Q9UHW9 (S12A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 12 member 6

Alternative name(s):
Electroneutral potassium-chloride cotransporter 3
K-Cl cotransporter 3

Gene names

Name:	SLC12A6
Synonyms:	KCC3

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	1150 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates electroneutral potassium-chloride cotransport. May be activated by cell swelling. May contribute to cell volume homeostasis in single cells.
Enzyme regulation	Activated by N-ethylmaleimide (NEM). Inhibited by DIOA, bumetanide and furosemide. Inhibited by WNK3. Ref.15
Subunit structure	Homomultimer and heteromultimer with other K-Cl cotransporters By similarity. Ref.12
Subcellular location	Basolateral cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Highly expressed in heart, brain and kidney. Detected at lower levels in skeletal muscle, placenta, lung and pancreas. Detected in umbilical vein endothelial cells. Isoform 2 is more abundant in kidney. Isoform 5 is testis specific. Expressed in the proximal tubule of the kidney (at protein level). Ref.5
Induction	Up-regulated by VEGF. Down-regulated by TNF. Ref.2 Ref.15
Post-translational modification	N-glycosylated. Ref.2 Ref.4
Involvement in disease	Defects in SLC12A6 are a cause of agenesis of the corpus callosum with peripheral neuropathy (ACCPN) [MIM:218000]. ACCPN is characterized by severe progressive sensorimotor neuropathy, mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. Ref.4
Sequence similarities	Belongs to the SLC12A transporter family.
Biophysicochemical properties	Kinetic parameters: KM=10.7 mM for extracellular Rb+ (isoform 1) Ref.5 KM=7.3 mM for extracellular Cl- (isoform 1) KM=17.2 mM for extracellular Rb+ (isoform 2) KM=8.2 mM for extracellular Cl- (isoform 2)

Ontologies

Keywords
Biological process	Ion transport Potassium transport Symport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	angiogenesis Non-traceable author statement Ref.2. Source: UniProtKB cellular hypotonic salinity response Inferred from direct assay Ref.5. Source: UniProtKB potassium ion transport Inferred from electronic annotation. Source: UniProtKB-KW sodium ion transport Inferred from electronic annotation. Source: InterPro
Cellular component	basolateral plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Non-traceable author statement Ref.2. Source: UniProtKB
Molecular function	potassium:chloride symporter activity Inferred from direct assay Ref.2Ref.5. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UHW9-1)

Also known as: KCC3a;

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: Q9UHW9-2)

Also known as: KCC3b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
     52-90: PETSRSEPMS...RTSHPQDVIE → MPHFTVTKVE...KARIQDSDEP

Note: Produced by alternative promoter usage.

Isoform 3 (identifier: Q9UHW9-3)

Also known as: KCC3a-X2M;

The sequence of this isoform differs from the canonical sequence as follows:
     91-105: Missing.

Note: Does not differ in the osmotic set point of swelling activation but, activation is more rapid.

Isoform 4 (identifier: Q9UHW9-4)

Also known as: KCC3a-S3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: Missing.

Isoform 5 (identifier: Q9UHW9-5)

Also known as: KCC3a-S; KCC3a-S1; KCC3a-S2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.

Note: Does not differ in the osmotic set point of swelling activation but, activation is more rapid.

Isoform 6 (identifier: Q9UHW9-6)

Also known as: KCC3b-X2M;

