Solute carrier family 12 member 5 - Homo sapiens (Human)

Preferred order of sections

Names and origin

Protein names

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 names

Name:	SLC12A5
Synonyms:	KCC2, KIAA1176

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1139 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Ion transport Potassium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	potassium ion transport Inferred from electronic annotation. Source: UniProtKB-KW sodium ion transport Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	potassium: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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Sequence conflict

2

1

L → P in AAG43493. Ref.1

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1139

1139

Solute carrier family 12 member 5

PRO_0000178034

Regions

Topological domain

1 – 133

133

Cytoplasmic Potential

Transmembrane

134 – 154

21

Helical; Potential

Transmembrane

156 – 176

21

Helical; Potential

Topological domain

177 – 194

18

Cytoplasmic Potential

Transmembrane

195 – 215

21

Helical; Potential

Transmembrane

217 – 237

21

Helical; Potential

Topological domain

238 – 254

17

Cytoplasmic Potential

Transmembrane

255 – 275

21

Helical; Potential

Transmembrane

278 – 298

21

Helical; Potential

Topological domain

299 – 418

120

Cytoplasmic Potential

Transmembrane

419 – 439

21

Helical; Potential

Transmembrane

459 – 479

21

Helical; Potential

Topological domain

480 – 496

17

Cytoplasmic Potential

Transmembrane

497 – 517

21

Helical; Potential

Transmembrane

570 – 590

21

Helical; Potential

Topological domain

591 – 630

40

Cytoplasmic Potential

Transmembrane

631 – 651

21

Helical; Potential

Transmembrane

848 – 868

21

Helical; Potential

Topological domain

869 – 1139

271

Cytoplasmic Potential

Amino acid modifications

Glycosylation

442

1

N-linked (GlcNAc...) Potential

Glycosylation

833

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 40

40

MSRRF…GEDVK → MLNNLTDCEDGDGGANP in isoform 2.

VSP_029909

Natural variant

407

1

P → A.
Corresponds to variant rs16985442 [ dbSNP | Ensembl ].

VAR_027414

Natural variant

847

1

G → D in a colorectal cancer sample; somatic mutation. Ref.7

VAR_036557

Natural variant

1100

1

P → L. Ref.5
Corresponds to variant rs17297532 [ dbSNP | Ensembl ].

VAR_024994

Sequences

Sequence		Length	Mass (Da)
Isoform 1 (KCC2a) [UniParc]. Last modified December 4, 2007. Version 3. Checksum: 100C097AF1FD4B3E Show »	FASTA	1,139	126,184
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 »	FASTA	1,116	123,511
10 20 30 40 50 60 MLNNLTDCED GDGGANPGDG NPKESSPFIN STDTEKGKEY DGKNMALFEE EMDTSPMVSS 70 80 90 100 110 120 LLSGLANYTN LPQGSREHEE AENNEGGKKK PVQAPRMGTF MGVYLPCLQN IFGVILFLRL 130 140 150 160 170 180 TWVVGIAGIM ESFCMVFICC SCTMLTAISM SAIATNGVVP AGGSYYMISR SLGPEFGGAV 190 200 210 220 230 240 GLCFYLGTTF AGAMYILGTI EILLAYLFPA MAIFKAEDAS GEAAAMLNNM RVYGTCVLTC 250 260 270 280 290 300 MATVVFVGVK YVNKFALVFL GCVILSILAI YAGVIKSAFD PPNFPICLLG NRTLSRHGFD 310 320 330 340 350 360 VCAKLAWEGN ETVTTRLWGL FCSSRFLNAT CDEYFTRNNV TEIQGIPGAA SGLIKENLWS 370 380 390 400 410 420 SYLTKGVIVE RSGMTSVGLA DGTPIDMDHP YVFSDMTSYF TLLVGIYFPS VTGIMAGSNR 430 440 450 460 470 480 SGDLRDAQKS IPTGTILAIA TTSAVYISSV VLFGACIEGV VLRDKFGEAV NGNLVVGTLA 490 500 510 520 530 540 WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAISRDGIVP FLQVFGHGKA NGEPTWALLL 550 560 570 580 590 600 TACICEIGIL IASLDEVAPI LSMFFLMCYM FVNLACAVQT LLRTPNWRPR FRYYHWTLSF 610 620 630 640 650 660 LGMSLCLALM FICSWYYALV AMLIAGLIYK YIEYRGAEKE WGDGIRGLSL SAARYALLRL 670 680 690 700 710 720 EEGPPHTKNW RPQLLVLVRV DQDQNVVHPQ LLSLTSQLKA GKGLTIVGSV LEGTFLENHP 730 740 750 760 770 780 QAQRAEESIR RLMEAEKVKG FCQVVISSNL RDGVSHLIQS GGLGGLQHNT VLVGWPRNWR 790 800 810 820 830 840 QKEDHQTWRN FIELVRETTA GHLALLVTKN VSMFPGNPER FSEGSIDVWW IVHDGGMLML 850 860 870 880 890 900 LPFLLRHHKV WRKCKMRIFT VAQMDDNSIQ MKKDLTTFLY HLRITAEVEV VEMHESDISA 910 920 930 940 950 960 YTYEKTLVME QRSQILKQMH LTKNEREREI QSITDESRGS IRRKNPANTR LRLNVPEETA 970 980 990 1000 1010 1020 GDSEEKPEEE VQLIHDQSAP SCPSSSPSPG EEPEGEGETD PEKVHLTWTK DKSVAEKNKG 1030 1040 1050 1060 1070 1080 PSPVSSEGIK DFFSMKPEWE NLNQSNVRRM HTAVRLNEVI VKKSRDAKLV LLNMPGPPRN 1090 1100 1110 RNGDENYMEF LEVLTEHLDR VMLVRGGGRE VITIYS « Hide

References

	« Hide 'large scale' referencesShow '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: 12106695] [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. Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [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: 15489334] [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. Sugano S. Genome Res. 16:55-65(2006) [PubMed: 16344560] [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: 10574461] [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: 21613606] [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. Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [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.
IPI	IPI00301180. IPI00877110.
RefSeq	NP_001128243.1. NM_001134771.1. NP_065759.1. NM_020708.4.
UniGene	Hs.21413.
3D structure databases
ProteinModelPortal	Q9H2X9.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H2X9.
PTM databases
PhosphoSite	Q9H2X9.
Polymorphism databases
DMDM	161784306.
Proteomic databases
PRIDE	Q9H2X9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000454036; ENSP00000387694; ENSG00000124140.
GeneID	57468.
KEGG	hsa:57468.
UCSC	uc002xrb.1. human.
Organism-specific databases
CTD	57468.
GeneCards	GC20P044651.
HGNC	HGNC:13818. SLC12A5.
HPA	HPA004942.
MIM	606726. gene.
neXtProt	NX_Q9H2X9.
PharmGKB	PA37814.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05818.
GeneTree	ENSGT00560000076892.
HOGENOM	HBG590211.
HOVERGEN	HBG052852.
InParanoid	Q9H2X9.
OMA	TWRNFIE.
PhylomeDB	Q9H2X9.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9H2X9.
Bgee	Q9H2X9.
CleanEx	HS_SLC12A5.
Genevestigator	Q9H2X9.
GermOnline	ENSG00000124140. Homo sapiens.
Family and domain databases
InterPro	IPR004841. AA-permease_dom. IPR000076. KCL_cotranspt. IPR004842. Na/K/Cl_cotransptS. [Graphical view]
KO	K14427.
Pfam	PF00324. AA_permease. 2 hits. [Graphical view]
PRINTS	PR01081. KCLTRNSPORT.
TIGRFAMs	TIGR00930. 2a30. 1 hit.
ProtoNet	Search...
Other
DrugBank	DB00887. Bumetanide. DB00761. Potassium Chloride.
NextBio	63686.
SOURCE	Search...

Entry information

Entry name

S12A5_HUMAN

Accession

Primary (citable) accession number: Q9H2X9
Secondary accession number(s): A2RTX2

Q9ULP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2002
Last sequence update:	December 4, 2007
Last modified:	January 25, 2012
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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

Human chromosome 20

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents