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Protein

Solute carrier family 22 member 1

Gene

Slc22a1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.11 Publications

Kineticsi

  1. KM=3.73 mM for metformin5 Publications
  2. KM=42 µM for TEA5 Publications
  3. KM=9.6 µM for MPP5 Publications
  4. KM=0.34 mM for NMN5 Publications
  5. KM=1.1 mM for choline5 Publications
  6. KM=49.5 µM for pramipexole5 Publications
  7. KM=1.6 mM for dopamine5 Publications
  8. KM=0.9 mM for serotonin5 Publications
  9. KM=0.8 mM for norepinephrine5 Publications
  10. KM=1.1 mM for epinephrine5 Publications
  1. Vmax=145 pmol/min/mg enzyme uptake5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei451Involved in affinity and selectivity of cations as well as in translocation1

GO - Molecular functioni

  • acetylcholine transmembrane transporter activity Source: RGD
  • dopamine transmembrane transporter activity Source: RGD
  • monoamine transmembrane transporter activity Source: RGD
  • norepinephrine transmembrane transporter activity Source: RGD
  • organic cation transmembrane transporter activity Source: RGD
  • protein homodimerization activity Source: RGD
  • quaternary ammonium group transmembrane transporter activity Source: RGD
  • secondary active organic cation transmembrane transporter activity Source: RGD

GO - Biological processi

  • dopamine transport Source: RGD
  • drug transmembrane transport Source: RGD
  • epinephrine transport Source: RGD
  • establishment or maintenance of transmembrane electrochemical gradient Source: RGD
  • monoamine transport Source: RGD
  • norepinephrine transport Source: RGD
  • organic cation transport Source: RGD
  • protein homooligomerization Source: RGD
  • quaternary ammonium group transport Source: RGD
Complete GO annotation...

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-RNO-2161517. Abacavir transmembrane transport.
R-RNO-549127. Organic cation transport.

Protein family/group databases

TCDBi2.A.1.19.1. the major facilitator superfamily (mfs).

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 22 member 1
Alternative name(s):
Organic cation transporter 1
Short name:
rOCT1
Gene namesi
Name:Slc22a1
Synonyms:Oct1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi3224. Slc22a1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 21CytoplasmicSequence analysisAdd BLAST21
Transmembranei22 – 42HelicalSequence analysisAdd BLAST21
Topological domaini43 – 150ExtracellularSequence analysisAdd BLAST108
Transmembranei151 – 171HelicalSequence analysisAdd BLAST21
Topological domaini172 – 177CytoplasmicSequence analysis6
Transmembranei178 – 198HelicalSequence analysisAdd BLAST21
Topological domaini199 – 211ExtracellularSequence analysisAdd BLAST13
Transmembranei212 – 231HelicalSequence analysisAdd BLAST20
Topological domaini232 – 238CytoplasmicSequence analysis7
Transmembranei239 – 259HelicalSequence analysisAdd BLAST21
Topological domaini260 – 263ExtracellularSequence analysis4
Transmembranei264 – 284HelicalSequence analysisAdd BLAST21
Topological domaini285 – 348CytoplasmicSequence analysisAdd BLAST64
Transmembranei349 – 369HelicalSequence analysisAdd BLAST21
Topological domaini370 – 377ExtracellularSequence analysis8
Transmembranei378 – 398HelicalSequence analysisAdd BLAST21
Topological domaini399 – 403CytoplasmicSequence analysis5
Transmembranei404 – 424HelicalSequence analysisAdd BLAST21
Topological domaini425 – 429ExtracellularSequence analysis5
Transmembranei430 – 452HelicalSequence analysisAdd BLAST23
Topological domaini453 – 465CytoplasmicSequence analysisAdd BLAST13
Transmembranei466 – 486HelicalSequence analysisAdd BLAST21
Topological domaini487 – 493ExtracellularSequence analysis7
Transmembranei494 – 514HelicalSequence analysisAdd BLAST21
Topological domaini515 – 556CytoplasmicSequence analysisAdd BLAST42

