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Protein

Solute carrier family 12 member 5

Gene

Slc12a5

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

Functioni

Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl- homeostasis. As major extruder of intracellular chloride, it establishes the low neuronal Cl- levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (PubMed:9930699). Involved in the regulation of dendritic spine formation and maturation (PubMed:22345354).2 Publications

Enzyme regulationi

Inhibited by WNK3.By similarity

GO - Molecular functioni

GO - Biological processi

  • ammonium transport Source: RGD
  • chemical synaptic transmission Source: GO_Central
  • chloride transport Source: RGD
  • dendritic spine development Source: UniProtKB
  • intracellular pH reduction Source: RGD
  • potassium ion transport Source: RGD
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Symport, Transport

Keywords - Ligandi

Potassium

Protein family/group databases

TCDBi2.A.30.5.2. the cation-chloride cotransporter (ccc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 5
Alternative name(s):
Electroneutral potassium-chloride cotransporter 2
Furosemide-sensitive K-Cl cotransporter
K-Cl cotransporter 2
Short name:
rKCC2
Neuronal K-Cl cotransporter
Gene namesi
Name:Slc12a5
Synonyms:Kcc2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620811. Slc12a5.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 133133CytoplasmicSequence analysisAdd
BLAST
Transmembranei134 – 15421HelicalSequence analysisAdd
BLAST
Transmembranei156 – 17621HelicalSequence analysisAdd
BLAST
Topological domaini177 – 19418CytoplasmicSequence analysisAdd
BLAST
Transmembranei195 – 21521HelicalSequence analysisAdd
BLAST
Transmembranei217 – 23721HelicalSequence analysisAdd
BLAST
Topological domaini238 – 25417CytoplasmicSequence analysisAdd
BLAST
Transmembranei255 – 27521HelicalSequence analysisAdd
BLAST
Transmembranei278 – 29821HelicalSequence analysisAdd
BLAST
Topological domaini299 – 418120CytoplasmicSequence analysisAdd
BLAST
Transmembranei419 – 43921HelicalSequence analysisAdd
BLAST
Transmembranei459 – 47921HelicalSequence analysisAdd
BLAST
Topological domaini480 – 49617CytoplasmicSequence analysisAdd
BLAST
Transmembranei497 – 51721HelicalSequence analysisAdd
BLAST
Transmembranei570 – 59021HelicalSequence analysisAdd
BLAST
Topological domaini591 – 63040CytoplasmicSequence analysisAdd
BLAST
Transmembranei631 – 65121HelicalSequence analysisAdd
BLAST
Transmembranei848 – 86821HelicalSequence analysisAdd
BLAST
Topological domaini869 – 1139271CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • dendrite membrane Source: RGD
  • integral component of plasma membrane Source: InterPro
  • perikaryon Source: RGD
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL1075108.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11391139Solute carrier family 12 member 5PRO_0000178036Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei57 – 571PhosphothreonineCombined sources
Glycosylationi442 – 4421N-linked (GlcNAc...)Sequence analysis
Glycosylationi833 – 8331N-linked (GlcNAc...)Sequence analysis
Modified residuei1045 – 10451PhosphoserineCombined sources
Modified residuei1048 – 10481PhosphoserineCombined sources
Modified residuei1049 – 10491PhosphoserineCombined sources

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ63633.
PRIDEiQ63633.

PTM databases

iPTMnetiQ63633.
PhosphoSiteiQ63633.

Expressioni

Tissue specificityi

Highly expressed in brain. Not detected in other tissues. Highly expressed in pyramidal neurons and in neurons throughout the cortex, hippocampus, the granular layer of the cerebellum and in groups of neurons throughout the brainstem. Barely detectable in dorsal-root ganglions.

Developmental stagei

Detected in thalamus, but not in hippocampus and neocortex at E20. At birth barely detectable in hippocampus. Expression increases steeply from day 5 to day 9 and then stabilizes at adult levels.

Interactioni

Subunit structurei

Homomultimer and heteromultimer with other K-Cl cotransporters. Interacts with AP2A1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Mycbp2Q7TPH64EBI-1811510,EBI-1811542From a different organism.

Protein-protein interaction databases

BioGridi251211. 1 interaction.
IntActiQ63633. 1 interaction.
STRINGi10116.ENSRNOP00000062103.

Chemistry

BindingDBiQ63633.

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2082. Eukaryota.
COG0531. LUCA.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ63633.
KOiK14427.
PhylomeDBiQ63633.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030358. KCC2.
IPR000076. KCL_cotranspt.
IPR018491. SLC12_C.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF54. PTHR11827:SF54. 4 hits.
PfamiPF00324. AA_permease. 2 hits.
PF03522. SLC12. 3 hits.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q63633-1) [UniParc]FASTAAdd to basket
Also known as: KCC2a

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
MSRRFTVTSL PPAASAASAD PESRRHSVAD PRRLPREDVK GDGNPKESSP
60 70 80 90 100
FINSTDTEKG REYDGRNMAL FEEEMDTSPM VSSLLSGLAN YTNLPQGSKE
110 120 130 140 150
HEEAENNEGG KKKPVQAPRM GTFMGVYLPC LQNIFGVILF LRLTWVVGIA
160 170 180 190 200
GIMESFCMVF ICCSCTMLTA ISMSAIATNG VVPAGGSYYM ISRSLGPEFG
210 220 230 240 250
GAVGLCFYLG TTFAGAMYIL GTIEILLAYL FPAMAIFKAE DASGEAAAML
260 270 280 290 300
NNMRVYGTCV LTCMATVVFV GVKYVNKFAL VFLGCVILSI LAIYAGVIKS
310 320 330 340 350
AFDPPNFPIC LLGNRTLSRH GFDVCAKLAW EGNETVTTRL WGLFCSSRLL
360 370 380 390 400
NATCDEYFTR NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERRGMPSV
410 420 430 440 450
GLADGTPVDM DHPYVFSDMT SYFTLLVGIY FPSVTGIMAG SNRSGDLRDA
460 470 480 490 500
QKSIPTGTIL AIATTSAVYI SSVVLFGACI EGVVLRDKFG EAVNGNLVVG
510 520 530 540 550
TLAWPSPWVI VIGSFFSTCG AGLQSLTGAP RLLQAISRDG IVPFLQVFGH
560 570 580 590 600
GKANGEPTWA LLLTACICEI GILIASLDEV APILSMFFLM CYMFVNLACA
610 620 630 640 650
VQTLLRTPNW RPRFRYYHWT LSFLGMSLCL ALMFICSWYY ALVAMLIAGL
660 670 680 690 700
IYKYIEYRGA EKEWGDGIRG LSLSAARYAL LRLEEGPPHT KNWRPQLLVL
710 720 730 740 750
VRVDQDQNVV HPQLLSLTSQ LKAGKGLTIV GSVLEGTFLD NHPQAQRAEE
760 770 780 790 800
SIRRLMEAEK VKGFCQVVIS SNLRDGVSHL IQSGGLGGLQ HNTVLVGWPR
810 820 830 840 850
NWRQKEDHQT WRNFIELVRE TTAGHLALLV TKNVSMFPGN PERFSEGSID
860 870 880 890 900
VWWIVHDGGM LMLLPFLLRH HKVWRKCKMR IFTVAQMDDN SIQMKKDLTT
910 920 930 940 950
FLYHLRITAE VEVVEMHESD ISAYTYEKTL VMEQRSQILK QMHLTKNERE
960 970 980 990 1000
REIQSITDES RGSIRRKNPA NTRLRLNVPE ETACDNEEKP EEEVQLIHDQ
1010 1020 1030 1040 1050
SAPSCPSSSP SPGEEPEGEG ETDPEKVHLT WTKDKSAAQK NKGPSPVSSE
1060 1070 1080 1090 1100
GIKDFFSMKP EWENLNQSNV RRMHTAVRLN EVIVNKSRDA KLVLLNMPGP
1110 1120 1130
PRNRNGDENY MEFLEVLTEQ LDRVMLVRGG GREVITIYS
Length:1,139
Mass (Da):126,247
Last modified:December 4, 2007 - v2
Checksum:i79748F3813EBEFA0
GO
Isoform 2 (identifier: Q63633-2) [UniParc]FASTAAdd to basket
Also known as: KCC2b

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: MSRRFTVTSLPPAASAASADPESRRHSVADPRRLPREDVK → MLNNLTDCEDGDGGANP

Show »
Length:1,116
Mass (Da):123,563
Checksum:i8E2FDACDD7FDE2F6
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4040MSRRF…REDVK → MLNNLTDCEDGDGGANP in isoform 2. 1 PublicationVSP_029911Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U55816 mRNA. Translation: AAC52635.1.
EF641113 mRNA. Translation: ABV03586.1.
PIRiT31432.
RefSeqiNP_599190.1. NM_134363.1. [Q63633-2]
UniGeneiRn.10513.

Genome annotation databases

GeneIDi171373.
KEGGirno:171373.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U55816 mRNA. Translation: AAC52635.1.
EF641113 mRNA. Translation: ABV03586.1.
PIRiT31432.
RefSeqiNP_599190.1. NM_134363.1. [Q63633-2]
UniGeneiRn.10513.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi251211. 1 interaction.
IntActiQ63633. 1 interaction.
STRINGi10116.ENSRNOP00000062103.

Chemistry

BindingDBiQ63633.
ChEMBLiCHEMBL1075108.

Protein family/group databases

TCDBi2.A.30.5.2. the cation-chloride cotransporter (ccc) family.

PTM databases

iPTMnetiQ63633.
PhosphoSiteiQ63633.

Proteomic databases

PaxDbiQ63633.
PRIDEiQ63633.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi171373.
KEGGirno:171373.

Organism-specific databases

CTDi57468.
RGDi620811. Slc12a5.

Phylogenomic databases

eggNOGiKOG2082. Eukaryota.
COG0531. LUCA.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ63633.
KOiK14427.
PhylomeDBiQ63633.

Miscellaneous databases

PROiQ63633.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030358. KCC2.
IPR000076. KCL_cotranspt.
IPR018491. SLC12_C.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF54. PTHR11827:SF54. 4 hits.
PfamiPF00324. AA_permease. 2 hits.
PF03522. SLC12. 3 hits.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiS12A5_RAT
AccessioniPrimary (citable) accession number: Q63633
Secondary accession number(s): A7Y821
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: September 7, 2016
This is version 125 of the entry and version 2 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.