CA4 carbonic anhydrase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CA4provided by HGNC
Official Full Name: carbonic anhydrase 4provided by HGNC
Primary source: HGNC:HGNC:1375
See related: Ensembl:ENSG00000167434 MIM:114760
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: CAIV; Car4; RP17
Summary: Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This gene encodes a glycosylphosphatidyl-inositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and proximal renal tubules. Its exact function is not known; however, it may have a role in inherited renal abnormalities of bicarbonate transport. [provided by RefSeq, Jul 2008]
Expression: Biased expression in colon (RPKM 23.2), fat (RPKM 10.2) and 9 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 17q23.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	17	NC_000017.11 (60149942..60179021)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (58227302..58236907)

Chromosome 17 - NC_000017.11 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

carbonic anhydrase 1 (CA1) and CA4 were identified as potential biomarkers of Colon adenocarcinoma due to their predictive roles in diagnosis and prognosis, and the results were further confirmed by a series of analyses.
Title: Comprehensive Analysis for Identifying Diagnostic and Prognostic Biomarkers in Colon Adenocarcinoma.
highest susceptibility effect was noticed in the rs2274328 of carbonic anhydrase VI (AA vs CC) model (d = 0.18; 95% CI (confidence interval): -1.77, 2.13), but this effect was not significant [meta-analysis]
Title: Effects of the carbonic anhydrase VI gene polymorphisms on dental caries: A meta-analysis.
This study analyzed the direct interaction between CAIV and the two Monocarboxylate transporters (MCTs) chaperones basigin (CD147) and embigin (GP70). In human CD147, binding of CAIV was mediated by the negatively charged Glu-73.
Title: Membrane-anchored carbonic anhydrase IV interacts with monocarboxylate transporters via their chaperones CD147 and GP70.
CA4 is a novel tumour suppressor in Colorectal cancer through the inhibition of the Wnt signalling pathway by targeting the WTAP-WT1-TBL1 axis. CA4 methylation may serve as an independent biomarker for the recurrence of Colorectal cancer .
Title: Carbonic anhydrase IV inhibits colon cancer development by inhibiting the Wnt signalling pathway through targeting the WTAP-WT1-TBL1 axis.
Carbonic anhydrase 4 is lost in papillary thyroid carcinoma but not thyroid nodules
Title: Carbonic anhydrase 4 and crystallin α-B immunoreactivity may distinguish benign from malignant thyroid nodules in patients with indeterminate thyroid cytology.
Although CA IV has been shown to be active in mediating CO2 and HCO3 (-) transport in many important tissues like kidney and lung, and in isolated cells from brain and muscle, the gene for CA IV appears not to be essential.
Title: Membrane associated carbonic anhydrase IV (CA IV): a personal and historical perspective.
Coexpression of CAIV with MCT1 and MCT4 resulted in a significant increase in MCT transport activity.
Title: Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters.
The generation of CA III and IV autoantibodies, antioxidant enzymes, and cytokines might influence each other.
Title: Carbonic anhydrases III and IV autoantibodies in rheumatoid arthritis, systemic lupus erythematosus, diabetes, hypertensive renal disease, and heart failure.
membrane-associated CA IV contributes robust catalytic activity intracellularly, and this activity participates in regulating H(+) dynamics in the cytosol
Title: GPI-anchored carbonic anhydrase IV displays both intra- and extracellular activity in cRNA-injected oocytes and in mouse neurons.
Two SNPs of carbonic anhydrase IV, which are responsible for amino acid changes, were found. The frequencies of these SNPs were not significantly different between the caries-free group and the group with caries
Title: Carbonic anhydrase VI exon 2 genetic polymorphism in Turkish subjects with low caries experience (preliminary study).

Submit: New GeneRIF Correction See all GeneRIFs (24)

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
Retinitis pigmentosa 17 MedGen: C1833245 OMIM: 600852 GeneReviews: Nonsyndromic Retinitis Pigmentosa Overview	Compare labs

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

RH79679 (e-PCR)
- UniSTS:84250

NoName (e-PCR)
- UniSTS:480878

NoName (e-PCR)
- UniSTS:481935

RH71355 (e-PCR)
- UniSTS:66453

D17S808 (e-PCR), detects polymorphism
- UniSTS:9123

D17S807 (e-PCR)
- UniSTS:65958

Homology

Homologs of the CA4 gene: The CA4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 232 organisms have orthologs with human gene CA4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
carbonate dehydratase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
hydro-lyase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
bicarbonate transport	IMP Inferred from Mutant Phenotype more info	PubMed
bicarbonate transport	TAS Traceable Author Statement more info
one-carbon metabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
anchored component of external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
NOT basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
brush border membrane	IDA Inferred from Direct Assay more info	PubMed
cell surface	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum-Golgi intermediate compartment	IDA Inferred from Direct Assay more info	PubMed
extracellular exosome	HDA more info	PubMed
extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
membrane	TAS Traceable Author Statement more info	PubMed
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
rough endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
secretory granule membrane	IDA Inferred from Direct Assay more info	PubMed
trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed
transport vesicle membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: carbonic anhydrase 4

Names: CA-IV; carbonate dehydratase IV; carbonic anhydrase IV; carbonic dehydratase IV

NP_000708.1

EC 4.2.1.1

XP_005257696.1

EC 4.2.1.1

XP_011523485.1

EC 4.2.1.1

XP_016880501.1

EC 4.2.1.1

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.

Genomic

NG_012050.2 RefSeqGene

Range

5033..14606

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000717.5 → NP_000708.1 carbonic anhydrase 4 preproprotein

See identical proteins and their annotated locations for NP_000708.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the protein.

Source sequence(s)

AI990988, BC057792, BC074768

Consensus CDS

CCDS11624.1

UniProtKB/Swiss-Prot

P22748

Related

ENSP00000300900.3, ENST00000300900.9

Conserved Domains (1) summary

cd03117
Location:48 → 283

alpha_CA_IV_XV_like; Carbonic anhydrase alpha, CA_IV, CA_XV, like isozymes. Carbonic anhydrases (CAs) are zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide in a two-step mechanism: a nucleophilic attack of a zinc-bound hydroxide ion on carbon ...

RNA

NR_137422.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains several alternate exons compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC025048

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p13 Primary Assembly

Range

60149942..60179021

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005257639.3 → XP_005257696.1 carbonic anhydrase 4 isoform X1

See identical proteins and their annotated locations for XP_005257696.1

Conserved Domains (1) summary

cd03117
Location:48 → 307

alpha_CA_IV_XV_like; Carbonic anhydrase alpha, CA_IV, CA_XV, like isozymes. Carbonic anhydrases (CAs) are zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide in a two-step mechanism: a nucleophilic attack of a zinc-bound hydroxide ion on carbon ...
XM_011525183.2 → XP_011523485.1 carbonic anhydrase 4 isoform X2

Conserved Domains (1) summary

cl00012
Location:1 → 217

alpha_CA; Carbonic anhydrase alpha (vertebrate-like) group. Carbonic anhydrases (CAs) are zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide in a two-step mechanism: a nucleophilic attack of a zinc-bound hydroxide ion on carbon ...
XM_017025012.1 → XP_016880501.1 carbonic anhydrase 4 isoform X3

UniProtKB/Swiss-Prot

P22748

Conserved Domains (1) summary

cl00012
Location:1 → 193

alpha_CA; Carbonic anhydrase alpha (vertebrate-like) group. Carbonic anhydrases (CAs) are zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide in a two-step mechanism: a nucleophilic attack of a zinc-bound hydroxide ion on carbon ...