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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

CA2 Gene

protein-coding GIFtS: 74
GCID: GC08P086376

carbonic anhydrase II

Explore 70 diseases affiliated with
CA2 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Carbonic Anhydrase II¹ ² ³		CAC² ³
CA-II¹ ² ³		EC 4.2.1.1³ ⁸
CAII¹ ²		Carbonic Anhydrase 2²
Car2¹ ²		Carbonic Anhydrase B²
Carbonate Dehydratase II² ³		Carbonic Dehydratase²
Carbonic Anhydrase C² ³

External Ids:	HGNC: 1373¹	Entrez Gene: 760²	Ensembl: ENSG00000104267⁷	OMIM: 611492⁵	UniProtKB: P00918³

Export aliases for CA2 gene to outside databases

Previous GC identifers: GC08P085200 GC08P086333 GC08P086156 GC08P086450 GC08P086563 GC08P081870

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CA2:

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)

UniProtKB/Swiss-Prot: CAH2_HUMAN, P00918

Function: Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon

dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the

eye

summary for CA2:

Carbonic anhydrases�are zinc-containing enzymes belonging to the lyases family, and are primarily

responsible for catalyzing the reversible hydration of carbon dioxide to form bicarbonate (HCO3-) and

hydrogen (H+) ions. There are several different carbonic anhydrase isoforms; these can be broadly grouped

into cytosolic (CA I, CA II, CA III, CA VII, CA XIII), mitochondrial (CA VA, CA VB), secreted (CA VI) and

membrane-associated (CA IV, CA IX, CA XII, CA XIV) carbonic anhydrases. The functions of the remaining

carbonic anhydrases are yet to be elucidated. Expression of the membrane-bound carbonic anhydrase, CA IX,

has been reported in hypoxic tumors where its activity is linked to promoting survival of tumor cells and

aiding�cancer�progression. This is thought to occur through the carbonic anhyrase-mediated production of

bicarbonate ions, which neutralizes the abnormally acidic pH of the extracellular environment induced during

hypoxia. Furthermore, as CA IX is a hypoxia- and HIF-1-inducible enzyme, its expression can be used as a

biomarker for hypoxic tumors.

Gene Wiki entry for CA2 (Carbonic anhydrase II)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000008.10 NC_018919.1 NT_008183.19

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the CA2 gene promoter:
NF-1/L NF-1 GATA-3 POU3F2 (N-Oct-5b) POU3F2 (N-Oct-5a) POU3F2 GATA-1 Evi-1 GATA-2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: CA2 promoter sequence

Search SABiosciences Chromatin IP Primers for CA2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CA2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 8q22 Ensembl cytogenetic band: 8q21.2 HGNC cytogenetic band: 8q21.2

CA2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CA2 gene location

GeneLoc information about chromosome 8 GeneLoc Exon Structure

GeneLoc location for GC08P086376: view genomic region (about GC identifiers)

Start:	86,376,081 bp from pter	End:	86,393,721 bp from pter
Size:	17,641 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: CAH2_HUMAN, P00918 (See protein sequence)

Recommended Name: Carbonic anhydrase 2

Size: 260 amino acids; 29246 Da

Cofactor: Zinc. Can also use cobalt(II) with lower efficiency, but not copper(II), nickel(II) and manganese(II)

Subunit: Interacts with SLC4A4. Interaction with SLC4A7 regulates SLC4A7 transporter activity

Subcellular location: Cytoplasm

Miscellaneous: Target of drugs used in treatments against glaucoma disorder and breast cancer

6/419 PDB 3D structures from and Proteopedia for CA2 (see all 419):

12CA (3D)

1A42 (3D)

1AM6 (3D)

1AVN (3D)

1BCD (3D)

1BIC (3D)

Secondary accessions: B2R7G8 Q6FI12 Q96ET9

Explore the universe of human proteins at neXtProt for CA2: NX_P00918

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P00918

4/7 DME Specific Peptides for CA2 (P00918) (see all 7)

QFHFHWG

TYPGSLT

AELHLVH

MVDNWRP

CA2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000058.1

ENSEMBL proteins:

ENSP00000285379 ENSP00000428443 ENSP00000428947

Reactome Protein details: P00918
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for CA2 (Carbonic Anhydrase II/CA2)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: CA2 OriGene Protein Over-expression Lysate: CA2 OriGene Custom Protein Services for CA2
	GenScript Custom Purified and Recombinant Proteins Services for CA2
	Novus Biologicals CA2 Proteins Novus Biologicals CA2 Lysate
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for CA2
	Uscn Proteins for CA2

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005615	extracellular space	IEA	--
GO:0005737	cytoplasm	IDA	--
GO:0005829	cytosol	TAS	--
GO:0005902	microvillus	IEA	--
GO:0016323	basolateral plasma membrane	IEA	--

CA2 for ontologies About GeneDecksing

CA2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of CA2
	R&D Systems Antibodies for CA2 (Carbonic Anhydrase II/CA2)
	Cell Signaling Technology (CST) Antibodies for CA2
	OriGene Antibodies: CA2 OriGene Custom Antibody Services for CA2
	GenScript Superior Antibodies for CA2
	Novus Biologicals CA2 Antibodies
	Abcam antibodies for CA2
	Uscn Antibodies for CA2
	ThermoFisher Antibodies for CA2

Assay Products for CA2:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for CA2
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for CA2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

CA2 for domains About GeneDecksing

4 InterPro domains/families:

IPR001148 Carbonic_anhydrase_a

IPR018338 Carbonic_anhydrase_a-class_CS

IPR018440 Carbonic_anhydrase_CA2

IPR023561 Carbonic_anhydrase_a-class

Graphical View of Domain Structure for InterPro Entry P00918

ProtoNet protein and cluster: P00918

1 Blocks protein family: IPB001148 Carbonic anhydrase

UniProtKB/Swiss-Prot: CAH2_HUMAN, P00918

Similarity: Belongs to the alpha-carbonic anhydrase family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: CAH2_HUMAN, P00918

Function: Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon

dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the

eye

Catalytic activity: H(2)CO(3) = CO(2) + H(2)O

Enzyme regulation: Activated by X-ray, histamine, L-adrenaline, L- and D-phenylalanine, L- and D-histidine, L-His-OMe

and beta-Ala-His (carnosine). Competitively inhibited by saccharin, thioxolone, coumarins, 667-coumate, celecoxib

(Celebrex), valdecoxib (Bextra), SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide derivatives such as

acetazolamide (AZA), methazolamide (MZA), ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide, dansylamide,

thiabendazole-5-sulfonamide, trifluoromethane sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate

RWJ-37497, and Foscarnet (phosphonoformate trisodium salt). Repressed strongly by hydrogen sulfide(HS) and weakly by

nitrate (NO(3)). Esterase activity weakly reduced by cyanamide. N-hydroxyurea interfers with zinc binding and inhibit

activity

Biophysicochemical properties: Absorption: Abs(max)=550 nm; Note=At pH 7.0. Shows a second maximum at 618 nm; Kinetic

parameters: KM=10 mM for CO(2); KM=82 mM for H(2)CO(3); KM=3 mM for 4-nitrophenyl acetate; pH dependence: Optimum pH

is 6-8;

Genatlas biochemistry entry for CA2:

carbonic anhydrase II,cytosolic,ubiquitous

Enzyme Number (IUBMB): EC 4.2.1.1¹ ²

miRNA Products:		OriGene 3'-UTR Clone: CA2 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CA2
		8/17 QIAGEN miScript miRNA Assays for microRNAs that regulate CA2 (see all 17):
		hsa-miR-16-2* hsa-miR-3664-5p hsa-miR-29a hsa-miR-29c hsa-miR-23a hsa-miR-330-3p hsa-miR-3688-3p hsa-miR-130a*

		SwitchGear 3'UTR luciferase reporter plasmid: CA2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CA2 (see all 4) OriGene shRNA RFP: CA2 OriGene siRNA: CA2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CA2

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for CA2

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CA2 (see all 2) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for CA2 (see all 2) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): CA2 (NM_212533)
		Sino Biological Human cDNA Clone for CA2
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CA2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CA2

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for CA2
		Search LifeMap BioReagents cell lines for CA2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CA2

Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004089	carbonate dehydratase activity	IEA	--
GO:0005515	protein binding	--	--
GO:0008270	zinc ion binding	IDA	3151020

CA2 for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for CA2:

Synthetic lethal with imatinib

Animal Models:
8 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Car2):

digestive/alimentary	endocrine/exocrine gland	growth/size	homeostasis/metabolism	mortality/aging
renal/urinary system	reproductive system	skeleton

CA2 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/11 super-pathways (see all 11) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

O2/CO2 exchange in erythrocytes

	O2/CO2 exchange in erythrocytes	1.00			Uptake of Carbon Dioxide and Release of Oxygen by Erythrocytes	1.00
	Uptake of Oxygen and Release of Carbon Dioxide by Erythrocytes	1.00

Transcription_Role of VDR in regulation of genes involved in osteoporosis

Transcription_Role of VDR in regulation of genes involved in osteoporosis

1.00

Transcription Role of VDR in regulation of genes involved in osteoporosis

0.80

Reversible Hydration of Carbon Dioxide

Reversible Hydration of Carbon Dioxide

1.00

Nitrogen metabolism

0.52

Neuroscience

Neuroscience

1.00

Glucose / Energy Metabolism

Glucose / Energy Metabolism

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for CA2

Transcription Role of VDR in regulation of genes involved in osteoporosis

2 Cell Signaling Technology (CST) Pathways for CA2

	Neuroscience
	Glucose / Energy Metabolism

1 GeneGo (Thomson Reuters) Pathway for CA2

Transcription Role of VDR in regulation of genes involved in osteoporosis

5 Reactome Pathways for CA2

	Uptake of Carbon Dioxide and Release of Oxygen by Erythrocytes
	Reversible Hydration of Carbon Dioxide
	Metabolism
	Uptake of Oxygen and Release of Carbon Dioxide by Erythrocytes
	O2/CO2 exchange in erythrocytes

5/6 Kegg Pathways (Kegg details for CA2) (see all 6):

	Nitrogen metabolism
	Proximal tubule bicarbonate reclamation
	Collecting duct acid secretion
	Gastric acid secretion
	Pancreatic secretion

CA2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for CA2

STRING Interaction Network Preview (showing 5 interactants - click image to see 10)

5/26 Interacting proteins for CA2 (P00918^{2, 3} ENSP00000285379⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 26)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
ANKZF1	Q9H8Y5²^,³	MINT-65644 I2D: score=3
PTCHD2	Q9P2K9²^,³	MINT-63343 I2D: score=3
PCNA	P12004²^,³	MINT-7995220 I2D: score=2
HSPD1	P10809³, ENSP00000340019⁴	I2D: score=3 STRING: ENSP00000340019
SLC4A8	Q2Y0W8³, ENSP00000405812⁴	I2D: score=3 STRING: ENSP00000405812

About this table

Gene Ontology (GO): 5/17 biological process terms (GO ID links to tree view) (see all 17): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001822	kidney development	IEA	--
GO:0002009	morphogenesis of an epithelium	IEA	--
GO:0006730	one-carbon metabolic process	IEA	--
GO:0006950	response to stress	IEA	--
GO:0009268	response to pH	IEA	--

CA2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

CA2 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Compounds for CA2 available from Tocris Bioscience About this table

Compound	Action	CAS #
Topiramate	Inhibits carbonic anhydrase (CA) II and IV	[97240-79-4]

