Slc4a4 solute carrier family 4 member 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Symbol: Slc4a4provided by RGD
Full Name: solute carrier family 4 member 4provided by RGD
Primary source: RGD:68936
See related: Ensembl:ENSRNOG00000003134 AllianceGenome:RGD:68936
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: KNBC; NBC2; Nbc1; Nbc4; PNBC; HHNMC; HNBC1; SLC4A5
Summary: Predicted to enable identical protein binding activity and sodium:bicarbonate symporter activity. Predicted to be involved in bicarbonate transport; regulation of intracellular pH; and sodium ion export across plasma membrane. Located in membrane. Used to study nephrogenic diabetes insipidus. Biomarker of hypertension. 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 (RPKM 1388.3), Brain (RPKM 248.9) and 3 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 14p22

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	14	NC_086032.1 (19125394..19577379, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	14	NC_051349.1 (18841289..19293297, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	14	NC_005113.4 (20476258..20817042, complement)

Chromosome 14 - NC_086032.1 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?

Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction.
Title: Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction.
the sodium bicarbonate cotransporter NBCe1-B is expressed in rat and human thyroid
Title: Expression, Localization, and Regulation of the Sodium Bicarbonate Cotransporter NBCe1 in the Thyroid.
NBCe1 inhibition limits cell death, improves myocardial post-ischemic contractility and mitochondrial state through calcineurin/P38MAPK/HSP27-dependent pathways.
Title: Calcineurin/P38MAPK/HSP27-dependent pathways are involved in the attenuation of postischemic mitochondrial injury afforded by sodium bicarbonate co-transporter (NBCe1) inhibition.
Endurance training increased NHE1 and NBC1 genes and proteins expression in both Extensor digitorum longus and Soleus in the diabetic training group compared to control groups.
Title: Modulation of oxidative and glycolytic skeletal muscle fibers Na+/H+ exchanger1 (NHE1) and Na+/HCO3- co-transporter1 (NBC1) genes and proteins expression in type 2 diabetic rat (Streptozotocin + high fat diet) following long term endurance training.
NBCe1 is the NBC isoform activated by aldosterone in the heart
Title: The cardiac electrogenic sodium/bicarbonate cotransporter (NBCe1) is activated by aldosterone through the G protein-coupled receptor 30 (GPR 30).
NBC1 is diversely expressed in the pancreas at different developmental stages, where it may exert its functions in pancreatic development, especially islet cell growth, through HCO3(-) transport and pH regulation.
Title: Na(+)/HCO(3)(-) cotransporter is expressed on β and α cells during rat pancreatic development.
Aldosterone stimulates NBC by GPR30 activation, reactive oxygen species production and AKT stimulation.
Title: Aldosterone stimulates the cardiac sodium/bicarbonate cotransporter via activation of the g protein-coupled receptor gpr30.
Results demonstrate that transcriptional regulation and targeting of NBCe1, as well as functional operation of NBCe1, may occur through multiple signaling pathways
Title: Regulation of functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), in mouse astrocytes.
These results revealed that insulin can stimulate PT sodium transport even in type 2 diabetes with overt nephropathy.
Title: Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy.
NBCe1 hyperactivity during myocardial reperfusion leads to Na(+) and Ca(2+) loading, causing Ca(2+) overload and myocardial damage.
Title: The electrogenic cardiac sodium bicarbonate co-transporter (NBCe1) contributes to the reperfusion injury.

Submit: New GeneRIF Correction See all GeneRIFs (33)

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

G46840 (e-PCR)
- UniSTS:107636

AW527043 (e-PCR)
- UniSTS:245992

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables identical protein binding	IEA Inferred from Electronic Annotation more info
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 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	IEA Inferred from Electronic Annotation more info
enables sodium:bicarbonate symporter activity	IMP Inferred from Mutant Phenotype 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
enables sodium:bicarbonate symporter activity	TAS Traceable Author Statement 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
involved_in bicarbonate transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within bicarbonate transport	ISO Inferred from Sequence Orthology more info
involved_in bicarbonate transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within establishment of localization in cell	ISO Inferred from Sequence Orthology more info
involved_in inorganic anion transport	IEA Inferred from Electronic Annotation more info
involved_in metanephric proximal tubule development	IEP Inferred from Expression Pattern more info	PubMed
involved_in monoatomic anion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of glycolytic process	IEA Inferred from Electronic Annotation more info
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
involved_in regulation of intracellular pH	IEA Inferred from Electronic Annotation more info
acts_upstream_of regulation of intracellular pH	ISO Inferred from Sequence Orthology more info
involved_in regulation of intracellular pH	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane potential	IEA Inferred from Electronic Annotation more info
acts_upstream_of regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in regulation of pH	TAS Traceable Author Statement more info	PubMed
involved_in sodium ion export across plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in sodium ion export across plasma membrane	ISO Inferred from Sequence Orthology more info
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
acts_upstream_of_or_within sodium ion transport	ISO Inferred from Sequence Orthology more info
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
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	IEA Inferred from Electronic Annotation more info
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
located_in basolateral plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in basolateral plasma membrane	TAS Traceable Author Statement more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in lateral plasma membrane	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
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	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: electrogenic sodium bicarbonate cotransporter 1

Names: NBC-like protein; Na(+)/HCO3(-) cotransporter; Na+HCO3- cotransporter 4; sodium bicarbonate cotransporter; solute carrier family 4 (anion exchanger), 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_053424.1 → NP_445876.1 electrogenic sodium bicarbonate cotransporter 1

See identical proteins and their annotated locations for NP_445876.1

Status: PROVISIONAL

Source sequence(s)

AF254802

UniProtKB/Swiss-Prot

O35422, O54815, Q9JI66, Q9JJ32, Q9QXH6

UniProtKB/TrEMBL

A0A8I6ABC3, A6KKH6

Related

ENSRNOP00000035006.2, ENSRNOT00000033806.3

Conserved Domains (3) summary

TIGR00834
Location:109 → 1003

ae; anion exchange protein

pfam00955
Location:436 → 954

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:137 → 387

Band_3_cyto; Band 3 cytoplasmic domain

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_086032.1 Reference GRCr8

Range

19125394..19577379 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039092509.2 → XP_038948437.1 electrogenic sodium bicarbonate cotransporter 1 isoform X3

UniProtKB/TrEMBL

A0A0H2UHB7, A0A8I6AFE1

Related

ENSRNOP00000092374.1

Conserved Domains (1) summary

TIGR00834
Location:114 → 1008

ae; anion exchange protein
XM_006250791.5 → XP_006250853.1 electrogenic sodium bicarbonate cotransporter 1 isoform X4

See identical proteins and their annotated locations for XP_006250853.1

UniProtKB/TrEMBL

A0A0H2UHB7, A6KKH5

Conserved Domains (1) summary

TIGR00834
Location:109 → 1003

ae; anion exchange protein
XM_039092511.2 → XP_038948439.1 electrogenic sodium bicarbonate cotransporter 1 isoform X4

UniProtKB/TrEMBL

A0A0H2UHB7, A6KKH5

Conserved Domains (1) summary

TIGR00834
Location:109 → 1003

ae; anion exchange protein
XM_039092507.1 → XP_038948435.1 electrogenic sodium bicarbonate cotransporter 1 isoform X1

UniProtKB/TrEMBL

A0A0H2UHB7

Conserved Domains (1) summary

TIGR00834
Location:149 → 1043

ae; anion exchange protein
XM_039092508.2 → XP_038948436.1 electrogenic sodium bicarbonate cotransporter 1 isoform X2

UniProtKB/TrEMBL

A0A8I6ABC3

Conserved Domains (1) summary

TIGR00834
Location:149 → 1043

ae; anion exchange protein