The sequence of this isoform differs from the canonical sequence as follows:
     1-51: Missing.
     52-90: PETSRSEPMS...RTSHPQDVIE → MPHFTVTKVE...KARIQDSDEP
     91-105: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1150	1150	Solute carrier family 12 member 6		PRO_0000178037
Regions
	Topological domain	1 – 185	185	Cytoplasmic Potential
	Transmembrane	186 – 208	23	Helical; Potential
	Topological domain	209 – 223	15	Extracellular Potential
	Transmembrane	224 – 245	22	Helical; Potential
	Topological domain	246 – 271	26	Cytoplasmic Potential
	Transmembrane	272 – 295	24	Helical; Potential
	Topological domain	296 – 318	23	Extracellular Potential
	Transmembrane	319 – 343	25	Helical; Potential
	Topological domain	344 – 346	3	Cytoplasmic Potential
	Transmembrane	347 – 371	25	Helical; Potential
	Topological domain	372 – 479	108	Extracellular Potential
	Transmembrane	480 – 501	22	Helical; Potential
	Topological domain	502 – 515	14	Cytoplasmic Potential
	Transmembrane	516 – 543	28	Helical; Potential
	Topological domain	544 – 557	14	Extracellular Potential
	Transmembrane	558 – 581	24	Helical; Potential
	Topological domain	582 – 620	39	Cytoplasmic Potential
	Transmembrane	621 – 644	24	Helical; Potential
	Topological domain	645 – 647	3	Extracellular Potential
	Transmembrane	648 – 670	23	Helical; Potential
	Topological domain	671 – 676	6	Cytoplasmic Potential
	Transmembrane	677 – 695	19	Helical; Potential
	Topological domain	696	1	Extracellular Potential
	Transmembrane	697 – 719	23	Helical; Potential
	Topological domain	720 – 1150	431	Cytoplasmic Potential
	Compositional bias	227 – 230	4	Poly-Cys
Amino acid modifications
	Modified residue	32	1	Phosphoserine Ref.14
	Modified residue	1007	1	Phosphoserine By similarity
	Modified residue	1029	1	Phosphoserine Ref.13
	Modified residue	1032	1	Phosphoserine Ref.13
	Glycosylation	379	1	N-linked (GlcNAc...) Potential
	Glycosylation	398	1	N-linked (GlcNAc...) Potential
	Glycosylation	411	1	N-linked (GlcNAc...) Potential
	Glycosylation	428	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 59	59	Missing in isoform 5.		VSP_041387
	Alternative sequence	1 – 51	51	Missing in isoform 2 and isoform 6.		VSP_006115
	Alternative sequence	1 – 9	9	Missing in isoform 4.		VSP_041388
	Alternative sequence	52 – 90	39	PETSR…QDVIE → MPHFTVTKVEDPEEGAAASI SQEPSLADIKARIQDSDEP in isoform 2 and isoform 6.		VSP_006116
	Alternative sequence	91 – 105	15	Missing in isoform 3 and isoform 6.		VSP_041389
	Natural variant	415	1	F → S. Corresponds to variant rs2705339 [ dbSNP | Ensembl ].		VAR_014960
Experimental info
	Sequence conflict	802	1	E → H in AAF24986. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (KCC3a) [UniParc]. Last modified December 13, 2002. Version 2. Checksum: F8BDD39181294EDD	FASTA	1,150	127,617
	10 20 30 40 50 60 MHPPETTTKM ASVRFMVTPT KIDDIPGLSD TSPDLSSRSS SRVRFSSRES VPETSRSEPM 70 80 90 100 110 120 SEMSGATTSL ATVALDPPSD RTSHPQDVIE DLSQNSITGE HSQLLDDGHK KARNAYLNNS 130 140 150 160 170 180 NYEEGDEYFD KNLALFEEEM DTRPKVSSLL NRMANYTNLT QGAKEHEEAE NITEGKKKPT 190 200 210 220 230 240 KTPQMGTFMG VYLPCLQNIF GVILFLRLTW VVGTAGVLQA FAIVLICCCC TMLTAISMSA 250 260 270 280 290 300 IATNGVVPAG GSYFMISRAL GPEFGGAVGL CFYLGTTFAA AMYILGAIEI FLVYIVPRAA 310 320 330 340 350 360 IFHSDDALKE SAAMLNNMRV YGTAFLVLMV LVVFIGVRYV NKFASLFLAC VIVSILAIYA 370 380 390 400 410 420 GAIKSSFAPP HFPVCMLGNR TLSSRHIDVC SKTKEINNMT VPSKLWGFFC NSSQFFNATC 430 440 450 460 470 480 DEYFVHNNVT SIQGIPGLAS GIITENLWSN YLPKGEIIEK PSAKSSDVLG SLNHEYVLVD 490 500 510 520 530 540 ITTSFTLLVG IFFPSVTGIM AGSNRSGDLK DAQKSIPIGT ILAILTTSFV YLSNVVLFGA 550 560 570 580 590 600 CIEGVVLRDK FGDAVKGNLV VGTLSWPSPW VIVIGSFFST CGAGLQSLTG APRLLQAIAK 610 620 630 640 650 660 DNIIPFLRVF GHSKANGEPT WALLLTAAIA ELGILIASLD LVAPILSMFF LMCYLFVNLA 670 680 690 700 710 720 CALQTLLRTP NWRPRFRYYH WALSFMGMSI CLALMFISSW YYAIVAMVIA GMIYKYIEYQ 730 740 750 760 770 780 GAEKEWGDGI RGLSLSAARF ALLRLEEGPP HTKNWRPQLL VLLKLDEDLH VKHPRLLTFA 790 800 810 820 830 840 SQLKAGKGLT IVGSVIVGNF LENYGEALAA EQTIKHLMEA EKVKGFCQLV VAAKLREGIS 850 860 870 880 890 900 HLIQSCGLGG MKHNTVVMGW PNGWRQSEDA RAWKTFIGTV RVTTAAHLAL LVAKNISFFP 910 920 930 940 950 960 SNVEQFSEGN IDVWWIVHDG GMLMLLPFLL KQHKVWRKCS IRIFTVAQLE DNSIQMKKDL 970 980 990 1000 1010 1020 ATFLYHLRIE AEVEVVEMHD SDISAYTYER TLMMEQRSQM LRHMRLSKTE RDREAQLVKD 1030 1040 1050 1060 1070 1080 RNSMLRLTSI GSDEDEETET YQEKVHMTWT KDKYMASRGQ KAKSMEGFQD LLNMRPDQSN 1090 1100 1110 1120 1130 1140 VRRMHTAVKL NEVIVNKSHE AKLVLLNMPG PPRNPEGDEN YMEFLEVLTE GLERVLLVRG 1150 GGSEVITIYS
	Isoform 2 (KCC3b) [UniParc]. Checksum: 1C9D8FE2A060E0DC	FASTA	1,099	122,091
	10 20 30 40 50 60 MPHFTVTKVE DPEEGAAASI SQEPSLADIK ARIQDSDEPD LSQNSITGEH SQLLDDGHKK 70 80 90 100 110 120 ARNAYLNNSN YEEGDEYFDK NLALFEEEMD TRPKVSSLLN RMANYTNLTQ GAKEHEEAEN 130 140 150 160 170 180 ITEGKKKPTK TPQMGTFMGV YLPCLQNIFG VILFLRLTWV VGTAGVLQAF AIVLICCCCT 190 200 210 220 230 240 MLTAISMSAI ATNGVVPAGG SYFMISRALG PEFGGAVGLC FYLGTTFAAA MYILGAIEIF 250 260 270 280 290 300 LVYIVPRAAI FHSDDALKES AAMLNNMRVY GTAFLVLMVL VVFIGVRYVN KFASLFLACV 310 320 330 340 350 360 IVSILAIYAG AIKSSFAPPH FPVCMLGNRT LSSRHIDVCS KTKEINNMTV PSKLWGFFCN 370 380 390 400 410 420 SSQFFNATCD EYFVHNNVTS IQGIPGLASG IITENLWSNY LPKGEIIEKP SAKSSDVLGS 430 440 450 460 470 480 LNHEYVLVDI TTSFTLLVGI FFPSVTGIMA GSNRSGDLKD AQKSIPIGTI LAILTTSFVY 490 500 510 520 530 540 LSNVVLFGAC IEGVVLRDKF GDAVKGNLVV GTLSWPSPWV IVIGSFFSTC GAGLQSLTGA 550 560 570 580 590 600 PRLLQAIAKD NIIPFLRVFG HSKANGEPTW ALLLTAAIAE LGILIASLDL VAPILSMFFL 610 620 630 640 650 660 MCYLFVNLAC ALQTLLRTPN WRPRFRYYHW ALSFMGMSIC LALMFISSWY YAIVAMVIAG 670 680 690 700 710 720 MIYKYIEYQG AEKEWGDGIR GLSLSAARFA LLRLEEGPPH TKNWRPQLLV LLKLDEDLHV 730 740 750 760 770 780 KHPRLLTFAS QLKAGKGLTI VGSVIVGNFL ENYGEALAAE QTIKHLMEAE KVKGFCQLVV 790 800 810 820 830 840 AAKLREGISH LIQSCGLGGM KHNTVVMGWP NGWRQSEDAR AWKTFIGTVR VTTAAHLALL 850 860 870 880 890 900 VAKNISFFPS NVEQFSEGNI DVWWIVHDGG MLMLLPFLLK QHKVWRKCSI RIFTVAQLED 910 920 930 940 950 960 NSIQMKKDLA TFLYHLRIEA EVEVVEMHDS DISAYTYERT LMMEQRSQML RHMRLSKTER 970 980 990 1000 1010 1020 DREAQLVKDR NSMLRLTSIG SDEDEETETY QEKVHMTWTK DKYMASRGQK AKSMEGFQDL 1030 1040 1050 1060 1070 1080 LNMRPDQSNV RRMHTAVKLN EVIVNKSHEA KLVLLNMPGP PRNPEGDENY MEFLEVLTEG 1090 LERVLLVRGG GSEVITIYS
	Isoform 3 (KCC3a-X2M) [UniParc]. Checksum: ED4C3E7101CB0378	FASTA	1,135	125,993
	10 20 30 40 50 60 MHPPETTTKM ASVRFMVTPT KIDDIPGLSD TSPDLSSRSS SRVRFSSRES VPETSRSEPM 70 80 90 100 110 120 SEMSGATTSL ATVALDPPSD RTSHPQDVIE DDGHKKARNA YLNNSNYEEG DEYFDKNLAL 130 140 150 160 170 180 FEEEMDTRPK VSSLLNRMAN YTNLTQGAKE HEEAENITEG KKKPTKTPQM GTFMGVYLPC 190 200 210 220 230 240 LQNIFGVILF LRLTWVVGTA GVLQAFAIVL ICCCCTMLTA ISMSAIATNG VVPAGGSYFM 250 260 270 280 290 300 ISRALGPEFG GAVGLCFYLG TTFAAAMYIL GAIEIFLVYI VPRAAIFHSD DALKESAAML 310 320 330 340 350 360 NNMRVYGTAF LVLMVLVVFI GVRYVNKFAS LFLACVIVSI LAIYAGAIKS SFAPPHFPVC 370 380 390 400 410 420 MLGNRTLSSR HIDVCSKTKE INNMTVPSKL WGFFCNSSQF FNATCDEYFV HNNVTSIQGI 430 440 450 460 470 480 PGLASGIITE NLWSNYLPKG EIIEKPSAKS SDVLGSLNHE YVLVDITTSF TLLVGIFFPS 490 500 510 520 530 540 VTGIMAGSNR SGDLKDAQKS IPIGTILAIL TTSFVYLSNV VLFGACIEGV VLRDKFGDAV 550 560 570 580 590 600 KGNLVVGTLS WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP FLRVFGHSKA 610 620 630 640 650 660 NGEPTWALLL TAAIAELGIL IASLDLVAPI LSMFFLMCYL FVNLACALQT LLRTPNWRPR 670 680 690 700 710 720 FRYYHWALSF MGMSICLALM FISSWYYAIV AMVIAGMIYK YIEYQGAEKE WGDGIRGLSL 730 740 750 760 770 780 SAARFALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKHPR LLTFASQLKA GKGLTIVGSV 790 800 810 820 830 840 IVGNFLENYG EALAAEQTIK HLMEAEKVKG FCQLVVAAKL REGISHLIQS CGLGGMKHNT 850 860 870 880 890 900 VVMGWPNGWR QSEDARAWKT FIGTVRVTTA AHLALLVAKN ISFFPSNVEQ FSEGNIDVWW 910 920 930 940 950 960 IVHDGGMLML LPFLLKQHKV WRKCSIRIFT VAQLEDNSIQ MKKDLATFLY HLRIEAEVEV 970 980 990 1000 1010 1020 VEMHDSDISA YTYERTLMME QRSQMLRHMR LSKTERDREA QLVKDRNSML RLTSIGSDED 1030 1040 1050 1060 1070 1080 EETETYQEKV HMTWTKDKYM ASRGQKAKSM EGFQDLLNMR PDQSNVRRMH TAVKLNEVIV 1090 1100 1110 1120 1130 NKSHEAKLVL LNMPGPPRNP EGDENYMEFL EVLTEGLERV LLVRGGGSEV ITIYS
	Isoform 4 (KCC3a-S3) [UniParc]. Checksum: 1B71C660733649AF	FASTA	1,141	126,594
