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P55011

- S12A2_HUMAN

UniProt

P55011 - S12A2_HUMAN

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Protein
Solute carrier family 12 member 2
Gene
SLC12A2, NKCC1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.

Enzyme regulationi

Activated by WNK3.1 Publication

GO - Molecular functioni

  1. ammonium transmembrane transporter activity Source: UniProtKB
  2. protein binding Source: IntAct
  3. sodium:potassium:chloride symporter activity Source: ProtInc

GO - Biological processi

  1. ammonium transmembrane transport Source: GOC
  2. ammonium transport Source: UniProtKB
  3. branching involved in mammary gland duct morphogenesis Source: Ensembl
  4. chloride transmembrane transport Source: GOC
  5. detection of mechanical stimulus involved in sensory perception of sound Source: Ensembl
  6. gamma-aminobutyric acid signaling pathway Source: Ensembl
  7. hyperosmotic response Source: Ensembl
  8. ion transport Source: Reactome
  9. mammary duct terminal end bud growth Source: Ensembl
  10. multicellular organism growth Source: Ensembl
  11. positive regulation of cell volume Source: Ensembl
  12. potassium ion transport Source: UniProtKB-KW
  13. sodium ion transport Source: UniProtKB-KW
  14. transepithelial ammonium transport Source: UniProtKB
  15. transepithelial chloride transport Source: UniProtKB
  16. transmembrane transport Source: Reactome
  17. transport Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Ion transport, Potassium transport, Sodium transport, Symport, Transport

Keywords - Ligandi

Potassium, Sodium

Enzyme and pathway databases

ReactomeiREACT_19315. Cation-coupled Chloride cotransporters.
SignaLinkiP55011.

Protein family/group databases

TCDBi2.A.30.3.1. the cation-chloride cotransporter (ccc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 2
Alternative name(s):
Basolateral Na-K-Cl symporter
Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1
Gene namesi
Name:SLC12A2
Synonyms:NKCC1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:10911. SLC12A2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 285285Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei286 – 30621Helical; Reviewed prediction
Add
BLAST
Topological domaini307 – 31812Extracellular Reviewed prediction
Add
BLAST
Transmembranei319 – 34123Helical; Reviewed prediction
Add
BLAST
Topological domaini342 – 36625Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei367 – 38721Helical; Reviewed prediction
Add
BLAST
Topological domaini388 – 41023Extracellular Reviewed prediction
Add
BLAST
Transmembranei411 – 43121Helical; Reviewed prediction
Add
BLAST
Topological domaini432 – 4354Cytoplasmic Reviewed prediction
Transmembranei436 – 45621Helical; Reviewed prediction
Add
BLAST
Topological domaini457 – 48630Extracellular Reviewed prediction
Add
BLAST
Transmembranei487 – 50721Helical; Reviewed prediction
Add
BLAST
Topological domaini508 – 52013Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei521 – 54121Helical; Reviewed prediction
Add
BLAST
Topological domaini542 – 59150Extracellular Reviewed prediction
Add
BLAST
Transmembranei592 – 61221Helical; Reviewed prediction
Add
BLAST
Topological domaini613 – 65442Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei655 – 67521Helical; Reviewed prediction
Add
BLAST
Topological domaini676 – 6805Extracellular Reviewed prediction
Transmembranei681 – 69919Helical; Reviewed prediction
Add
BLAST
Topological domaini700 – 72425Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei725 – 74521Helical; Reviewed prediction
Add
BLAST
Topological domaini746 – 899154Extracellular Reviewed prediction
Add
BLAST
Transmembranei900 – 92021Helical; Reviewed prediction
Add
BLAST
Topological domaini921 – 1212292Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: Ensembl
  2. basolateral plasma membrane Source: Ensembl
  3. extracellular vesicular exosome Source: UniProt
  4. integral component of plasma membrane Source: ProtInc
  5. membrane Source: ProtInc
  6. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35806.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12121212Solute carrier family 12 member 2
PRO_0000178023Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei77 – 771Phosphoserine1 Publication
Modified residuei79 – 791Phosphoserine1 Publication
Modified residuei266 – 2661Phosphothreonine By similarity
Modified residuei940 – 9401Phosphoserine By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP55011.
PaxDbiP55011.
PRIDEiP55011.

PTM databases

PhosphoSiteiP55011.

Expressioni

Tissue specificityi

Expressed in many tissues.

Gene expression databases

ArrayExpressiP55011.
BgeeiP55011.
CleanExiHS_SLC12A2.
GenevestigatoriP55011.

Organism-specific databases

HPAiHPA020130.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
OXSR1O957472EBI-2801449,EBI-620853

Protein-protein interaction databases

BioGridi112447. 8 interactions.
DIPiDIP-43979N.
IntActiP55011. 4 interactions.
MINTiMINT-5004359.
STRINGi9606.ENSP00000262461.

Structurei

3D structure databases

ProteinModelPortaliP55011.
SMRiP55011. Positions 347-692.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi90 – 12233Ala-rich
Add
BLAST
Compositional biasi188 – 1947Poly-Gly

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiP55011.
KOiK10951.
OMAiHDAFDIQ.
OrthoDBiEOG75MVVC.
PhylomeDBiP55011.
TreeFamiTF313191.

Family and domain databases

InterProiIPR004841. 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]
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view]
PRINTSiPR01207. NAKCLTRNSPRT.
PR01208. NAKCLTRSPRT1.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P55011-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MEPRPTAPSS GAPGLAGVGE TPSAAALAAA RVELPGTAVP SVPEDAAPAS     50
RDGGGVRDEG PAAAGDGLGR PLGPTPSQSR FQVDLVSENA GRAAAAAAAA 100
AAAAAAAGAG AGAKQTPADG EASGESEPAK GSEEAKGRFR VNFVDPAASS 150
SAEDSLSDAA GVGVDGPNVS FQNGGDTVLS EGSSLHSGGG GGSGHHQHYY 200
YDTHTNTYYL RTFGHNTMDA VPRIDHYRHT AAQLGEKLLR PSLAELHDEL 250
EKEPFEDGFA NGEESTPTRD AVVTYTAESK GVVKFGWIKG VLVRCMLNIW 300
GVMLFIRLSW IVGQAGIGLS VLVIMMATVV TTITGLSTSA IATNGFVRGG 350
GAYYLISRSL GPEFGGAIGL IFAFANAVAV AMYVVGFAET VVELLKEHSI 400
LMIDEINDIR IIGAITVVIL LGISVAGMEW EAKAQIVLLV ILLLAIGDFV 450
IGTFIPLESK KPKGFFGYKS EIFNENFGPD FREEETFFSV FAIFFPAATG 500
ILAGANISGD LADPQSAIPK GTLLAILITT LVYVGIAVSV GSCVVRDATG 550
NVNDTIVTEL TNCTSAACKL NFDFSSCESS PCSYGLMNNF QVMSMVSGFT 600
PLISAGIFSA TLSSALASLV SAPKIFQALC KDNIYPAFQM FAKGYGKNNE 650
PLRGYILTFL IALGFILIAE LNVIAPIISN FFLASYALIN FSVFHASLAK 700
SPGWRPAFKY YNMWISLLGA ILCCIVMFVI NWWAALLTYV IVLGLYIYVT 750
YKKPDVNWGS STQALTYLNA LQHSIRLSGV EDHVKNFRPQ CLVMTGAPNS 800
RPALLHLVHD FTKNVGLMIC GHVHMGPRRQ AMKEMSIDQA KYQRWLIKNK 850
MKAFYAPVHA DDLREGAQYL MQAAGLGRMK PNTLVLGFKK DWLQADMRDV 900
DMYINLFHDA FDIQYGVVVI RLKEGLDISH LQGQEELLSS QEKSPGTKDV 950
VVSVEYSKKS DLDTSKPLSE KPITHKVEEE DGKTATQPLL KKESKGPIVP 1000
LNVADQKLLE ASTQFQKKQG KNTIDVWWLF DDGGLTLLIP YLLTTKKKWK 1050
DCKIRVFIGG KINRIDHDRR AMATLLSKFR IDFSDIMVLG DINTKPKKEN 1100
IIAFEEIIEP YRLHEDDKEQ DIADKMKEDE PWRITDNELE LYKTKTYRQI 1150
RLNELLKEHS STANIIVMSL PVARKGAVSS ALYMAWLEAL SKDLPPILLV 1200
RGNHQSVLTF YS 1212
Length:1,212
Mass (Da):131,447
Last modified:October 1, 1996 - v1
Checksum:iA6BF174ACCDA2EC1
GO
Isoform 2 (identifier: P55011-3) [UniParc]FASTAAdd to Basket

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

Show »
Length:1,196
Mass (Da):129,679
Checksum:i651AF731842344AD
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei976 – 99116Missing in isoform 2.
VSP_006105Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U30246 mRNA. Translation: AAC50561.1.
AF439152 mRNA. Translation: AAL32454.1.
CCDSiCCDS4144.1. [P55011-1]
CCDS58965.1. [P55011-3]
PIRiA57187.
RefSeqiNP_001037.1. NM_001046.2. [P55011-1]
UniGeneiHs.162585.
Hs.712970.

Genome annotation databases

EnsembliENST00000262461; ENSP00000262461; ENSG00000064651. [P55011-1]
ENST00000343225; ENSP00000340878; ENSG00000064651. [P55011-3]
GeneIDi6558.
KEGGihsa:6558.
UCSCiuc003kus.3. human. [P55011-1]
uc010jdg.3. human. [P55011-3]

Polymorphism databases

DMDMi1709292.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U30246 mRNA. Translation: AAC50561.1 .
AF439152 mRNA. Translation: AAL32454.1 .
CCDSi CCDS4144.1. [P55011-1 ]
CCDS58965.1. [P55011-3 ]
PIRi A57187.
RefSeqi NP_001037.1. NM_001046.2. [P55011-1 ]
UniGenei Hs.162585.
Hs.712970.

3D structure databases

ProteinModelPortali P55011.
SMRi P55011. Positions 347-692.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112447. 8 interactions.
DIPi DIP-43979N.
IntActi P55011. 4 interactions.
MINTi MINT-5004359.
STRINGi 9606.ENSP00000262461.

Chemistry

ChEMBLi CHEMBL1615383.
DrugBanki DB00887. Bumetanide.
DB00761. Potassium Chloride.
GuidetoPHARMACOLOGYi 969.

Protein family/group databases

TCDBi 2.A.30.3.1. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSitei P55011.

Polymorphism databases

DMDMi 1709292.

Proteomic databases

MaxQBi P55011.
PaxDbi P55011.
PRIDEi P55011.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000262461 ; ENSP00000262461 ; ENSG00000064651 . [P55011-1 ]
ENST00000343225 ; ENSP00000340878 ; ENSG00000064651 . [P55011-3 ]
GeneIDi 6558.
KEGGi hsa:6558.
UCSCi uc003kus.3. human. [P55011-1 ]
uc010jdg.3. human. [P55011-3 ]

Organism-specific databases

CTDi 6558.
GeneCardsi GC05P127419.
HGNCi HGNC:10911. SLC12A2.
HPAi HPA020130.
MIMi 600840. gene.
neXtProti NX_P55011.
PharmGKBi PA35806.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0531.
HOGENOMi HOG000062855.
HOVERGENi HBG052851.
InParanoidi P55011.
KOi K10951.
OMAi HDAFDIQ.
OrthoDBi EOG75MVVC.
PhylomeDBi P55011.
TreeFami TF313191.

Enzyme and pathway databases

Reactomei REACT_19315. Cation-coupled Chloride cotransporters.
SignaLinki P55011.

Miscellaneous databases

ChiTaRSi SLC12A2. human.
GenomeRNAii 6558.
NextBioi 25519.
PROi P55011.
SOURCEi Search...

Gene expression databases

ArrayExpressi P55011.
Bgeei P55011.
CleanExi HS_SLC12A2.
Genevestigatori P55011.

Family and domain databases

InterProi IPR004841. 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 ]
Pfami PF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view ]
PRINTSi PR01207. NAKCLTRNSPRT.
PR01208. NAKCLTRSPRT1.
TIGRFAMsi TIGR00930. 2a30. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77 AND SER-79, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  5. 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].

Entry informationi

Entry nameiS12A2_HUMAN
AccessioniPrimary (citable) accession number: P55011
Secondary accession number(s): Q8N713, Q8WWH7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 3, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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