine )
Cyclobenzaprine
Delucemine
Dextromethorphan
Dextrorphan
Efavirenz
Hypidone
Medifoxamine
Mesembrine
Mifepristone
MIN-117 (WF-516)
N-Me-5-HT
Opioids (e.g., dextropropoxyphene , methadone , pethidine (meperidine) , levorphanol , tapentadol , tramadol )
Roxindole
VMATs
Amiodarone
Amphetamines (e.g., amphetamine , methamphetamine , MDMA )
Bietaserpine
Deserpidine
Deutetrabenazine
Dihydrotetrabenazine
Efavirenz
GBR-12935
Ibogaine
Ketanserin
Lobeline
Reserpine
Rose bengal
Tetrabenazine
Valbenazine
Vanoxerine (GBR-12909)
Others
DAT modulators: Agonist-like: SoRI-9804
; Antagonist-like: SoRI-20041
See also: Receptor/signaling modulators • Monoamine releasing agents • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins
Monoamine releasing agents
DRAs
Piperazines: 2C-B-BZP
BZP
MBZP
MDBZP
MeOPP
oMPP
NRAs
Piperazines: 2C-B-BZP
BZP
MBZP
mCPP
MDBZP
MeOPP
oMPP
pFPP
SRAs
Oxazolines: 4-Methylaminorex
Aminorex
Clominorex
Fluminorex
Piperazines: 2C-B-BZP
BZP
MBZP
mCPP
MDBZP
MeOPP
Mepiprazole
oMPP
pCPP
pFPP
pTFMPP
TFMPP
Tryptamines: 4-Methyl-αET
4-Methyl-αMT
5-CT
5-MeO-αET
5-MeO-αMT
5-MT
αET
αMT
DMT
Tryptamine
Others
DAT modulators: Agonist-like: SoRI-9804
; Antagonist-like: SoRI-20041
Adrenergic release blockers: Bethanidine
Bretylium
Guanadrel
Guanazodine
Guanethidine
Guanoxan
See also: Receptor/signaling modulators • Monoamine reuptake inhibitors • Adrenergics • Dopaminergics • Serotonergics • Monoamine metabolism modulators • Monoamine neurotoxins