Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q13621

- S12A1_HUMAN

UniProt

Q13621 - S12A1_HUMAN

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 2 (04 Nov 2008)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    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. extracellular vesicular exosome Source: UniProtKB
    2. integral component of membrane Source: UniProtKB-KW
    3. membrane Source: ProtInc
    4. plasma membrane Source: Reactome

    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

    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.
    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.
    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, 234:C->A.

    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

    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.
    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 . [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.
    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

    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 1, 2014
    This is version 137 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