Q9UP95 (S12A4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 12 member 4

Alternative name(s):
Electroneutral potassium-chloride cotransporter 1
Erythroid K-Cl cotransporter 1
Short name=hKCC1

Gene names

Name:	SLC12A4
Synonyms:	KCC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1085 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl- exit in NaCl absorbing epithelia By similarity. Isoform 4 has no transport activity.
Enzyme regulation	Inhibited by WNK3. Ref.12
Subunit structure	Homomultimer and heteromultimer with other K-Cl cotransporters. Ref.7
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Ubiquitous. Levels are much higher in erythrocytes from patients with Hb SC and Hb SS compared to normal AA erythrocytes. This may contribute to red blood cell dehydration and to the manifestation of sickle cell disease by increasing the intracellular concentration of HbS. Isoform 1 was not detected in circulating reticulocytes.
Post-translational modification	N-glycosylated.
Sequence similarities	Belongs to the SLC12A transporter family.
Sequence caution	The sequence AAC35282.1 differs from that shown. Reason: Frameshift at position 454. The sequence BAG57330.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell volume homeostasis Traceable author statement Ref.2. Source: ProtInc potassium ion transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	potassium:chloride symporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9UP95-1)

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: Q9UP95-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1056-1068: YMEFLEVLTEGLE → CIPLWRGRQLGGG
     1069-1085: Missing.

Isoform 3 (identifier: Q9UP95-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1012-1085: Missing.

Isoform 4 (identifier: Q9UP95-4)

The sequence of this isoform differs from the canonical sequence as follows:
     749-955: Missing.
     956-958: RHS → PCA
     963-987: ESLYSDEEDESAVGADKIQMTWTRD → PTWPCSCPRTSPSTPATTSATWRAT
     988-1085: Missing.

Isoform 5 (identifier: Q9UP95-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAELDDSD → MGDTLSP

Note: No experimental confirmation available.

Isoform 6 (identifier: Q9UP95-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-38: MPHFTVVPVDGPRRGDYDNLEGLSWVDYGERAELDDSD → MAAEGAVCGFVYLEGTAWAVPEDTEPLASCTL

Note: No experimental confirmation available.

Isoform 7 (identifier: Q9UP95-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-70: MPHFTVVPVD...YYDRNLALFE → MRAGGACRPG...GSAPSWMTRT

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1085	1085	Solute carrier family 12 member 4		PRO_0000178030
Regions
	Topological domain	1 – 118	118	Cytoplasmic Potential
	Transmembrane	119 – 139	21	Helical; Potential
	Transmembrane	149 – 169	21	Helical; Potential
	Topological domain	170 – 214	45	Cytoplasmic Potential
	Transmembrane	215 – 235	21	Helical; Potential
	Transmembrane	253 – 273	21	Helical; Potential
	Topological domain	274 – 275	2	Cytoplasmic Potential
	Transmembrane	276 – 296	21	Helical; Potential
	Transmembrane	356 – 376	21	Helical; Potential
	Topological domain	377 – 407	31	Cytoplasmic Potential
	Transmembrane	408 – 428	21	Helical; Potential
	Transmembrane	453 – 473	21	Helical; Potential
	Topological domain	474 – 493	20	Cytoplasmic Potential
	Transmembrane	494 – 514	21	Helical; Potential
	Transmembrane	567 – 587	21	Helical; Potential
	Topological domain	588 – 627	40	Cytoplasmic Potential
	Transmembrane	628 – 648	21	Helical; Potential
	Transmembrane	845 – 865	21	Helical; Potential
	Topological domain	866 – 1085	220	Cytoplasmic Potential
	Compositional bias	160 – 163	4	Poly-Cys
Amino acid modifications
	Modified residue	47	1	Phosphoserine By similarity
	Modified residue	51	1	Phosphoserine Ref.9
	Modified residue	967	1	Phosphoserine Ref.9 Ref.10 Ref.11 Ref.13
	Modified residue	983	1	Phosphothreonine By similarity
	Glycosylation	245	1	N-linked (GlcNAc...) Potential
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
	Glycosylation	331	1	N-linked (GlcNAc...) Potential
	Glycosylation	347	1	N-linked (GlcNAc...) Potential
	Glycosylation	439	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 70	70	MPHFT…LALFE → MRAGGACRPGAAGTAAGTAA GGWDGGCGGAEPARCLTSPW CQWTGRGAATMTTSRGSVGW TTGSAPSWMTRT in isoform 7.		VSP_046369
	Alternative sequence	1 – 38	38	MPHFT…LDDSD → MGDTLSP in isoform 5.		VSP_044596
	Alternative sequence	1 – 38	38	MPHFT…LDDSD → MAAEGAVCGFVYLEGTAWAV PEDTEPLASCTL in isoform 6.		VSP_046146
	Alternative sequence	749 – 955	207	Missing in isoform 4.		VSP_006108
	Alternative sequence	956 – 958	3	RHS → PCA in isoform 4.		VSP_006109
	Alternative sequence	963 – 987	25	ESLYS…TWTRD → PTWPCSCPRTSPSTPATTSA TWRAT in isoform 4.		VSP_006110
	Alternative sequence	988 – 1085	98	Missing in isoform 4.		VSP_006111
	Alternative sequence	1012 – 1085	74	Missing in isoform 3.		VSP_006112
	Alternative sequence	1056 – 1068	13	YMEFL…TEGLE → CIPLWRGRQLGGG in isoform 2.		VSP_006113
	Alternative sequence	1069 – 1085	17	Missing in isoform 2.		VSP_006114
Experimental info
	Sequence conflict	42	1	N → D in BAG61116. Ref.3
	Sequence conflict	211	1	F → L in BAG63994. Ref.3
	Sequence conflict	288	1	I → N in BAG63994. Ref.3
	Sequence conflict	370	1	G → R in BAG57330. Ref.3
	Sequence conflict	697	1	L → P in BAG63994. Ref.3
	Sequence conflict	1016	1	V → A in BAG57330. Ref.3
	Sequence conflict	1055	1	N → D in BAG57330. Ref.3
Isoform 6:
	Sequence conflict	4	1	E → G in BAH14786. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 13, 2002. Version 2. Checksum: 42B590EC3D94EA4D	FASTA	1,085	120,650
	10 20 30 40 50 60 MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAELDDSDGH GNHRESSPFL SPLEASRGID 70 80 90 100 110 120 YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGTRR RAAEAPSMGT 130 140 150 160 170 180 LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV 190 200 210 220 230 240 PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGA 250 260 270 280 290 300 HDTSNATLNN MRVYGTIFLT FMTLVVFVGV KYVNKFASLF LACVIISILS IYAGGIKSIF 310 320 330 340 350 360 DPPVFPVCML GNRTLSRDQF DICAKTAVVD NETVATQLWS FFCHSPNLTT DSCDPYFMLN 370 380 390 400 410 420 NVTEIPGIPG AAAGVLQENL WSAYLEKGDI VEKHGLPSAD APSLKESLPL YVVADIATSF 430 440 450 460 470 480 TVLVGIFFPS VTGIMAGSNR SGDLRDAQKS IPVGTILAII TTSLVYFSSV VLFGACIEGV 490 500 510 520 530 540 VLRDKYGDGV SRNLVVGTLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP 550 560 570 580 590 600 FLRVFGHGKV NGEPTWALLL TALIAELGIL IASLDMVAPI LSMFFLMCYL FVNLACAVQT 610 620 630 640 650 660 LLRTPNWRPR FKYYHWALSF LGMSLCLALM FVSSWYYALV AMLIAGMIYK YIEYQGAEKE 670 680 690 700 710 720 WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA 730 740 750 760 770 780 GKGLTIVGSV IQGSFLESYG EAQAAEQTIK NMMEIEKVKG FCQVVVASKV REGLAHLIQS 790 800 810 820 830 840 CGLGGMRHNS VVLGWPYGWR QSEDPRAWKT FIDTVRCTTA AHLALLVPKN IAFYPSNHER 850 860 870 880 890 900 YLEGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQMDDNSIQ MKKDLAVFLY 910 920 930 940 950 960 HLRLEAEVEV VEMHNSDISA YTYERTLMME QRSQMLRQMR LTKTEREREA QLVKDRHSAL 970 980 990 1000 1010 1020 RLESLYSDEE DESAVGADKI QMTWTRDKYM TETWDPSHAP DNFRELVHIK PDQSNVRRMH 1030 1040 1050 1060 1070 1080 TAVKLNEVIV TRSHDARLVL LNMPGPPRNS EGDENYMEFL EVLTEGLERV LLVRGGGREV ITIYS
	Isoform 2 [UniParc]. Checksum: 7A1FB4FD47252C88	FASTA	1,068	118,620
	10 20 30 40 50 60 MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAELDDSDGH GNHRESSPFL SPLEASRGID 70 80 90 100 110 120 YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGTRR RAAEAPSMGT 130 140 150 160 170 180 LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV 190 200 210 220 230 240 PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGA 250 260 270 280 290 300 HDTSNATLNN MRVYGTIFLT FMTLVVFVGV KYVNKFASLF LACVIISILS IYAGGIKSIF 310 320 330 340 350 360 DPPVFPVCML GNRTLSRDQF DICAKTAVVD NETVATQLWS FFCHSPNLTT DSCDPYFMLN 370 380 390 400 410 420 NVTEIPGIPG AAAGVLQENL WSAYLEKGDI VEKHGLPSAD APSLKESLPL YVVADIATSF 430 440 450 460 470 480 TVLVGIFFPS VTGIMAGSNR SGDLRDAQKS IPVGTILAII TTSLVYFSSV VLFGACIEGV 490 500 510 520 530 540 VLRDKYGDGV SRNLVVGTLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP 550 560 570 580 590 600 FLRVFGHGKV NGEPTWALLL TALIAELGIL IASLDMVAPI LSMFFLMCYL FVNLACAVQT 610 620 630 640 650 660 LLRTPNWRPR FKYYHWALSF LGMSLCLALM FVSSWYYALV AMLIAGMIYK YIEYQGAEKE 670 680 690 700 710 720 WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA 730 740 750 760 770 780 GKGLTIVGSV IQGSFLESYG EAQAAEQTIK NMMEIEKVKG FCQVVVASKV REGLAHLIQS 790 800 810 820 830 840 CGLGGMRHNS VVLGWPYGWR QSEDPRAWKT FIDTVRCTTA AHLALLVPKN IAFYPSNHER 850 860 870 880 890 900 YLEGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQMDDNSIQ MKKDLAVFLY 910 920 930 940 950 960 HLRLEAEVEV VEMHNSDISA YTYERTLMME QRSQMLRQMR LTKTEREREA QLVKDRHSAL 970 980 990 1000 1010 1020 RLESLYSDEE DESAVGADKI QMTWTRDKYM TETWDPSHAP DNFRELVHIK PDQSNVRRMH 1030 1040 1050 1060 TAVKLNEVIV TRSHDARLVL LNMPGPPRNS EGDENCIPLW RGRQLGGG
