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Q9H2X9

- S12A5_HUMAN

UniProt

Q9H2X9 - S12A5_HUMAN

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Protein

Solute carrier family 12 member 5

Gene

SLC12A5

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. potassium:chloride symporter activity Source: UniProtKB
  2. protein kinase binding Source: BHF-UCL

GO - Biological processi

  1. cellular ion homeostasis Source: UniProtKB
  2. chloride transmembrane transport Source: GOC
  3. ion transport Source: Reactome
  4. learning Source: Ensembl
  5. multicellular organism growth Source: Ensembl
  6. potassium ion transport Source: UniProtKB-KW
  7. response to drug Source: Ensembl
  8. synaptic transmission Source: Ensembl
  9. thermosensory behavior Source: Ensembl
  10. transmembrane transport Source: Reactome
  11. 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: 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

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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37814.

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
Glycosylationi442 – 4421N-linked (GlcNAc...)Sequence Analysis
Glycosylationi833 – 8331N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

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.
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: 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]

Polymorphism databases

DMDMi161784306.

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.
CCDSi CCDS13391.1. [Q9H2X9-2 ]
CCDS46610.1. [Q9H2X9-1 ]
RefSeqi NP_001128243.1. NM_001134771.1. [Q9H2X9-1 ]
NP_065759.1. NM_020708.4. [Q9H2X9-2 ]
UniGenei Hs.21413.

3D structure databases

ProteinModelPortali Q9H2X9.
SMRi Q9H2X9. Positions 412-662.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 121538. 2 interactions.
STRINGi 9606.ENSP00000387694.

Chemistry

BindingDBi Q9H2X9.
ChEMBLi CHEMBL1615384.
DrugBanki DB00887. Bumetanide.
DB00761. Potassium Chloride.
GuidetoPHARMACOLOGYi 972.

Protein family/group databases

TCDBi 2.A.30.5.6. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSitei Q9H2X9.

Polymorphism databases

DMDMi 161784306.

Proteomic databases

MaxQBi Q9H2X9.
PaxDbi Q9H2X9.
PRIDEi Q9H2X9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000243964 ; ENSP00000243964 ; ENSG00000124140 . [Q9H2X9-2 ]
ENST00000454036 ; ENSP00000387694 ; ENSG00000124140 . [Q9H2X9-1 ]
GeneIDi 57468.
KEGGi hsa:57468.
UCSCi uc002xrb.2. human. [Q9H2X9-2 ]
uc010zxl.1. human. [Q9H2X9-1 ]

Organism-specific databases

CTDi 57468.
GeneCardsi GC20P044651.
HGNCi HGNC:13818. SLC12A5.
MIMi 606726. gene.
neXtProti NX_Q9H2X9.
PharmGKBi PA37814.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0531.
GeneTreei ENSGT00760000119053.
HOGENOMi HOG000092644.
HOVERGENi HBG052852.
InParanoidi Q9H2X9.
KOi K14427.
OMAi HLTWTKD.
OrthoDBi EOG78M01J.
PhylomeDBi Q9H2X9.
TreeFami TF313657.

Enzyme and pathway databases

Reactomei REACT_19315. Cation-coupled Chloride cotransporters.

Miscellaneous databases

GeneWikii Chloride_potassium_symporter_5.
GenomeRNAii 57468.
NextBioi 63686.
PROi Q9H2X9.
SOURCEi Search...

Gene expression databases

Bgeei Q9H2X9.
CleanExi HS_SLC12A5.
ExpressionAtlasi Q9H2X9. baseline and differential.
Genevestigatori Q9H2X9.

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. "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: November 26, 2014
This is version 119 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