Slc12a1 solute carrier family 12 member 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Slc12a1provided by RGD
Official Full Name: solute carrier family 12 member 1provided by RGD
Primary source: RGD:3685
See related: EnsemblRapid:ENSRNOG00000005367 AllianceGenome:RGD:3685
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: BSC1; Nkcc2
Summary: Enables sodium:potassium:chloride symporter activity. Involved in several processes, including chloride transport; metal ion transport; and protein insertion into membrane from inner side. Located in apical plasma membrane and cell surface. 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, Dec 2024]
Expression: Restricted expression toward (RPKM 2494.1) See more
Orthologs: human mouse all
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Genomic context

Location:: 3q36

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	3	NC_086021.1 (132859581..132936354)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	3	NC_051338.1 (112406140..112482913)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	3	NC_005102.4 (117421531..117498372)

Chromosome 3 - NC_086021.1 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.
Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin ligase family in the thick ascending limb of the loop of Henle.
Title: Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin ligase family in the thick ascending limb of the loop of Henle.
Elevations in luminal flow enhance NaCl reabsorption in thick ascending limbs by stimulating NKCC2 via NOX4 activation and increased [Formula: see text]. NKCC2 activation is primarily the result of insertion of new transporters in the membrane.
Title: NADPH oxidase 4-derived superoxide mediates flow-stimulated NKCC2 activity in thick ascending limbs.
Suggest complex effect of cyclosporine A to activate renal Nkcc2 requires concomitant stimulation by AVP.
Title: Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms.
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.
the upregulation in the expression of NKCC2 in apical membranes during the postobstructive phase of bilateral ureteral obstruction could contribute to improving the excretion of sodium and consequently also the excretion of potassium, osmolytes, and water.
Title: Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in Obstructive Nephropathy.
This study demonstrated that disregulation nkcc1 and nkcc2 in neuropathic pain.
Title: Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury.
Report tubuloglomerular and connecting tubuloglomerular feedback during inhibition of various Na transporters in the nephron.
Title: Tubuloglomerular and connecting tubuloglomerular feedback during inhibition of various Na transporters in the nephron.
data suggest the presence of the inhibitory factors for NKCC2 expression in dehydration. Considering the role of NKCC2 for the countercurrent multiplier system, NKCC2f expressed in MAL might be more important than NKCC2a/b
Title: Expression of three isoforms of Na-K-2Cl cotransporter (NKCC2) in the kidney and regulation by dehydration.
In vivo silencing of VAMP2 but not VAMP3 in TALs blunted cAMP-stimulated steady-state surface NKCC2 expression and completely blocked cAMP-stimulated NKCC2 exocytic delivery
Title: Vesicle-associated membrane protein 2 (VAMP2) but Not VAMP3 mediates cAMP-stimulated trafficking of the renal Na+-K+-2Cl- co-transporter NKCC2 in thick ascending limbs.

Submit: New GeneRIF Correction See all GeneRIFs (56)

General gene information

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Markers

AU048716 (e-PCR)
- UniSTS:145166

RH133257 (e-PCR)
- UniSTS:216540

Gene Ontology Provided by RGD

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 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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation 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	IDA Inferred from Direct Assay more info	PubMed
involved_in diterpenoid metabolic process	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within kidney development	ISO Inferred from Sequence Orthology more info
involved_in monoatomic ion transmembrane transport	IDA Inferred from Direct Assay 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 potassium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein insertion into membrane from inner side	IDA Inferred from Direct Assay more info	PubMed
involved_in renal sodium ion absorption	IC Inferred by Curator more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within urea transmembrane transport	ISO Inferred from Sequence Orthology 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
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	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	IEA Inferred from Electronic Annotation 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: Na-K-2Cl cotransporter 2; Solute carrier family 12, member 1 (bumetanide-sensitive sodium-[potassium]-chloride cotransporter); bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2; kidney-specific Na-K-Cl symporter; solute carrier family 12 (sodium/potassium/chloride transporter), member 1; solute carrier family 12 (sodium/potassium/chloride transporters), member 1

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_001270617.1 → NP_001257546.1 solute carrier family 12 member 1 isoform 1

See identical proteins and their annotated locations for NP_001257546.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

BC087017, JAXUCZ010000003

UniProtKB/TrEMBL

F7EUW9, G8HI66, Q5PQV1

Related

ENSRNOP00000008857.3, ENSRNOT00000008857.9

Conserved Domains (3) summary

TIGR00930
Location:100 → 1095

2a30; K-Cl cotransporter

pfam03522
Location:690 → 1095

SLC12; Solute carrier family 12

pfam08403
Location:86 → 152

AA_permease_N; Amino acid permease N-terminal
NM_001270618.1 → NP_001257547.1 solute carrier family 12 member 1 isoform 2

See identical proteins and their annotated locations for NP_001257547.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) has an alternate exon of the same size replacing another exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini and is the same length, but it has an internal region of alternate sequence compared to isoform 1.

Source sequence(s)

BC087017, FM059245, JAXUCZ010000003

UniProtKB/Swiss-Prot

P55016

UniProtKB/TrEMBL

A6HPW2, G3V6U1

Related

ENSRNOP00000008860.2, ENSRNOT00000008860.7

Conserved Domains (3) summary

TIGR00930
Location:100 → 1095

2a30; K-Cl cotransporter

pfam03522
Location:690 → 1095

SLC12; Solute carrier family 12

pfam08403
Location:86 → 152

AA_permease_N; Amino acid permease N-terminal

RNA

NR_073053.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate 5' exon structure, compared to variant 1. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC087017

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_086021.1 Reference GRCr8

Range

132859581..132936354

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063283138.1 → XP_063139208.1 solute carrier family 12 member 1 isoform X1

UniProtKB/TrEMBL

F7EUW9, G8HI66, Q5PQV1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_019134.2: Suppressed sequence

Description

NM_019134.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.