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Protein

Solute carrier family 12 member 5

Gene

Slc12a5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Involved in the regulation of dendritic spine formation and maturation.By similarity

Enzyme regulationi

Inhibited by WNK3.By similarity

GO - Molecular functioni

  • chloride transmembrane transporter activity Source: MGI
  • potassium:chloride symporter activity Source: MGI
  • protein kinase binding Source: MGI

GO - Biological processi

  • cellular chloride ion homeostasis Source: MGI
  • cellular ion homeostasis Source: MGI
  • chemical synaptic transmission Source: MGI
  • chloride transport Source: MGI
  • dendritic spine development Source: MGI
  • hypotonic response Source: MGI
  • ion transport Source: MGI
  • learning Source: MGI
  • multicellular organism growth Source: MGI
  • response to drug Source: MGI
  • thermosensory behavior Source: MGI

Keywordsi

Biological processIon transport, Potassium transport, Symport, Transport
LigandChloride, Potassium

Enzyme and pathway databases

ReactomeiR-MMU-426117 Cation-coupled Chloride cotransporters

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 5
Alternative name(s):
Electroneutral potassium-chloride cotransporter 2
K-Cl cotransporter 2
Short name:
mKCC2
Neuronal K-Cl cotransporter
Gene namesi
Name:Slc12a5
Synonyms:Kcc2, Kiaa1176
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1862037 Slc12a5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 133CytoplasmicSequence analysisAdd BLAST133
Transmembranei134 – 154HelicalSequence analysisAdd BLAST21
Transmembranei156 – 176HelicalSequence analysisAdd BLAST21
Topological domaini177 – 194CytoplasmicSequence analysisAdd BLAST18
Transmembranei195 – 215HelicalSequence analysisAdd BLAST21
Transmembranei217 – 237HelicalSequence analysisAdd BLAST21
Topological domaini238 – 254CytoplasmicSequence analysisAdd BLAST17
Transmembranei255 – 275HelicalSequence analysisAdd BLAST21
Transmembranei278 – 298HelicalSequence analysisAdd BLAST21
Topological domaini299 – 418CytoplasmicSequence analysisAdd BLAST120
Transmembranei419 – 439HelicalSequence analysisAdd BLAST21
Transmembranei459 – 479HelicalSequence analysisAdd BLAST21
Topological domaini480 – 496CytoplasmicSequence analysisAdd BLAST17
Transmembranei497 – 517HelicalSequence analysisAdd BLAST21
Transmembranei570 – 590HelicalSequence analysisAdd BLAST21
Topological domaini591 – 630CytoplasmicSequence analysisAdd BLAST40
Transmembranei631 – 651HelicalSequence analysisAdd BLAST21
Transmembranei848 – 868HelicalSequence analysisAdd BLAST21
Topological domaini869 – 1138CytoplasmicSequence analysisAdd BLAST270

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Disruption phenotypei

Death at birth due to severe motor deficits including respiratory failure. Mice lacking isoform 2 die within 2 weeks after birth.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi680 – 681LL → AA: Inhibits endocytosis. Abolishes interaction with AP2A1. 1 Publication2
Mutagenesisi684 – 685EE → AA: Decreases endocytosis. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001780351 – 1138Solute carrier family 12 member 5Add BLAST1138

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei57PhosphothreonineBy similarity1
Glycosylationi442N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi833N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1044PhosphoserineCombined sources1
Modified residuei1047PhosphoserineCombined sources1
Modified residuei1048PhosphoserineCombined sources1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ91V14
PeptideAtlasiQ91V14
PRIDEiQ91V14

PTM databases

iPTMnetiQ91V14
PhosphoSitePlusiQ91V14
SwissPalmiQ91V14

Expressioni

Tissue specificityi

Isoform 2 expressed in brainstem and spinal cord, isoform 1 expressed in brainstem, spinal cord and olfactory bulb of E17 embryos. Isoforms 1 and 2 expressed in all parts of the brain and spinal cord in postnatal day 14 mice.1 Publication

Developmental stagei

Isoform 1 predominant isoform in E17 brain. Isoform 2 predominant isoform during postnatal development. Detected in the ventral horns of the spinal cord at E12.5, and throughout the spinal cord at birth.

Gene expression databases

BgeeiENSMUSG00000017740
CleanExiMM_SLC12A5
ExpressionAtlasiQ91V14 baseline and differential
GenevisibleiQ91V14 MM

Interactioni

Subunit structurei

Homomultimer and heteromultimer with other K-Cl cotransporters (By similarity). Interacts with AP2A1.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi208213, 1 interactor
IntActiQ91V14, 6 interactors
MINTiQ91V14
STRINGi10090.ENSMUSP00000096690

Structurei

3D structure databases

ProteinModelPortaliQ91V14
SMRiQ91V14
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2082 Eukaryota
COG0531 LUCA
GeneTreeiENSGT00760000119053
HOGENOMiHOG000092644
HOVERGENiHBG052852
InParanoidiQ91V14
KOiK14427
OMAiPYVFSDM
PhylomeDBiQ91V14
TreeFamiTF313657

Family and domain databases

InterProiView protein in InterPro
IPR004841 AA-permease/SLC12A_dom
IPR030358 KCC2
IPR000076 KCL_cotranspt
IPR018491 SLC12_C
IPR004842 SLC12A_fam
PANTHERiPTHR11827:SF54 PTHR11827:SF54, 1 hit
PfamiView protein in Pfam
PF00324 AA_permease, 2 hits
PF03522 SLC12, 3 hits
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: Q91V14-1) [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 YTNLPQGSRE
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 NPRLRLNVPE ETACDNEEKP EEEVQLIHDQ
1010 1020 1030 1040 1050
SAPSCPSSSP SPGEEPEGER ETDPEVHLTW TKDKSVAEKN KGPSPVSSEG
1060 1070 1080 1090 1100
IKDFFSMKPE WENLNQSNVR RMHTAVRLNE VIVNKSRDAK LVLLNMPGPP
1110 1120 1130
RNRNGDENYM EFLEVLTEQL DRVMLVRGGG REVITIYS
Length:1,138
Mass (Da):126,271
Last modified:December 4, 2007 - v2
Checksum:i56059F065B89C407
GO
Isoform 2 (identifier: Q91V14-2) [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:1,115
Mass (Da):123,587
Checksum:iDD506AC24D8492B4
GO

Sequence cautioni

The sequence BAC65742 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti64Missing in AAH54808 (PubMed:15489334).Curated1
Sequence conflicti859G → D in BAE27805 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0299101 – 40MSRRF…REDVK → MLNNLTDCEDGDGGANP in isoform 2. 4 PublicationsAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF332063 mRNA Translation: AAK56092.1
AF332064 mRNA Translation: AAK56093.1
AK122460 mRNA Translation: BAC65742.1 Different initiation.
AK147262 mRNA Translation: BAE27805.1
AL591495 Genomic DNA Translation: CAM26466.1
BC054808 mRNA Translation: AAH54808.1
AJ011033 Genomic DNA Translation: CAA09464.1
CCDSiCCDS38332.1 [Q91V14-2]
RefSeqiNP_065066.2, NM_020333.2 [Q91V14-2]
XP_006500006.2, XM_006499943.3
UniGeneiMm.252987

Genome annotation databases

EnsembliENSMUST00000099092; ENSMUSP00000096690; ENSMUSG00000017740 [Q91V14-2]
ENSMUST00000202623; ENSMUSP00000144623; ENSMUSG00000017740 [Q91V14-1]
GeneIDi57138
KEGGimmu:57138
UCSCiuc056zqu.1 mouse [Q91V14-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiS12A5_MOUSE
AccessioniPrimary (citable) accession number: Q91V14
Secondary accession number(s): A2A5L0
, Q3UHQ2, Q7TQC9, Q80TI5, Q9Z0M7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: April 25, 2018
This is version 144 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health