CA2 carbonic anhydrase II [Homo sapiens (human)] - Gene

Summary

Go to the top of the page Help

Official Symbol: CA2provided by HGNC
Official Full Name: carbonic anhydrase IIprovided by HGNC
Primary source: HGNC:1373
See related: Ensembl:ENSG00000104267; HPRD:02023; MIM:611492; Vega:OTTHUMG00000164944
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: CAC; CAII; Car2; CA-II
Summary: CA2 is one of several (at least 7) isozymes of carbonic anhydrase. Carbonic anhydrase catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis. [provided by RefSeq, Jul 2008]

Genomic context

Go to the top of the page Help

Location :: 8q22

Sequence :: Chromosome: 8; NC_000008.10 (86376131..86393721)

See CA2 in Epigenomics, MapViewer

Chromosome 8 - NC_000008.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions What's a GeneRIF?

The rate constants for transfer of a proton from His64 to the zinc-bound hydroxide during catalysis were 4 and 9 mus(-1) for Y7F and Y7F/N67Q, respectively, compared with a value of 0.8 mus(-1) for wild-type CAII.
Title: Water networks in fast proton transfer during catalysis by human carbonic anhydrase II.
reconstitution of the zinc active site of human CA II
Title: Revisiting zinc coordination in human carbonic anhydrase II.
data suggest that the Ile substitution at position 143 reduced the catalytic efficiency, likely due to steric crowding resulting in destabilization of the transition state for conversion of CO(2) into bicarbonate and a decreased product dissociation rate.
Title: Structural and kinetic effects on changes in the CO(2) binding pocket of human carbonic anhydrase II.
A significant correlation was found between positive carbonic anhydrase II staining and oral squamous cell carcinoma for more advanced clinical stage and larger tumor size, but not for positive lymph node metastasis, distal metastasis, and recurrence.
Title: Expression of carbonic anhydrases I/II and the correlation to clinical aspects of oral squamous cell carcinoma analyzed using tissue microarray.
pKa shifts of zinc-bound water due to mutations of CA II active site support conclusion that changes in conformation and electronic polarization of mutated active sites account for altered deprotonation behavior of zinc-bound water.
Title: Combined density functional theory (DFT) and continuum calculations of pKa in carbonic anhydrase.
study reports the catalytic properties of three hCA II mutants (Asn67Ile, Gln92Val and Leu204Ser) and the inhibition of these enzymes; small perturbations within the active site architecture have influences on the catalytic efficiency but dramatically change affinity for inhibitors among the CA enzymes
Title: Mutation of active site residues Asn67 to Ile, Gln92 to Val and Leu204 to Ser in human carbonic anhydrase II: influences on the catalytic activity and affinity for inhibitors.
Studies indicate that cytosolic isoform carbonic anhydrase II (hCA II) was very weakly inhibited by the aliphatic, C1-C5 carboxylates as well as by branched aliphatic ones.
Title: (In)organic anions as carbonic anhydrase inhibitors.
The apparent values of the pK(a) of the zinc-bound water and the proton shuttle residue suggest that different active-site conformations influence the two stages of catalysis, the proton transfer stage and the interconversion of CO(2) and bicarbonate.
Title: Structure and catalysis by carbonic anhydrase II: role of active-site tryptophan 5.
Detailed analysis and comparison to the previously determined structure of CAII at pH 10.0 show important differences in protonation of key catalytic residues in the active site as well as a rearrangement of the hydrogen-bonded water network.
Title: Neutron structure of human carbonic anhydrase II: a hydrogen-bonded water network "switch" is observed between pH 7.8 and 10.0.
The expression of CA2 is significantly increased in the spermatozoa of asthenozoospermic men, which might be responsible for low sperm motility.
Title: [Expression of carbonic anhydrase II in human testes and spermatozoa and its clinical significance].

Submit: New GeneRIF Correction See all (74)

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

Osteopetrosis with renal tubular acidosis

MIM: 259730

Genetic Testing Registry

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Source	Pubs	Description
P00918	Q9H8Y5	ANKZF1	HPRD	PubMed
P00918	P63167	DYNLL1	HPRD	PubMed
P00918	P10809	HSPD1	HPRD	PubMed
P00918	Q15233	NONO	HPRD	PubMed
P00918	Patched domain containing 2	PTCHD2	HPRD	PubMed
P00918	P02730	SLC4A1	HPRD	PubMed
P00918	P04920	SLC4A2	HPRD	PubMed
P00918	P48751	SLC4A3	HPRD	PubMed
P00918	Q9Y6R1	SLC4A4	HPRD	PubMed
P00918	Solute carrier family 4, member 8	SLC4A8	HPRD	PubMed
P00918	P19634	SLC9A1	HPRD	PubMed
BioGRID:107215	BioGRID:107223	CA9	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107215	BioGRID:114032	CUL1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107215	BioGRID:114029	CUL4A	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107215	BioGRID:198624	Cdk1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107215	BioGRID:109561	HSPD1	BioGRID	PubMed	Co-crystal Structure
BioGRID:107215	BioGRID:110904	NONO	BioGRID	PubMed	Reconstituted Complex
BioGRID:107215	BioGRID:111142	PCNA	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107215	BioGRID:112412	SLC4A1	BioGRID	PubMed	Reconstituted Complex
BioGRID:107215	BioGRID:114877	SLC4A8	BioGRID	PubMed	Reconstituted Complex
BioGRID:107215	BioGRID:112438	SLC9A1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107215	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107215	BioGRID:123904	USP42	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

Go to the top of the page Help

Bile secretion, organism-specific biosystem (from KEGG)
Bile secretion, organism-specific biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
Bile secretion, conserved biosystem (from KEGG)
Bile secretion, conserved biosystemBile is a vital secretion, essential for digestion and absorption of fats and fat-soluble vitamins in the small intestine. Moreover, bile is an important route of elimination for excess cholesterol a...
Collecting duct acid secretion, organism-specific biosystem (from KEGG)
Collecting duct acid secretion, organism-specific biosystemOne of the important roles of the collecting duct segment of the kidney nephron is acid secretion. As daily food intake loads acid into the body, urinary acid excretion is essential, and urine pH can...
Collecting duct acid secretion, conserved biosystem (from KEGG)
Collecting duct acid secretion, conserved biosystemOne of the important roles of the collecting duct segment of the kidney nephron is acid secretion. As daily food intake loads acid into the body, urinary acid excretion is essential, and urine pH can...
Gastric acid secretion, organism-specific biosystem (from KEGG)
Gastric acid secretion, organism-specific biosystemGastric acid is a key factor in normal upper gastrointestinal functions, including protein digestion and calcium and iron absorption, as well as providing some protection against bacterial infections...
Gastric acid secretion, conserved biosystem (from KEGG)
Gastric acid secretion, conserved biosystemGastric acid is a key factor in normal upper gastrointestinal functions, including protein digestion and calcium and iron absorption, as well as providing some protection against bacterial infections...
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...
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...
Pancreatic secretion, organism-specific biosystem (from KEGG)
Pancreatic secretion, organism-specific biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
Pancreatic secretion, conserved biosystem (from KEGG)
Pancreatic secretion, conserved biosystemThe pancreas performs both exocrine and endocrine functions. The exocrine pancreas consists of two parts, the acinar and duct cells. The primary functions of pancreatic acinar cells are to synthesiz...
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,...
Uptake of Carbon Dioxide and Release of Oxygen by Erythrocytes, organism-specific biosystem (from REACTOME)
Uptake of Carbon Dioxide and Release of Oxygen by Erythrocytes, 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...
Uptake of Oxygen and Release of Carbon Dioxide by Erythrocytes, organism-specific biosystem (from REACTOME)
Uptake of Oxygen and Release of Carbon Dioxide by Erythrocytes, 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...