	10 20 30 40 50 60 MASVRFMVTP TKIDDIPGLS DTSPDLSSRS SSRVRFSSRE SVPETSRSEP MSEMSGATTS 70 80 90 100 110 120 LATVALDPPS DRTSHPQDVI EDLSQNSITG EHSQLLDDGH KKARNAYLNN SNYEEGDEYF 130 140 150 160 170 180 DKNLALFEEE MDTRPKVSSL LNRMANYTNL TQGAKEHEEA ENITEGKKKP TKTPQMGTFM 190 200 210 220 230 240 GVYLPCLQNI FGVILFLRLT WVVGTAGVLQ AFAIVLICCC CTMLTAISMS AIATNGVVPA 250 260 270 280 290 300 GGSYFMISRA LGPEFGGAVG LCFYLGTTFA AAMYILGAIE IFLVYIVPRA AIFHSDDALK 310 320 330 340 350 360 ESAAMLNNMR VYGTAFLVLM VLVVFIGVRY VNKFASLFLA CVIVSILAIY AGAIKSSFAP 370 380 390 400 410 420 PHFPVCMLGN RTLSSRHIDV CSKTKEINNM TVPSKLWGFF CNSSQFFNAT CDEYFVHNNV 430 440 450 460 470 480 TSIQGIPGLA SGIITENLWS NYLPKGEIIE KPSAKSSDVL GSLNHEYVLV DITTSFTLLV 490 500 510 520 530 540 GIFFPSVTGI MAGSNRSGDL KDAQKSIPIG TILAILTTSF VYLSNVVLFG ACIEGVVLRD 550 560 570 580 590 600 KFGDAVKGNL VVGTLSWPSP WVIVIGSFFS TCGAGLQSLT GAPRLLQAIA KDNIIPFLRV 610 620 630 640 650 660 FGHSKANGEP TWALLLTAAI AELGILIASL DLVAPILSMF FLMCYLFVNL ACALQTLLRT 670 680 690 700 710 720 PNWRPRFRYY HWALSFMGMS ICLALMFISS WYYAIVAMVI AGMIYKYIEY QGAEKEWGDG 730 740 750 760 770 780 IRGLSLSAAR FALLRLEEGP PHTKNWRPQL LVLLKLDEDL HVKHPRLLTF ASQLKAGKGL 790 800 810 820 830 840 TIVGSVIVGN FLENYGEALA AEQTIKHLME AEKVKGFCQL VVAAKLREGI SHLIQSCGLG 850 860 870 880 890 900 GMKHNTVVMG WPNGWRQSED ARAWKTFIGT VRVTTAAHLA LLVAKNISFF PSNVEQFSEG 910 920 930 940 950 960 NIDVWWIVHD GGMLMLLPFL LKQHKVWRKC SIRIFTVAQL EDNSIQMKKD LATFLYHLRI 970 980 990 1000 1010 1020 EAEVEVVEMH DSDISAYTYE RTLMMEQRSQ MLRHMRLSKT ERDREAQLVK DRNSMLRLTS 1030 1040 1050 1060 1070 1080 IGSDEDEETE TYQEKVHMTW TKDKYMASRG QKAKSMEGFQ DLLNMRPDQS NVRRMHTAVK 1090 1100 1110 1120 1130 1140 LNEVIVNKSH EAKLVLLNMP GPPRNPEGDE NYMEFLEVLT EGLERVLLVR GGGSEVITIY S
	Isoform 5 (KCC3a-S) (KCC3a-S1) (KCC3a-S2) [UniParc]. Checksum: CFF92252688CAC1A	FASTA	1,091	121,125
	10 20 30 40 50 60 MSEMSGATTS LATVALDPPS DRTSHPQDVI EDLSQNSITG EHSQLLDDGH KKARNAYLNN 70 80 90 100 110 120 SNYEEGDEYF DKNLALFEEE MDTRPKVSSL LNRMANYTNL TQGAKEHEEA ENITEGKKKP 130 140 150 160 170 180 TKTPQMGTFM GVYLPCLQNI FGVILFLRLT WVVGTAGVLQ AFAIVLICCC CTMLTAISMS 190 200 210 220 230 240 AIATNGVVPA GGSYFMISRA LGPEFGGAVG LCFYLGTTFA AAMYILGAIE IFLVYIVPRA 250 260 270 280 290 300 AIFHSDDALK ESAAMLNNMR VYGTAFLVLM VLVVFIGVRY VNKFASLFLA CVIVSILAIY 310 320 330 340 350 360 AGAIKSSFAP PHFPVCMLGN RTLSSRHIDV CSKTKEINNM TVPSKLWGFF CNSSQFFNAT 370 380 390 400 410 420 CDEYFVHNNV TSIQGIPGLA SGIITENLWS NYLPKGEIIE KPSAKSSDVL GSLNHEYVLV 430 440 450 460 470 480 DITTSFTLLV GIFFPSVTGI MAGSNRSGDL KDAQKSIPIG TILAILTTSF VYLSNVVLFG 490 500 510 520 530 540 ACIEGVVLRD KFGDAVKGNL VVGTLSWPSP WVIVIGSFFS TCGAGLQSLT GAPRLLQAIA 550 560 570 580 590 600 KDNIIPFLRV FGHSKANGEP TWALLLTAAI AELGILIASL DLVAPILSMF FLMCYLFVNL 610 620 630 640 650 660 ACALQTLLRT PNWRPRFRYY HWALSFMGMS ICLALMFISS WYYAIVAMVI AGMIYKYIEY 670 680 690 700 710 720 QGAEKEWGDG IRGLSLSAAR FALLRLEEGP PHTKNWRPQL LVLLKLDEDL HVKHPRLLTF 730 740 750 760 770 780 ASQLKAGKGL TIVGSVIVGN FLENYGEALA AEQTIKHLME AEKVKGFCQL VVAAKLREGI 790 800 810 820 830 840 SHLIQSCGLG GMKHNTVVMG WPNGWRQSED ARAWKTFIGT VRVTTAAHLA LLVAKNISFF 850 860 870 880 890 900 PSNVEQFSEG NIDVWWIVHD GGMLMLLPFL LKQHKVWRKC SIRIFTVAQL EDNSIQMKKD 910 920 930 940 950 960 LATFLYHLRI EAEVEVVEMH DSDISAYTYE RTLMMEQRSQ MLRHMRLSKT ERDREAQLVK 970 980 990 1000 1010 1020 DRNSMLRLTS IGSDEDEETE TYQEKVHMTW TKDKYMASRG QKAKSMEGFQ DLLNMRPDQS 1030 1040 1050 1060 1070 1080 NVRRMHTAVK LNEVIVNKSH EAKLVLLNMP GPPRNPEGDE NYMEFLEVLT EGLERVLLVR 1090 GGGSEVITIY S
	Isoform 6 (KCC3b-X2M) [UniParc]. Checksum: 1A8328CEC2EC3E54	FASTA	1,084	120,467
	10 20 30 40 50 60 MPHFTVTKVE DPEEGAAASI SQEPSLADIK ARIQDSDEPD DGHKKARNAY LNNSNYEEGD 70 80 90 100 110 120 EYFDKNLALF EEEMDTRPKV SSLLNRMANY TNLTQGAKEH EEAENITEGK KKPTKTPQMG 130 140 150 160 170 180 TFMGVYLPCL QNIFGVILFL RLTWVVGTAG VLQAFAIVLI CCCCTMLTAI SMSAIATNGV 190 200 210 220 230 240 VPAGGSYFMI SRALGPEFGG AVGLCFYLGT TFAAAMYILG AIEIFLVYIV PRAAIFHSDD 250 260 270 280 290 300 ALKESAAMLN NMRVYGTAFL VLMVLVVFIG VRYVNKFASL FLACVIVSIL AIYAGAIKSS 310 320 330 340 350 360 FAPPHFPVCM LGNRTLSSRH IDVCSKTKEI NNMTVPSKLW GFFCNSSQFF NATCDEYFVH 370 380 390 400 410 420 NNVTSIQGIP GLASGIITEN LWSNYLPKGE IIEKPSAKSS DVLGSLNHEY VLVDITTSFT 430 440 450 460 470 480 LLVGIFFPSV TGIMAGSNRS GDLKDAQKSI PIGTILAILT TSFVYLSNVV LFGACIEGVV 490 500 510 520 530 540 LRDKFGDAVK GNLVVGTLSW PSPWVIVIGS FFSTCGAGLQ SLTGAPRLLQ AIAKDNIIPF 550 560 570 580 590 600 LRVFGHSKAN GEPTWALLLT AAIAELGILI ASLDLVAPIL SMFFLMCYLF VNLACALQTL 610 620 630 640 650 660 LRTPNWRPRF RYYHWALSFM GMSICLALMF ISSWYYAIVA MVIAGMIYKY IEYQGAEKEW 670 680 690 700 710 720 GDGIRGLSLS AARFALLRLE EGPPHTKNWR PQLLVLLKLD EDLHVKHPRL LTFASQLKAG 730 740 750 760 770 780 KGLTIVGSVI VGNFLENYGE ALAAEQTIKH LMEAEKVKGF CQLVVAAKLR EGISHLIQSC 790 800 810 820 830 840 GLGGMKHNTV VMGWPNGWRQ SEDARAWKTF IGTVRVTTAA HLALLVAKNI SFFPSNVEQF 850 860 870 880 890 900 SEGNIDVWWI VHDGGMLMLL PFLLKQHKVW RKCSIRIFTV AQLEDNSIQM KKDLATFLYH 910 920 930 940 950 960 LRIEAEVEVV EMHDSDISAY TYERTLMMEQ RSQMLRHMRL SKTERDREAQ LVKDRNSMLR 970 980 990 1000 1010 1020 LTSIGSDEDE ETETYQEKVH MTWTKDKYMA SRGQKAKSME GFQDLLNMRP DQSNVRRMHT 1030 1040 1050 1060 1070 1080 AVKLNEVIVN KSHEAKLVLL NMPGPPRNPE GDENYMEFLE VLTEGLERVL LVRGGGSEVI TIYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter." Race J.E., Makhlouf F.N., Logue P.J., Wilson F.H., Dunham P.B., Holtzman E.J. Am. J. Physiol. 277:C1210-C1219(1999) [PubMed: 10600773] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TOPOLOGY. Tissue: Placenta.
[2]	"Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter." Hiki K., D'Andrea R.J., Furze J., Crawford J., Woollatt E., Sutherland G.R., Vadas M.A., Gamble J.R. J. Biol. Chem. 274:10661-10667(1999) [PubMed: 10187864] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), GLYCOSYLATION, REGULATION BY VEGF AND TNF. Tissue: Umbilical vein.
[3]	"Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family." Mount D.B., Mercado A., Song L., Xu J., George A.L. Jr., Delpire E., Gamba G. J. Biol. Chem. 274:16355-16362(1999) [PubMed: 10347194] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum." Howard H.C., Mount D.B., Rochefort D., Byun N., Dupre N., Lu J., Fan X., Song L., Riviere J.-B., Prevost C., Horst J., Simonati A., Lemcke B., Welch R., England R., Zhan F.Q., Mercado A., Siesser W.B. , George A.L. Jr., McDonald M.P., Bouchard J.-P., Mathieu J., Delpire E., Rouleau G.A. Nat. Genet. 32:384-392(2002) [PubMed: 12368912] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), GLYCOSYLATION, DISEASE.
[5]	"NH2-terminal heterogeneity in the KCC3 K+-Cl- cotransporter." Mercado A., Vazquez N., Song L., Cortes R., Enck A.H., Welch R., Delpire E., Gamba G., Mount D.B. Am. J. Physiol. 289:F1246-1261(2005) [PubMed: 16048901] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4; 5), ALTERNATIVE SPLICING (ISOFORM 6), ALTERNATIVE PROMOTER USAGE, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Uterus.
[7]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"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). Tissue: Brain.
[10]	Guo J.H., Yu L. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 70-1150 (ISOFORM 1). Tissue: Testis.
[11]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 137-1150 (ISOFORM 1). Tissue: Testis.
[12]	"A dominant negative mutant of the KCC1 K-Cl cotransporter: both N- and C-terminal cytoplasmic domains are required for K-Cl cotransport activity." Casula S., Shmukler B.E., Wilhelm S., Stuart-Tilley A.K., Su W., Chernova M.N., Brugnara C., Alper S.L. J. Biol. Chem. 276:41870-41878(2001) [PubMed: 11551954] [Abstract] Cited for: SUBUNIT.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1029 AND SER-1032, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"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.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF116242 mRNA. Translation: AAF24986.1. AF108831 mRNA. Translation: AAD25337.1. AF105366 mRNA. Translation: AAD39742.1. AF314956 , AF314931, AF314933, AF314934, AF314935, AF314936, AF314937, AF314938, AF314939, AF314940, AF314941, AF314942, AF314943, AF314944, AF314945, AF314946, AF314947, AF314948, AF314949, AF314950, AF314951, AF314952, AF314953, AF314954, AF314955 Genomic DNA. Translation: AAM96215.1. AF314956 , AF314932, AF314933, AF314934, AF314935, AF314936, AF314937, AF314938, AF314939, AF314940, AF314941, AF314942, AF314943, AF314944, AF314945, AF314946, AF314947, AF314948, AF314949, AF314950, AF314951, AF314952, AF314953, AF314954, AF314955 Genomic DNA. Translation: AAM96216.1. AF531258 mRNA. Translation: AAQ10026.1. AF531259 mRNA. Translation: AAQ10027.1. AF531260 mRNA. Translation: AAQ10028.1. DQ138323 mRNA. Translation: ABA02873.1. AK315283 