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FLASH GENE

Symbol

SLC18A2

contributors: mct - updated : 11-04-2020

HGNC name	solute carrier family 18 (vesicular monoamine), member 2
HGNC id	10935

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	PKDYS2 Parkinsonism-dystonia, infantile, 2
Location	10q25.3      Physical location : 119.000.583 - 119.038.941
Synonym name	synaptic vesicular amine transporter
	vesicular monoamine transporter 2
	monoamine transporter
Synonym symbol(s)	SVMT, VAT2, VMAT2, SVAT, MGC26538, PKDYS2, MGC120477, MGC120478

DNA

TYPE	functioning gene
STRUCTURE	36.38 kb     16 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003054 16 - 1894 NP_003045 - 514 - 2002 12009896

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine adrenal gland       highly   pancreas       highly Homo sapiens   thyroid       highly Nervous brain midbrain       Homo sapiens   brain basal nuclei striatum   highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens Nervous neuron Homo sapiens not specific adipocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

twelve transmembrane spanning segments (12TM)

HOMOLOGY

interspecies

homolog to murine Slc18a2

Homologene

FAMILY	major facilitator superfamily
	vesicular transporter family

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
text	vesicular membrane

basic FUNCTION	involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters
	essential for loading monoamines into vesicles and maintaining normal neurotransmission
	regulates neurotransmission and reduces cytosolic toxicity of monoamines
	during the stimulus, the endocytosis of VMAT2 (but not VGLUT1) accelerates dramatically in midbrain dopamine but not hippocampal neurons, indicating a novel, cell-specific mechanism to sustain high rates of release
	sequesters cytoplasmic dopamine into synaptic vesicles for storage and release
	catalyzes transport of monoamines into storage vesicles in a process that involves exchange of the charged monoamine with two protons
	is responsible for sequestering cytosolically toxic dopamine into intracellular secretory vesicles
	by regulating the storage of monoamines transmitters into synaptic vesicles, has a protective role against their cytoplasmic toxicity
	causal link between reduced SLC18A2 expression and fear behavior, consistent with the correlational relationship between SLC18A2 genotype and post-traumatic stress disorder (PTSD) risk

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	direct binding between the N-terminus and the third cytoplasmic loop of SLC18A2, as well as, a region containing the substrate binding and the C-terminal domains of HSPA8
	PARK7 stimulates SLC18A2 activity in the synapse by transactivation of the SLC18A2 gene and by direct binding to SLC18A2 and cysteine 106 is necessary for the stimulating activity of PARK7 toward SLC18A2

cell & other

REGULATION

inhibited by

fluoxetine (inhibited the activity of SLC18A2 by a mechanism different from that of reserpine and did not directly interact with the active site of SLC18A2

Other

regulated by HSPA8 (important role for HSPA8 in SLC18A2 function and regulation)

ASSOCIATED DISORDERS

corresponding disease(s)

PKDYS2

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   in platelets from patients with Parkinson disease constitutional     --over   might be a compensatory mechanism to restore and maintain synaptic transmission in dopaminergic midbrain neurons during nicotine withdrawal tumoral     --low   silencing by DNA hypermethylation and/or allelic loss is a frequent event in prostate cancer and a novel independent predictor of biochemical recurrence after prostatectomy constitutional germinal mutation       in microphthalmia

Susceptibility

to alcoholism to Parkinson disease to schizophrenia and bipolar disorder to heroin dependence to sporadic amyotrophic lateral sclerosis (SALS)

Variant & Polymorphism SNP	14234G>A and 2504T>C decreasing the risk of alcoholism
	protective role for gain-of -function haplotypes in sporadic Parkinson disease, through increasing of sequestration of dopamine in secretory vesicles
	GG of rs363371 in SLC18A2 may reduce the risk for sporadic amyotrophic lateral sclerosis (SALS)
	SLC18A2 SNPs (rs363332, rs363334 and rs363338) associated with heroin dependence

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative Parkinson/dementia Parkinsonism target of genetic medications for PD neurology neurodegenerative   SLC18A2 may be considered a therapeutic target for the treatment and/or prevention of Tardive dyskinesia (TD)

ANIMAL & CELL MODELS

Vmat2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity