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:: 14

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	17	NC_000017.11 (60149936..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

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

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

Go to the top of the page Help

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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).
data suggest that extracellular membrane-bound CAIV, but not cytosolic CAII, augments transport activity of MCT2 in a non-catalytic manner, possibly by facilitating a proton pathway other than His-88
Title: Transport activity of the high-affinity monocarboxylate transporter MCT2 is enhanced by extracellular carbonic anhydrase IV but not by intracellular carbonic anhydrase II.
compared the subcellular localization and post-translational processing of wild-type (WT)- and retinitis pigmentosa 17 mutant-CAIV in three cell types
Title: Cell-specific differences in the processing of the R14W CAIV mutant associated with retinitis pigmentosa 17.
Observational study of genetic testing. (HuGE Navigator)
Title: Simultaneous mutation detection in 90 retinal disease genes in multiple patients using a custom-designed 300-kb retinal resequencing chip.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

Go to the top of the page Help

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

Go to the top of the page Help

Erythrocytes take up carbon dioxide and release oxygen, organism-specific biosystem (from REACTOME)
Erythrocytes take up carbon dioxide and release oxygen, organism-specific biosystemCarbon dioxide (CO2) in plasma is hydrated to yield protons (H+) and bicarbonate (HCO3-) by carbonic anhydrase IV (CA4) located on the apical plasma membranes of endothelial cells. Plasma CO2 is also...
Erythrocytes take up oxygen and release carbon dioxide, organism-specific biosystem (from REACTOME)
Erythrocytes take up oxygen and release carbon dioxide, organism-specific biosystemErythrocytes circulating through the capillaries of the lung must exchange carbon dioxide (CO2) for oxygen (O2) during their short (0.5-1 sec.) transit time in pulmonary tissue (Reviewed in Jensen 20...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Nitrogen metabolism, organism-specific biosystem (from KEGG)
Nitrogen metabolism, organism-specific biosystemThe biological process of the nitrogen cycle is a complex interplay among many microorganisms catalyzing different reactions, where nitrogen is found in various oxidation states ranging from +5 in ni...
Nitrogen metabolism, conserved biosystem (from KEGG)
Nitrogen metabolism, conserved biosystemThe biological process of the nitrogen cycle is a complex interplay among many microorganisms catalyzing different reactions, where nitrogen is found in various oxidation states ranging from +5 in ni...
O2/CO2 exchange in erythrocytes, organism-specific biosystem (from REACTOME)
O2/CO2 exchange in erythrocytes, organism-specific biosystemIn capillaries of the lungs erythrocytes release carbon dioxide (CO2) and acquire oxygen (O2). In other tissues of the body the reverse reaction occurs (reviewed in Nikinmaa 1997, Jensen 2004).In the...
Proximal tubule bicarbonate reclamation, organism-specific biosystem (from KEGG)
Proximal tubule bicarbonate reclamation, organism-specific biosystemOne of the major tasks of the renal proximal tubule (PT) is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered bicarbonate (HCO3(-)), as well as generating "...
Proximal tubule bicarbonate reclamation, conserved biosystem (from KEGG)
Proximal tubule bicarbonate reclamation, conserved biosystemOne of the major tasks of the renal proximal tubule (PT) is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered bicarbonate (HCO3(-)), as well as generating "...
Reversible hydration of carbon dioxide, organism-specific biosystem (from REACTOME)
Reversible hydration of carbon dioxide, organism-specific biosystemCarbonic anhydrases reversibly catalyze the hydration of carbon dioxide and directly produce bicarbonate and protons, bypassing the formation of carbonic acid (reviewed in Lindskog 1997, Breton 2001,...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

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: 199 organisms have orthologs with human gene CA4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
carbonate dehydratase activity	TAS Traceable Author Statement more info
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

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	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

Go to the top of the page Help

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)

Go to the top of the page Help

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

4996..14606

Download

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, ENST00000300900.8

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_137422.1 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 Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p12 Primary Assembly

Range

60149936..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 ...