O75751 · S22A3_HUMAN
- ProteinSolute carrier family 22 member 3
- GeneSLC22A3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids556 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707).
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924).
Functions as a Na+- and Cl--independent, bidirectional uniporter (PubMed:12538837).
Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707).
Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754).
May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924).
May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity).
Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837).
Also transports guanidine (PubMed:10966924).
May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity).
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924).
Functions as a Na+- and Cl--independent, bidirectional uniporter (PubMed:12538837).
Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707).
Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754).
May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924).
May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity).
Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837).
Also transports guanidine (PubMed:10966924).
May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity).
Miscellaneous
Mediates the uptake of clinically used drugs including neurotoxin 1-methyl-4-phenylpyridinium (MPP+) and platinum-based drug oxaliplatin (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:15817714, PubMed:16263091, PubMed:16581093, PubMed:16914559, PubMed:20858707).
Plays a role in the anticancer activity of oxaliplatin and may contribute to antitumor specificity (PubMed:16914559).
Plays a role in the anticancer activity of oxaliplatin and may contribute to antitumor specificity (PubMed:16914559).
Catalytic activity
- (R)-noradrenaline(out) = (R)-noradrenaline(in)
- (R)-adrenaline(out) = (R)-adrenaline(in)
- serotonin(out) = serotonin(in)
- dopamine(out) = dopamine(in)
- histamine(out) = histamine(in)
- tyramine(in) = tyramine(out)
- guanidine(out) = guanidine(in)
- agmatine(out) = agmatine(in)
- spermidine(in) = spermidine(out)
- L-histidyl-L-proline diketopiperazine(in) = L-histidyl-L-proline diketopiperazine(out)
- (R)-salsolinol(in) = (R)-salsolinol(out)
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
126 μM | cyclo(his-pro) | |||||
139 μM | salsolinol | |||||
220 μM | histamine | |||||
641 μM | histamine | |||||
240 μM | adrenaline | |||||
458 μM | adrenaline | |||||
923 μM | noradrenaline | |||||
2630 μM | noradrenaline | |||||
988 μM | serotonin | |||||
1033 μM | dopamine | |||||
2500 μM | agmatine |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.4 nmol/min/mg | for cyclo(his-pro) uptake | ||||
0.5 nmol/min/mg | for salsolinol uptake | ||||
34.6 nmol/min/mg | for histamine uptake | ||||
12.76 nmol/min/mg | for adrenaline uptake | ||||
30.13 nmol/min/mg | for noradrenaline uptake | ||||
11.56 nmol/min/mg | for serotonin uptake | ||||
22.68 nmol/min/mg | for dopamine uptake | ||||
15.9 nmol/min/mg | for agmatine uptake |
pH Dependence
Optimum pH is 8.5 for agmatine and MPP+ transport.
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSolute carrier family 22 member 3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO75751
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Apical cell membrane ; Multi-pass membrane protein
Basolateral cell membrane ; Multi-pass membrane protein
Note: Localized to the apical/brush border membrane of enterocytes (PubMed:16263091).
Localized to the luminal/apical membrane of ciliated epithelial cells in bronchi (PubMed:15817714).
Localized to the basolateral membrane of intermediate cells in bronchi (PubMed:15817714).
Localized to the entire plasma membrane of basal cells in bronchi (PubMed:15817714).
Localized to the luminal/apical membrane of ciliated epithelial cells in bronchi (PubMed:15817714).
Localized to the basolateral membrane of intermediate cells in bronchi (PubMed:15817714).
Localized to the entire plasma membrane of basal cells in bronchi (PubMed:15817714).
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 21-41 | Helical | ||||
Sequence: VFLLLCLTGVTFAFLFVGVVF | ||||||
Transmembrane | 182-202 | Helical | ||||
Sequence: IVIYLLSCLGVGVTGVVVAFA | ||||||
Transmembrane | 241-261 | Helical | ||||
Sequence: IVGIVIQMFFTLGIIILPGIA | ||||||
Transmembrane | 269-289 | Helical | ||||
Sequence: GIQLAITLPSFLFLLYYWVVP | ||||||
Transmembrane | 381-401 | Helical | ||||
Sequence: IDFFISGVVELPGALLILLTI | ||||||
Transmembrane | 468-488 | Helical | ||||
Sequence: FGVSLCSGLCDFGGIIAPFLL | ||||||
Transmembrane | 498-518 | Helical | ||||
Sequence: LPLIIFGILASICGGLVMLLP |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_020351 | 44 | in dbSNP:rs8187715 | |||
Sequence: T → M | ||||||
Natural variant | VAR_020352 | 116 | in dbSNP:rs8187717 | |||
Sequence: A → S | ||||||
Mutagenesis | 289 | Decreased TEA uptake. | ||||
Sequence: P → A | ||||||
Mutagenesis | 363 | Decreased TEA uptake. | ||||
Sequence: V → F | ||||||
Mutagenesis | 380 | Decreased TEA uptake. | ||||
Sequence: Y → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 700 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000220503 | 1-556 | Solute carrier family 22 member 3 | |||
Sequence: MPSFDEALQRVGEFGRFQRRVFLLLCLTGVTFAFLFVGVVFLGTQPDHYWCRGPSAAALAERCGWSPEEEWNRTAPASRGPEPPERRGRCQRYLLEAANDSASATSALSCADPLAAFPNRSAPLVPCRGGWRYAQAHSTIVSEFDLVCVNAWMLDLTQAILNLGFLTGAFTLGYAADRYGRIVIYLLSCLGVGVTGVVVAFAPNFPVFVIFRFLQGVFGKGTWMTCYVIVTEIVGSKQRRIVGIVIQMFFTLGIIILPGIAYFIPNWQGIQLAITLPSFLFLLYYWVVPESPRWLITRKKGDKALQILRRIAKCNGKYLSSNYSEITVTDEEVSNPSFLDLVRTPQMRKCTLILMFAWFTSAVVYQGLVMRLGIIGGNLYIDFFISGVVELPGALLILLTIERLGRRLPFAASNIVAGVACLVTAFLPEGIAWLRTTVATLGRLGITMAFEIVYLVNSELYPTTLRNFGVSLCSGLCDFGGIIAPFLLFRLAAVWLELPLIIFGILASICGGLVMLLPETKGIALPETVDDVEKLGSPHSCKCGRNKKTPVSRSHL | ||||||
Glycosylation | 72 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 99 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 119 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 322 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in liver (PubMed:10196521, PubMed:9933568).
Expressed in intestine (PubMed:16263091, PubMed:20858707).
Expressed in kidney in proximal tubular cells (PubMed:10966924).
Expressed in placenta (PubMed:10966924, PubMed:9933568).
Expressed throughout the brain, including cerebral cortex, cerebrellum, substancia nigra, medulla oblongata, hippocampus, caudate nucleus, nucleus accumbens and pons with low levels of expression detected in nearly all brain regions (PubMed:10196521, PubMed:20858707).
In testis, mostly localized to peritubular myoid cells and Leydig cells, and weakly expressed in developing germ cells (PubMed:35307651).
Expressed in tracheal and bronchial epithelium of the respiratory tract, where it localizes to the apical membrane of ciliated cells, the entire membrane of basal cells and the basolateral membrane of intermediate cells (PubMed:15817714).
Expressed in skeletal muscle, adrenal gland, heart, prostate, aorta, salivary gland, adrenal gland, uterus, lymph node, lung, trachea and spinal cord (PubMed:10196521, PubMed:20858707, PubMed:9933568).
Expressed in fetal lung and liver (PubMed:9933568).
Expressed in intestine (PubMed:16263091, PubMed:20858707).
Expressed in kidney in proximal tubular cells (PubMed:10966924).
Expressed in placenta (PubMed:10966924, PubMed:9933568).
Expressed throughout the brain, including cerebral cortex, cerebrellum, substancia nigra, medulla oblongata, hippocampus, caudate nucleus, nucleus accumbens and pons with low levels of expression detected in nearly all brain regions (PubMed:10196521, PubMed:20858707).
In testis, mostly localized to peritubular myoid cells and Leydig cells, and weakly expressed in developing germ cells (PubMed:35307651).
Expressed in tracheal and bronchial epithelium of the respiratory tract, where it localizes to the apical membrane of ciliated cells, the entire membrane of basal cells and the basolateral membrane of intermediate cells (PubMed:15817714).
Expressed in skeletal muscle, adrenal gland, heart, prostate, aorta, salivary gland, adrenal gland, uterus, lymph node, lung, trachea and spinal cord (PubMed:10196521, PubMed:20858707, PubMed:9933568).
Expressed in fetal lung and liver (PubMed:9933568).
Gene expression databases
Organism-specific databases
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O75751 | ABL1 P00519 | 2 | EBI-1752674, EBI-375543 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 289-293 | Proline-rich sequence | ||||
Sequence: PESPR |
Domain
Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.
Sequence similarities
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length556
- Mass (Da)61,280
- Last updated1998-11-01 v1
- ChecksumC3CA2D77DD21C658
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ001417 EMBL· GenBank· DDBJ | CAA04751.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314590 EMBL· GenBank· DDBJ | BAG37164.1 EMBL· GenBank· DDBJ | mRNA | ||
AL591069 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL355506 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471051 EMBL· GenBank· DDBJ | EAW47599.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF078749 EMBL· GenBank· DDBJ | AAD20977.1 EMBL· GenBank· DDBJ | mRNA |