GO - Cellular componenti

  • basolateral plasma membrane Source: RGD
  • integral component of plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi26C → A: Choline affinity is increased fourfold by MMTS; when associated with A-155; A-179; S-322; A-358; A-418; S-437; A-470 and A-474. 1 Publication1
Mutagenesisi155C → A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-179; S-322; A-358; A-418; S-437; A-470 and A-474. 1 Publication1
Mutagenesisi179C → A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; S-322; A-358; A-418; S-437; A-470 and A-474. 1 Publication1
Mutagenesisi286S → A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-292; A-296; A-328 and A-550. No effect of PKA activation on ASP uptake. No effect of PKA activation on ASP uptake; when associated with A-292; A-296; A-328 and A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-292; A-296; A-328 and A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-292; A-296; A-328 and A-550. suppresses phosphorylation by PKC; when associated with A-292; A-296; A-328 and A-550. 1 Publication1
Mutagenesisi292S → A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-296; A-328 and A-550. No effect of PKA activation on ASP uptake. No effect of PKA activation on ASP uptake; when associated with A-286; A-296; A-328 and A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-296; A-328 and A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-296; A-328 and A-550. suppresses phosphorylation by PKC; when associated with A-286; A-296; A-328 and A-550. 1 Publication1
Mutagenesisi296T → A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-292; A-328; A-550. Significant increase of the ASP uptake by PKA activation. No effect of PKA activation on ASP uptake; when associated with A-286; A-292; A-328; A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-292; A-328; A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-292; A-328 and A-550. suppresses phosphorylation by PKC; when associated with A-286; A-292; A-328 and A-550. 1 Publication1
Mutagenesisi322C → S: Reduces the activation by MMTS. Abolishes the activation by MMTs; when associated with M-451. Choline affinity is increased fivefold by MMTS. Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; A-358; A-418; S-437; A-470 and A-474. Choline affinity is increased four-to fivefold; when associated with M-451. 1 Publication1
Mutagenesisi328S → A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-292; A-296 and A-550. No effect of PKA activation on ASP uptake. No effect of PKA activation on ASP uptake; when associated with A-286; A-292; A-296 and A-550. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-292; A-296; A-550. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-292; A-296 and A-550. suppresses phosphorylation by PKC; when associated with A-286; A-292; A-296 and A-550. 1 Publication1
Mutagenesisi358C → A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-418; S-437; A-470 and A-474. 1 Publication1
Mutagenesisi418C → A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; S-437; A-470 and A-474. 1 Publication1
Mutagenesisi437C → S: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; A-418; A-470 and A-474. 1 Publication1
Mutagenesisi451C → M: Reduces the activation by MMTS. Abolishes the activation by MMTs; when associated with S-322. Abolishes the effect of MMTs on choline-induced currents. Choline affinity is not influenced by MMTS. Choline affinity is increased four-to fivefold; when associated with S-322. 1 Publication1
Mutagenesisi470C → A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; A-418; A-437 and A-474. 1 Publication1
Mutagenesisi474C → A: Choline affinity is increased fourfold by MMTS; when associated with A-26; A-155; A-179; S-322; A-358; A-418; A-437 and A-470. 1 Publication1
Mutagenesisi550T → A: No effect of PKC-induced stimulation on ASP uptake. No effect of PKC-induced stimulation on ASP uptake; when associated with A-286; A-292; A-296; A-328. Significant increase of the ASP uptake by PKA activation. No effect of PKA activation on ASP uptake; when associated with A-286; A-292; A-296 and A-328. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition. Significant reduction of ASP uptake by p56(lck) tyrosine kinase-induced inhibition; when associated with A-286; A-292; A-296; A-328. No significant effect on trafficking from intracellular pools to the cell membrane; when associated with A-286; A-292; A-296 and A-328. suppresses phosphorylation by PKC; when associated withA-286; A-292; A-296 and A-328. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2073670.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003338791 – 556Solute carrier family 22 member 1Add BLAST556

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi71N-linked (GlcNAc...)Sequence analysis1
Modified residuei334PhosphoserineCombined sources1
Modified residuei543PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ63089.
PRIDEiQ63089.

PTM databases

iPTMnetiQ63089.
PhosphoSitePlusiQ63089.

Expressioni

Tissue specificityi

Expressed in kidney, kidney cortex, kidney medulla, liver, intestine and colon. Expressed in proximal tubules in kidney, hepatocytes in liver and enterocytes of villi and crypts in smallintestine. Expressed throughout the liver lobuli. Expressed in hepatocytes surrounding the central veins (at protein level). Expressed in S1, S2 segments of proximal tubules in kidney (at protein level). Highly expressed in kidney and spleen, moderately in skin, and weakly in the gastrointestinal tract, brain, lung, thymus, muscle, and prostate. Weakly expressed in some white matter regions like the corpus callosum and in the granular layer of the cerebellum.5 Publications

Developmental stagei

Renal level increases gradually from postnatal day 0 through day 45 in both genders.1 Publication

Inductioni

Down-regulated in obstructive cholestasis. Up-regulated by treatment with pregnenolone-16 alpha-carbonitrile (PCN) and by overexpression of pregnane X receptor (PXR).2 Publications

Gene expression databases

BgeeiENSRNOG00000016337.
GenevisibleiQ63089. RN.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-5261153,EBI-5261153

GO - Molecular functioni

  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

IntActiQ63089. 1 interactor.
MINTiMINT-8292690.
STRINGi10116.ENSRNOP00000022254.

Chemistry databases

BindingDBiQ63089.

Structurei

3D structure databases

ProteinModelPortaliQ63089.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IRH7. Eukaryota.
ENOG410XR5P. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234568.
HOVERGENiHBG061545.
InParanoidiQ63089.
KOiK08198.
OMAiDLFQSCL.
OrthoDBiEOG091G05AC.
PhylomeDBiQ63089.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR004749. Orgcat_transp/SVOP.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q63089-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPTVDDVLEQ VGEFGWFQKQ AFLLLCLISA SLAPIYVGIV FLGFTPGHYC
60 70 80 90 100
QNPGVAELSQ RCGWSQAEEL NYTVPGLGPS DEASFLSQCM RYEVDWNQST
110 120 130 140 150
LDCVDPLSSL VANRSQLPLG PCEHGWVYDT PGSSIVTEFN LVCGDAWKVD
160 170 180 190 200
LFQSCVNLGF FLGSLVVGYI ADRFGRKLCL LVTTLVTSVS GVLTAVAPDY
210 220 230 240 250
TSMLLFRLLQ GMVSKGSWVS GYTLITEFVG SGYRRTTAIL YQMAFTVGLV
260 270 280 290 300
GLAGVAYAIP DWRWLQLAVS LPTFLFLLYY WFVPESPRWL LSQKRTTRAV
310 320 330 340 350
RIMEQIAQKN GKVPPADLKM LCLEEDASEK RSPSFADLFR TPNLRKHTVI
360 370 380 390 400
LMYLWFSCAV LYQGLIMHVG ATGANLYLDF FYSSLVEFPA AFIILVTIDR
410 420 430 440 450
IGRIYPIAAS NLVTGAACLL MIFIPHELHW LNVTLACLGR MGATIVLQMV
460 470 480 490 500
CLVNAELYPT FIRNLGMMVC SALCDLGGIF TPFMVFRLME VWQALPLILF
510 520 530 540 550
GVLGLTAGAM TLLLPETKGV ALPETIEEAE NLGRRKSKAK ENTIYLQVQT

GKSSST
Length:556
Mass (Da):61,541
Last modified:November 1, 1996 - v1
Checksum:i9F42131CCCEC0920
GO
Isoform 2 (identifier: Q63089-2) [UniParc]FASTAAdd to basket
Also known as: rOCT1A

