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Protein

Solute carrier family 12 member 2

Gene

SLC12A2

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

Activity regulationi

Activated by WNK3.1 Publication

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Biological processIon transport, Potassium transport, Sodium transport, Symport, Transport
LigandChloride, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-426117 Cation-coupled Chloride cotransporters
SignaLinkiP55011
SIGNORiP55011

Protein family/group databases

TCDBi2.A.30.1.4 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

EuPathDBiHostDB:ENSG00000064651.13
HGNCiHGNC:10911 SLC12A2
MIMi600840 gene
neXtProtiNX_P55011

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 residuei212PhosphothreonineBy similarity1
Modified residuei217PhosphothreonineCombined sources1
Modified residuei230PhosphothreonineBy similarity1
Modified residuei242PhosphoserineBy similarity1
Modified residuei266PhosphothreonineBy similarity1
Modified residuei940PhosphoserineCombined sources1
Modified residuei944PhosphoserineBy similarity1
Modified residuei994PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP55011
PaxDbiP55011
PeptideAtlasiP55011
PRIDEiP55011
ProteomicsDBi56757
56758 [P55011-3]

PTM databases

GlyConnecti1761
iPTMnetiP55011
PhosphoSitePlusiP55011

Expressioni

Tissue specificityi

Expressed in many tissues.

Gene expression databases

BgeeiENSG00000064651 Expressed in 222 organ(s), highest expression level in corpus callosum
CleanExiHS_SLC12A2
ExpressionAtlasiP55011 baseline and differential
GenevisibleiP55011 HS

Organism-specific databases

HPAiHPA020130
HPA063697

Interactioni

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112447, 38 interactors
DIPiDIP-43979N
IntActiP55011, 19 interactors
MINTiP55011
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
OMAiNPCSYGL
OrthoDBiEOG091G04G2
PhylomeDBiP55011
TreeFamiTF313191

Family and domain databases

InterProiView protein in InterPro
IPR004841 AA-permease/SLC12A_dom
IPR013612 AA_permease_N
IPR002443 Na/K/Cl_cotranspt
IPR002444 NKCC1
IPR018491 SLC12_C
IPR004842 SLC12A_fam
PANTHERiPTHR11827:SF58 PTHR11827:SF58, 1 hit
PfamiView protein in Pfam
PF00324 AA_permease, 1 hit
PF08403 AA_permease_N, 1 hit
PF03522 SLC12, 1 hit
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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3XAL9G3XAL9_HUMAN
Solute carrier family 12 (Sodium/po...
SLC12A2 hCG_27034
1,150Annotation score:

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

Similar proteinsi

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, 38 interactors
DIPiDIP-43979N
IntActiP55011, 19 interactors
MINTiP55011
STRINGi9606.ENSP00000262461

Chemistry databases

BindingDBiP55011
ChEMBLiCHEMBL1615383
DrugBankiDB00887 Bumetanide
DB00761 Potassium Chloride
DB01325 Quinethazone
GuidetoPHARMACOLOGYi969

Protein family/group databases

TCDBi2.A.30.1.4 the cation-chloride cotransporter (ccc) family

PTM databases

GlyConnecti1761
iPTMnetiP55011
PhosphoSitePlusiP55011

Polymorphism and mutation databases

BioMutaiSLC12A2
DMDMi1709292

Proteomic databases

EPDiP55011
PaxDbiP55011
PeptideAtlasiP55011
PRIDEiP55011
ProteomicsDBi56757
56758 [P55011-3]

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
EuPathDBiHostDB:ENSG00000064651.13
GeneCardsiSLC12A2
HGNCiHGNC:10911 SLC12A2
HPAiHPA020130
HPA063697
MIMi600840 gene
neXtProtiNX_P55011
OpenTargetsiENSG00000064651
PharmGKBiPA35806
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-HSA-426117 Cation-coupled Chloride cotransporters
SignaLinkiP55011
SIGNORiP55011

Miscellaneous databases

ChiTaRSiSLC12A2 human
GenomeRNAii6558
PROiPR:P55011
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000064651 Expressed in 222 organ(s), highest expression level in corpus callosum
CleanExiHS_SLC12A2
ExpressionAtlasiP55011 baseline and differential
GenevisibleiP55011 HS

Family and domain databases

InterProiView protein in InterPro
IPR004841 AA-permease/SLC12A_dom
IPR013612 AA_permease_N
IPR002443 Na/K/Cl_cotranspt
IPR002444 NKCC1
IPR018491 SLC12_C
IPR004842 SLC12A_fam
PANTHERiPTHR11827:SF58 PTHR11827:SF58, 1 hit
PfamiView protein in Pfam
PF00324 AA_permease, 1 hit
PF08403 AA_permease_N, 1 hit
PF03522 SLC12, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 7, 2018
This is version 171 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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