mRNA. Translation: BAG37692.1. AC021822 Genomic DNA. No translation available. AC079203 Genomic DNA. No translation available. CH471125 Genomic DNA. Translation: EAW92295.1. CH471125 Genomic DNA. Translation: EAW92297.1. CH471125 Genomic DNA. Translation: EAW92301.1. BC126241 mRNA. Translation: AAI26242.1. BC126243 mRNA. Translation: AAI26244.1. AF477977 mRNA. Translation: AAL85335.1. AL117500 mRNA. Translation: CAB55965.1.
IPI	IPI00220151. IPI00465299. IPI00783274. IPI00783541. IPI00797408. IPI01018802.
PIR	T17275.
RefSeq	NP_001035959.1. NM_001042494.1. NP_001035960.1. NM_001042495.1. NP_001035961.1. NM_001042496.1. NP_001035962.1. NM_001042497.1. NP_005126.1. NM_005135.2. NP_598408.1. NM_133647.1.
UniGene	Hs.510939.
3D structure databases
ProteinModelPortal	Q9UHW9.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UHW9. 1 interaction.
STRING	Q9UHW9.
Protein family/group databases
TCDB	2.A.30.5.3. cation-chloride cotransporter (CCC) family.
PTM databases
PhosphoSite	Q9UHW9.
Polymorphism databases
DMDM	27151690.
Proteomic databases
PRIDE	Q9UHW9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354181; ENSP00000346112; ENSG00000140199. ENST00000397702; ENSP00000380814; ENSG00000140199. ENST00000397707; ENSP00000380819; ENSG00000140199. ENST00000451844; ENSP00000390199; ENSG00000140199. ENST00000458406; ENSP00000387725; ENSG00000140199.
GeneID	9990.
KEGG	hsa:9990.
UCSC	uc001zhv.1. human. uc001zhw.1. human.
Organism-specific databases
CTD	9990.
GeneCards	GC15M034522.
HGNC	HGNC:10914. SLC12A6.
HPA	HPA034563.
MIM	218000. phenotype. 604878. gene.
neXtProt	NX_Q9UHW9.
Orphanet	1496. Corpus callosum agenesis - neuronopathy.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00560000076892.
HOGENOM	HBG590211.
HOVERGEN	HBG052852.
InParanoid	Q9UHW9.
PhylomeDB	Q9UHW9.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9UHW9.
Bgee	Q9UHW9.
CleanEx	HS_SLC12A6.
Genevestigator	Q9UHW9.
GermOnline	ENSG00000140199. Homo sapiens.
Family and domain databases
InterPro	IPR004841. AA-permease_dom. IPR018491. K/Cl_cotranspt_1/3. IPR000076. KCL_cotranspt. IPR004842. Na/K/Cl_cotransptS. [Graphical view]
KO	K14427.
Pfam	PF00324. AA_permease. 2 hits. PF03522. KCl_Cotrans_1. 1 hit. [Graphical view]
PRINTS	PR01081. KCLTRNSPORT.
TIGRFAMs	TIGR00930. 2a30. 1 hit.
ProtoNet	Search...
Other
DrugBank	DB00761. Potassium Chloride.
NextBio	37729.
SOURCE	Search...

Entry information

Entry name

S12A6_HUMAN

Accession

Primary (citable) accession number: Q9UHW9
Secondary accession number(s): A0AV76 , Q2VI00, Q7Z2E7, Q7Z4G5, Q8TDD4, Q9UFR2, Q9Y642, Q9Y665

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2002
Last sequence update:	December 13, 2002
Last modified:	January 25, 2012
This is version 114 of the entry and version 2 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.