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Q13621

- S12A1_HUMAN

UniProt

Q13621 - S12A1_HUMAN

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Protein
Solute carrier family 12 member 1
Gene
SLC12A1, NKCC2
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. sodium:potassium:chloride symporter activity Source: ProtInc

GO - Biological processi

  1. cell death Source: UniProtKB-KW
  2. chloride transmembrane transport Source: GOC
  3. chloride transport Source: GOC
  4. ion transmembrane transport Source: BHF-UCL
  5. ion transport Source: Reactome
  6. potassium ion transport Source: UniProtKB-KW
  7. sodium ion transport Source: UniProtKB-KW
  8. transmembrane transport Source: Reactome
  9. 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.

Protein family/group databases

TCDBi2.A.30.1.2. the cation-chloride cotransporter (ccc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Solute carrier family 12 member 1
Alternative name(s):
Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
Kidney-specific Na-K-Cl symporter
Gene namesi
Name:SLC12A1
Synonyms:NKCC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:10910. SLC12A1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 177177Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei178 – 19821Helical; Reviewed prediction
Add
BLAST
Transmembranei202 – 22221Helical; Reviewed prediction
Add
BLAST
Topological domaini223 – 25937Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei260 – 28021Helical; Reviewed prediction
Add
BLAST
Transmembranei303 – 32321Helical; Reviewed prediction
Add
BLAST
Topological domaini324 – 3274Cytoplasmic Reviewed prediction
Transmembranei328 – 34821Helical; Reviewed prediction
Add
BLAST
Transmembranei380 – 40021Helical; Reviewed prediction
Add
BLAST
Topological domaini401 – 41717Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei418 – 43821Helical; Reviewed prediction
Add
BLAST
Transmembranei485 – 50521Helical; Reviewed prediction
Add
BLAST
Topological domaini506 – 55045Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei551 – 57121Helical; Reviewed prediction
Add
BLAST
Transmembranei572 – 59221Helical; Reviewed prediction
Add
BLAST
Topological domaini593 – 60917Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei610 – 63021Helical; Reviewed prediction
Add
BLAST
Transmembranei793 – 81321Helical; Reviewed prediction
Add
BLAST
Topological domaini814 – 1099286Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
  2. integral component of membrane Source: UniProtKB-KW
  3. membrane Source: ProtInc
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Bartter syndrome 1 (BS1) [MIM:601678]: An autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. Bartter syndrome type 1 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti272 – 2721V → F in BS1. 1 Publication
VAR_010223
Natural varianti648 – 6481D → N in BS1. 1 Publication
VAR_010224

Keywords - Diseasei

Bartter syndrome, Disease mutation, Neurodegeneration

Organism-specific databases

MIMi601678. phenotype.
Orphaneti93604. Antenatal Bartter syndrome.
PharmGKBiPA320.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10991099Solute carrier family 12 member 1
PRO_0000178018Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei130 – 1301Phosphoserine; by AMPK By similarity
Glycosylationi446 – 4461N-linked (GlcNAc...) Reviewed prediction
Glycosylationi456 – 4561N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ13621.
PaxDbiQ13621.
PRIDEiQ13621.

PTM databases

PhosphoSiteiQ13621.

Expressioni

Tissue specificityi

Kidney specific.

Gene expression databases

ArrayExpressiQ13621.
BgeeiQ13621.
CleanExiHS_SLC12A1.
GenevestigatoriQ13621.

Organism-specific databases

HPAiHPA014967.
HPA018107.

Interactioni

Protein-protein interaction databases

IntActiQ13621. 3 interactions.
STRINGi9606.ENSP00000370381.

Structurei

3D structure databases

ProteinModelPortaliQ13621.
SMRiQ13621. Positions 239-585.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
HOGENOMiHOG000062855.
HOVERGENiHBG052851.
InParanoidiQ13621.
KOiK14425.
OMAiESWKVFE.
PhylomeDBiQ13621.
TreeFamiTF313191.

Family and domain databases

InterProiIPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR002443. Na/K/Cl_cotranspt.
IPR002445. Na/K/Cl_cotranspt2.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view]
PfamiPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view]
PRINTSiPR01207. NAKCLTRNSPRT.
PR01209. NAKCLTRSPRT2.
TIGRFAMsiTIGR00930. 2a30. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform A (identifier: Q13621-1) [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

MSLNNSSNVF LDSVPSNTNR FQVSVINENH ESSAAADDNT DPPHYEETSF     50
GDEAQKRLRI SFRPGNQECY DNFLQSGETA KTDASFHAYD SHTNTYYLQT 100
FGHNTMDAVP KIEYYRNTGS ISGPKVNRPS LLEIHEQLAK NVAVTPSSAD 150
RVANGDGIPG DEQAENKEDD QAGVVKFGWV KGVLVRCMLN IWGVMLFIRL 200
SWIVGEAGIG LGVLIILLST MVTSITGLST SAIATNGFVR GGGAYYLISR 250
SLGPEFGGSI GLIFAFANAV AVAMYVVGFA ETVVDLLKES DSMMVDPTND 300
IRIIGSITVV ILLGISVAGM EWEAKAQVIL LVILLIAIAN FFIGTVIPSN 350
NEKKSRGFFN YQASIFAENF GPRFTKGEGF FSVFAIFFPA ATGILAGANI 400
SGDLEDPQDA IPRGTMLAIF ITTVAYLGVA ICVGACVVRD ATGNMNDTII 450
SGMNCNGSAA CGLGYDFSRC RHEPCQYGLM NNFQVMSMVS GFGPLITAGI 500
FSATLSSALA SLVSAPKVFQ ALCKDNIYKA LQFFAKGYGK NNEPLRGYIL 550
TFLIAMAFIL IAELNTIAPI ISNFFLASYA LINFSCFHAS YAKSPGWRPA 600
YGIYNMWVSL FGAVLCCAVM FVINWWAAVI TYVIEFFLYV YVTCKKPDVN 650
WGSSTQALSY VSALDNALEL TTVEDHVKNF RPQCIVLTGG PMTRPALLDI 700
THAFTKNSGL CICCEVFVGP RKLCVKEMNS GMAKKQAWLI KNKIKAFYAA 750
VAADCFRDGV RSLLQASGLG RMKPNTLVIG YKKNWRKAPL TEIENYVGII 800
HDAFDFEIGV VIVRISQGFD ISQVLQVQEE LERLEQERLA LEATIKDNEC 850
EEESGGIRGL FKKAGKLNIT KTTPKKDGSI NTSQSMHVGE FNQKLVEAST 900
QFKKKQEKGT IDVWWLFDDG GLTLLIPYIL TLRKKWKDCK LRIYVGGKIN 950
RIEEEKIVMA SLLSKFRIKF ADIHIIGDIN IRPNKESWKV FEEMIEPYRL 1000
HESCKDLTTA EKLKRETPWK ITDAELEAVK EKSYRQVRLN ELLQEHSRAA 1050
NLIVLSLPVA RKGSISDLLY MAWLEILTKN LPPVLLVRGN HKNVLTFYS 1099
Length:1,099
Mass (Da):121,450
Last modified:November 4, 2008 - v2
Checksum:iC1C868B7F8B563AC
GO
Isoform B (identifier: Q13621-2)

Sequence is not available
Length:
Mass (Da):
Isoform F (identifier: Q13621-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     214-238: LIILLSTMVTSITGLSTSAIATNGF → IIIGLSVVVTTLTGISMSAICTNGV

Note: Ref.1 (AAB07364) sequence is in conflict in positions: 220:VV->TI, 225:L->I 228:I->M, 230:T->M and 234:C->A.

Show »
Length:1,099
Mass (Da):121,388
Checksum:i6C8CF44143E5D074
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti272 – 2721V → F in BS1. 1 Publication
VAR_010223
Natural varianti648 – 6481D → N in BS1. 1 Publication
VAR_010224
Natural varianti958 – 9581V → A.2 Publications
Corresponds to variant rs1552311 [ dbSNP | Ensembl ].
VAR_047257

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei214 – 23825LIILL…ATNGF → IIIGLSVVVTTLTGISMSAI CTNGV in isoform F.
VSP_035701Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti75 – 751Q → H in AAB07364. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U58130 mRNA. Translation: AAB07364.1.
EF559316 mRNA. Translation: ABU69043.2.
AC023355 Genomic DNA. No translation available.
AC066612 Genomic DNA. No translation available.
CCDSiCCDS10129.2. [Q13621-1]
CCDS53940.1. [Q13621-3]
RefSeqiNP_000329.2. NM_000338.2. [Q13621-1]
NP_001171761.1. NM_001184832.1. [Q13621-3]
UniGeneiHs.123116.
Hs.605373.

