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Protein

Solute carrier family 12 member 5

Gene

SLC12A5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Mediates electroneutral potassium-chloride cotransport in mature neurons. Transport occurs under isotonic conditions, but is activated 20-fold by cell swelling. Important for Cl- homeostasis in neurons.

Enzyme regulationi

Inhibited by WNK3.1 Publication

GO - Molecular functioni

  • potassium:chloride symporter activity Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • cellular ion homeostasis Source: UniProtKB
  • ion transport Source: Reactome
  • learning Source: Ensembl
  • multicellular organism growth Source: Ensembl
  • potassium ion transport Source: UniProtKB-KW
  • response to drug Source: Ensembl
  • synaptic transmission Source: Ensembl
  • thermosensory behavior Source: Ensembl
  • transmembrane transport Source: Reactome
  • transport Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Symport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

ReactomeiREACT_19315. Cation-coupled Chloride cotransporters.

Protein family/group databases

TCDBi2.A.30.5.6. 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
K-Cl cotransporter 2
Short name:
hKCC2
Neuronal K-Cl cotransporter
Gene namesi
Name:SLC12A5
Synonyms:KCC2, KIAA1176
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:13818. 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

Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37814.

Chemistry

DrugBankiDB00887. Bumetanide.
DB00761. Potassium Chloride.

Polymorphism and mutation databases

BioMutaiSLC12A5.
DMDMi161784306.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11391139Solute carrier family 12 member 5PRO_0000178034Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei49 – 491PhosphoserineBy similarity
Glycosylationi442 – 4421N-linked (GlcNAc...)Sequence Analysis
Glycosylationi833 – 8331N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9H2X9.
PaxDbiQ9H2X9.
PRIDEiQ9H2X9.

PTM databases

PhosphoSiteiQ9H2X9.

Expressioni

Tissue specificityi

Brain specific. Detected in neuronal cells.

Gene expression databases

BgeeiQ9H2X9.
CleanExiHS_SLC12A5.
ExpressionAtlasiQ9H2X9. baseline and differential.
GenevestigatoriQ9H2X9.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi121538. 2 interactions.
STRINGi9606.ENSP00000387694.

Structurei

3D structure databases

ProteinModelPortaliQ9H2X9.
SMRiQ9H2X9. Positions 412-662.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ9H2X9.
KOiK14427.
OMAiHLTWTKD.
OrthoDBiEOG78M01J.
PhylomeDBiQ9H2X9.
TreeFamiTF313657.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030358. KCC2.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PANTHERiPTHR11827:SF54. PTHR11827:SF54. 1 hit.
PfamiPF00324. AA_permease. 2 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: Q9H2X9-1) [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 PPAGPARSPD PESRRHSVAD PRHLPGEDVK GDGNPKESSP
60 70 80 90 100
FINSTDTEKG KEYDGKNMAL 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 WGLFCSSRFL
360 370 380 390 400
NATCDEYFTR NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERSGMTSV
410 420 430 440 450
GLADGTPIDM 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 GSVLEGTFLE 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 ETAGDSEEKP EEEVQLIHDQ
1010 1020 1030 1040 1050
SAPSCPSSSP SPGEEPEGEG ETDPEKVHLT WTKDKSVAEK NKGPSPVSSE
1060 1070 1080 1090 1100
GIKDFFSMKP EWENLNQSNV RRMHTAVRLN EVIVKKSRDA KLVLLNMPGP
1110 1120 1130
PRNRNGDENY MEFLEVLTEH LDRVMLVRGG GREVITIYS
Length:1,139
Mass (Da):126,184
Last modified:December 4, 2007 - v3
Checksum:i100C097AF1FD4B3E
GO
Isoform 2 (identifier: Q9H2X9-2) [UniParc]FASTAAdd to basket

Also known as: KCC2b

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

Show »
Length:1,116
Mass (Da):123,511
Checksum:i68D46DECF8592FCF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Isoform 2 (identifier: Q9H2X9-2)
Sequence conflicti2 – 21L → P in AAG43493 (PubMed:12106695).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti407 – 4071P → A.
Corresponds to variant rs16985442 [ dbSNP | Ensembl ].
VAR_027414
Natural varianti847 – 8471G → D in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036557
Natural varianti1100 – 11001P → L.1 Publication
Corresponds to variant rs17297532 [ dbSNP | Ensembl ].
VAR_024994

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4040MSRRF…GEDVK → MLNNLTDCEDGDGGANP in isoform 2. 3 PublicationsVSP_029909Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF208159 mRNA. Translation: AAG43493.1.
AL162458 Genomic DNA. Translation: CAH74054.2.
BC132668 mRNA. Translation: AAI32669.1.
BC132670 mRNA. Translation: AAI32671.1.
AB033002 mRNA. Translation: BAA86490.1.
DA102113 mRNA. No translation available.
DA328785 mRNA. No translation available.
CCDSiCCDS13391.1. [Q9H2X9-2]
CCDS46610.1. [Q9H2X9-1]
RefSeqiNP_001128243.1. NM_001134771.1. [Q9H2X9-1]
NP_065759.1. NM_020708.4. [Q9H2X9-2]
UniGeneiHs.21413.

Genome annotation databases

EnsembliENST00000243964; ENSP00000243964; ENSG00000124140. [Q9H2X9-2]
ENST00000454036; ENSP00000387694; ENSG00000124140. [Q9H2X9-1]
GeneIDi57468.
KEGGihsa:57468.
UCSCiuc002xrb.2. human. [Q9H2X9-2]
uc010zxl.1. human. [Q9H2X9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF208159 mRNA. Translation: AAG43493.1.
AL162458 Genomic DNA. Translation: CAH74054.2.
BC132668 mRNA. Translation: AAI32669.1.
BC132670 mRNA. Translation: AAI32671.1.
AB033002 mRNA. Translation: BAA86490.1.
DA102113 mRNA. No translation available.
DA328785 mRNA. No translation available.
CCDSiCCDS13391.1. [Q9H2X9-2]
CCDS46610.1. [Q9H2X9-1]
RefSeqiNP_001128243.1. NM_001134771.1. [Q9H2X9-1]
NP_065759.1. NM_020708.4. [Q9H2X9-2]
UniGeneiHs.21413.

3D structure databases

ProteinModelPortaliQ9H2X9.
SMRiQ9H2X9. Positions 412-662.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121538. 2 interactions.
STRINGi9606.ENSP00000387694.

Chemistry

BindingDBiQ9H2X9.
ChEMBLiCHEMBL1615384.
DrugBankiDB00887. Bumetanide.
DB00761. Potassium Chloride.
GuidetoPHARMACOLOGYi972.

Protein family/group databases

TCDBi2.A.30.5.6. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSiteiQ9H2X9.

Polymorphism and mutation databases

BioMutaiSLC12A5.
DMDMi161784306.

Proteomic databases

MaxQBiQ9H2X9.
PaxDbiQ9H2X9.
PRIDEiQ9H2X9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000243964; ENSP00000243964; ENSG00000124140. [Q9H2X9-2]
ENST00000454036; ENSP00000387694; ENSG00000124140. [Q9H2X9-1]
GeneIDi57468.
KEGGihsa:57468.
UCSCiuc002xrb.2. human. [Q9H2X9-2]
uc010zxl.1. human. [Q9H2X9-1]

Organism-specific databases

CTDi57468.
GeneCardsiGC20P044651.
HGNCiHGNC:13818. SLC12A5.
MIMi606726. gene.
neXtProtiNX_Q9H2X9.
PharmGKBiPA37814.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ9H2X9.
KOiK14427.
OMAiHLTWTKD.
OrthoDBiEOG78M01J.
PhylomeDBiQ9H2X9.
TreeFamiTF313657.

Enzyme and pathway databases

ReactomeiREACT_19315. Cation-coupled Chloride cotransporters.

Miscellaneous databases

GeneWikiiChloride_potassium_symporter_5.
GenomeRNAii57468.
NextBioi63686.
PROiQ9H2X9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9H2X9.
CleanExiHS_SLC12A5.
ExpressionAtlasiQ9H2X9. baseline and differential.
GenevestigatoriQ9H2X9.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR030358. KCC2.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PANTHERiPTHR11827:SF54. PTHR11827:SF54. 1 hit.
PfamiPF00324. AA_permease. 2 hits.
[Graphical view]
PRINTSiPR01081. KCLTRNSPORT.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter."
    Song L., Mercado A., Vazquez N., Xie Q., Desai R., George A.L. Jr., Gamba G., Mount D.B.
    Brain Res. Mol. Brain Res. 103:91-105(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Brain.
  2. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-175 (ISOFORM 1).
  5. "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain."
    Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.
    DNA Res. 6:329-336(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-1109 (ISOFORM 2), VARIANT LEU-1100.
    Tissue: Brain.
  6. Cited for: ENZYME REGULATION.
  7. Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-847.

Entry informationi

Entry nameiS12A5_HUMAN
AccessioniPrimary (citable) accession number: Q9H2X9
Secondary accession number(s): A2RTX2
, Q5VZ41, Q9H4Z0, Q9ULP4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: April 29, 2015
This is version 122 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Inhibited by furosemide and bumetanide.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.