The sequence of this isoform differs from the canonical sequence as follows:
     1-126: Missing.
     127-172: VYDTPGSSIV...GSLVVGYIAD → MRWTGTRAPL...TTLPAPPSSL

Show »
Length:430
Mass (Da):47,678
Checksum:iB5C5FA5A304430B4
GO

Sequence cautioni

The sequence AAH78883 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0335911 – 126Missing in isoform 2. 2 PublicationsAdd BLAST126
Alternative sequenceiVSP_033592127 – 172VYDTP…GYIAD → MRWTGTRAPLTVWTHCPAWL PTGVSCHWAPASMAGYTTLP APPSSL in isoform 2. 2 PublicationsAdd BLAST46

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78855 mRNA. Translation: CAA55411.1.
U76379 mRNA. Translation: AAB67702.1.
BC078883 mRNA. Translation: AAH78883.1. Different initiation.
PIRiS50862.
RefSeqiNP_036829.1. NM_012697.1. [Q63089-1]
UniGeneiRn.11186.

Genome annotation databases

EnsembliENSRNOT00000022068; ENSRNOP00000022068; ENSRNOG00000016337. [Q63089-2]
ENSRNOT00000022254; ENSRNOP00000022254; ENSRNOG00000016337. [Q63089-1]
GeneIDi24904.
KEGGirno:24904.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78855 mRNA. Translation: CAA55411.1.
U76379 mRNA. Translation: AAB67702.1.
BC078883 mRNA. Translation: AAH78883.1. Different initiation.
PIRiS50862.
RefSeqiNP_036829.1. NM_012697.1. [Q63089-1]
UniGeneiRn.11186.

3D structure databases

ProteinModelPortaliQ63089.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63089. 1 interactor.
MINTiMINT-8292690.
STRINGi10116.ENSRNOP00000022254.

Chemistry databases

BindingDBiQ63089.
ChEMBLiCHEMBL2073670.

Protein family/group databases

TCDBi2.A.1.19.1. the major facilitator superfamily (mfs).

PTM databases

iPTMnetiQ63089.
PhosphoSitePlusiQ63089.

Proteomic databases

PaxDbiQ63089.
PRIDEiQ63089.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000022068; ENSRNOP00000022068; ENSRNOG00000016337. [Q63089-2]
ENSRNOT00000022254; ENSRNOP00000022254; ENSRNOG00000016337. [Q63089-1]
GeneIDi24904.
KEGGirno:24904.

Organism-specific databases

CTDi6580.
RGDi3224. Slc22a1.

Phylogenomic databases

eggNOGiENOG410IRH7. Eukaryota.
ENOG410XR5P. LUCA.
GeneTreeiENSGT00760000118852.
HOGENOMiHOG000234568.
HOVERGENiHBG061545.
InParanoidiQ63089.
KOiK08198.
OMAiDLFQSCL.
OrthoDBiEOG091G05AC.
PhylomeDBiQ63089.

Enzyme and pathway databases

ReactomeiR-RNO-2161517. Abacavir transmembrane transport.
R-RNO-549127. Organic cation transport.

Miscellaneous databases

PROiQ63089.

Gene expression databases

BgeeiENSRNOG00000016337.
GenevisibleiQ63089. RN.

Family and domain databases

CDDicd06174. MFS. 1 hit.
InterProiIPR020846. MFS_dom.
IPR005828. MFS_sugar_transport-like.
IPR004749. Orgcat_transp/SVOP.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PfamiPF00083. Sugar_tr. 1 hit.
[Graphical view]
SUPFAMiSSF103473. SSF103473. 1 hit.
TIGRFAMsiTIGR00898. 2A0119. 1 hit.
PROSITEiPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS22A1_RAT
AccessioniPrimary (citable) accession number: Q63089
Secondary accession number(s): O35882, Q6AYW1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.