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Q13621 (S12A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Solute carrier family 12 member 1
Alternative name(s):
Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
Kidney-specific Na-K-Cl symporter
Gene names
Name:SLC12A1
Synonyms:NKCC2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1099 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Enzyme regulation

Activated by WNK3. Ref.4

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Kidney specific.

Involvement in disease

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. Ref.1

Sequence similarities

Belongs to the SLC12A transporter family.

Ontologies

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: Q13621-1)

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.
Isoform B (identifier: Q13621-2)

The sequence of this isoform is not available.
Isoform F (identifier: Q13621-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10991099Solute carrier family 12 member 1
PRO_0000178018

Regions

Topological domain1 – 177177Cytoplasmic Potential
Transmembrane178 – 19821Helical; Potential
Transmembrane202 – 22221Helical; Potential
Topological domain223 – 25937Cytoplasmic Potential
Transmembrane260 – 28021Helical; Potential
Transmembrane303 – 32321Helical; Potential
Topological domain324 – 3274Cytoplasmic Potential
Transmembrane328 – 34821Helical; Potential
Transmembrane380 – 40021Helical; Potential
Topological domain401 – 41717Cytoplasmic Potential
Transmembrane418 – 43821Helical; Potential
Transmembrane485 – 50521Helical; Potential
Topological domain506 – 55045Cytoplasmic Potential
Transmembrane551 – 57121Helical; Potential
Transmembrane572 – 59221Helical; Potential
Topological domain593 – 60917Cytoplasmic Potential
Transmembrane610 – 63021Helical; Potential
Transmembrane793 – 81321Helical; Potential
Topological domain814 – 1099286Cytoplasmic Potential

Amino acid modifications

Modified residue1301Phosphoserine; by AMPK By similarity
Glycosylation4461N-linked (GlcNAc...) Potential
Glycosylation4561N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence214 – 23825LIILL…ATNGF → IIIGLSVVVTTLTGISMSAI CTNGV in isoform F.
VSP_035701
Natural variant2721V → F in BS1. Ref.1
VAR_010223
Natural variant6481D → N in BS1. Ref.1
VAR_010224
Natural variant9581V → A. Ref.1 Ref.2
Corresponds to variant rs1552311 [ dbSNP | Ensembl ].
VAR_047257

Experimental info

Sequence conflict751Q → H in AAB07364. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified November 4, 2008. Version 2.
Checksum: C1C868B7F8B563AC

FASTA1,099121,450
        10         20         30         40         50         60 
MSLNNSSNVF LDSVPSNTNR FQVSVINENH ESSAAADDNT DPPHYEETSF GDEAQKRLRI 

        70         80         90        100        110        120 
SFRPGNQECY DNFLQSGETA KTDASFHAYD SHTNTYYLQT FGHNTMDAVP KIEYYRNTGS 

       130        140        150        160        170        180 
ISGPKVNRPS LLEIHEQLAK NVAVTPSSAD RVANGDGIPG DEQAENKEDD QAGVVKFGWV 

       190        200        210        220        230        240 
KGVLVRCMLN IWGVMLFIRL SWIVGEAGIG LGVLIILLST MVTSITGLST SAIATNGFVR 

       250        260        270        280        290        300 
GGGAYYLISR SLGPEFGGSI GLIFAFANAV AVAMYVVGFA ETVVDLLKES DSMMVDPTND 

       310        320        330        340        350        360 
IRIIGSITVV ILLGISVAGM EWEAKAQVIL LVILLIAIAN FFIGTVIPSN NEKKSRGFFN 

       370        380        390        400        410        420 
YQASIFAENF GPRFTKGEGF FSVFAIFFPA ATGILAGANI SGDLEDPQDA IPRGTMLAIF 

       430        440        450        460        470        480 
ITTVAYLGVA ICVGACVVRD ATGNMNDTII SGMNCNGSAA CGLGYDFSRC RHEPCQYGLM 

       490        500        510        520        530        540 
NNFQVMSMVS GFGPLITAGI FSATLSSALA SLVSAPKVFQ ALCKDNIYKA LQFFAKGYGK 

       550        560        570        580        590        600 
NNEPLRGYIL TFLIAMAFIL IAELNTIAPI ISNFFLASYA LINFSCFHAS YAKSPGWRPA 

       610        620        630        640        650        660 
YGIYNMWVSL FGAVLCCAVM FVINWWAAVI TYVIEFFLYV YVTCKKPDVN WGSSTQALSY 

       670        680        690        700        710        720 
VSALDNALEL TTVEDHVKNF RPQCIVLTGG PMTRPALLDI THAFTKNSGL CICCEVFVGP 

       730        740        750        760        770        780 
RKLCVKEMNS GMAKKQAWLI KNKIKAFYAA VAADCFRDGV RSLLQASGLG RMKPNTLVIG 

       790        800        810        820        830        840 
YKKNWRKAPL TEIENYVGII HDAFDFEIGV VIVRISQGFD ISQVLQVQEE LERLEQERLA 

       850        860        870        880        890        900 
LEATIKDNEC EEESGGIRGL FKKAGKLNIT KTTPKKDGSI NTSQSMHVGE FNQKLVEAST 

       910        920        930        940        950        960 
QFKKKQEKGT IDVWWLFDDG GLTLLIPYIL TLRKKWKDCK LRIYVGGKIN RIEEEKIVMA 

       970        980        990       1000       1010       1020 
SLLSKFRIKF ADIHIIGDIN IRPNKESWKV FEEMIEPYRL HESCKDLTTA EKLKRETPWK 

      1030       1040       1050       1060       1070       1080 
ITDAELEAVK EKSYRQVRLN ELLQEHSRAA NLIVLSLPVA RKGSISDLLY MAWLEILTKN 

      1090 
LPPVLLVRGN HKNVLTFYS 

« Hide

Isoform B (Sequence not available).
Isoform F [UniParc].

Checksum: 6C8CF44143E5D074
Show »

FASTA1,099121,388

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Similar Effects of all WNK3 Variants upon SLC12 Cotransporters."
Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A., Pasantes-Morales H., Gamba G., Mercado A.
Am. J. Physiol. 301:C601-C608(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U58130 mRNA. Translation: AAB07364.1.
EF559316 mRNA. Translation: ABU69043.2.
AC023355 Genomic DNA. No translation available.
AC066612 Genomic DNA. No translation available.
RefSeqNP_000329.2. NM_000338.2.
NP_001171761.1. NM_001184832.1.
UniGeneHs.123116.
Hs.605373.

3D structure databases

ProteinModelPortalQ13621.
SMRQ13621. Positions 239-585.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ13621. 3 interactions.
STRING9606.ENSP00000370381.

Chemistry

ChEMBLCHEMBL1874.
DrugBankDB00887. Bumetanide.
DB00534. Chlormerodrin.
DB00310. Chlorthalidone.
DB00903. Ethacrynic acid.
DB00695. Furosemide.
DB00774. Hydroflumethiazide.
DB00232. Methyclothiazide.
DB00524. Metolazone.
DB00761. Potassium Chloride.
DB00214. Torasemide.
DB01021. Trichlormethiazide.
GuidetoPHARMACOLOGY968.

Protein family/group databases

TCDB2.A.30.1.2. the cation-chloride cotransporter (ccc) family.

PTM databases

PhosphoSiteQ13621.

Polymorphism databases

DMDM212276464.

Proteomic databases

PaxDbQ13621.
PRIDEQ13621.

Protocols and materials databases

DNASU6557.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380993; ENSP00000370381; ENSG00000074803. [Q13621-1]
ENST00000396577; ENSP00000379822; ENSG00000074803.
ENST00000558405; ENSP00000453409; ENSG00000074803. [Q13621-1]
GeneID6557.
KEGGhsa:6557.
UCSCuc001zwn.4. human. [Q13621-1]

Organism-specific databases

CTD6557.
GeneCardsGC15P048498.
H-InvDBHIX0026769.
HGNCHGNC:10910. SLC12A1.
HPAHPA014967.
HPA018107.
MIM600839. gene.
601678. phenotype.
neXtProtNX_Q13621.
Orphanet93604. Antenatal Bartter syndrome.
PharmGKBPA320.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0531.
HOGENOMHOG000062855.
HOVERGENHBG052851.
InParanoidQ13621.
KOK14425.
OMAESWKVFE.
PhylomeDBQ13621.
TreeFamTF313191.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ13621.
BgeeQ13621.
CleanExHS_SLC12A1.
GenevestigatorQ13621.

Family and domain databases

InterProIPR004841. 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]
PfamPF00324. AA_permease. 1 hit.
PF08403. AA_permease_N. 1 hit.
[Graphical view]
PRINTSPR01207. NAKCLTRNSPRT.
PR01209. NAKCLTRSPRT2.
TIGRFAMsTIGR00930. 2a30. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC12A1. human.
GenomeRNAi6557.
NextBio25515.
PROQ13621.
SOURCESearch...

Entry information

Entry nameS12A1_HUMAN
AccessionPrimary (citable) accession number: Q13621
Secondary accession number(s): A8JYA2, E9PDW4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 4, 2008
Last modified: April 16, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM