SLC4A2 solute carrier family 4 member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SLC4A2provided by HGNC
Official Full Name: solute carrier family 4 member 2provided by HGNC
Primary source: HGNC:HGNC:11028
See related: Ensembl:ENSG00000164889 MIM:109280; AllianceGenome:HGNC:11028
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: AE2; HKB3; BND3L; NBND3; OPTB9; EPB3L1
Summary: This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]
Expression: Ubiquitous expression in placenta (RPKM 16.3), stomach (RPKM 13.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q36.1

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (151058200..151076527)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (152231288..152249645)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (150755287..150773614)

Chromosome 7 - NC_000007.14 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Acid-adapted cancer cells alkalinize their cytoplasm by degrading the acid-loading membrane transporter anion exchanger 2, SLC4A2.
Title: Acid-adapted cancer cells alkalinize their cytoplasm by degrading the acid-loading membrane transporter anion exchanger 2, SLC4A2.
SLC4A2, another gene involved in acid-base balancing machinery of osteoclasts, causes osteopetrosis.
Title: SLC4A2, another gene involved in acid-base balancing machinery of osteoclasts, causes osteopetrosis.
Alterations in SLC4A2, SLC26A7 and SLC26A9 Drive Acid-Base Imbalance in Gastric Neuroendocrine Tumors and Uncover a Novel Mechanism for a Co-Occurring Polyautoimmune Scenario.
Title: Alterations in SLC4A2, SLC26A7 and SLC26A9 Drive Acid-Base Imbalance in Gastric Neuroendocrine Tumors and Uncover a Novel Mechanism for a Co-Occurring Polyautoimmune Scenario.
Both IRBIT and long-IRBIT bind to and coordinately regulate Cl(-)/HCO3(-) exchanger AE2 activity through modulating the lysosomal degradation of AE2.
Title: Both IRBIT and long-IRBIT bind to and coordinately regulate Cl(-)/HCO(3)(-) exchanger AE2 activity through modulating the lysosomal degradation of AE2.
SLC4A2 anion exchanger promotes tumour cell malignancy via enhancing net acid efflux across golgi membranes.
Title: SLC4A2 anion exchanger promotes tumour cell malignancy via enhancing net acid efflux across golgi membranes.
Intracellular Ca(2+)-Mediated AE2 Is Involved in the Vectorial Movement of HaCaT Keratinocyte.
Title: Intracellular Ca(2+)-Mediated AE2 Is Involved in the Vectorial Movement of HaCaT Keratinocyte.
Study found that AE2 was overexpressed in ovarian cancer samples, and up-regulated AE2 expression can activate the mTOR/p70S6K1 pathway, promoting ovarian cancer cell growth.
Title: Knockdown of anion exchanger 2 suppressed the growth of ovarian cancer cells via mTOR/p70S6K1 signaling.
The regulation of a basolateral located, DIDS-sensitive, Cl(-)/HCO3(-) exchanger, anion exchanger 2 (AE2; SLC4A2) which is postulated to act as an acid loader, and therefore potential regulator of HCO3(-) secretion, in human airway epithelial cells.
Title: CK2 is a key regulator of SLC4A2-mediated Cl(-)/HCO(3)(-) exchange in human airway epithelia.
To match the stimulatory effect on acid uptake, cell-to-cell coupling in NHDF-Ad and CCD-112-CoN cells was strengthened with TGFbeta1.Importantly, the activities of stromal AE2 and connexin-43 do not place an energetic burden on cancer cells, allowing resources to be diverted for other activities
Title: Stromal uptake and transmission of acid is a pathway for venting cancer cell-generated acid.
ABA transport in human nucleated cells occurs via the anion exchanger AE2
Title: Abscisic acid influx into human nucleated cells occurs through the anion exchanger AE2.

Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Osteopetrosis, autosomal recessive 9 MedGen: C5830487 OMIM: 620366 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH48801 (e-PCR)
- UniSTS:28354

RH71298 (e-PCR)
- UniSTS:9183

STS-X62137 (e-PCR)
- UniSTS:46057

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chloride:bicarbonate antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables chloride:bicarbonate antiporter activity	IEA Inferred from Electronic Annotation more info
enables chloride:bicarbonate antiporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables enzyme binding	IEA Inferred from Electronic Annotation more info
enables monoatomic anion transmembrane transporter activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables solute:inorganic anion antiporter activity	TAS Traceable Author Statement more info
enables transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in amelogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in bicarbonate transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in bicarbonate transport	TAS Traceable Author Statement more info
involved_in chloride transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in digestive tract development	IEA Inferred from Electronic Annotation more info
involved_in monoatomic anion transport	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of CD8-positive, alpha-beta T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of CD8-positive, alpha-beta T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in osteoclast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of enamel mineralization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of actin cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of bone resorption	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of intracellular pH	IBA Inferred from Biological aspect of Ancestor more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in focal adhesion	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: anion exchange protein 2

Names: anion exchanger 2 type a; anion exchanger 2 type b1; anion exchanger 2 type b2; erythrocyte membrane protein band 3-like 1; non-erythroid band 3-like protein; solute carrier family 4 (anion exchanger), member 2

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.

Genomic

NG_051947.1 RefSeqGene

Range

6390..23324

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001199692.3 → NP_001186621.1 anion exchange protein 2 isoform 1

See identical proteins and their annotated locations for NP_001186621.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' UTR exon, and encodes the same isoform (1), as compared to variant 1.

Source sequence(s)

AB209158, BM680391, DB065890

Consensus CDS

CCDS5917.1

UniProtKB/Swiss-Prot

B2R6T0, B4DIT0, D3DX05, F8W682, P04920, Q45EY5, Q969L3

UniProtKB/TrEMBL

Q9UEY6

Related

ENSP00000419412.1, ENST00000485713.5

Conserved Domains (3) summary

TIGR00834
Location:324 → 1240

ae; anion exchange protein

pfam00955
Location:675 → 1167

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:359 → 620

Band_3_cyto; Band 3 cytoplasmic domain
NM_001199693.1 → NP_001186622.1 anion exchange protein 2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two exons from the 5' end and contains an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a shorter and different N-terminus, as compared to isoform 1.

Source sequence(s)

AB209158, AK295767, BM680391

Consensus CDS

CCDS56520.1

UniProtKB/TrEMBL

Q9UEY5

Related

ENSP00000376571.2, ENST00000392826.6

Conserved Domains (3) summary

TIGR00834
Location:315 → 1231

ae; anion exchange protein

pfam00955
Location:666 → 1158

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:350 → 611

Band_3_cyto; Band 3 cytoplasmic domain
NM_001199694.2 → NP_001186623.1 anion exchange protein 2 isoform 3

See identical proteins and their annotated locations for NP_001186623.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two exons from the 5' end and contains an alternate 5' exon, as compared to variant 1. The resulting isoform (3) has a shorter and different N-terminus, as compared to isoform 1.

Source sequence(s)

AB209158, BC009386, BM680391, DA237239

Consensus CDS

CCDS56521.1

UniProtKB/TrEMBL

Q9UEY4

Related

ENSP00000419164.1, ENST00000461735.1

Conserved Domains (3) summary

TIGR00834
Location:310 → 1226

ae; anion exchange protein

pfam00955
Location:661 → 1153

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:345 → 606

Band_3_cyto; Band 3 cytoplasmic domain
NM_003040.4 → NP_003031.3 anion exchange protein 2 isoform 1

See identical proteins and their annotated locations for NP_003031.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) and variant 2 encode the same isoform (1).

Source sequence(s)

AK295767, AK312699, BM680391, DA103528

Consensus CDS

CCDS5917.1

UniProtKB/Swiss-Prot

B2R6T0, B4DIT0, D3DX05, F8W682, P04920, Q45EY5, Q969L3

UniProtKB/TrEMBL

Q9UEY6

Related

ENSP00000405600.2, ENST00000413384.7

Conserved Domains (3) summary

TIGR00834
Location:324 → 1240

ae; anion exchange protein

pfam00955
Location:675 → 1167

HCO3_cotransp; HCO3- transporter family

pfam07565
Location:359 → 620

Band_3_cyto; Band 3 cytoplasmic domain