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Q91V14

- S12A5_MOUSE

UniProt

Q91V14 - S12A5_MOUSE

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Protein

Solute carrier family 12 member 5

Gene

Slc12a5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein 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.By similarity

GO - Molecular functioni

  1. potassium:chloride symporter activity Source: MGI

GO - Biological processi

  1. chloride transmembrane transport Source: GOC
  2. chloride transport Source: MGI
  3. learning Source: MGI
  4. multicellular organism growth Source: MGI
  5. potassium ion transport Source: UniProtKB-KW
  6. response to drug Source: MGI
  7. synaptic transmission Source: MGI
  8. thermosensory behavior Source: MGI
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Symport, Transport

Keywords - Ligandi

Potassium

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:1862037. Slc12a5.

Subcellular locationi

Cell projectiondendrite 1 Publication. Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication
Note: Detected on dendrites, but not on axons of spinal cord neurons and at GPHN-positive inhibitory synapses.

GO - Cellular componenti

  1. dendritic shaft Source: MGI
  2. integral component of membrane Source: UniProtKB-KW
  3. neuronal cell body Source: MGI
  4. plasma membrane Source: MGI
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi680 – 6812LL → AA: Inhibits endocytosis. Abolishes interaction with AP2A1. 1 Publication
Mutagenesisi684 – 6852EE → AA: Decreases endocytosis. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11381138Solute carrier family 12 member 5PRO_0000178035Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ91V14.
PaxDbiQ91V14.
PRIDEiQ91V14.

PTM databases

PhosphoSiteiQ91V14.

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

CleanExiMM_SLC12A5.
ExpressionAtlasiQ91V14. baseline and differential.
GenevestigatoriQ91V14.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

IntActiQ91V14. 4 interactions.
MINTiMINT-4133713.

Structurei

3D structure databases

ProteinModelPortaliQ91V14.
SMRiQ91V14. Positions 412-662.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 133133CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini177 – 19418CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini238 – 25417CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini299 – 418120CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini480 – 49617CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini591 – 63040CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini869 – 1138270CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei134 – 15421HelicalSequence AnalysisAdd
BLAST
Transmembranei156 – 17621HelicalSequence AnalysisAdd
BLAST
Transmembranei195 – 21521HelicalSequence AnalysisAdd
BLAST
Transmembranei217 – 23721HelicalSequence AnalysisAdd
BLAST
Transmembranei255 – 27521HelicalSequence AnalysisAdd
BLAST
Transmembranei278 – 29821HelicalSequence AnalysisAdd
BLAST
Transmembranei419 – 43921HelicalSequence AnalysisAdd
BLAST
Transmembranei459 – 47921HelicalSequence AnalysisAdd
BLAST
Transmembranei497 – 51721HelicalSequence AnalysisAdd
BLAST
Transmembranei570 – 59021HelicalSequence AnalysisAdd
BLAST
Transmembranei631 – 65121HelicalSequence AnalysisAdd
BLAST
Transmembranei848 – 86821HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000092644.
HOVERGENiHBG052852.
InParanoidiQ91V14.
KOiK14427.
OMAiHLTWTKD.
OrthoDBiEOG78M01J.
PhylomeDBiQ91V14.
TreeFamiTF313657.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
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. Align

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti64 – 641Missing in AAH54808. (PubMed:15489334)Curated
Sequence conflicti859 – 8591G → D in BAE27805. (PubMed:16141072)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4040MSRRF…REDVK → MLNNLTDCEDGDGGANP in isoform 2. 4 PublicationsVSP_029910Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
UniGeneiMm.252987.

Genome annotation databases

EnsembliENSMUST00000099092; ENSMUSP00000096690; ENSMUSG00000017740. [Q91V14-2]
GeneIDi57138.
KEGGimmu:57138.
UCSCiuc008nwu.2. mouse. [Q91V14-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS38332.1. [Q91V14-2 ]
RefSeqi NP_065066.2. NM_020333.2. [Q91V14-2 ]
UniGenei Mm.252987.

3D structure databases

ProteinModelPortali Q91V14.
SMRi Q91V14. Positions 412-662.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q91V14. 4 interactions.
MINTi MINT-4133713.

PTM databases

PhosphoSitei Q91V14.

Proteomic databases

MaxQBi Q91V14.
PaxDbi Q91V14.
PRIDEi Q91V14.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000099092 ; ENSMUSP00000096690 ; ENSMUSG00000017740 . [Q91V14-2 ]
GeneIDi 57138.
KEGGi mmu:57138.
UCSCi uc008nwu.2. mouse. [Q91V14-2 ]

Organism-specific databases

CTDi 57468.
MGIi MGI:1862037. Slc12a5.
Rougei Search...

Phylogenomic databases

eggNOGi COG0531.
GeneTreei ENSGT00760000119053.
HOGENOMi HOG000092644.
HOVERGENi HBG052852.
InParanoidi Q91V14.
KOi K14427.
OMAi HLTWTKD.
OrthoDBi EOG78M01J.
PhylomeDBi Q91V14.
TreeFami TF313657.

Miscellaneous databases

NextBioi 313501.
PROi Q91V14.
SOURCEi Search...

Gene expression databases

CleanExi MM_SLC12A5.
ExpressionAtlasi Q91V14. baseline and differential.
Genevestigatori Q91V14.

Family and domain databases

InterProi IPR004841. AA-permease/SLC12A_dom.
IPR000076. KCL_cotranspt.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view ]
Pfami PF00324. AA_permease. 2 hits.
[Graphical view ]
PRINTSi PR01081. KCLTRNSPORT.
TIGRFAMsi TIGR00930. 2a30. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.

Entry informationi

Entry nameiS12A5_MOUSE
AccessioniPrimary (citable) accession number: Q91V14
Secondary accession number(s): A2A5L0
, Q3UHQ2, Q7TQC9, Q80TI5, Q9Z0M7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 13, 2002
Last sequence update: December 4, 2007
Last modified: October 29, 2014
This is version 115 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, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3