Genome annotation databases

EnsembliENST00000380993; ENSP00000370381; ENSG00000074803. [Q13621-1]
ENST00000396577; ENSP00000379822; ENSG00000074803.
ENST00000558405; ENSP00000453409; ENSG00000074803. [Q13621-1]
GeneIDi6557.
KEGGihsa:6557.
UCSCiuc001zwn.4. human. [Q13621-1]

Polymorphism databases

DMDMi212276464.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U58130 mRNA. Translation: AAB07364.1 .
EF559316 mRNA. Translation: ABU69043.2 .
AC023355 Genomic DNA. No translation available.
AC066612 Genomic DNA. No translation available.
CCDSi CCDS10129.2. [Q13621-1 ]
CCDS53940.1. [Q13621-3 ]
RefSeqi NP_000329.2. NM_000338.2. [Q13621-1 ]
NP_001171761.1. NM_001184832.1. [Q13621-3 ]
UniGenei Hs.123116.
Hs.605373.

3D structure databases

ProteinModelPortali Q13621.
SMRi Q13621. Positions 239-585.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q13621. 3 interactions.
STRINGi 9606.ENSP00000370381.

Chemistry

ChEMBLi CHEMBL1874.
DrugBanki DB00887. Bumetanide.
DB00534. Chlormerodrin.
DB00310. Chlorthalidone.
DB00903. Ethacrynic acid.
DB00695. Furosemide.
DB00774. Hydroflumethiazide.
DB00232. Methyclothiazide.
DB00524. Metolazone.
DB00761. Potassium Chloride.
DB00214. Torasemide.
DB01021. Trichlormethiazide.
GuidetoPHARMACOLOGYi 968.

Protein family/group databases

TCDBi 2.A.30.1.2. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSitei Q13621.

Polymorphism databases

DMDMi 212276464.

Proteomic databases

MaxQBi Q13621.
PaxDbi Q13621.
PRIDEi Q13621.

Protocols and materials databases

DNASUi 6557.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000380993 ; ENSP00000370381 ; ENSG00000074803 . [Q13621-1 ]
ENST00000396577 ; ENSP00000379822 ; ENSG00000074803 .
ENST00000558405 ; ENSP00000453409 ; ENSG00000074803 . [Q13621-1 ]
GeneIDi 6557.
KEGGi hsa:6557.
UCSCi uc001zwn.4. human. [Q13621-1 ]

Organism-specific databases

CTDi 6557.
GeneCardsi GC15P048498.
H-InvDB HIX0026769.
HGNCi HGNC:10910. SLC12A1.
HPAi HPA014967.
HPA018107.
MIMi 600839. gene.
601678. phenotype.
neXtProti NX_Q13621.
Orphaneti 93604. Antenatal Bartter syndrome.
PharmGKBi PA320.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0531.
HOGENOMi HOG000062855.
HOVERGENi HBG052851.
InParanoidi Q13621.
KOi K14425.
OMAi ESWKVFE.
PhylomeDBi Q13621.
TreeFami TF313191.

Enzyme and pathway databases

Reactomei REACT_19315. Cation-coupled Chloride cotransporters.

Miscellaneous databases

ChiTaRSi SLC12A1. human.
GenomeRNAii 6557.
NextBioi 25515.
PROi Q13621.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q13621.
Bgeei Q13621.
CleanExi HS_SLC12A1.
Genevestigatori Q13621.

Family and domain databases

InterProi IPR004841. AA-permease/SLC12A_dom.
IPR013612. AA_permease_N.
IPR002443. Na/K/Cl_cotranspt.
IPR002445. Na/K/Cl_cotranspt2.
IPR004842. Na/K/Cl_cotransptS.
[Graphical view ]
Pfami PF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view ]
PRINTSi PR01207. NAKCLTRNSPRT.
PR01209. NAKCLTRSPRT2.
TIGRFAMsi TIGR00930. 2a30. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Bartter's syndrome, hypokalemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2."
    Simon D.B., Karet F.E., Hamdan J.M., Di Pietro A., Sanjad S.A., Lifton R.P.
    Nat. Genet. 13:183-188(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM F), VARIANTS BS1 PHE-272 AND ASN-648, VARIANT ALA-958, ALTERNATIVE SPLICING.
  2. "Molecular cloning and characterization of NKCC2A in non-renal tissues."
    Di Fulvio M., Garzon-Muvdi T., Alvarez-Leefmans F.J.
    Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), VARIANT ALA-958.
    Tissue: Spinal ganglion.
  3. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: ENZYME REGULATION.

Entry informationi

Entry nameiS12A1_HUMAN
AccessioniPrimary (citable) accession number: Q13621
Secondary accession number(s): A8JYA2, E9PDW4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 4, 2008
Last modified: September 3, 2014
This is version 136 of the entry and version 2 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 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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