P55011 (S12A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Solute carrier family 12 member 2

Alternative name(s):
Basolateral Na-K-Cl symporter
Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1

Gene names

Name:	SLC12A2
Synonyms:	NKCC1

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	1212 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
Enzyme regulation	Activated by WNK3. Ref.5
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in many tissues.
Sequence similarities	Belongs to the SLC12A transporter family.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Sodium transport Symport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Potassium Sodium
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branching involved in mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara detection of mechanical stimulus involved in sensory perception of sound Inferred from electronic annotation. Source: Compara mammary duct terminal end bud growth Inferred from electronic annotation. Source: Compara multicellular organism growth Inferred from electronic annotation. Source: Compara potassium ion transport Inferred from electronic annotation. Source: UniProtKB-KW sodium ion transport Inferred from electronic annotation. Source: UniProtKB-KW transepithelial ammonium transport Inferred from direct assay PubMed 18032481. Source: UniProtKB transepithelial chloride transport Inferred from direct assay PubMed 12946942. Source: UniProtKB
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara basolateral plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ammonia transmembrane transporter activity Inferred from direct assay PubMed 12946942PubMed 18032481. Source: UniProtKB sodium:potassium:chloride symporter activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P55011-1)

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: P55011-3)

The sequence of this isoform differs from the canonical sequence as follows:
     976-991: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1212	1212	Solute carrier family 12 member 2		PRO_0000178023
Regions
	Topological domain	1 – 285	285	Cytoplasmic Potential
	Transmembrane	286 – 306	21	Helical; Potential
	Topological domain	307 – 318	12	Extracellular Potential
	Transmembrane	319 – 341	23	Helical; Potential
	Topological domain	342 – 366	25	Cytoplasmic Potential
	Transmembrane	367 – 387	21	Helical; Potential
	Topological domain	388 – 410	23	Extracellular Potential
	Transmembrane	411 – 431	21	Helical; Potential
	Topological domain	432 – 435	4	Cytoplasmic Potential
	Transmembrane	436 – 456	21	Helical; Potential
	Topological domain	457 – 486	30	Extracellular Potential
	Transmembrane	487 – 507	21	Helical; Potential
	Topological domain	508 – 520	13	Cytoplasmic Potential
	Transmembrane	521 – 541	21	Helical; Potential
	Topological domain	542 – 591	50	Extracellular Potential
	Transmembrane	592 – 612	21	Helical; Potential
	Topological domain	613 – 654	42	Cytoplasmic Potential
	Transmembrane	655 – 675	21	Helical; Potential
	Topological domain	676 – 680	5	Extracellular Potential
	Transmembrane	681 – 699	19	Helical; Potential
	Topological domain	700 – 724	25	Cytoplasmic Potential
	Transmembrane	725 – 745	21	Helical; Potential
	Topological domain	746 – 899	154	Extracellular Potential
	Transmembrane	900 – 920	21	Helical; Potential
	Topological domain	921 – 1212	292	Cytoplasmic Potential
	Compositional bias	90 – 122	33	Ala-rich
	Compositional bias	188 – 194	7	Poly-Gly
Amino acid modifications
	Modified residue	77	1	Phosphoserine Ref.4
	Modified residue	79	1	Phosphoserine Ref.4
Natural variations
	Alternative sequence	976 – 991	16	Missing in isoform 2.		VSP_006105

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: A6BF174ACCDA2EC1	FASTA	1,212	131,447
	10 20 30 40 50 60 MEPRPTAPSS GAPGLAGVGE TPSAAALAAA RVELPGTAVP SVPEDAAPAS RDGGGVRDEG 70 80 90 100 110 120 PAAAGDGLGR PLGPTPSQSR FQVDLVSENA GRAAAAAAAA AAAAAAAGAG AGAKQTPADG 130 140 150 160 170 180 EASGESEPAK GSEEAKGRFR VNFVDPAASS SAEDSLSDAA GVGVDGPNVS FQNGGDTVLS 190 200 210 220 230 240 EGSSLHSGGG GGSGHHQHYY YDTHTNTYYL RTFGHNTMDA VPRIDHYRHT AAQLGEKLLR 250 260 270 280 290 300 PSLAELHDEL EKEPFEDGFA NGEESTPTRD AVVTYTAESK GVVKFGWIKG VLVRCMLNIW 310 320 330 340 350 360 GVMLFIRLSW IVGQAGIGLS VLVIMMATVV TTITGLSTSA IATNGFVRGG GAYYLISRSL 370 380 390 400 410 420 GPEFGGAIGL IFAFANAVAV AMYVVGFAET VVELLKEHSI LMIDEINDIR IIGAITVVIL 430 440 450 460 470 480 LGISVAGMEW EAKAQIVLLV ILLLAIGDFV IGTFIPLESK KPKGFFGYKS EIFNENFGPD 490 500 510 520 530 540 FREEETFFSV FAIFFPAATG ILAGANISGD LADPQSAIPK GTLLAILITT LVYVGIAVSV 550 560 570 580 590 600 GSCVVRDATG NVNDTIVTEL TNCTSAACKL NFDFSSCESS PCSYGLMNNF QVMSMVSGFT 610 620 630 640 650 660 PLISAGIFSA TLSSALASLV SAPKIFQALC KDNIYPAFQM FAKGYGKNNE PLRGYILTFL 670 680 690 700 710 720 IALGFILIAE LNVIAPIISN FFLASYALIN FSVFHASLAK SPGWRPAFKY YNMWISLLGA 730 740 750 760 770 780 ILCCIVMFVI NWWAALLTYV IVLGLYIYVT YKKPDVNWGS STQALTYLNA LQHSIRLSGV 790 800 810 820 830 840 EDHVKNFRPQ CLVMTGAPNS RPALLHLVHD FTKNVGLMIC GHVHMGPRRQ AMKEMSIDQA 850 860 870 880 890 900 KYQRWLIKNK MKAFYAPVHA DDLREGAQYL MQAAGLGRMK PNTLVLGFKK DWLQADMRDV 910 920 930 940 950 960 DMYINLFHDA FDIQYGVVVI RLKEGLDISH LQGQEELLSS QEKSPGTKDV VVSVEYSKKS 970 980 990 1000 1010 1020 DLDTSKPLSE KPITHKVEEE DGKTATQPLL KKESKGPIVP LNVADQKLLE ASTQFQKKQG 1030 1040 1050 1060 1070 1080 KNTIDVWWLF DDGGLTLLIP YLLTTKKKWK DCKIRVFIGG KINRIDHDRR AMATLLSKFR 1090 1100 1110 1120 1130 1140 IDFSDIMVLG DINTKPKKEN IIAFEEIIEP YRLHEDDKEQ DIADKMKEDE PWRITDNELE 1150 1160 1170 1180 1190 1200 LYKTKTYRQI RLNELLKEHS STANIIVMSL PVARKGAVSS ALYMAWLEAL SKDLPPILLV 1210 RGNHQSVLTF YS
	Isoform 2 [UniParc]. Checksum: 651AF731842344AD	FASTA	1,196	129,679
	10 20 30 40 50 60 MEPRPTAPSS GAPGLAGVGE TPSAAALAAA RVELPGTAVP SVPEDAAPAS RDGGGVRDEG 70 80 90 100 110 120 PAAAGDGLGR PLGPTPSQSR FQVDLVSENA GRAAAAAAAA AAAAAAAGAG AGAKQTPADG 130 140 150 160 170 180 EASGESEPAK GSEEAKGRFR VNFVDPAASS SAEDSLSDAA GVGVDGPNVS FQNGGDTVLS 190 200 210 220 230 240 EGSSLHSGGG GGSGHHQHYY YDTHTNTYYL RTFGHNTMDA VPRIDHYRHT AAQLGEKLLR 250 260 270 280 290 300 PSLAELHDEL EKEPFEDGFA NGEESTPTRD AVVTYTAESK GVVKFGWIKG VLVRCMLNIW 310 320 330 340 350 360 GVMLFIRLSW IVGQAGIGLS VLVIMMATVV TTITGLSTSA IATNGFVRGG GAYYLISRSL 370 380 390 400 410 420 GPEFGGAIGL IFAFANAVAV AMYVVGFAET VVELLKEHSI LMIDEINDIR IIGAITVVIL 430 440 450 460 470 480 LGISVAGMEW EAKAQIVLLV ILLLAIGDFV IGTFIPLESK KPKGFFGYKS EIFNENFGPD 490 500 510 520 530 540 FREEETFFSV FAIFFPAATG ILAGANISGD LADPQSAIPK GTLLAILITT LVYVGIAVSV 550 560 570 580 590 600 GSCVVRDATG NVNDTIVTEL TNCTSAACKL NFDFSSCESS PCSYGLMNNF QVMSMVSGFT 610 620 630 640 650 660 PLISAGIFSA TLSSALASLV SAPKIFQALC KDNIYPAFQM FAKGYGKNNE PLRGYILTFL 670 680 690 700 710 720 IALGFILIAE LNVIAPIISN FFLASYALIN FSVFHASLAK SPGWRPAFKY YNMWISLLGA 730 740 750 760 770 780 ILCCIVMFVI NWWAALLTYV IVLGLYIYVT YKKPDVNWGS STQALTYLNA LQHSIRLSGV 790 800 810 820 830 840 EDHVKNFRPQ CLVMTGAPNS RPALLHLVHD FTKNVGLMIC GHVHMGPRRQ AMKEMSIDQA 850 860 870 880 890 900 KYQRWLIKNK MKAFYAPVHA DDLREGAQYL MQAAGLGRMK PNTLVLGFKK DWLQADMRDV 910 920 930 940 950 960 DMYINLFHDA FDIQYGVVVI RLKEGLDISH LQGQEELLSS QEKSPGTKDV VVSVEYSKKS 970 980 990 1000 1010 1020 DLDTSKPLSE KPITHKESKG PIVPLNVADQ KLLEASTQFQ KKQGKNTIDV WWLFDDGGLT 1030 1040 1050 1060 1070 1080 LLIPYLLTTK KKWKDCKIRV FIGGKINRID HDRRAMATLL SKFRIDFSDI MVLGDINTKP 1090 1100 1110 1120 1130 1140 KKENIIAFEE IIEPYRLHED DKEQDIADKM KEDEPWRITD NELELYKTKT YRQIRLNELL 1150 1160 1170 1180 1190 KEHSSTANII VMSLPVARKG AVSSALYMAW LEALSKDLPP ILLVRGNHQS VLTFYS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure, functional expression, and chromosomal localization of the bumetanide-sensitive Na-K-Cl cotransporter in human colon." Payne J.A., Xu J.-C., Haas M., Lytle Y.C., Ward D., Forbush B. III J. Biol. Chem. 270:17977-17985(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Colon.
[2]	"Quantitation of Na(+)-K(+)-2Cl(-) cotransport splice variants in human tissues using kinetic polymerase chain reaction." Vibat C.R., Holland M.J., Kang J.J., Putney L.K., O'Donnell M.E. Anal. Biochem. 298:218-230(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 740-1066 (ISOFORM 2). Tissue: Eye.
[3]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[4]	"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-77 AND SER-79, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[5]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U30246 mRNA. Translation: AAC50561.1. AF439152 mRNA. Translation: AAL32454.1.
IPI	IPI00022649. IPI00220844.
PIR	A57187.
RefSeq	NP_001037.1. NM_001046.2.
UniGene	Hs.162585. Hs.712970.
3D structure databases
ProteinModelPortal	P55011.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-43979N.
IntAct	P55011. 2 interactions.
MINT	MINT-5004359.
STRING	9606.ENSP00000262461.
Protein family/group databases
TCDB	2.A.30.3.1. cation-chloride cotransporter (CCC) family.
PTM databases
PhosphoSite	P55011.
Polymorphism databases
DMDM	1709292.
Proteomic databases
PaxDb	P55011.
PRIDE	P55011.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262461; ENSP00000262461; ENSG00000064651. ENST00000343225; ENSP00000340878; ENSG00000064651.
GeneID	6558.
KEGG	hsa:6558.
UCSC	uc003kus.3. human. uc010jdg.3. human.
Organism-specific databases
CTD	6558.
GeneCards	GC05P127419.
HGNC	HGNC:10911. SLC12A2.
HPA	HPA020130.
MIM	600840. gene.
neXtProt	NX_P55011.
PharmGKB	PA35806.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0531.
HOGENOM	HOG000062855.
HOVERGEN	HBG052851.
InParanoid	P55011.
KO	K10951.
OMA	KENIIAF.
OrthoDB	EOG4FR0QZ.
PhylomeDB	P55011.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
SignaLink	P55011.
Gene expression databases
ArrayExpress	P55011.
Bgee	P55011.
CleanEx	HS_SLC12A2.
Genevestigator	P55011.
GermOnline	ENSG00000064651. Homo sapiens.
Family and domain databases
InterPro	IPR004841. AA-permease_dom. IPR013612. AA_permease_N. IPR002443. Na/K/Cl_cotranspt. IPR002444. Na/K/Cl_cotranspt1. IPR004842. Na/K/Cl_cotransptS. [Graphical view]
Pfam	PF00324. AA_permease. 1 hit. PF08403. AA_permease_N. 1 hit. [Graphical view]
PRINTS	PR01207. NAKCLTRNSPRT. PR01208. NAKCLTRSPRT1.
TIGRFAMs	TIGR00930. 2a30. 1 hit.
ProtoNet	Search...
Other
ChEMBL	CHEMBL1615383.
ChiTaRS	SLC12A2. human.
DrugBank	DB00887. Bumetanide. DB00761. Potassium Chloride.
GenomeRNAi	6558.
NextBio	25519.
SOURCE	Search...

Entry information

Entry name

S12A2_HUMAN

Accession

Primary (citable) accession number: P55011
Secondary accession number(s): Q8N713, Q8WWH7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 117 of the entry and version 1 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.