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    Slc12a1 solute carrier family 12, member 1 [ Mus musculus (house mouse) ]

    Gene ID: 20495, updated on 2-Nov-2024

    Summary

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    Official Symbol
    Slc12a1provided by MGI
    Official Full Name
    solute carrier family 12, member 1provided by MGI
    Primary source
    MGI:MGI:103150
    See related
    Ensembl:ENSMUSG00000027202 AllianceGenome:MGI:103150
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Nkcc2; mBSC1; mNKCC2; urehr3; D630042G03Rik
    Summary
    Enables sodium:potassium:chloride symporter activity. Acts upstream of or within kidney development and urea transmembrane transport. Located in apical plasma membrane. Is expressed in several structures, including alimentary system and urinary system. Used to study Bartter disease type 1. Human ortholog(s) of this gene implicated in Bartter disease and Bartter disease type 1. Orthologous to human SLC12A1 (solute carrier family 12 member 1). [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Restricted expression toward kidney adult (RPKM 70.5) See more
    Orthologs
    human all
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    Genomic context

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    See Slc12a1 in Genome Data Viewer
    Location:
    2 F1; 2 61.23 cM
    Exon count:
    29
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 2 NC_000068.8 (124994430..125071922)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 2 NC_000068.7 (125152510..125230002)

    Chromosome 2 - NC_000068.8Genomic Context describing neighboring genes Neighboring gene myelin basic protein expression factor 2, repressor Neighboring gene predicted gene, 46759 Neighboring gene cortexin 2 Neighboring gene STARR-positive B cell enhancer mm9_chr2:125014961-125015261 Neighboring gene predicted gene, 46760 Neighboring gene predicted gene 14002 Neighboring gene STARR-seq mESC enhancer starr_05586 Neighboring gene STARR-positive B cell enhancer mm9_chr2:125073047-125073348 Neighboring gene STARR-seq mESC enhancer starr_05587 Neighboring gene deoxyuridine triphosphatase Neighboring gene STARR-seq mESC enhancer starr_05588 Neighboring gene fibrillin 1 Neighboring gene STARR-seq mESC enhancer starr_05589

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK). Fraser SA, et al. Biochem J, 2007 Jul 1. PMID 17341212, Free PMC Article
    2. Renal-Specific Silencing of TNF (Tumor Necrosis Factor) Unmasks Salt-Dependent Increases in Blood Pressure via an NKCC2A (Na(+)-K(+)-2Cl(-) Cotransporter Isoform A)-Dependent Mechanism. Hao S, et al. Hypertension, 2018 Jun. PMID 29735631, Free PMC Article
    3. Multiple evolutionarily conserved Di-leucine like motifs in the carboxyl terminus control the anterograde trafficking of NKCC2. Zaarour N, et al. J Biol Chem, 2012 Dec 14. PMID 23105100, Free PMC Article
    4. Impaired glucose tolerance, glucagon, and insulin responses in mice lacking the loop diuretic-sensitive Nkcc2a transporter. Kelly L, et al. Am J Physiol Cell Physiol, 2019 Oct 1. PMID 31365295, Free PMC Article
    5. Posttranscriptional compensation for heterozygous disruption of the kidney-specific NaK2Cl cotransporter gene. Takahashi N, et al. J Am Soc Nephrol, 2002 Mar. PMID 11856763

    See all (134) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Dysregulation of the WNK4-SPAK/OSR1 pathway has a minor effect on baseline NKCC2 phosphorylation.
      Title: Dysregulation of the WNK4-SPAK/OSR1 pathway has a minor effect on baseline NKCC2 phosphorylation.
    2. Tubular-specific CDK12 knockout causes a defect in urine concentration due to premature cleavage of the slc12a1 gene.
      Title: Tubular-specific CDK12 knockout causes a defect in urine concentration due to premature cleavage of the slc12a1 gene.
    3. Renal NKCC2 Is Dual Regulated by the Synergy of 20-HETE and High-Fat Diet in CYP4F2 Transgenic Mice.
      Title: Renal NKCC2 Is Dual Regulated by the Synergy of 20-HETE and High-Fat Diet in CYP4F2 Transgenic Mice.
    4. Upregulation of renal Na-K-2Cl cotransporter 2 in obese diabetes mellitus via a vasopressin receptor 2-dependent pathway.
      Title: Upregulation of renal Na-K-2Cl cotransporter 2 in obese diabetes mellitus via a vasopressin receptor 2-dependent pathway.
    5. Collectively, these findings demonstrate that downregulation of renal TNF-alpha production in response to low-salt conditions contributes to the regulation of NaCl reabsorption via an NKCC2B-dependent mechanism.
      Title: Regulation of NKCC2B by TNF-α in response to salt restriction.
    6. that WNK4 increases the abundance of phosphorylated NKCC2
      Title: With no lysine kinase 4 modulates sodium potassium 2 chloride cotransporter activity in vivo.
    7. Moesin regulates the internalization of NKCC2.
      Title: Internalization of NKCC2 is impaired in thick ascending limb of Henle in moesin knockout mice.
    8. the decrease in urine volume and NaCl excretion induced by renal TNF silencing was abolished when NKCC2A was concurrently silenced, suggesting that this isoform contributes to the transition from a salt-resistant to salt-sensitive phenotype.
      Title: Renal-Specific Silencing of TNF (Tumor Necrosis Factor) Unmasks Salt-Dependent Increases in Blood Pressure via an NKCC2A (Na(+)-K(+)-2Cl(-) Cotransporter Isoform A)-Dependent Mechanism.
    9. The differential regulation of ROMK, large-conductance Ca(2+)-activated K(+) (BK) channel, BK-alpha and NKCC2 between female and male mice, at least, were partly mediated via WNK1 pathway, which may contribute to the sexual dimorphism of plasma K(+) and blood pressure control.
      Title: Involvement of WNK1-mediated potassium channels in the sexual dimorphism of blood pressure.
    10. VAMP3 is required for normal NKCC2 expression, renal function, and blood pressure.
      Title: Vesicle-associated Membrane Protein 3 (VAMP3) Mediates Constitutive Trafficking of the Renal Co-transporter NKCC2 in Thick Ascending Limbs: ROLE IN RENAL FUNCTION AND BLOOD PRESSURE.
    Submit: New GeneRIF Correction See all GeneRIFs (39)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables chloride:monoatomic cation symporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables potassium ion transmembrane transporter activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sodium:potassium:chloride symporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables sodium:potassium:chloride symporter activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables sodium:potassium:chloride symporter activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell volume homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell volume homeostasis ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in chloride ion homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in chloride transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in chloride transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in chloride transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within kidney development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in monoatomic ion transmembrane transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in potassium ion homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in potassium ion import across plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in potassium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in potassium ion transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein insertion into membrane from inner side ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in sodium ion homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sodium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in sodium ion transmembrane transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in sodium ion transport ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within urea transmembrane transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in apical plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in apical plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in apical plasma membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in apical plasma membrane ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in cell surface ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in extracellular exosome ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    solute carrier family 12 member 1
    Names
    BSC1
    Na-K-2Cl cotransporter 2
    bumetanide-sensitive cotransporter type 1
    bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1
    bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
    kidney-specific Na-K-Cl symporter

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001079690.2 → NP_001073158.2  solute carrier family 12 member 1 isoform F

      Status: VALIDATED

      Source sequence(s)
      AK052750, AL844547, AL929451, BY716143
      Consensus CDS
      CCDS50694.1
      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      UniProtKB/TrEMBL
      A2AQ51
      Related
      ENSMUSP00000106121.3, ENSMUST00000110495.3
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1090
      2a30; K-Cl cotransporter

    2. NM_183354.3 → NP_899197.3  solute carrier family 12 member 1 isoform A

      Status: VALIDATED

      Source sequence(s)
      AK052750, AL844547, AL929451, BY716143
      Consensus CDS
      CCDS50693.1
      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      UniProtKB/TrEMBL
      A2AQ50
      Related
      ENSMUSP00000028630.3, ENSMUST00000028630.9
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1090
      2a30; K-Cl cotransporter

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000068.8 Reference GRCm39 C57BL/6J

      Range
      124994430..125071922
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_030248885.1 → XP_030104745.1  solute carrier family 12 member 1 isoform X1

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1154
      2a30; K-Cl cotransporter

    2. XM_030248888.1 → XP_030104748.1  solute carrier family 12 member 1 isoform X3

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1122
      2a30; K-Cl cotransporter

    3. XM_030248890.1 → XP_030104750.1  solute carrier family 12 member 1 isoform X5

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      UniProtKB/TrEMBL
      A2AQ52
      Related
      ENSMUSP00000106120.3, ENSMUST00000110494.9
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1090
      2a30; K-Cl cotransporter

    4. XM_030248887.1 → XP_030104747.1  solute carrier family 12 member 1 isoform X2

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1122
      2a30; K-Cl cotransporter

    5. XM_030248886.1 → XP_030104746.1  solute carrier family 12 member 1 isoform X1

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1154
      2a30; K-Cl cotransporter

    6. XM_030248891.1 → XP_030104751.1  solute carrier family 12 member 1 isoform X5

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      UniProtKB/TrEMBL
      A2AQ52
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1090
      2a30; K-Cl cotransporter

    7. XM_030248892.1 → XP_030104752.1  solute carrier family 12 member 1 isoform X6

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      UniProtKB/TrEMBL
      A2AQ50
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1090
      2a30; K-Cl cotransporter

    8. XM_030248889.1 → XP_030104749.1  solute carrier family 12 member 1 isoform X4

      UniProtKB/Swiss-Prot
      O35938, P55014, Q91W55, Q9Z1E0
      UniProtKB/TrEMBL
      A2AQ51
      Conserved Domains (1) summary
      TIGR00930
      Location:96 → 1090
      2a30; K-Cl cotransporter

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_011389.1: Suppressed sequence

      Description
      NM_011389.1: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P55014.2 GenPept UniProtKB/Swiss-Prot:P55014

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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