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Q91V14 (S12A5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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=mKCC2
Neuronal K-Cl cotransporter
Gene names
Name:Slc12a5
Synonyms:Kcc2, Kiaa1176
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1138 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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 By similarity.

Subunit structure

Homomultimer and heteromultimer with other K-Cl cotransporters By similarity. Interacts with AP2A1. Ref.10

Subcellular location

Cell projectiondendrite. Cell membrane; Multi-pass membrane protein. Note: Detected on dendrites, but not on axons of spinal cord neurons and at GPHN-positive inhibitory synapses. Ref.9

Tissue specificity

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. Ref.7

Developmental stage

Isoform 1 predominant isoform inE17 brain. Isoform 2 predominant isoform duringpostnatal development. Detected in the ventral horns of the spinal cord at E12.5, and throughout the spinal cord at birth.

Disruption phenotype

Death at birth due to severe motor deficits including respiratory failure. Mice lacking isoform 2 die within 2 weeks after birth. Ref.7

Sequence similarities

Belongs to the SLC12A transporter family.

Sequence caution

The sequence BAC65742.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Symport
Transport
   Cellular componentCell membrane
Cell projection
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   PTMGlycoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processchloride transmembrane transport

Inferred from mutant phenotype Ref.9. Source: GOC

chloride transport

Inferred from mutant phenotype Ref.9. Source: MGI

learning

Inferred from mutant phenotype PubMed 15813942. Source: MGI

multicellular organism growth

Inferred from mutant phenotype PubMed 15813942. Source: MGI

potassium ion transport

Inferred from electronic annotation. Source: UniProtKB-KW

response to drug

Inferred from mutant phenotype PubMed 15813942. Source: MGI

synaptic transmission

Inferred from mutant phenotype Ref.9. Source: MGI

thermosensory behavior

Inferred from mutant phenotype PubMed 15813942. Source: MGI

   Cellular_componentdendrite

Inferred from electronic annotation. Source: UniProtKB-SubCell

dendritic shaft

Inferred from direct assay PubMed 19307176. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuronal cell body

Inferred from direct assay PubMed 19307176. Source: MGI

plasma membrane

Inferred from direct assay Ref.9. Source: MGI

   Molecular_functionpotassium:chloride symporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q91V14-1)

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: Q91V14-2)

Also known as: KCC2b;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11381138Solute carrier family 12 member 5
PRO_0000178035

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 – 1138270Cytoplasmic Potential

Amino acid modifications

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

Natural variations

Alternative sequence1 – 4040MSRRF…REDVK → MLNNLTDCEDGDGGANP in isoform 2.
VSP_029910

Experimental info

Mutagenesis680 – 6812LL → AA: Inhibits endocytosis. Abolishes interaction with AP2A1. Ref.10
Mutagenesis684 – 6852EE → AA: Decreases endocytosis. Ref.10
Sequence conflict641Missing in AAH54808. Ref.5
Sequence conflict8591G → D in BAE27805. Ref.3

Sequences

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

Last modified December 4, 2007. Version 2.
Checksum: 56059F065B89C407

FASTA1,138126,271
        10         20         30         40         50         60 
MSRRFTVTSL PPAASAASAD PESRRHSVAD PRRLPREDVK GDGNPKESSP FINSTDTEKG 

        70         80         90        100        110        120 
REYDGRNMAL 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 WGLFCSSRLL NATCDEYFTR 

       370        380        390        400        410        420 
NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERRGMPSV GLADGTPVDM 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 GSVLEGTFLD 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 NPRLRLNVPE ETACDNEEKP EEEVQLIHDQ SAPSCPSSSP SPGEEPEGER 

      1030       1040       1050       1060       1070       1080 
ETDPEVHLTW TKDKSVAEKN KGPSPVSSEG IKDFFSMKPE WENLNQSNVR RMHTAVRLNE 

      1090       1100       1110       1120       1130 
VIVNKSRDAK LVLLNMPGPP RNRNGDENYM EFLEVLTEQL DRVMLVRGGG REVITIYS 

« Hide

Isoform 2 (KCC2b) [UniParc].

Checksum: DD506AC24D8492B4
Show »

FASTA1,115123,587

References

« Hide 'large scale' references
[1]"High-throughput sequence identification of gene coding variants within alcohol-related QTLs."
Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J., Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.
Mamm. Genome 12:657-663(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Strain: ILS and ISS.
[2]"Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
DNA Res. 10:35-48(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6.
Tissue: Brain.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"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).
Strain: C57BL/6.
Tissue: Brain.
[6]"An efficient DNA sequencing strategy based on bacteriophage Mu in vitro DNA transposition reaction."
Haapa S., Suomalainen S., Eerikaeinen S., Airaksinen M., Paulin L., Savilahti H.
Genome Res. 9:308-315(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-227 (ISOFORM 2).
[7]"A novel N-terminal isoform of the neuron-specific K-Cl cotransporter KCC2."
Uvarov P., Ludwig A., Markkanen M., Pruunsild P., Kaila K., Delpire E., Timmusk T., Rivera C., Airaksinen M.S.
J. Biol. Chem. 282:30570-30576(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72 (ISOFORM 1), TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[8]Lubec G., Kang S.U.
Submitted (APR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 532-538; 726-747; 813-819; 833-843; 952-961; 1042-1052; 1078-1085 AND 1091-1101, IDENTIFICATION BY MASS SPECTROMETRY.
Strain: C57BL/6.
Tissue: Brain.
[9]"Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition."
Huebner C.A., Stein V., Hermans-Borgmeyer I., Meyer T., Ballanyi K., Jentsch T.J.
Neuron 30:515-524(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"Identification of a novel di-leucine motif mediating K(+)/Cl(-) cotransporter KCC2 constitutive endocytosis."
Zhao B., Wong A.Y.C., Murshid A., Bowie D., Presley J.F., Bedford F.K.
Cell. Signal. 20:1769-1779(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AP2A1, MUTAGENESIS OF 680-LEU-LEU-681 AND 684-GLU-GLU-685.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_065066.2. NM_020333.2.
UniGeneMm.252987.

3D structure databases

ProteinModelPortalQ91V14.
SMRQ91V14. Positions 412-662.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ91V14. 4 interactions.
MINTMINT-4133713.

PTM databases

PhosphoSiteQ91V14.

Proteomic databases

PaxDbQ91V14.
PRIDEQ91V14.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000099092; ENSMUSP00000096690; ENSMUSG00000017740. [Q91V14-2]
GeneID57138.
KEGGmmu:57138.
UCSCuc008nwu.2. mouse. [Q91V14-2]

Organism-specific databases

CTD57468.
MGIMGI:1862037. Slc12a5.
RougeSearch...

Phylogenomic databases

eggNOGCOG0531.
GeneTreeENSGT00560000076892.
HOGENOMHOG000092644.
HOVERGENHBG052852.
InParanoidQ91V14.
KOK14427.
OMAPYVFSDM.
OrthoDBEOG78M01J.
PhylomeDBQ91V14.
TreeFamTF313657.

Gene expression databases

ArrayExpressQ91V14.
CleanExMM_SLC12A5.
GenevestigatorQ91V14.

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

NextBio313501.
PROQ91V14.
SOURCESearch...

Entry information

Entry nameS12A5_MOUSE
AccessionPrimary (citable) accession number: Q91V14
Secondary accession number(s): A2A5L0 expand/collapse secondary AC list , Q3UHQ2, Q7TQC9, Q80TI5, Q9Z0M7
Entry history
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: April 16, 2014
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot