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Protein

Solute carrier family 12 member 2

Gene

SLC12A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

  • ammonium transmembrane transporter activity Source: UniProtKB
  • protein kinase binding Source: ParkinsonsUK-UCL
  • sodium:potassium:chloride symporter activity Source: Reactome

GO - Biological processi

  • aging Source: Ensembl
  • ammonium transport Source: UniProtKB
  • gamma-aminobutyric acid signaling pathway Source: Ensembl
  • hyperosmotic response Source: Ensembl
  • ion transport Source: Reactome
  • positive regulation of cell volume Source: Ensembl
  • potassium ion transport Source: UniProtKB-KW
  • sodium ion transport Source: UniProtKB-KW
  • transepithelial ammonium transport Source: UniProtKB
  • transepithelial chloride transport Source: UniProtKB
  • 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

BioCyciZFISH:ENSG00000064651-MONOMER.
ReactomeiR-HSA-426117. Cation-coupled Chloride cotransporters.
SignaLinkiP55011.
SIGNORiP55011.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:10911. SLC12A2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 285CytoplasmicSequence analysisAdd BLAST285
Transmembranei286 – 306HelicalSequence analysisAdd BLAST21
Topological domaini307 – 318ExtracellularSequence analysisAdd BLAST12
Transmembranei319 – 341HelicalSequence analysisAdd BLAST23
Topological domaini342 – 366CytoplasmicSequence analysisAdd BLAST25
Transmembranei367 – 387HelicalSequence analysisAdd BLAST21
Topological domaini388 – 410ExtracellularSequence analysisAdd BLAST23
Transmembranei411 – 431HelicalSequence analysisAdd BLAST21
Topological domaini432 – 435CytoplasmicSequence analysis4
Transmembranei436 – 456HelicalSequence analysisAdd BLAST21
Topological domaini457 – 486ExtracellularSequence analysisAdd BLAST30
Transmembranei487 – 507HelicalSequence analysisAdd BLAST21
Topological domaini508 – 520CytoplasmicSequence analysisAdd BLAST13
Transmembranei521 – 541HelicalSequence analysisAdd BLAST21
Topological domaini542 – 591ExtracellularSequence analysisAdd BLAST50
Transmembranei592 – 612HelicalSequence analysisAdd BLAST21
Topological domaini613 – 654CytoplasmicSequence analysisAdd BLAST42
Transmembranei655 – 675HelicalSequence analysisAdd BLAST21
Topological domaini676 – 680ExtracellularSequence analysis5
Transmembranei681 – 699HelicalSequence analysisAdd BLAST19
Topological domaini700 – 724CytoplasmicSequence analysisAdd BLAST25
Transmembranei725 – 745HelicalSequence analysisAdd BLAST21
Topological domaini746 – 899ExtracellularSequence analysisAdd BLAST154
Transmembranei900 – 920HelicalSequence analysisAdd BLAST21
Topological domaini921 – 1212CytoplasmicSequence analysisAdd BLAST292

GO - Cellular componenti

  • apical plasma membrane Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • extracellular vesicle Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6558.
OpenTargetsiENSG00000064651.
PharmGKBiPA35806.

Chemistry databases

ChEMBLiCHEMBL1615383.
DrugBankiDB00887. Bumetanide.
DB00761. Potassium Chloride.
DB01325. Quinethazone.
GuidetoPHARMACOLOGYi969.

Polymorphism and mutation databases

BioMutaiSLC12A2.
DMDMi1709292.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001780231 – 1212Solute carrier family 12 member 2Add BLAST1212

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei77PhosphoserineCombined sources1
Modified residuei79PhosphoserineCombined sources1
Modified residuei217PhosphothreonineCombined sources1
Modified residuei266PhosphothreonineBy similarity1
Modified residuei940PhosphoserineCombined sources1
Modified residuei944PhosphoserineBy similarity1
Modified residuei994PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP55011.
PaxDbiP55011.
PeptideAtlasiP55011.
PRIDEiP55011.

PTM databases

iPTMnetiP55011.
PhosphoSitePlusiP55011.

Expressioni

Tissue specificityi

Expressed in many tissues.

Gene expression databases

BgeeiENSG00000064651.
CleanExiHS_SLC12A2.
ExpressionAtlasiP55011. baseline and differential.
GenevisibleiP55011. HS.

Organism-specific databases

HPAiHPA020130.
HPA063697.

Interactioni

Binary interactionsi

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

GO - Molecular functioni

  • protein kinase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi112447. 31 interactors.
DIPiDIP-43979N.
IntActiP55011. 14 interactors.
MINTiMINT-5004359.
STRINGi9606.ENSP00000262461.

Chemistry databases

BindingDBiP55011.

Structurei

3D structure databases

ProteinModelPortaliP55011.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi90 – 122Ala-richAdd BLAST33
Compositional biasi188 – 194Poly-Gly7

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2083. Eukaryota.
COG0531. LUCA.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiP55011.
KOiK10951.
OMAiLSMEYSK.
OrthoDBiEOG091G04G2.
PhylomeDBiP55011.
TreeFamiTF313191.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR002443. Na/K/Cl_cotranspt.
IPR002444. NKCC1.
IPR018491. SLC12_C.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF58. PTHR11827:SF58. 3 hits.
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
PF03522. SLC12. 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. AlignAdd to basket

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

        10         20         30         40         50
MEPRPTAPSS GAPGLAGVGE TPSAAALAAA RVELPGTAVP SVPEDAAPAS
60 70 80 90 100
RDGGGVRDEG PAAAGDGLGR PLGPTPSQSR FQVDLVSENA GRAAAAAAAA
110 120 130 140 150
AAAAAAAGAG AGAKQTPADG EASGESEPAK GSEEAKGRFR VNFVDPAASS
160 170 180 190 200
SAEDSLSDAA GVGVDGPNVS FQNGGDTVLS EGSSLHSGGG GGSGHHQHYY
210 220 230 240 250
YDTHTNTYYL RTFGHNTMDA VPRIDHYRHT AAQLGEKLLR PSLAELHDEL
260 270 280 290 300
EKEPFEDGFA NGEESTPTRD AVVTYTAESK GVVKFGWIKG VLVRCMLNIW
310 320 330 340 350
GVMLFIRLSW IVGQAGIGLS VLVIMMATVV TTITGLSTSA IATNGFVRGG
360 370 380 390 400
GAYYLISRSL GPEFGGAIGL IFAFANAVAV AMYVVGFAET VVELLKEHSI
410 420 430 440 450
LMIDEINDIR IIGAITVVIL LGISVAGMEW EAKAQIVLLV ILLLAIGDFV
460 470 480 490 500
IGTFIPLESK KPKGFFGYKS EIFNENFGPD FREEETFFSV FAIFFPAATG
510 520 530 540 550
ILAGANISGD LADPQSAIPK GTLLAILITT LVYVGIAVSV GSCVVRDATG
560 570 580 590 600
NVNDTIVTEL TNCTSAACKL NFDFSSCESS PCSYGLMNNF QVMSMVSGFT
610 620 630 640 650
PLISAGIFSA TLSSALASLV SAPKIFQALC KDNIYPAFQM FAKGYGKNNE
660 670 680 690 700
PLRGYILTFL IALGFILIAE LNVIAPIISN FFLASYALIN FSVFHASLAK
710 720 730 740 750
SPGWRPAFKY YNMWISLLGA ILCCIVMFVI NWWAALLTYV IVLGLYIYVT
760 770 780 790 800
YKKPDVNWGS STQALTYLNA LQHSIRLSGV EDHVKNFRPQ CLVMTGAPNS
810 820 830 840 850
RPALLHLVHD FTKNVGLMIC GHVHMGPRRQ AMKEMSIDQA KYQRWLIKNK
860 870 880 890 900
MKAFYAPVHA DDLREGAQYL MQAAGLGRMK PNTLVLGFKK DWLQADMRDV
910 920 930 940 950
DMYINLFHDA FDIQYGVVVI RLKEGLDISH LQGQEELLSS QEKSPGTKDV
960 970 980 990 1000
VVSVEYSKKS DLDTSKPLSE KPITHKVEEE DGKTATQPLL KKESKGPIVP
1010 1020 1030 1040 1050
LNVADQKLLE ASTQFQKKQG KNTIDVWWLF DDGGLTLLIP YLLTTKKKWK
1060 1070 1080 1090 1100
DCKIRVFIGG KINRIDHDRR AMATLLSKFR IDFSDIMVLG DINTKPKKEN
1110 1120 1130 1140 1150
IIAFEEIIEP YRLHEDDKEQ DIADKMKEDE PWRITDNELE LYKTKTYRQI
1160 1170 1180 1190 1200
RLNELLKEHS STANIIVMSL PVARKGAVSS ALYMAWLEAL SKDLPPILLV
1210
RGNHQSVLTF YS
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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006105976 – 991Missing in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
UCSCiuc010jdg.4. human. [P55011-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliP55011.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112447. 31 interactors.
DIPiDIP-43979N.
IntActiP55011. 14 interactors.
MINTiMINT-5004359.
STRINGi9606.ENSP00000262461.

Chemistry databases

BindingDBiP55011.
ChEMBLiCHEMBL1615383.
DrugBankiDB00887. Bumetanide.
DB00761. Potassium Chloride.
DB01325. Quinethazone.
GuidetoPHARMACOLOGYi969.

Protein family/group databases

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

PTM databases

iPTMnetiP55011.
PhosphoSitePlusiP55011.

Polymorphism and mutation databases

BioMutaiSLC12A2.
DMDMi1709292.

Proteomic databases

EPDiP55011.
PaxDbiP55011.
PeptideAtlasiP55011.
PRIDEiP55011.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262461; ENSP00000262461; ENSG00000064651. [P55011-1]
ENST00000343225; ENSP00000340878; ENSG00000064651. [P55011-3]
GeneIDi6558.
KEGGihsa:6558.
UCSCiuc010jdg.4. human. [P55011-1]

Organism-specific databases

CTDi6558.
DisGeNETi6558.
GeneCardsiSLC12A2.
HGNCiHGNC:10911. SLC12A2.
HPAiHPA020130.
HPA063697.
MIMi600840. gene.
neXtProtiNX_P55011.
OpenTargetsiENSG00000064651.
PharmGKBiPA35806.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2083. Eukaryota.
COG0531. LUCA.
GeneTreeiENSGT00760000119053.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiP55011.
KOiK10951.
OMAiLSMEYSK.
OrthoDBiEOG091G04G2.
PhylomeDBiP55011.
TreeFamiTF313191.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000064651-MONOMER.
ReactomeiR-HSA-426117. Cation-coupled Chloride cotransporters.
SignaLinkiP55011.
SIGNORiP55011.

Miscellaneous databases

ChiTaRSiSLC12A2. human.
GenomeRNAii6558.
PROiP55011.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000064651.
CleanExiHS_SLC12A2.
ExpressionAtlasiP55011. baseline and differential.
GenevisibleiP55011. HS.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR002443. Na/K/Cl_cotranspt.
IPR002444. NKCC1.
IPR018491. SLC12_C.
IPR004842. SLC12A_fam.
[Graphical view]
PANTHERiPTHR11827:SF58. PTHR11827:SF58. 3 hits.
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
PF03522. SLC12. 1 hit.
[Graphical view]
PRINTSiPR01207. NAKCLTRNSPRT.
PR01208. NAKCLTRSPRT1.
TIGRFAMsiTIGR00930. 2a30. 1 hit.
ProtoNetiSearch...

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: November 2, 2016
This is version 154 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.