	Isoform 3 [UniParc]. Checksum: 33860CBEC1BE578B	FASTA	1,011	112,275
	10 20 30 40 50 60 MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAELDDSDGH GNHRESSPFL SPLEASRGID 70 80 90 100 110 120 YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGTRR RAAEAPSMGT 130 140 150 160 170 180 LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV 190 200 210 220 230 240 PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGA 250 260 270 280 290 300 HDTSNATLNN MRVYGTIFLT FMTLVVFVGV KYVNKFASLF LACVIISILS IYAGGIKSIF 310 320 330 340 350 360 DPPVFPVCML GNRTLSRDQF DICAKTAVVD NETVATQLWS FFCHSPNLTT DSCDPYFMLN 370 380 390 400 410 420 NVTEIPGIPG AAAGVLQENL WSAYLEKGDI VEKHGLPSAD APSLKESLPL YVVADIATSF 430 440 450 460 470 480 TVLVGIFFPS VTGIMAGSNR SGDLRDAQKS IPVGTILAII TTSLVYFSSV VLFGACIEGV 490 500 510 520 530 540 VLRDKYGDGV SRNLVVGTLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP 550 560 570 580 590 600 FLRVFGHGKV NGEPTWALLL TALIAELGIL IASLDMVAPI LSMFFLMCYL FVNLACAVQT 610 620 630 640 650 660 LLRTPNWRPR FKYYHWALSF LGMSLCLALM FVSSWYYALV AMLIAGMIYK YIEYQGAEKE 670 680 690 700 710 720 WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA 730 740 750 760 770 780 GKGLTIVGSV IQGSFLESYG EAQAAEQTIK NMMEIEKVKG FCQVVVASKV REGLAHLIQS 790 800 810 820 830 840 CGLGGMRHNS VVLGWPYGWR QSEDPRAWKT FIDTVRCTTA AHLALLVPKN IAFYPSNHER 850 860 870 880 890 900 YLEGHIDVWW IVHDGGMLML LPFLLRQHKV WRKCRMRIFT VAQMDDNSIQ MKKDLAVFLY 910 920 930 940 950 960 HLRLEAEVEV VEMHNSDISA YTYERTLMME QRSQMLRQMR LTKTEREREA QLVKDRHSAL 970 980 990 1000 1010 RLESLYSDEE DESAVGADKI QMTWTRDKYM TETWDPSHAP DNFRELVHIK P
	Isoform 4 [UniParc]. Checksum: 63DD249B6CA8689C	FASTA	780	84,701
	10 20 30 40 50 60 MPHFTVVPVD GPRRGDYDNL EGLSWVDYGE RAELDDSDGH GNHRESSPFL SPLEASRGID 70 80 90 100 110 120 YYDRNLALFE EELDIRPKVS SLLGKLVSYT NLTQGAKEHE EAESGEGTRR RAAEAPSMGT 130 140 150 160 170 180 LMGVYLPCLQ NIFGVILFLR LTWMVGTAGV LQALLIVLIC CCCTLLTAIS MSAIATNGVV 190 200 210 220 230 240 PAGGSYFMIS RSLGPEFGGA VGLCFYLGTT FAAAMYILGA IEILLTYIAP PAAIFYPSGA 250 260 270 280 290 300 HDTSNATLNN MRVYGTIFLT FMTLVVFVGV KYVNKFASLF LACVIISILS IYAGGIKSIF 310 320 330 340 350 360 DPPVFPVCML GNRTLSRDQF DICAKTAVVD NETVATQLWS FFCHSPNLTT DSCDPYFMLN 370 380 390 400 410 420 NVTEIPGIPG AAAGVLQENL WSAYLEKGDI VEKHGLPSAD APSLKESLPL YVVADIATSF 430 440 450 460 470 480 TVLVGIFFPS VTGIMAGSNR SGDLRDAQKS IPVGTILAII TTSLVYFSSV VLFGACIEGV 490 500 510 520 530 540 VLRDKYGDGV SRNLVVGTLA WPSPWVIVIG SFFSTCGAGL QSLTGAPRLL QAIAKDNIIP 550 560 570 580 590 600 FLRVFGHGKV NGEPTWALLL TALIAELGIL IASLDMVAPI LSMFFLMCYL FVNLACAVQT 610 620 630 640 650 660 LLRTPNWRPR FKYYHWALSF LGMSLCLALM FVSSWYYALV AMLIAGMIYK YIEYQGAEKE 670 680 690 700 710 720 WGDGIRGLSL SAARYALLRL EEGPPHTKNW RPQLLVLLKL DEDLHVKYPR LLTFASQLKA 730 740 750 760 770 780 GKGLTIVGSV IQGSFLESYG EAQAAEQTPC AALRLPTWPC SCPRTSPSTP ATTSATWRAT
	Isoform 5 [UniParc]. Checksum: 328721D9B50DF738	FASTA	1,054	117,046
	10 20 30 40 50 60 MGDTLSPGHG NHRESSPFLS PLEASRGIDY YDRNLALFEE ELDIRPKVSS LLGKLVSYTN 70 80 90 100 110 120 LTQGAKEHEE AESGEGTRRR AAEAPSMGTL MGVYLPCLQN IFGVILFLRL TWMVGTAGVL 130 140 150 160 170 180 QALLIVLICC CCTLLTAISM SAIATNGVVP AGGSYFMISR SLGPEFGGAV GLCFYLGTTF 190 200 210 220 230 240 AAAMYILGAI EILLTYIAPP AAIFYPSGAH DTSNATLNNM RVYGTIFLTF MTLVVFVGVK 250 260 270 280 290 300 YVNKFASLFL ACVIISILSI YAGGIKSIFD PPVFPVCMLG NRTLSRDQFD ICAKTAVVDN 310 320 330 340 350 360 ETVATQLWSF FCHSPNLTTD SCDPYFMLNN VTEIPGIPGA AAGVLQENLW SAYLEKGDIV 370 380 390 400 410 420 EKHGLPSADA PSLKESLPLY VVADIATSFT VLVGIFFPSV TGIMAGSNRS GDLRDAQKSI 430 440 450 460 470 480 PVGTILAIIT TSLVYFSSVV LFGACIEGVV LRDKYGDGVS RNLVVGTLAW PSPWVIVIGS 490 500 510 520 530 540 FFSTCGAGLQ SLTGAPRLLQ AIAKDNIIPF LRVFGHGKVN GEPTWALLLT ALIAELGILI 550 560 570 580 590 600 ASLDMVAPIL SMFFLMCYLF VNLACAVQTL LRTPNWRPRF KYYHWALSFL GMSLCLALMF 610 620 630 640 650 660 VSSWYYALVA MLIAGMIYKY IEYQGAEKEW GDGIRGLSLS AARYALLRLE EGPPHTKNWR 670 680 690 700 710 720 PQLLVLLKLD EDLHVKYPRL LTFASQLKAG KGLTIVGSVI QGSFLESYGE AQAAEQTIKN 730 740 750 760 770 780 MMEIEKVKGF CQVVVASKVR EGLAHLIQSC GLGGMRHNSV VLGWPYGWRQ SEDPRAWKTF 790 800 810 820 830 840 IDTVRCTTAA HLALLVPKNI AFYPSNHERY LEGHIDVWWI VHDGGMLMLL PFLLRQHKVW 850 860 870 880 890 900 RKCRMRIFTV AQMDDNSIQM KKDLAVFLYH LRLEAEVEVV EMHNSDISAY TYERTLMMEQ 910 920 930 940 950 960 RSQMLRQMRL TKTEREREAQ LVKDRHSALR LESLYSDEED ESAVGADKIQ MTWTRDKYMT 970 980 990 1000 1010 1020 ETWDPSHAPD NFRELVHIKP DQSNVRRMHT AVKLNEVIVT RSHDARLVLL NMPGPPRNSE 1030 1040 1050 GDENYMEFLE VLTEGLERVL LVRGGGREVI TIYS
	Isoform 6 [UniParc]. Checksum: EC9A4E5C31C90A87	FASTA	1,079	119,629
	10 20 30 40 50 60 MAAEGAVCGF VYLEGTAWAV PEDTEPLASC TLGHGNHRES SPFLSPLEAS RGIDYYDRNL 70 80 90 100 110 120 ALFEEELDIR PKVSSLLGKL VSYTNLTQGA KEHEEAESGE GTRRRAAEAP SMGTLMGVYL 130 140 150 160 170 180 PCLQNIFGVI LFLRLTWMVG TAGVLQALLI VLICCCCTLL TAISMSAIAT NGVVPAGGSY 190 200 210 220 230 240 FMISRSLGPE FGGAVGLCFY LGTTFAAAMY ILGAIEILLT YIAPPAAIFY PSGAHDTSNA 250 260 270 280 290 300 TLNNMRVYGT IFLTFMTLVV FVGVKYVNKF ASLFLACVII SILSIYAGGI KSIFDPPVFP 310 320 330 340 350 360 VCMLGNRTLS RDQFDICAKT AVVDNETVAT QLWSFFCHSP NLTTDSCDPY FMLNNVTEIP 370 380 390 400 410 420 GIPGAAAGVL QENLWSAYLE KGDIVEKHGL PSADAPSLKE SLPLYVVADI ATSFTVLVGI 430 440 450 460 470 480 FFPSVTGIMA GSNRSGDLRD AQKSIPVGTI LAIITTSLVY FSSVVLFGAC IEGVVLRDKY 490 500 510 520 530 540 GDGVSRNLVV GTLAWPSPWV IVIGSFFSTC GAGLQSLTGA PRLLQAIAKD NIIPFLRVFG 550 560 570 580 590 600 HGKVNGEPTW ALLLTALIAE LGILIASLDM VAPILSMFFL MCYLFVNLAC AVQTLLRTPN 610 620 630 640 650 660 WRPRFKYYHW ALSFLGMSLC LALMFVSSWY YALVAMLIAG MIYKYIEYQG AEKEWGDGIR 670 680 690 700 710 720 GLSLSAARYA LLRLEEGPPH TKNWRPQLLV LLKLDEDLHV KYPRLLTFAS QLKAGKGLTI 730 740 750 760 770 780 VGSVIQGSFL ESYGEAQAAE QTIKNMMEIE KVKGFCQVVV ASKVREGLAH LIQSCGLGGM 790 800 810 820 830 840 RHNSVVLGWP YGWRQSEDPR AWKTFIDTVR CTTAAHLALL VPKNIAFYPS NHERYLEGHI 850 860 870 880 890 900 DVWWIVHDGG MLMLLPFLLR QHKVWRKCRM RIFTVAQMDD NSIQMKKDLA VFLYHLRLEA 910 920 930 940 950 960 EVEVVEMHNS DISAYTYERT LMMEQRSQML RQMRLTKTER EREAQLVKDR HSALRLESLY 970 980 990 1000 1010 1020 SDEEDESAVG ADKIQMTWTR DKYMTETWDP SHAPDNFREL VHIKPDQSNV RRMHTAVKLN 1030 1040 1050 1060 1070 EVIVTRSHDA RLVLLNMPGP PRNSEGDENY MEFLEVLTEG LERVLLVRGG GREVITIYS
	Isoform 7 [UniParc]. Checksum: 701F57E7F5732CBD	FASTA	1,087	119,745
	10 20 30 40 50 60 MRAGGACRPG AAGTAAGTAA GGWDGGCGGA EPARCLTSPW CQWTGRGAAT MTTSRGSVGW 70 80 90 100 110 120 TTGSAPSWMT RTEELDIRPK VSSLLGKLVS YTNLTQGAKE HEEAESGEGT RRRAAEAPSM 130 140 150 160 170 180 GTLMGVYLPC LQNIFGVILF LRLTWMVGTA GVLQALLIVL ICCCCTLLTA ISMSAIATNG 190 200 210 220 230 240 VVPAGGSYFM ISRSLGPEFG GAVGLCFYLG TTFAAAMYIL GAIEILLTYI APPAAIFYPS 250 260 270 280 290 300 GAHDTSNATL NNMRVYGTIF LTFMTLVVFV GVKYVNKFAS LFLACVIISI LSIYAGGIKS 310 320 330 340 350 360 IFDPPVFPVC MLGNRTLSRD QFDICAKTAV VDNETVATQL WSFFCHSPNL TTDSCDPYFM 370 380 390 400 410 420 LNNVTEIPGI PGAAAGVLQE NLWSAYLEKG DIVEKHGLPS ADAPSLKESL PLYVVADIAT 430 440 450 460 470 480 SFTVLVGIFF PSVTGIMAGS NRSGDLRDAQ KSIPVGTILA IITTSLVYFS SVVLFGACIE 490 500 510 520 530 540 GVVLRDKYGD GVSRNLVVGT LAWPSPWVIV IGSFFSTCGA GLQSLTGAPR LLQAIAKDNI 550 560 570 580 590 600 IPFLRVFGHG KVNGEPTWAL LLTALIAELG ILIASLDMVA PILSMFFLMC YLFVNLACAV 610 620 630 640 650 660 QTLLRTPNWR PRFKYYHWAL SFLGMSLCLA LMFVSSWYYA LVAMLIAGMI YKYIEYQGAE 670 680 690 700 710 720 KEWGDGIRGL SLSAARYALL RLEEGPPHTK NWRPQLLVLL KLDEDLHVKY PRLLTFASQL 730 740 750 760 770 780 KAGKGLTIVG SVIQGSFLES YGEAQAAEQT IKNMMEIEKV KGFCQVVVAS KVREGLAHLI 790 800 810 820 830 840 QSCGLGGMRH NSVVLGWPYG WRQSEDPRAW KTFIDTVRCT TAAHLALLVP KNIAFYPSNH 850 860 870 880 890 900 ERYLEGHIDV WWIVHDGGML MLLPFLLRQH KVWRKCRMRI FTVAQMDDNS IQMKKDLAVF 910 920 930 940 950 960 LYHLRLEAEV EVVEMHNSDI SAYTYERTLM MEQRSQMLRQ MRLTKTERER EAQLVKDRHS 970 980 990 1000 1010 1020 ALRLESLYSD EEDESAVGAD KIQMTWTRDK YMTETWDPSH APDNFRELVH IKPDQSNVRR 1030 1040 1050 1060 1070 1080 MHTAVKLNEV IVTRSHDARL VLLNMPGPPR NSEGDENYME FLEVLTEGLE RVLLVRGGGR EVITIYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family." Gillen C.M., Brill S., Payne J.A., Forbush B. III J. Biol. Chem. 271:16237-16244(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Embryonic kidney.
[2]	"Molecular identification and expression of erythroid K:Cl cotransporter in human and mouse erythroleukemic cells." Pellegrino C.M., Rybicki A.C., Musto S., Nagel R.L., Schwartz R.S. Blood Cells Mol. Dis. 24:31-40(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Erythroleukemia.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 25-1087 (ISOFORM 7). Tissue: Cerebellum and Testis.
[4]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 1). Tissue: Eye.
[6]	Golding S., Culliford S.J., Ellory J.C. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 280-517. Tissue: Erythroleukemia.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 684-1085 (ISOFORM 4), SUBUNIT.
[8]	"Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation." Su W., Shmukler B.E., Chernova M.N., Stuart-Tilley A.K., de Franceschi L., Brugnara C., Alper S.L. Am. J. Physiol. 277:C899-C912(1999) [PubMed] [Europe PMC] [Abstract] Cited for: EXPRESSION IN ERYTHROCYTE MEMBRANES.
[9]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51 AND SER-967, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"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] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-967, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U55054 mRNA. Translation: AAC50563.1. AF047338 mRNA. Translation: AAC32815.1. AF054505 mRNA. Translation: AAC39684.1. AF054506 mRNA. Translation: AAC39685.1. AK293956 mRNA. Translation: BAG57330.1. Different initiation. AK299042 mRNA. Translation: BAG61116.1. AK302790 mRNA. Translation: BAG63994.1. AK316415 mRNA. Translation: BAH14786.1. AC040162 Genomic DNA. No translation available. BC021193 mRNA. Translation: AAH21193.1. AF053402 mRNA. Translation: AAC35282.1. Frameshift. AY026038 mRNA. Translation: AAK01946.1.
IPI	IPI00021057. IPI00215693. IPI00215694. IPI00215695. IPI00924945. IPI00927160. IPI00927273.
RefSeq	NP_001139433.1. NM_001145961.1. NP_001139434.1. NM_001145962.1. NP_001139435.1. NM_001145963.1. NP_001139436.1. NM_001145964.1. NP_005063.1. NM_005072.4.
UniGene	Hs.10094.
3D structure databases
ProteinModelPortal	Q9UP95.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1191426.
STRING	9606.ENSP00000318557.
PTM databases
PhosphoSite	Q9UP95.
Polymorphism databases
DMDM	27151691.
Proteomic databases
PaxDb	Q9UP95.
PRIDE	Q9UP95.
Protocols and materials databases
DNASU	6560.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000316341; ENSP00000318557; ENSG00000124067. ENST00000338335; ENSP00000343374; ENSG00000124067. ENST00000422611; ENSP00000395983; ENSG00000124067. ENST00000537830; ENSP00000445962; ENSG00000124067. ENST00000541864; ENSP00000438334; ENSG00000124067. ENST00000576616; ENSP00000458902; ENSG00000124067.
GeneID	6560.
KEGG	hsa:6560.
UCSC	uc002euz.2. human. uc002eva.2. human.
Organism-specific databases
CTD	6560.
GeneCards	GC16M067979.
HGNC	HGNC:10913. SLC12A4.
HPA	HPA041138.
MIM	604119. gene.
neXtProt	NX_Q9UP95.
PharmGKB	PA35807.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0531.
HOGENOM	HOG000092644.
HOVERGEN	HBG052852.
InParanoid	Q9UP95.
KO	K14427.
OrthoDB	EOG476JZG.
PhylomeDB	Q9UP95.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9UP95.
Bgee	Q9UP95.
CleanEx	HS_SLC12A4.
Genevestigator	Q9UP95.
GermOnline	ENSG00000124067. Homo sapiens.
Family and domain databases
InterPro	IPR004841. AA-permease_dom. IPR000622. K/Cl_cotranspt1. IPR018491. K/Cl_cotranspt_1/3. IPR000076. KCL_cotranspt. IPR004842. Na/K/Cl_cotransptS. [Graphical view]
Pfam	PF00324. AA_permease. 2 hits. PF03522. KCl_Cotrans_1. 1 hit. [Graphical view]
PRINTS	PR01081. KCLTRNSPORT. PR01082. KCLTRNSPORT1.
TIGRFAMs	TIGR00930. 2a30. 1 hit.
ProtoNet	Search...
Other
DrugBank	DB00887. Bumetanide. DB00761. Potassium Chloride.
GenomeRNAi	6560.
NextBio	25527.
SOURCE	Search...

Entry information

Entry name

S12A4_HUMAN

Accession

Primary (citable) accession number: Q9UP95
Secondary accession number(s): B4DF69 , B4DR04, B4DZ82, B7ZAV0, F5H066, F5H0S9, F5H3C0, O60632, O75893, Q13953, Q96LD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2002
Last sequence update:	December 13, 2002
Last modified:	May 1, 2013
This is version 117 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.