SLC12A2 solute carrier family 12 (sodium/potassium/chloride transporters), member 2 [Homo sapiens] - Gene

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Summary

Official Symbol: SLC12A2provided by HGNC
Official Full Name: solute carrier family 12 (sodium/potassium/chloride transporters), member 2provided by HGNC
Primary source: HGNC:10911
See related: Ensembl:ENSG00000064651; HPRD:06775; MIM:600840; Vega:OTTHUMG00000128983
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: BSC; BSC2; NKCC1; MGC104233
Summary: The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

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Genomic context

Location :: 5q23.3

Sequence :: Chromosome: 5; NC_000005.9 (127419483..127525380)

See SLC12A2 in Epigenomics, MapViewer

Chromosome 5 - NC_000005.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

NKCC1 activation occurred through time-dependent increases in protein-protein interaction between ERK1/2 and NKCC1, which were proportional to EGF concentration
Title: Dependence of corneal epithelial cell proliferation on modulation of interactions between ERK1/2 and NKCC1.
NKCC1 plays an important and yet partial role in RVI in C-20/A4 chondrocytes.
Title: siRNA-mediated inhibition of Na(+)-K(+)-2Cl- cotransporter (NKCC1) and regulatory volume increase in the chondrocyte cell line C-20/A4.
The Wnk3 protein isoforms have a similar effect on SLC12 cotransporters. NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions.
Title: Similar effects of all WNK3 variants on SLC12 cotransporters.
The coupling between salt and water transport in NKCC1 represents a novel aspect of cellular water homeostasis where cells can change their volume independently of the direction of an osmotic gradient across the membrane.
Title: Cotransport of water by the Na+-K+-2Cl(-) cotransporter NKCC1 in mammalian epithelial cells.
In schizophrenia, increased expression levels of OXSR1 and WNK3 may shift the balance of chloride transport by NKCC1 and KCC2 and alter the nature of gamma-aminobutyric acid neurotransmission in the prefrontal cortex.
Title: Altered expression of regulators of the cortical chloride transporters NKCC1 and KCC2 in schizophrenia.
PKC{delta} and PKC{epsilon}-regulated NKCC1 surface expression plays an important role in the regulation of chloride secretion
Title: Activated PKC{delta} and PKC{epsilon} inhibit epithelial chloride secretion response to cAMP via inducing internalization of the Na+-K+-2Cl- cotransporter NKCC1.
phosphorylation-induced activation of NKCC1 by osmotic shrinkage does not involve AMP-activated protein kinase and is likely to be due to STE20/SPS1-related proline/alanine-rich kinase activation
Title: Stimulation of human and mouse erythrocyte Na(+)-K(+)-2Cl(-) cotransport by osmotic shrinkage does not involve AMP-activated protein kinase, but is associated with STE20/SPS1-related proline/alanine-rich kinase activation.
The result points at secretion as the main mechanism of cyst filling, and NKCC1 as the key candidate of fluid transport.
Title: Increased NKCC1 expression in arachnoid cysts supports secretory basis for cyst formation.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
NKCC1 modulates blood pressure through vascular and renal effects--REVIEW
Title: NKCC1 and hypertension: a novel therapeutic target involved in the regulation of vascular tone and renal function.

Submit: New GeneRIF Correction See all (30)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype.

A pilot genome-wide association study shows genomic variants enriched in the non-tumor cells of patients with well-differentiated neuroendocrine tumors of the ileum.

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Products	Interactant	Other Gene	Source	Pubs	Description
P55011	O95747	OXSR1	HPRD	PubMed
P55011	P55011	SLC12A2	HPRD	PubMed
P55011	Q9UEW8	STK39	HPRD	PubMed
BioGRID:112447	BioGRID:107819	MAPK14	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112447	BioGRID:112447	SLC12A2	BioGRID	PubMed	Co-purification
BioGRID:112447	BioGRID:118159	STK39	BioGRID	PubMed	Two-hybrid
BioGRID:112447	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
ammonia transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
sodium:potassium:chloride symporter activity	TAS Traceable Author Statement more info	PubMed
symporter activity	IEA Inferred from Electronic Annotation more info
transporter activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
ammonium transport	IDA Inferred from Direct Assay more info	PubMed
branching involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
detection of mechanical stimulus involved in sensory perception of sound	IEA Inferred from Electronic Annotation more info
ion transport	TAS Traceable Author Statement more info
mammary duct terminal end bud growth	IEA Inferred from Electronic Annotation more info
multicellular organism growth	IEA Inferred from Electronic Annotation more info
potassium ion transport	IEA Inferred from Electronic Annotation more info
sodium ion transport	IEA Inferred from Electronic Annotation more info
transepithelial ammonium transport	IDA Inferred from Direct Assay more info	PubMed
transepithelial chloride transport	IDA Inferred from Direct Assay more info	PubMed
transmembrane transport	TAS Traceable Author Statement more info
transport	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
apical plasma membrane	IEA Inferred from Electronic Annotation more info
basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
membrane fraction	TAS Traceable Author Statement more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

Preferred Names: solute carrier family 12 member 2

Names: solute carrier family 12 member 2; basolateral Na-K-Cl symporter; bumetanide-sensitive sodium-(potassium)-chloride cotransporter 1

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NCBI Reference Sequences (RefSeq)

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_001046.2 → NP_001037.1 solute carrier family 12 member 2 isoform 1

Status: REVIEWED

Description

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

Source sequence(s)

AA425438, AA425619, AA843086, AI493213, AK025062, AV708692, AY280459, BC033003, BM978607, U30246

Consensus CDS

CCDS4144.1

UniProtKB/Swiss-Prot

P55011

UniProtKB/TrEMBL

Q53ZR1

Related

ENSP00000262461, OTTHUMP00000159234, ENST00000262461, OTTHUMT00000250972

Conserved Domains (2) summary

pfam08403
Location:210 – 267
Blast Score: 242

AA_permease_N; Amino acid permease N-terminal

TIGR00930
Location:216 – 1212
Blast Score: 4032

2a30; K-Cl cotransporter
NM_001256461.1 → NP_001243390.1 solute carrier family 12 member 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC008577, AC011332, AI493213, AY280459, BC144221

UniProtKB/TrEMBL

B7ZM24

UniProtKB/TrEMBL

Q53ZR1

Conserved Domains (2) summary

pfam08403
Location:210 – 267
Blast Score: 242

AA_permease_N; Amino acid permease N-terminal

TIGR00930
Location:216 – 1196
Blast Score: 4037

2a30; K-Cl cotransporter

RNA

NR_046207.1 RNA Sequence

Description

Transcript Variant: This variant (3) uses an alternate splice junction in the 3' end that truncates the coding sequence compared to variant 1. The resulting transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is therefore thought not to be proten-coding.

Source sequence(s)

AC008577, AC011332, AI493213, AY280459, BC033003

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000005.9 Reference GRCh37.p5 Primary Assembly

Range

127419483..127525380

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000137.1 Alternate HuRef

Range

122610291..122716113

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC008577.7 (26033..27840)	None
genomic	AC011332.8	None
genomic	CH471062.2	EAW62392.1
		EAW62393.1
		EAW62394.1
mRNA	AA425438.1	None
mRNA	AA425619.1	None
mRNA	AA843086.1	None
mRNA	AB209192.1	BAD92429.1
mRNA	AF439152.1	AAL32454.1
mRNA	AI493213.1	None
mRNA	AK025062.1	None
mRNA	AV708692.2	None
mRNA	AY280459.1	AAP33906.1
mRNA	BC033003.2	None
mRNA	BC144221.1	AAI44222.1
mRNA	BC146839.1	AAI46840.1
mRNA	BM978607.1	None
mRNA	U30246.1	AAC50561.1
mRNA	Z36839.1	None

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P55011.1	GenPept	UniProtKB/Swiss-Prot:P55011
Q53ZR1	GenPept	UniProtKB/TrEMBL:Q53ZR1
Q59GB7	GenPept	UniProtKB/TrEMBL:Q59GB7