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FLASH GENE

Symbol

SLC22A3

contributors: mct/npt - updated : 07-10-2015

HGNC name	solute carrier family 22 (extraneuronal monoamine transporter), member 3
HGNC id	10967

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
text	part of the cluster SLC22A3-LPAL2-LPA
STRUCTURE	106.59 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	promoter with binding sites for ubiquitous transcription factors SP1

MAPPING

cloned

N

linked

status

confirmed

regionally located

clustered with SLC22A1 and SLC22A2

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed variant 1 11 - 5624 isoform 1 61.15 556 - Gründemann (2000)

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 Hearing/Equilibrium ear       predominantly Nervous brain       highly Reproductive male system prostate     highly

cell lineage	endometrial stroma (Bottalico 2007)
cell lines
fluid/secretion

at STAGE

physiological period

pregnancy

Text	placenta, most abundantly

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	twelve transmembrane domains (12TM)
	cytoplasmic N and C termini
	one nucleotide (ATP/GTP) binding site motif

HOMOLOGY

Homologene

FAMILY	major facilitator superfamily
	organic cation transporter family
	solute carrier family 22, extraneuronal monoamine

CATEGORY

transport carrier

SUBCELLULAR LOCALIZATION	plasma membrane
text	to the basolateral membrane (BLM) (Glube 2008)

basic FUNCTION	polyspecific transporter of organic cations, sodium independent
	playing a key role in the clearance of monoamines from extracellular compartments (Bottalico 2007)
	can potentially regulate reuptake of monoamines in general and histamine in particular (Bottalico 2007)
	participate in the renal secretion of several therapeutic agents, and interacts with renally secreted drugs (Glube 2008)
	may modulate dopaminergic damage by bidirectionally regulating the local bioavailability of exogenous and endogenous toxic species (Cui 2009)
	pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway (Cui 2009)
	functions as a cation transporter in various organs, including prostate tissue, and plays a role eliminating small organic cations and toxins
	NUDT11, SLC22A3, HNF1b contribute to prostate cancer pathogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

facilitated diffusion transport

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein

cell & other

REGULATION

Other

regulated by phosphorylation/dephosphorylation mechanisms, active in the dephosphorylated state

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   lower expression of mRNAs in pre-eclamptic placentae as compared to the control group (Bottalico 2004) tumoral     --low   inversely correlated with Prostate carcinoma progression, with reduced expression as disease advances constitutional     --over   of SLC22A3 and SLC47A1 in human placenta indicates these transporters may play a role in fetal protection preferentially at earlier stages of gestation

Susceptibility

to coronary artery disease to the development of polysubstance use in Japanese patients with Methamphetamine (MAP) dependence to euphoria and potential for addiction and susceptibility to the toxicity of substances of abuse

Variant & Polymorphism SNP	four SNPs overlapping the SLC22A3-LPAL2-LPA gene cluster associated to risk of coronary artery disease (Tregouet 2009)
	polymorphisms of SLC22A3 related to the development of polysubstance use in Japanese patients with MAP dependence (Aoyama 2006)
	polymorphisms may reduce or inactivate the function of SLC22A3 and therefore enhance the euphoria and potential for addiction and susceptibility to the toxicity of substances of abuse (Cui 2009)

Candidate gene
Marker
Therapy target	Monoamine transporters may serve as a protective mechanism preventing vasoconstriction in the placental vascular bed and thereby securing a stable blood flow to the fetus (Bottalico 2004)

ANIMAL & CELL MODELS