General gene information

Go to the top of the page Help

Markers

RH11468 (e-PCR)
- UniSTS:23717

G44354 (e-PCR)
- UniSTS:95141

D8S1418E (e-PCR)
- UniSTS:151206

G60153 (e-PCR)
- UniSTS:137408

D8S1912 (e-PCR)
- UniSTS:19667

Genotypes

See CA2 SNP Geneview Report
See CA2 SNP Genotype Report
See CA2 SNP Variation Viewer Report

Homology

Homologs of the CA2 gene: The CA2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
carbonate dehydratase activity	IEA Inferred from Electronic Annotation more info
zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
bicarbonate transport	TAS Traceable Author Statement more info
carbon dioxide transport	IEA Inferred from Electronic Annotation more info
kidney development	IEA Inferred from Electronic Annotation more info
morphogenesis of an epithelium	IEA Inferred from Electronic Annotation more info
odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
one-carbon metabolic process	IEA Inferred from Electronic Annotation more info
positive regulation of bone resorption	IEA Inferred from Electronic Annotation more info
positive regulation of cellular pH reduction	IEA Inferred from Electronic Annotation more info
positive regulation of osteoclast differentiation	IEA Inferred from Electronic Annotation more info
response to estrogen stimulus	IEA Inferred from Electronic Annotation more info
response to pH	IEA Inferred from Electronic Annotation more info
response to stress	IEA Inferred from Electronic Annotation more info
response to zinc ion	IEA Inferred from Electronic Annotation more info
secretion	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
apical part of cell	IDA Inferred from Direct Assay more info	PubMed
axon	IEA Inferred from Electronic Annotation more info
basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
cytoplasm	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
extracellular space	IEA Inferred from Electronic Annotation more info
microvillus	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: carbonic anhydrase 2

Names: carbonic anhydrase 2; carbonic anhydrase B; carbonic anhydrase C; carbonic dehydratase; carbonate dehydratase II

NP_000058.1

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_007287.1 RefSeqGene

Range

4886..22476

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000067.2 → NP_000058.1 carbonic anhydrase 2

Status: REVIEWED

Source sequence(s)

DA431650, J03037, M36532

Consensus CDS

CCDS6239.1

UniProtKB/Swiss-Prot

P00918

Related

ENSP00000285379, OTTHUMP00000227991, ENST00000285379, OTTHUMT00000381097

Conserved Domains (1) summary

cd03119
Location:1 – 259
Blast Score: 1310

alpha_CA_I_II_III_XIII; Carbonic anhydrase alpha, isozymes I, II, and III and XIII. 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 ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000008.10 Reference GRCh37.p10 Primary Assembly

Range

86376131..86393721

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000140.1 Alternate HuRef

Range

81870322..81887902

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018919.1 Alternate CHM1_1.0

Range

86472694..86490273

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01004009.1 (4206..21786)	None
genomic	AC084734.4 (50422..67897)	None
genomic	AMYH01018835.1 (283331..300910)	None
genomic	CH471068.1	EAW87136.1
genomic	M77178.1	AAA51909.1
genomic	M77181.1	AAA51909.1
genomic	X03251.1	CAA27012.1
mRNA	AF015039.1	None
mRNA	AK312978.1	BAG35815.1
mRNA	BC011949.1	AAH11949.1
mRNA	BC035424.1	None
mRNA	CR536526.1	CAG38763.1
mRNA	CR541875.1	CAG46673.1
mRNA	DA431650.1	None
mRNA	J03037.1	AAA51908.1
mRNA	M36532.1	AAA51911.1
mRNA	S69526.1	AAB30170.1
mRNA	Y00339.1	CAA68426.1
other-genetic	DQ891320.2	ABM82246.1
other-genetic	DQ894504.2	ABM85430.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P00918.2	GenPept	UniProtKB/Swiss-Prot:P00918

Additional links

Go to the top of the page Help

Additional Links

Epigenomics
MIM 611492
CA2base: Mutation registry for Osteopetrosis with renal tubular acidosis CA2base/
GeneTests for MIM: 259730
GeneTests for MIM: 611492
UCSC UCSC
UniGene Hs.155097