Slc4a4 solute carrier family 4 (anion exchanger), member 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Slc4a4provided by MGI
Official Full Name: solute carrier family 4 (anion exchanger), member 4provided by MGI
Primary source: MGI:MGI:1927555
See related: Ensembl:ENSMUSG00000060961 AllianceGenome:MGI:1927555
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: NBC; NBC1
Summary: Predicted to enable identical protein binding activity and sodium:bicarbonate symporter activity. Involved in regulation of intracellular pH. Acts upstream of or within bicarbonate transport and sodium ion transport. Predicted to be located in cell surface and membrane. Predicted to be active in basolateral plasma membrane. Is expressed in several structures, including brain; metanephros; spinal cord floor plate; and thyroid primordium. Used to study renal tubular acidosis. Human ortholog(s) of this gene implicated in renal tubular acidosis. Orthologous to human SLC4A4 (solute carrier family 4 member 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in kidney adult (RPKM 60.8), cerebellum adult (RPKM 27.2) and 9 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 E1; 5 44.1 cM

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (88941717..89387515)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (88793858..89239656)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The astrocytic Na[+] -HCO3 [-] cotransporter, NBCe1, is dispensable for respiratory chemosensitivity.
Title: The astrocytic Na(+) -HCO(3) (-) cotransporter, NBCe1, is dispensable for respiratory chemosensitivity.
The proximal tubule through an NBCe1-dependent mechanism regulates collecting duct phenotypic and remodeling responses to acidosis.
Title: The proximal tubule through an NBCe1-dependent mechanism regulates collecting duct phenotypic and remodeling responses to acidosis.
Targeting the bicarbonate transporter SLC4A4 overcomes immunosuppression and immunotherapy resistance in pancreatic cancer.
Title: Targeting the bicarbonate transporter SLC4A4 overcomes immunosuppression and immunotherapy resistance in pancreatic cancer.
Inhibition of the sodium-dependent HCO3(-) transporter SLC4A4, produces a cystic fibrosis-like airway disease phenotype.
Title: Inhibition of the sodium-dependent HCO(3)(-) transporter SLC4A4, produces a cystic fibrosis-like airway disease phenotype.
Acid-base effects of combined renal deletion of NBCe1-A and NBCe1-B.
Title: Acid-base effects of combined renal deletion of NBCe1-A and NBCe1-B.
STAT3-dependent regulation of the electrogenic Na(+/) HCO3 (-) cotransporter 1 (NBCe1) functional expression in cortical astrocytes.
Title: STAT3-dependent regulation of the electrogenic Na(+/) HCO(3)(-) cotransporter 1 (NBCe1) functional expression in cortical astrocytes.
Rapid volume pulsation of the extracellular space coincides with epileptiform activity in mice and depends on the NBCe1 transporter.
Title: Rapid volume pulsation of the extracellular space coincides with epileptiform activity in mice and depends on the NBCe1 transporter.
Neddylation-mediated Nedd4-2 activation regulates ubiquitination modification of renal NBCe1.
Title: Neddylation-mediated Nedd4-2 activation regulates ubiquitination modification of renal NBCe1.
Activation of mouse NBCe1-B by Xenopus laevis and mouse IRBITs: Role of the variable Nt appendage of IRBITs.
Title: Activation of mouse NBCe1-B by Xenopus laevis and mouse IRBITs: Role of the variable Nt appendage of IRBITs.
NBCe1-A is critical for the effect of diet-induced hypokalemia to increase cortical proximal tubule ammonia generation and for the expected decrease in urinary K(+) excretion
Title: NBCe1-A is required for the renal ammonia and K(+) response to hypokalemia.

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)

Targeted (3) 1 citation
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Slc4a4 (e-PCR), detects polymorphism
- UniSTS:547350

AI176955 (e-PCR)
- UniSTS:250394

AI835705 (e-PCR)
- UniSTS:165407

D5Mit274 (e-PCR), detects polymorphism
- UniSTS:130413

D5Mit311 (e-PCR), detects polymorphism
- UniSTS:130454

AW527043 (e-PCR)
- UniSTS:245992

D5Mit40 (e-PCR), detects polymorphism
- UniSTS:130554

D5Mit17 (e-PCR), detects polymorphism
- UniSTS:130299

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables monoatomic anion transmembrane transporter activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium:bicarbonate symporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium:bicarbonate symporter activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium:bicarbonate symporter activity	ISO Inferred from Sequence Orthology more info
enables sodium:bicarbonate symporter activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables solute:inorganic anion antiporter activity	IEA Inferred from Electronic Annotation more info
enables symporter activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in bicarbonate transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within bicarbonate transport	IGI Inferred from Genetic Interaction more info	PubMed
involved_in bicarbonate transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within bicarbonate transport	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of_or_within establishment of localization in cell	IGI Inferred from Genetic Interaction more info	PubMed
involved_in monoatomic anion transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of glycolytic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of glycolytic process	ISO Inferred from Sequence Orthology more info
involved_in regulation of intracellular pH	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of regulation of intracellular pH	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of intracellular pH	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of regulation of intracellular pH	ISO Inferred from Sequence Orthology more info
acts_upstream_of regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of regulation of membrane potential	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of pH	TAS Traceable Author Statement more info	PubMed
involved_in sodium ion export across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in transmembrane transport	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
is_active_in membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: electrogenic sodium bicarbonate cotransporter 1

Names: Na(+)/HCO3(-) cotransporter; pancreas sodium bicarbonate cotransporter; sodium bicarbonate cotransporter; solute carrier family 4 member 4; solute carrier family 4, sodium bicarbonate cotransporter, member 4

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_001136260.1 → NP_001129732.1 electrogenic sodium bicarbonate cotransporter 1 isoform b

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon and another exon in the 3' end compared to variant 4, that causes a frameshift. The resulting isoform (b) lacks an alternate internal segment and has a shorter and distinct C-terminus compared to isoform d.

Source sequence(s)

AC165240, AF020195, AF141934, BC129864, BF460877

Consensus CDS

CCDS51541.1

UniProtKB/TrEMBL

A2VDF7, E9Q8N8

Related

ENSMUSP00000121744.2, ENSMUST00000156238.8

Conserved Domains (1) summary

TIGR00834
Location:109 → 1003

ae; anion exchange protein
NM_001197147.1 → NP_001184076.1 electrogenic sodium bicarbonate cotransporter 1 isoform c

See identical proteins and their annotated locations for NP_001184076.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon and uses an alternate in-frame splice junction compared to variant 4, that causes a frameshift. The resulting isoform (c) has the same N- and C-termini but is shorter compared to isoform d.

Source sequence(s)

AC165240, AK163619, BF460877, CD364018, HQ204220

Consensus CDS

CCDS57352.1

UniProtKB/TrEMBL

A2VDF7, A7E1Z5

Related

ENSMUSP00000108844.4, ENSMUST00000113218.10

Conserved Domains (3) summary

TIGR00834
Location:109 → 994

ae; anion exchange protein

pfam00955
Location:427 → 946

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:137 → 379

Band_3_cyto; Band 3 cytoplasmic domain
NM_001359211.1 → NP_001346140.1 electrogenic sodium bicarbonate cotransporter 1 isoform d

Status: VALIDATED

Description

Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (d).

Source sequence(s)

AC140492, AC162690, AC165240

UniProtKB/TrEMBL

A0A668KM61, A2VDF7

Related

ENSMUSP00000159229.2, ENSMUST00000239214.2

Conserved Domains (1) summary

cl26877
Location:109 → 1035

Band_3_cyto; Band 3 cytoplasmic domain
NM_001359212.1 → NP_001346141.1 electrogenic sodium bicarbonate cotransporter 1 isoform e

Status: VALIDATED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (e) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform d.

Source sequence(s)

AC140492, AC165240, HQ018820

Consensus CDS

CCDS89936.1

UniProtKB/TrEMBL

A2VDF7, E1AWU4

Related

ENSMUSP00000118413.2, ENSMUST00000130041.8

Conserved Domains (1) summary

TIGR00834
Location:65 → 959

ae; anion exchange protein
NM_001359213.1 → NP_001346142.1 electrogenic sodium bicarbonate cotransporter 1 isoform f

Status: VALIDATED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence, lacks an alternate in-frame exon, and uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (f) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform d.

Source sequence(s)

AC140492, AC165240, HQ285250

UniProtKB/TrEMBL

A2VDF7, E3VWA1

Conserved Domains (1) summary

cl26877
Location:65 → 950

Band_3_cyto; Band 3 cytoplasmic domain
NM_018760.2 → NP_061230.2 electrogenic sodium bicarbonate cotransporter 1 isoform a

See identical proteins and their annotated locations for NP_061230.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) lacks an alternate in-frame exon compared to variant 4. The resulting isoform (a) has the same N- and C-termini but is shorter compared to isoform d.

Source sequence(s)

AC165240, AF141934, AW124701, BC129863, BF460877, CB524421, CF744823

Consensus CDS

CCDS19406.1

UniProtKB/Swiss-Prot

O88343, Q3USE4, Q8BUG0, Q8QZR9, Q9R1C4

UniProtKB/TrEMBL

A2VDF7

Related

ENSMUSP00000119325.2, ENSMUST00000148750.8

Conserved Domains (3) summary

TIGR00834
Location:109 → 1003

ae; anion exchange protein

pfam00955
Location:436 → 955

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:137 → 388

Band_3_cyto; Band 3 cytoplasmic domain

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

NC_000071.7 Reference GRCm39 C57BL/6J

Range

88941717..89387515

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030254704.1 → XP_030110564.1 electrogenic sodium bicarbonate cotransporter 1 isoform X4

UniProtKB/TrEMBL

A2VDF7

Conserved Domains (1) summary

TIGR00834
Location:114 → 1008

ae; anion exchange protein
XM_017320995.2 → XP_017176484.1 electrogenic sodium bicarbonate cotransporter 1 isoform X2

UniProtKB/TrEMBL

A2VDF7

Conserved Domains (1) summary

cl26877
Location:114 → 1040

Band_3_cyto; Band 3 cytoplasmic domain
XM_006535136.5 → XP_006535199.1 electrogenic sodium bicarbonate cotransporter 1 isoform X3

UniProtKB/TrEMBL

A2VDF7

Conserved Domains (1) summary

cl26877
Location:109 → 1035

Band_3_cyto; Band 3 cytoplasmic domain
XM_030254705.2 → XP_030110565.1 electrogenic sodium bicarbonate cotransporter 1 isoform X6

UniProtKB/TrEMBL

A2VDF7

Conserved Domains (1) summary

TIGR00834
Location:109 → 994

ae; anion exchange protein
XM_036165313.1 → XP_036021206.1 electrogenic sodium bicarbonate cotransporter 1 isoform X5

UniProtKB/TrEMBL

A2VDF7, E9Q8N8

Conserved Domains (1) summary

TIGR00834
Location:109 → 1003

ae; anion exchange protein
XM_011249542.1 → XP_011247844.1 electrogenic sodium bicarbonate cotransporter 1 isoform X1

UniProtKB/TrEMBL

A2VDF7

Conserved Domains (1) summary

cl26877
Location:109 → 1026

Band_3_cyto; Band 3 cytoplasmic domain