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Q9H2X9 (S12A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC12A5
Synonyms:KCC2, KIAA1176
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1139 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 regulation

Inhibited by WNK3. Ref.6

Subunit structure

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

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Brain specific. Detected in neuronal cells.

Miscellaneous

Inhibited by furosemide and bumetanide.

Sequence similarities

Belongs to the SLC12A transporter family.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular ion homeostasis

Non-traceable author statement Ref.1. Source: UniProtKB

chloride transmembrane transport

Non-traceable author statement Ref.1. Source: GOC

ion transport

Traceable author statement. Source: Reactome

learning

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

potassium ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

response to drug

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Inferred from electronic annotation. Source: Ensembl

thermosensory behavior

Inferred from electronic annotation. Source: Ensembl

transmembrane transport

Traceable author statement. Source: Reactome

transport

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentdendritic shaft

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Non-traceable author statement Ref.1. Source: UniProtKB

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionpotassium:chloride symporter activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9H2X9-1)

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.
Isoform 2 (identifier: Q9H2X9-2)

Also known as: KCC2b;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11391139Solute carrier family 12 member 5
PRO_0000178034

Regions

Topological domain1 – 133133Cytoplasmic Potential
Transmembrane134 – 15421Helical; Potential
Transmembrane156 – 17621Helical; Potential
Topological domain177 – 19418Cytoplasmic Potential
Transmembrane195 – 21521Helical; Potential
Transmembrane217 – 23721Helical; Potential
Topological domain238 – 25417Cytoplasmic Potential
Transmembrane255 – 27521Helical; Potential
Transmembrane278 – 29821Helical; Potential
Topological domain299 – 418120Cytoplasmic Potential
Transmembrane419 – 43921Helical; Potential
Transmembrane459 – 47921Helical; Potential
Topological domain480 – 49617Cytoplasmic Potential
Transmembrane497 – 51721Helical; Potential
Transmembrane570 – 59021Helical; Potential
Topological domain591 – 63040Cytoplasmic Potential
Transmembrane631 – 65121Helical; Potential
Transmembrane848 – 86821Helical; Potential
Topological domain869 – 1139271Cytoplasmic Potential

Amino acid modifications

Glycosylation4421N-linked (GlcNAc...) Potential
Glycosylation8331N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 4040MSRRF…GEDVK → MLNNLTDCEDGDGGANP in isoform 2.
VSP_029909
Natural variant4071P → A.
Corresponds to variant rs16985442 [ dbSNP | Ensembl ].
VAR_027414
Natural variant8471G → D in a colorectal cancer sample; somatic mutation. Ref.7
VAR_036557
Natural variant11001P → L. Ref.5
Corresponds to variant rs17297532 [ dbSNP | Ensembl ].
VAR_024994

Experimental info

Isoform 2:
Sequence conflict21L → P in AAG43493. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (KCC2a) [UniParc].

Last modified December 4, 2007. Version 3.
Checksum: 100C097AF1FD4B3E

FASTA1,139126,184
        10         20         30         40         50         60 
MSRRFTVTSL PPAGPARSPD PESRRHSVAD PRHLPGEDVK GDGNPKESSP FINSTDTEKG 

        70         80         90        100        110        120 
KEYDGKNMAL FEEEMDTSPM VSSLLSGLAN YTNLPQGSRE HEEAENNEGG KKKPVQAPRM 

       130        140        150        160        170        180 
GTFMGVYLPC LQNIFGVILF LRLTWVVGIA GIMESFCMVF ICCSCTMLTA ISMSAIATNG 

       190        200        210        220        230        240 
VVPAGGSYYM ISRSLGPEFG GAVGLCFYLG TTFAGAMYIL GTIEILLAYL FPAMAIFKAE 

       250        260        270        280        290        300 
DASGEAAAML NNMRVYGTCV LTCMATVVFV GVKYVNKFAL VFLGCVILSI LAIYAGVIKS 

       310        320        330        340        350        360 
AFDPPNFPIC LLGNRTLSRH GFDVCAKLAW EGNETVTTRL WGLFCSSRFL NATCDEYFTR 

       370        380        390        400        410        420 
NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERSGMTSV GLADGTPIDM DHPYVFSDMT 

       430        440        450        460        470        480 
SYFTLLVGIY FPSVTGIMAG SNRSGDLRDA QKSIPTGTIL AIATTSAVYI SSVVLFGACI 

       490        500        510        520        530        540 
EGVVLRDKFG EAVNGNLVVG TLAWPSPWVI VIGSFFSTCG AGLQSLTGAP RLLQAISRDG 

       550        560        570        580        590        600 
IVPFLQVFGH GKANGEPTWA LLLTACICEI GILIASLDEV APILSMFFLM CYMFVNLACA 

       610        620        630        640        650        660 
VQTLLRTPNW RPRFRYYHWT LSFLGMSLCL ALMFICSWYY ALVAMLIAGL IYKYIEYRGA 

       670        680        690        700        710        720 
EKEWGDGIRG LSLSAARYAL LRLEEGPPHT KNWRPQLLVL VRVDQDQNVV HPQLLSLTSQ 

       730        740        750        760        770        780 
LKAGKGLTIV GSVLEGTFLE NHPQAQRAEE SIRRLMEAEK VKGFCQVVIS SNLRDGVSHL 

       790        800        810        820        830        840 
IQSGGLGGLQ HNTVLVGWPR NWRQKEDHQT WRNFIELVRE TTAGHLALLV TKNVSMFPGN 

       850        860        870        880        890        900 
PERFSEGSID VWWIVHDGGM LMLLPFLLRH HKVWRKCKMR IFTVAQMDDN SIQMKKDLTT 

       910        920        930        940        950        960 
FLYHLRITAE VEVVEMHESD ISAYTYEKTL VMEQRSQILK QMHLTKNERE REIQSITDES 

       970        980        990       1000       1010       1020 
RGSIRRKNPA NTRLRLNVPE ETAGDSEEKP EEEVQLIHDQ SAPSCPSSSP SPGEEPEGEG 

      1030       1040       1050       1060       1070       1080 
ETDPEKVHLT WTKDKSVAEK NKGPSPVSSE GIKDFFSMKP EWENLNQSNV RRMHTAVRLN 

      1090       1100       1110       1120       1130 
EVIVKKSRDA KLVLLNMPGP PRNRNGDENY MEFLEVLTEH LDRVMLVRGG GREVITIYS 

« Hide

Isoform 2 (KCC2b) [UniParc].

Checksum: 68D46DECF8592FCF
Show »

FASTA1,116123,511

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes."
Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R., Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T., Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R. expand/collapse author list , Kanda K., Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T., Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T., Sugano S.
Genome Res. 16:55-65(2006) [PubMed] [Europe PMC] [Abstract]
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]"Similar Effects of all WNK3 Variants upon SLC12 Cotransporters."
Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A., Pasantes-Morales H., Gamba G., Mercado A.
Am. J. Physiol. 301:C601-C608(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[7]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-847.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS13391.1. [Q9H2X9-2]
CCDS46610.1. [Q9H2X9-1]
RefSeqNP_001128243.1. NM_001134771.1. [Q9H2X9-1]
NP_065759.1. NM_020708.4. [Q9H2X9-2]
UniGeneHs.21413.

3D structure databases

ProteinModelPortalQ9H2X9.
SMRQ9H2X9. Positions 412-662.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000387694.

Chemistry

ChEMBLCHEMBL1615384.
DrugBankDB00887. Bumetanide.
DB00761. Potassium Chloride.
GuidetoPHARMACOLOGY972.

Protein family/group databases

TCDB2.A.30.5.6. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSiteQ9H2X9.

Polymorphism databases

DMDM161784306.

Proteomic databases

MaxQBQ9H2X9.
PaxDbQ9H2X9.
PRIDEQ9H2X9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000243964; ENSP00000243964; ENSG00000124140. [Q9H2X9-2]
ENST00000454036; ENSP00000387694; ENSG00000124140. [Q9H2X9-1]
GeneID57468.
KEGGhsa:57468.
UCSCuc002xrb.2. human. [Q9H2X9-2]
uc010zxl.1. human. [Q9H2X9-1]

Organism-specific databases

CTD57468.
GeneCardsGC20P044651.
HGNCHGNC:13818. SLC12A5.
MIM606726. gene.
neXtProtNX_Q9H2X9.
PharmGKBPA37814.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0531.
HOGENOMHOG000092644.
HOVERGENHBG052852.
InParanoidQ9H2X9.
KOK14427.
OMAHLTWTKD.
OrthoDBEOG78M01J.
PhylomeDBQ9H2X9.
TreeFamTF313657.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ9H2X9.
BgeeQ9H2X9.
CleanExHS_SLC12A5.
GenevestigatorQ9H2X9.

Family and domain databases

InterProIPR004841. AA-permease/SLC12A_dom.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PfamPF00324. AA_permease. 2 hits.
[Graphical view]
PRINTSPR01081. KCLTRNSPORT.
TIGRFAMsTIGR00930. 2a30. 1 hit.
ProtoNetSearch...

Other

GeneWikiChloride_potassium_symporter_5.
GenomeRNAi57468.
NextBio63686.
PROQ9H2X9.
SOURCESearch...

Entry information

Entry nameS12A5_HUMAN
AccessionPrimary (citable) accession number: Q9H2X9
Secondary accession number(s): A2RTX2 expand/collapse secondary AC list , Q5VZ41, Q9H4Z0, Q9ULP4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: July 9, 2014
This is version 115 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM