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P55011 (S12A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1212 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processIon transport
Potassium transport
Sodium transport
Symport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
Sodium
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Uncategorized?

Inferred from direct assay. Source: UniProtKB

   Biological_processammonium transport

Inferred from direct assay PubMed 12946942PubMed 18032481. Source: UniProtKB

branching involved in mammary gland duct morphogenesis

Inferred from electronic annotation. Source: Ensembl

chloride transmembrane transport

Traceable author statement Ref.1. Source: GOC

detection of mechanical stimulus involved in sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

gamma-aminobutyric acid signaling pathway

Inferred from electronic annotation. Source: Ensembl

hyperosmotic response

Inferred from electronic annotation. Source: Ensembl

ion transport

Traceable author statement. Source: Reactome

mammary duct terminal end bud growth

Inferred from electronic annotation. Source: Ensembl

multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell volume

Inferred from electronic annotation. Source: Ensembl

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

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708PubMed 20458337. Source: UniProt

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionsodium:potassium:chloride symporter activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

OXSR1O957472EBI-2801449,EBI-620853

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12121212Solute carrier family 12 member 2
PRO_0000178023

Regions

Topological domain1 – 285285Cytoplasmic Potential
Transmembrane286 – 30621Helical; Potential
Topological domain307 – 31812Extracellular Potential
Transmembrane319 – 34123Helical; Potential
Topological domain342 – 36625Cytoplasmic Potential
Transmembrane367 – 38721Helical; Potential
Topological domain388 – 41023Extracellular Potential
Transmembrane411 – 43121Helical; Potential
Topological domain432 – 4354Cytoplasmic Potential
Transmembrane436 – 45621Helical; Potential
Topological domain457 – 48630Extracellular Potential
Transmembrane487 – 50721Helical; Potential
Topological domain508 – 52013Cytoplasmic Potential
Transmembrane521 – 54121Helical; Potential
Topological domain542 – 59150Extracellular Potential
Transmembrane592 – 61221Helical; Potential
Topological domain613 – 65442Cytoplasmic Potential
Transmembrane655 – 67521Helical; Potential
Topological domain676 – 6805Extracellular Potential
Transmembrane681 – 69919Helical; Potential
Topological domain700 – 72425Cytoplasmic Potential
Transmembrane725 – 74521Helical; Potential
Topological domain746 – 899154Extracellular Potential
Transmembrane900 – 92021Helical; Potential
Topological domain921 – 1212292Cytoplasmic Potential
Compositional bias90 – 12233Ala-rich
Compositional bias188 – 1947Poly-Gly

Amino acid modifications

Modified residue11N-acetylmethionine Ref.6
Modified residue771Phosphoserine Ref.4
Modified residue791Phosphoserine Ref.4
Modified residue2661Phosphothreonine By similarity
Modified residue9401Phosphoserine By similarity

Natural variations

Alternative sequence976 – 99116Missing in isoform 2.
VSP_006105

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: A6BF174ACCDA2EC1

FASTA1,212131,447
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 651AF731842344AD
Show »

FASTA1,196129,679

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.
[6]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U30246 mRNA. Translation: AAC50561.1.
AF439152 mRNA. Translation: AAL32454.1.
PIRA57187.
RefSeqNP_001037.1. NM_001046.2.
UniGeneHs.162585.
Hs.712970.

3D structure databases

ProteinModelPortalP55011.
SMRP55011. Positions 347-692.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112447. 7 interactions.
DIPDIP-43979N.
IntActP55011. 3 interactions.
MINTMINT-5004359.
STRING9606.ENSP00000262461.

Chemistry

ChEMBLCHEMBL1615383.
DrugBankDB00887. Bumetanide.
DB00761. Potassium Chloride.
GuidetoPHARMACOLOGY969.

Protein family/group databases

TCDB2.A.30.3.1. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSiteP55011.

Polymorphism databases

DMDM1709292.

Proteomic databases

PaxDbP55011.
PRIDEP55011.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262461; ENSP00000262461; ENSG00000064651. [P55011-1]
ENST00000343225; ENSP00000340878; ENSG00000064651. [P55011-3]
GeneID6558.
KEGGhsa:6558.
UCSCuc003kus.3. human. [P55011-1]
uc010jdg.3. human. [P55011-3]

Organism-specific databases

CTD6558.
GeneCardsGC05P127419.
HGNCHGNC:10911. SLC12A2.
HPAHPA020130.
MIM600840. gene.
neXtProtNX_P55011.
PharmGKBPA35806.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0531.
HOGENOMHOG000062855.
HOVERGENHBG052851.
InParanoidP55011.
KOK10951.
OMAHDAFDIQ.
OrthoDBEOG75MVVC.
PhylomeDBP55011.
TreeFamTF313191.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.
SignaLinkP55011.

Gene expression databases

ArrayExpressP55011.
BgeeP55011.
CleanExHS_SLC12A2.
GenevestigatorP55011.

Family and domain databases

InterProIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR002443. Na/K/Cl_cotranspt.
IPR002444. Na/K/Cl_cotranspt1.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PfamPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view]
PRINTSPR01207. NAKCLTRNSPRT.
PR01208. NAKCLTRSPRT1.
TIGRFAMsTIGR00930. 2a30. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC12A2. human.
GenomeRNAi6558.
NextBio25519.
PROP55011.
SOURCESearch...

Entry information

Entry nameS12A2_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM