Slc12a3 solute carrier family 12 member 3 [Rattus norvegicus (Norway rat)] - Gene

Summary

Symbol: Slc12a3provided by RGD
Full Name: solute carrier family 12 member 3provided by RGD
Primary source: RGD:3686
See related: EnsemblRapid:ENSRNOG00000057072 AllianceGenome:RGD:3686
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: NCC; TSC
Summary: Enables enzyme binding activity and sodium:chloride symporter activity. Involved in chloride transport and sodium ion transmembrane transport. Located in apical plasma membrane and vesicle. Is active in plasma membrane. Human ortholog(s) of this gene implicated in Gitelman syndrome and essential hypertension. Orthologous to human SLC12A3 (solute carrier family 12 member 3). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Restricted expression toward (RPKM 821.7) See more
Orthologs: human mouse all
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Genomic context

Location:: 19p13-p12

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	19	NC_086037.1 (10636594..10690008, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	19	NC_051354.1 (10630651..10679250, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	19	NC_005118.4 (11106033..11144674, complement)

Chromosome 19 - NC_086037.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia.
Title: Renal CD81 interacts with sodium potassium 2 chloride cotransporter and sodium chloride cotransporter in rats with lipopolysaccharide-induced preeclampsia.
Kidney-specific WNK1 isoform is a potent activator of WNK4 and NCC-mediated sodium/chloride transport.
Title: Kidney-specific WNK1 isoform (KS-WNK1) is a potent activator of WNK4 and NCC.
The presence of active plasmin in urine in hydronephrosis could cause abnormal proteolytic activation of ENaC-gamma and impaired ability to excrete Na via NCC.
Title: Hydronephrosis is associated with elevated plasmin in urine in pediatric patients and rats and changes in NCC and γ-ENaC abundance in rat kidney.
Kidneys respond acutely to hyperkalemic challenges by decreasing the activity of NCC while increasing that of ENaC.
Title: Responses of distal nephron Na(+) transporters to acute volume depletion and hyperkalemia.
Direct epithelial action of calcineurin inhibitor cyclosporine A is sufficient for the activation of renal NCC.
Title: Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms.
Data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.
Title: Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.
Despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance or in apical localization in midpregnancy.
Title: Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention.
Estradiol, progesterone, and prolactin increase renal NaCl cotransporter phosphorylation and activity.
Title: Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation.
a model where NCC is constitutively cycled to the plasma membrane, and upon stimulation, it can be phosphorylated to both increase NCC activity and decrease NCC endocytosis, together increasing NaCl transport in the DCT.
Title: Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis.
findings indicate that hyperinsulinaemia is an important driving force of NCC (Na(+)-Cl(-) co-transporter) activity in the metabolic syndrome with possible consequences for blood pressure regulation.
Title: Enhanced phosphorylation of Na(+)-Cl- co-transporter in experimental metabolic syndrome: role of insulin.

Submit: New GeneRIF Correction See all GeneRIFs (30)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

DXS1162 (e-PCR)
- UniSTS:150188

BF391454 (e-PCR)
- UniSTS:249787

Slc12a3 (e-PCR), detects polymorphism
- UniSTS:545985

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables sodium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
enables sodium:chloride symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:chloride symporter activity	IEA Inferred from Electronic Annotation more info
enables sodium:chloride symporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables sodium:chloride symporter activity	ISO Inferred from Sequence Orthology more info
enables sodium:potassium:chloride symporter activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cell volume homeostasis	IBA Inferred from Biological aspect of Ancestor 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	IMP Inferred from Mutant Phenotype more info	PubMed
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 protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in renal sodium ion absorption	IC Inferred by Curator more info	PubMed
involved_in renal sodium ion absorption	IEA Inferred from Electronic Annotation more info
involved_in renal sodium ion absorption	ISO Inferred from Sequence Orthology more info
involved_in response to aldosterone	IEA Inferred from Electronic Annotation more info
involved_in response to aldosterone	ISO Inferred from Sequence Orthology more info
involved_in response to dietary excess	IEA Inferred from Electronic Annotation more info
involved_in response to dietary excess	ISO Inferred from Sequence Orthology more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	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	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transport	ISS Inferred from Sequence or Structural Similarity more info

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
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in extracellular exosome	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: solute carrier family 12 member 3

Names: Na-Cl symporter; solute carrier family 12 (sodium/chloride transporter), member 3; solute carrier family 12 (sodium/chloride transporters), member 3; thiazide-sensitive Na-Cl cotransporter; thiazide-sensitive sodium-chloride cotransporter

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)

NM_019345.4 → NP_062218.3 solute carrier family 12 member 3

See identical proteins and their annotated locations for NP_062218.3

Status: VALIDATED

Source sequence(s)

JAXUCZ010000019

UniProtKB/Swiss-Prot

P55018

UniProtKB/TrEMBL

A6JY68, G3V8G0

Related

ENSRNOP00000070064.1, ENSRNOT00000081246.3

Conserved Domains (1) summary

TIGR00930
Location:57 → 1001

2a30; K-Cl cotransporter

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086037.1 Reference GRCr8

Range

10636594..10690008 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063278264.1 → XP_063134334.1 solute carrier family 12 member 3 isoform X1

UniProtKB/Swiss-Prot

P55018
XM_063278266.1 → XP_063134336.1 solute carrier family 12 member 3 isoform X3

UniProtKB/Swiss-Prot

P55018
XM_063278265.1 → XP_063134335.1 solute carrier family 12 member 3 isoform X2

UniProtKB/Swiss-Prot

P55018