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Q13621

- S12A1_HUMAN

UniProt

Q13621 - S12A1_HUMAN

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Protein

Solute carrier family 12 member 1

Gene

SLC12A1

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. chemical homeostasis Source: Ensembl
  3. chloride transmembrane transport Source: GOC
  4. chloride transport Source: GOC
  5. excretion Source: Ensembl
  6. ion transmembrane transport Source: BHF-UCL
  7. ion transport Source: Reactome
  8. kidney development Source: Ensembl
  9. potassium ion transport Source: UniProtKB-KW
  10. sodium ion transport Source: UniProtKB-KW
  11. transmembrane transport Source: Reactome
  12. 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

GO - Cellular componenti

  1. apical plasma membrane Source: Ensembl
  2. extracellular vesicular exosome Source: UniProtKB
  3. integral component of membrane Source: UniProtKB-KW
  4. membrane Source: ProtInc
  5. 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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
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 1PRO_0000178018Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei130 – 1301Phosphoserine; by AMPKBy similarity
Glycosylationi446 – 4461N-linked (GlcNAc...)Sequence Analysis
Glycosylationi456 – 4561N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ13621.
PaxDbiQ13621.
PRIDEiQ13621.

PTM databases

PhosphoSiteiQ13621.

Expressioni

Tissue specificityi

Kidney specific.

Gene expression databases

BgeeiQ13621.
CleanExiHS_SLC12A1.
ExpressionAtlasiQ13621. baseline and differential.
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.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 177177CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini223 – 25937CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini324 – 3274CytoplasmicSequence Analysis
Topological domaini401 – 41717CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini506 – 55045CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini593 – 60917CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini814 – 1099286CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei178 – 19821HelicalSequence AnalysisAdd
BLAST
Transmembranei202 – 22221HelicalSequence AnalysisAdd
BLAST
Transmembranei260 – 28021HelicalSequence AnalysisAdd
BLAST
Transmembranei303 – 32321HelicalSequence AnalysisAdd
BLAST
Transmembranei328 – 34821HelicalSequence AnalysisAdd
BLAST
Transmembranei380 – 40021HelicalSequence AnalysisAdd
BLAST
Transmembranei418 – 43821HelicalSequence AnalysisAdd
BLAST
Transmembranei485 – 50521HelicalSequence AnalysisAdd
BLAST
Transmembranei551 – 57121HelicalSequence AnalysisAdd
BLAST
Transmembranei572 – 59221HelicalSequence AnalysisAdd
BLAST
Transmembranei610 – 63021HelicalSequence AnalysisAdd
BLAST
Transmembranei793 – 81321HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Sequence similaritiesi

Belongs to the SLC12A transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0531.
GeneTreeiENSGT00760000119053.
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

        10         20         30         40         50
MSLNNSSNVF LDSVPSNTNR FQVSVINENH ESSAAADDNT DPPHYEETSF
60 70 80 90 100
GDEAQKRLRI SFRPGNQECY DNFLQSGETA KTDASFHAYD SHTNTYYLQT
110 120 130 140 150
FGHNTMDAVP KIEYYRNTGS ISGPKVNRPS LLEIHEQLAK NVAVTPSSAD
160 170 180 190 200
RVANGDGIPG DEQAENKEDD QAGVVKFGWV KGVLVRCMLN IWGVMLFIRL
210 220 230 240 250
SWIVGEAGIG LGVLIILLST MVTSITGLST SAIATNGFVR GGGAYYLISR
260 270 280 290 300
SLGPEFGGSI GLIFAFANAV AVAMYVVGFA ETVVDLLKES DSMMVDPTND
310 320 330 340 350
IRIIGSITVV ILLGISVAGM EWEAKAQVIL LVILLIAIAN FFIGTVIPSN
360 370 380 390 400
NEKKSRGFFN YQASIFAENF GPRFTKGEGF FSVFAIFFPA ATGILAGANI
410 420 430 440 450
SGDLEDPQDA IPRGTMLAIF ITTVAYLGVA ICVGACVVRD ATGNMNDTII
460 470 480 490 500
SGMNCNGSAA CGLGYDFSRC RHEPCQYGLM NNFQVMSMVS GFGPLITAGI
510 520 530 540 550
FSATLSSALA SLVSAPKVFQ ALCKDNIYKA LQFFAKGYGK NNEPLRGYIL
560 570 580 590 600
TFLIAMAFIL IAELNTIAPI ISNFFLASYA LINFSCFHAS YAKSPGWRPA
610 620 630 640 650
YGIYNMWVSL FGAVLCCAVM FVINWWAAVI TYVIEFFLYV YVTCKKPDVN
660 670 680 690 700
WGSSTQALSY VSALDNALEL TTVEDHVKNF RPQCIVLTGG PMTRPALLDI
710 720 730 740 750
THAFTKNSGL CICCEVFVGP RKLCVKEMNS GMAKKQAWLI KNKIKAFYAA
760 770 780 790 800
VAADCFRDGV RSLLQASGLG RMKPNTLVIG YKKNWRKAPL TEIENYVGII
810 820 830 840 850
HDAFDFEIGV VIVRISQGFD ISQVLQVQEE LERLEQERLA LEATIKDNEC
860 870 880 890 900
EEESGGIRGL FKKAGKLNIT KTTPKKDGSI NTSQSMHVGE FNQKLVEAST
910 920 930 940 950
QFKKKQEKGT IDVWWLFDDG GLTLLIPYIL TLRKKWKDCK LRIYVGGKIN
960 970 980 990 1000
RIEEEKIVMA SLLSKFRIKF ADIHIIGDIN IRPNKESWKV FEEMIEPYRL
1010 1020 1030 1040 1050
HESCKDLTTA EKLKRETPWK ITDAELEAVK EKSYRQVRLN ELLQEHSRAA
1060 1070 1080 1090
NLIVLSLPVA RKGSISDLLY MAWLEILTKN LPPVLLVRGN HKNVLTFYS
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

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti75 – 751Q → H in AAB07364. (PubMed:8640224)Curated
Isoform F (identifier: Q13621-3)
Sequence conflicti220 – 2212VV → TI in AAB07364. (PubMed:8640224)
Sequence conflicti225 – 2251L → I in AAB07364. (PubMed:8640224)
Sequence conflicti228 – 2281I → M in AAB07364. (PubMed:8640224)
Sequence conflicti230 – 2301M → T in AAB07364. (PubMed:8640224)
Sequence conflicti234 – 2341C → A in AAB07364. (PubMed:8640224)

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. 1 PublicationVSP_035701Add
BLAST

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. [Q13621-3]
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.
DB00761. Potassium Chloride.
DB01325. Quinethazone.
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 . [Q13621-3 ]
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.
GeneTreei ENSGT00760000119053.
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

Bgeei Q13621.
CleanExi HS_SLC12A1.
ExpressionAtlasi Q13621. baseline and differential.
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: October 29, 2014
This is version 138 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