6 HMDB Compounds for CA2 About this table

Compound	Synonyms	CAS #	PubMed Ids
Carbon dioxide	Carbon oxide (see all 5)	124-38-9	--
Carbonic acid	acid of air (see all 24)	463-79-6	--
Hydrochlorothiazide	3,4-Dihydrochlorothiazide (see all 89)	58-93-5	--
Topiramate	Epitomax (see all 5)	97240-79-4	--
Water	Dihydrogen oxide (see all 2)	7732-18-5	--
Zinc	Zinc (see all 2)	7440-66-6	--

10/95 DrugBank Compounds for CA2 (see all 95) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Dorzolamide	--	120279-96-1	target	inhibitor	10048009 8875343 8781782 15258186 11752352 8070313 9029437 10614682 12356834
Zonisamide	Zonisamida [Spanish] (see all 2)	68291-97-4	target	inhibitor	18537527 17762320 19703035 15837316 18162396 18782051 17582922 8494570 18343915
Brinzolamide	--	138890-62-7	target	inhibitor	19668749 10665514 9541386 9865942 14684332 14971907 11003159
Hydrochlorothiazide	Dihydrochlorothiazid (see all 10)	58-93-5	target	inhibitor	17139284 1901209 19119014 2226620 17016423
Topiramate	Tipiramate [French] (see all 6)	97240-79-4	target	inhibitor	17251017 15478125 15771438 12617904 17521680
Chlorothiazide	Chlorothiazid (see all 3)	58-94-6	target	inhibitor	10954127 11752352 12388412 14656370
(4-sulfamoyl-phenyl)-thiocarbamic acid O-(2-thiophen-3-yl-ethyl) ester	--	--	target	--	17139284 17016423 10592235
(R)-N-(3-Indol-1-Yl-2-Methyl-Propyl)-4-Sulfamoyl-Benzamide	--	--	target	--	17139284 17016423 10592235
(S)-N-(3-Indol-1-Yl-2-Methyl-Propyl)-4-Sulfamoyl-Benzamide	--	--	target	--	17139284 17016423 10592235
1-Methyl-3-Oxo-1,3-Dihydro-Benzo[C]Isothiazole-5-Sulfonic Acid Amide	--	--	target	--	17139284 17016423 10592235

10/89 Novoseek chemical compound relationships for CA2 gene (see all 89) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
sulfonamide	83.2	28	17118494 (2), 8557623 (2), 18179217 (2), 12164389 (1) (see all 19)
dansylamide	82.9	8	8557623 (3), 8340917 (1), 7696263 (1)
benzenesulfonamide	79.9	9	11554714 (2), 10354450 (2), 20443227 (1), 14994755 (1) (see all 6)
p-nitrophenyl acetate	79.5	1	15807537 (1)
4-carboxybenzenesulfonamide	78.6	2	18179217 (1), 17640087 (1)
sulfamide	76.3	11	15771438 (3), 18363349 (2), 16759092 (2), 17627576 (2)
acetazolamide	76.3	32	15183767 (2), 19851004 (2), 2128470 (2), 9445204 (1) (see all 20)
bicarbonate	75.7	104	12933803 (8), 12372813 (6), 15499994 (5), 11606574 (4) (see all 41)
667-coumate	75.4	5	14623540 (2), 15453828 (1), 12617909 (1)
zinc hydroxide	75.3	1	1974931 (1)

Search CenterWatch for drugs/clinical trials and news about CA2 / CAH2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for CA2 gene:

NM_000067.2

Unigene Cluster for CA2:

Carbonic anhydrase II

Hs.155097 [show with all ESTs]

Unigene Representative Sequence: AK123309

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000285379(uc003ydk.2) ENST00000520127 ENST00000520996 ENST00000518231

ENST00000522742

miRNA Products:		OriGene 3'-UTR Clone: CA2 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CA2
		8/17 QIAGEN miScript miRNA Assays for microRNAs that regulate CA2 (see all 17):
		hsa-miR-16-2* hsa-miR-3664-5p hsa-miR-29a hsa-miR-29c hsa-miR-23a hsa-miR-330-3p hsa-miR-3688-3p hsa-miR-130a*

		SwitchGear 3'UTR luciferase reporter plasmid: CA2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CA2 (see all 4) OriGene shRNA RFP: CA2 OriGene siRNA: CA2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CA2

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CA2 (see all 2) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for CA2 (see all 2) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): CA2 (NM_212533)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for CA2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CA2

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for CA2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat CA2
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat CA2
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat CA2

Additional cDNA sequence:

AK123309.1 AK312978.1 BC011949.1 BC035424.1 CR536526.1 CR541875.1 J03037.1 M36532.1

Y00339.1

18 DOTS entries:

DT.95257530 DT.100674288 DT.100822205 DT.100727988 DT.415993 DT.101972566 DT.75155536 DT.100822203

DT.100822199 DT.121482821 DT.121482847 DT.121483012 DT.95257523 DT.95257527 DT.99972405 DT.99990999

DT.40301241 DT.95151518

24/401 AceView cDNA sequences (see all 401):

AF015039 BM702636 AI420180 BU663006 N50528 BF196676 AA970529 AA363515

CR541875 BI765269 AW294014 AW075795 CR591919 NM_000067 CR616325 CD013933

AI492357 AI630453 CR608877 BU661161 BU658744 H20705 AL043640 AI365607

GeneLoc Exon Structure

5/6 Alternative Splicing Database (ASD) splice patterns (SP) for CA2 (see all 6) About this scheme

ExUns:	1a	·	1b	·	1c	^	2	^	3	^	4a	·	4b	^	5a	·	5b	^	6	^	7a	·	7b	·	7c	^	8a	·	8b	·	8c	·	8d
SP1:									-								-
SP2:									-
SP3:									-		-		-				-
SP4:
SP5:									-				-		-		-		-		-

ECgene alternative splicing isoforms for CA2

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

CA2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: ATTTCAAGAT

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CA2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

10 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Brain

Choroid Plexus

Choroid Plexus Progenitor Cells

Choroid Plexus

Kidney

Proximal Tubule

Proximal Tubule Cells

Kidney

Eye

Inner Nuclear Layer

GABAergic Amacrine Cells

Amacrine, Retina

Heart

Cardiac Crescent

Cardiac Crescent Cells

Myocardium

Limb

Zeugopod

Prechondrocytic Mesenchymal Cells

Bone, Cartilage

Skeletal Muscle

Hyoid Arch Muscles

Muscle Progenitor Cells

Skeletal Muscle

Mandibular Arch Muscles

Muscle Progenitor Cells

Skeletal Muscle

Testis

Seminiferous Tubules

Spermatid

Germ Cells, Male Gametocytes

Brain

Liver

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

PureStem™ mesenchymal progenitor MEL2 (Embryonic Progenitor Cell)

Adipose, Bone, Cartilage

Definitive endoderm-like cells (A scalable, suspensi...)

See CA2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for CA2

SOURCE GeneReport for Unigene cluster: Hs.155097

SABiosciences Custom PCR Arrays for CA2

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for CA2 gene from 8/24 species (see all 24) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	CA2¹	carbonic anhydrase II	72.18(n) 70.77(a)		396257 NM_205317.1 NP_990648.1
lizard (Anolis carolinensis)	Reptilia	CA2⁶	--	69(a)	1 ↔ 1	4(23086113-23106131)
African clawed frog (Xenopus laevis)	Amphibia	ca2-prov²	carbonic anhydrase II	75.85(n)		BC042287.1
zebrafish (Danio rerio)	Actinopterygii	cahz²	carbonic anhydrase	74.16(n)		30331 NM_131110.1
fruit fly (Drosophila melanogaster)	Insecta	CAH1³	carbonate dehydratase	45(a) (best of 4)		34D4 --
worm (Caenorhabditis elegans)	Secernentea	cah-3³	carbonic anhydrase	35(a)		X(16518334-16519911) --
thale cress (Arabidopsis thaliana)	eudicotyledons	ATACA2⁶ ACA1⁶ (see all 8)	carbonic anhydrase (see all 8)	25(a) 23(a) (see all 8)	many ↔ many many ↔ many (see all 8)	2(12029997-12032420) 3(19538690-19541284)
rice (Oryza sativa)	Liliopsida	Os08g0424100¹	hypothetical protein	46.58(n) 38.39(a)		9267362 NM_001188659.1 NP_001175588.1

ENSEMBL Gene Tree for CA2 (if available)
TreeFam Gene Tree for CA2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for CA2 gene

CA12² CA7² CA6² CA3² CA11² CA5B² CA14² CA5A²

CA8² CA4² CA1² CA13² CA9² CA10²

17 SIMAP similar genes for CA2 using alignment to 3 protein entries: CAH2_HUMAN (see all proteins):

CA13 CA1 CA3 CA7 CA5B CA5A

CA8 DKFZp686I20267 CA10 CA6 CA11 CA12

CA14 PTPRZ1 CA4 CA9 PTPRG

CA2 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 8 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs2228063^1,2	C,F,H,	pathogenic	82213214(+)	`TGAAGA/GACAGG`	2	N D	mis¹ ese³		20		MN NS EA NA CSA WA	6486
rs72682966^1,2	C,F,	--	81868383(+)	`TCTTAC/TTTCAT`	2	--	us2k¹ int¹		1		NA	120
rs75827641^1,2		--	81869318(+)	`GTGTTT/CATGAA`	2	--	us2k¹ int¹		1		NA	120
rs77250341^1,2		--	81869581(+)	`CCTCAC/TCCACG`	2	--	us2k¹ nc-transcript-variant		2		CSA WA	120
rs112126108^1,2		--	81869771(+)	`ACTCAT/CGCTGC`	2	--	us2k¹ nc-transcript-variant		2		CSA WA	120
rs12115161^1,2		--	81871018(+)	`GCGCTC/TAGCAC`	2	--	int¹ us2k¹		0	--	--	--	--
rs76594593^1,2	C,	--	81871046(+)	`TTTCCA/TGTGCT`	2	--	int¹ us2k¹		2		CSA WA	120
rs60560003^1,2	C,F,	--	81872188(+)	`AAGATC/AAGTCA`	1	--	int¹		1		WA	118
rs73263432^1,2	C,	--	81872370(+)	`ACTTAT/AGAGTA`	1	--	int¹		2		WA	120
rs113588643^1,2		--	81872425(+)	`GATATC/TTACTC`	1	--	int¹		1		CSA	2

HapMap Linkage Disequilibrium report for CA2 (86376081 - 86393721 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for CA2
1 CNV: 4601
Human Gene Mutation Database (HGMD): CA2

Locus Specific Mutation Databases (LSDB): CA2

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

CA2 for disorders           About GeneDecksing

OMIM gene information: 611492
OMIM disorders: 259730
UniProtKB/Swiss-Prot: CAH2_HUMAN, P00918

Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:259730]; also known as

osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or

marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective

resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero,

infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive

osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated

with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation

20/70 diseases for CA2 (see all 70): About MalaCards

renal tubular acidosis osteopetrosis, autosomal recessive 3, with renal tubular acidosis osteopetrosis osteopetrosis autosomal recessive 3

hypoxia open-angle glaucoma multifocal fibrosclerosis myxopapillary ependymoma

giant cell tumor choroid plexus carcinoma ocular hypotension proliferative vitreoretinopathy

primary biliary cirrhosis sjogren's syndrome nephrocalcinosis metabolic disorders

gliosis cystic fibrosis portal hypertension glaucoma

4 diseases from the University of Copenhagen DISEASES database for CA2:

Renal tubular acidosis Osteopetrosis Glaucoma Metabolic acidosis

10/56 Novoseek disease relationships for CA2 gene (see all 56) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
acidosis renal tubular	86.5	39	9525974 (3), 15300855 (3), 1959222 (2), 9323296 (2) (see all 21)
osteopetrosis	83.3	46	1959222 (3), 1566113 (3), 15300855 (3), 12566520 (2) (see all 26)
osteopetrosis, autosomal recessive	61.4	3	17936098 (1), 11045400 (1)
distal renal tubular acidosis	51.1	1	12566520 (1)
calcification	47.9	30	16825953 (2), 1959222 (2), 15300855 (2), 11264157 (2) (see all 16)
metabolic acidosis	39.9	2	8285209 (1), 15771438 (1)
glaucoma	37	8	9541386 (1), 10634490 (1), 2322152 (1), 11021544 (1) (see all 8)
biliary cirrhosis primary	33.3	12	7768386 (3), 11117577 (2), 15026266 (1), 17516290 (1) (see all 6)
sjogrens syndrome	33.1	10	15254347 (5), 8613065 (2), 7722336 (1), 15694905 (1)
chronic pancreatitis	32.7	9	15254347 (5), 8613065 (2), 15831920 (1)

Genatlas disease: CA2

osteopetrosis with renal tubular acidosis and cerebral calcifications

Human Genome Epidemiology (HuGE) Navigator: CA2 (19 documents)

Export disorders for CA2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for CA2 gene, integrated from 9 sources (see all 583):
(articles sorted by number of sources associating them with CA2)

Utopia: connect your pdf to the dynamic
world of online information

Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme- drug discrimination. (PubMed id 9541386)^{1, 2, 7, 9} Stams T.... Christianson D.W. (1998)
Regulation of the human NBC3 Na+/HCO3- cotransporter by carbonic anhydrase II and PKA. (PubMed id 14736710)^{1, 2, 9} Loiselle F.B.... Casey J.R. (2004)
Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype- phenotype correlation. (PubMed id 15300855)^{1, 2, 9} Shah G.N.... Sly W.S. (2004)
Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells. (PubMed id 15218065)^{1, 2, 9} Pushkin A.... Kurtz I. (2004)
Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His-->Tyr): complete structure of the normal human CA II gene. (PubMed id 1928091)^{1, 2, 9} Venta P.J.... Tashian R.E. (1991)
Molecular basis of human carbonic anhydrase II deficiency. (PubMed id 1542674)^{1, 2, 9} Roth D.E.... Sly W.S. (1992)
Structural influence of hydrophobic core residues on metal binding and specificity in carbonic anhydrase II. (PubMed id 11076507)^{1, 2, 9} Cox J.D.... Christianson D.W. (2000)
Apo-human carbonic anhydrase II revisited: implicatio ns of the loss of a metal in protein structure, stability, and solvent network. (PubMed id 19583303)^{1, 2, 9} Avvaru B.S....McKenna R. (2009)
Role of hydrophilic residues in proton transfer during catalysis by human carbonic anhydrase II. (PubMed id 18942852)^{1, 2, 9} Zheng J.... Silverman D.N. (2008)
Atomic crystal and molecular dynamics simulation structures of human carbonic anhydrase II: insights into the proton transfer mechanism. (PubMed id 17319692)^{1, 2, 9} Fisher S.Z....McKenna R. (2007)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 760	HGNC: 1373	AceView: CA2	Ensembl:ENSG00000104267	euGenes: HUgn760
ECgene: CA2	Kegg: 760	H-InvDB: CA2

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for CA2	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CA2

Intellectual Property for CA2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for CA2 gene:
Search GeneIP for patents involving CA2

GeneCards and IP:
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Osteopetrosis
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carbonic anhydrase II

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