P07451 (CAH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbonic anhydrase 3
EC=4.2.1.1

Alternative name(s):
Carbonate dehydratase III
Carbonic anhydrase III
Short name=CA-III

Gene names

Name:

CA3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	260 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Reversible hydration of carbon dioxide.
Catalytic activity	H2CO3 = CO2 + H2O.
Cofactor	Zinc.
Enzyme regulation	Activated by proton donors such as imidazole and the dipeptide histidylhistidine. Inhibited by coumarins and sulfonamide derivatives such as acetazolamide. Ref.8 Ref.9 Ref.10
Subcellular location	Cytoplasm.
Tissue specificity	Muscle specific.
Developmental stage	At 6 weeks gestation, transcripts accumulate at low levels in the somites and at high levels throughout the notochord. As gestation continues, CA3 becomes abundant in all developing muscle masses and continues at high to moderate levels in the notochord. Ref.7
Post-translational modification	S-glutathionylated in hepatocytes under oxidative stress By similarity.
Sequence similarities	Belongs to the alpha-carbonic anhydrase family.
Biophysicochemical properties	Kinetic parameters: KM=52.0 mM for CO2 Ref.10

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Acetylation Glutathionylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bicarbonate transport Traceable author statement. Source: Reactome one-carbon metabolic process Inferred from electronic annotation. Source: InterPro response to oxidative stress Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	carbonate dehydratase activity Traceable author statement Ref.1. Source: ProtInc nickel cation binding Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 260

259

Carbonic anhydrase 3

PRO_0000077426

Regions

Region

64 – 67

4

Involved in proton transfer

Region

198 – 199

2

Substrate binding By similarity

Sites

Active site

127

1

By similarity

Metal binding

94

1

Zinc; catalytic

Metal binding

96

1

Zinc; catalytic

Metal binding

119

1

Zinc; catalytic

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

182

1

S-glutathionyl cysteine By similarity

Modified residue

187

1

S-glutathionyl cysteine By similarity

Natural variations

Natural variant

31

1

V → I. Ref.3 Ref.4 Ref.5
Corresponds to variant rs20571 [ dbSNP | Ensembl ].

VAR_016180

Experimental info

Mutagenesis

64

1

K → H: Enhanced proton transfer in catalysis. Ref.12

Mutagenesis

67

1

R → H: Enhanced proton transfer in catalysis. Ref.12

Mutagenesis

197

1

F → L: Enhanced activity by at least 10-fold. Ref.11

Secondary structure

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260

Helix Strand Turn

Details...

Turn

9 – 11

3

Turn

13 – 15

3

Helix

16 – 18

3

Helix

21 – 24

4

Beta strand

25 – 27

3

Helix

35 – 37

3

Beta strand

47 – 50

4

Helix

53 – 55

3

Beta strand

56 – 61

6

Beta strand

66 – 70

5

Beta strand

73 – 75

3

Beta strand

77 – 81

5

Beta strand

88 – 97

10

Beta strand

106 – 109

4

Beta strand

115 – 123

9

Helix

125 – 127

3

Helix

130 – 133

4

Beta strand

139 – 151

13

Helix

154 – 160

7

Helix

161 – 165

5

Beta strand

172 – 174

3

Helix

180 – 183

4

Beta strand

190 – 195

6

Beta strand

206 – 213

8

Beta strand

215 – 217

3

Helix

219 – 225

7

Beta strand

229 – 231

3

Beta strand

233 – 236

4

Beta strand

256 – 258

3

Sequences

	Sequence		Length	Mass (Da)
	P07451 [UniParc]. Last modified March 20, 2007. Version 3. Checksum: A305334167233FCF	FASTA	260	29,557
	10 20 30 40 50 60 MAKEWGYASH NGPDHWHELF PNAKGENQSP VELHTKDIRH DPSLQPWSVS YDGGSAKTIL 70 80 90 100 110 120 NNGKTCRVVF DDTYDRSMLR GGPLPGPYRL RQFHLHWGSS DDHGSEHTVD GVKYAAELHL 130 140 150 160 170 180 VHWNPKYNTF KEALKQRDGI AVIGIFLKIG HENGEFQIFL DALDKIKTKG KEAPFTKFDP 190 200 210 220 230 240 SCLFPACRDY WTYQGSFTTP PCEECIVWLL LKEPMTVSSD QMAKLRSLLS SAENEPPVPL 250 260 VSNWRPPQPI NNRVVRASFK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence and derived amino acid sequence of a cDNA encoding human muscle carbonic anhydrase." Lloyd J., McMillan S., Hopkinson D., Edwards Y.H. Gene 41:233-239(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Nucleotide sequence, tissue-specific expression, and chromosome location of human carbonic anhydrase III: the human CAIII gene is located on the same chromosome as the closely linked CAI and CAII genes." Wade R., Gunning P., Eddy R., Shows T., Kedes L. Proc. Natl. Acad. Sci. U.S.A. 83:9571-9575(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-31. Tissue: Pericardium and Skeletal muscle.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-31.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-31. Tissue: Muscle.
[6]	"Human muscle carbonic anhydrase: gene structure and DNA methylation patterns in fetal and adult tissues." Lloyd J., Brownson C., Tweedie S., Charlton J., Edwards Y.H. Genes Dev. 1:594-602(1987) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Sequence comparisons and functional studies of the proximal promoter of the carbonic anhydrase 3 (CA3) gene." Sowden J., Smith H., Morrison K., Edwards Y. Gene 214:157-165(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11, DEVELOPMENTAL STAGE.
[8]	"A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases." Crocetti L., Maresca A., Temperini C., Hall R.A., Scozzafava A., Muehlschlegel F.A., Supuran C.T. Bioorg. Med. Chem. Lett. 19:1371-1375(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[9]	"Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new class of suicide inhibitors." Maresca A., Temperini C., Vu H., Pham N.B., Poulsen S.-A., Scozzafava A., Quinn R.J., Supuran C.T. J. Am. Chem. Soc. 131:3057-3062(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[10]	"Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide." Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A., Pedone C., Scozzafava A., Supuran C.T., De Simone G. Proteins 74:164-175(2009) [PubMed] [Europe PMC] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[11]	"Human carbonic anhydrase III: structural and kinetic study of catalysis and proton transfer." Duda D.M., Tu C., Fisher S.Z., An H., Yoshioka C., Govindasamy L., Laipis P.J., Agbandje-McKenna M., Silverman D.N., McKenna R. Biochemistry 44:10046-10053(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-260 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF PHE-197, ACTIVATION BY IMIDAZOLE AND HISTIDYLHISTIDINE.
[12]	"Structural and kinetic analysis of proton shuttle residues in the active site of human carbonic anhydrase III." Elder I., Fisher Z., Laipis P.J., Tu C., McKenna R., Silverman D.N. Proteins 68:337-343(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-260 IN COMPLEX WITH ZINC ION, MUTAGENESIS OF LYS-64 AND ARG-67.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M29458 Genomic DNA. Translation: AAA52293.1.
M29452 Genomic DNA. No translation available.
AK096880 mRNA. Translation: BAG53390.1.
AK313254 mRNA. Translation: BAG36064.1.
CH471068 Genomic DNA. Translation: EAW87133.1.
BC004897 mRNA. Translation: AAH04897.1.
AJ006473 Genomic DNA. Translation: CAA07056.1.

IPI

IPI00216983.

PIR

CRHU3. A26658.

RefSeq

NP_005172.1. NM_005181.3.

UniGene

Hs.82129.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z93	X-ray	2.10	A	1-260	[»]
1Z97	X-ray	2.10	A	1-260	[»]
2HFW	X-ray	2.50	A	1-260	[»]
3UYN	X-ray	2.60	A	1-260	[»]
3UYQ	X-ray	1.70	A	1-260	[»]

ProteinModelPortal

P07451.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000285381.

PTM databases

PhosphoSite

P07451.

Polymorphism databases

DMDM

134047703.

2D gel databases

UCD-2DPAGE

P07451.

Proteomic databases

PaxDb

P07451.

PRIDE

P07451.

Protocols and materials databases

DNASU

761.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000285381; ENSP00000285381; ENSG00000164879.

GeneID

761.

KEGG

hsa:761.

UCSC

uc003ydj.3. human.

Organism-specific databases

CTD

761.

GeneCards

GC08P086285.

H-InvDB

HIX0078885.

HGNC

HGNC:1374. CA3.

HPA

CAB004967.
HPA021775.
HPA026700.

MIM

114750. gene.

neXtProt

NX_P07451.

PharmGKB

PA25990.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3338.

HOGENOM

HOG000112637.

HOVERGEN

HBG002837.

InParanoid

P07451.

KO

K01672.

OMA

CEECIVW.

PhylomeDB

P07451.

Enzyme and pathway databases

BRENDA

4.2.1.1. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P07451.

Bgee

P07451.

CleanEx

HS_CA3.

Genevestigator

P07451.

GermOnline

ENSG00000164879. Homo sapiens.

Family and domain databases

Gene3D

3.10.200.10. 1 hit.

InterPro

IPR001148. Carbonic_anhydrase_a.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018441. Carbonic_anhydrase_CA3.
[Graphical view]

PANTHER

PTHR18952. PTHR18952. 1 hit.
PTHR18952:SF29. PTHR18952:SF29. 1 hit.

Pfam

PF00194. Carb_anhydrase. 1 hit.
[Graphical view]

SMART

SM01057. Carb_anhydrase. 1 hit.
[Graphical view]

SUPFAM

SSF51069. Euk_COanhd. 1 hit.

PROSITE

PS00162. ALPHA_CA_1. 1 hit.
PS51144. ALPHA_CA_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P07451.

ChEMBL

CHEMBL2885.

EvolutionaryTrace

P07451.

GenomeRNAi

761.

NextBio

3078.

SOURCE

Search...

Entry information

Entry name

CAH3_HUMAN

Accession

Primary (citable) accession number: P07451
Secondary accession number(s): B2R867, B3KUC8, O60842

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	March 20, 2007
Last modified:	May 1, 2013
This is version 145 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.