P23280 (CAH6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbonic anhydrase 6
EC=4.2.1.1

Alternative name(s):
Carbonate dehydratase VI
Carbonic anhydrase VI
Short name=CA-VI
Salivary carbonic anhydrase
Secreted carbonic anhydrase

Gene names

Name:

CA6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	308 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. Its role in saliva is unknown.
Catalytic activity	H2CO3 = CO2 + H2O.
Cofactor	Zinc By similarity.
Enzyme regulation	Inhibited by coumarins, sulfonamide derivatives such as acetazolamide (AZA), saccharin and Foscarnet (phosphonoformate trisodium salt). Ref.4 Ref.5 Ref.6 Ref.7
Subcellular location	Secreted.
Tissue specificity	Major constituent of saliva.
Sequence similarities	Belongs to the alpha-carbonic anhydrase family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	one-carbon metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	carbonate dehydratase activity Traceable author statement. Source: ProtInc 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

Signal peptide

1 – 17

17

Potential

Chain

18 – 308

291

Carbonic anhydrase 6

PRO_0000004241

Regions

Region

220 – 221

2

Substrate binding By similarity

Sites

Active site

85

1

Proton acceptor By similarity

Active site

146

1

By similarity

Metal binding

111

1

Zinc; catalytic

Metal binding

113

1

Zinc; catalytic

Metal binding

138

1

Zinc; catalytic

Amino acid modifications

Glycosylation

67

1

N-linked (GlcNAc...) Potential

Glycosylation

256

1

N-linked (GlcNAc...) Potential

Disulfide bond

42 ↔ 224

Potential

Natural variations

Natural variant

37

1

Q → L.
Corresponds to variant rs34265054 [ dbSNP | Ensembl ].

VAR_033712

Natural variant

55

1

T → M.
Corresponds to variant rs2274327 [ dbSNP | Ensembl ].

VAR_028268

Natural variant

58

1

R → W.
Corresponds to variant rs58800854 [ dbSNP | Ensembl ].

VAR_061093

Natural variant

68

1

M → L.
Corresponds to variant rs2274328 [ dbSNP | Ensembl ].

VAR_028269

Natural variant

70

1

G → A.
Corresponds to variant rs2274329 [ dbSNP | Ensembl ].

VAR_028270

Natural variant

90

1

S → G. Ref.1 Ref.2
Corresponds to variant rs2274333 [ dbSNP | Ensembl ].

VAR_028271

Experimental info

Sequence conflict

103

1

T → I in AAA51892. Ref.1

Sequence conflict

148

1

S → T in AAA51892. Ref.1

Sequence conflict

148

1

S → T in AAF22565. Ref.2

Sequence conflict

270

1

N → K in AAA51892. Ref.1

Sequence conflict

270

1

N → K in AAF22565. Ref.2

Secondary structure

1

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308

Helix Strand Turn

Details...

Helix

35 – 38

4

Helix

54 – 56

3

Beta strand

78 – 82

5

Beta strand

87 – 90

4

Beta strand

96 – 98

3

Beta strand

104 – 113

10

Beta strand

126 – 128

3

Beta strand

134 – 143

10

Beta strand

146 – 148

3

Helix

149 – 152

4

Beta strand

160 – 167

8

Helix

175 – 177

3

Helix

178 – 183

6

Helix

184 – 187

4

Beta strand

193 – 196

4

Helix

201 – 204

4

Beta strand

212 – 215

4

Beta strand

229 – 235

7

Helix

241 – 249

9

Beta strand

256 – 258

3

Beta strand

275 – 277

3

Sequences

	Sequence		Length	Mass (Da)
	P23280 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 6EBFF15085E7112D	FASTA	308	35,367
	10 20 30 40 50 60 MRALVLLLSL FLLGGQAQHV SDWTYSEGAL DEAHWPQHYP ACGGQRQSPI NLQRTKVRYN 70 80 90 100 110 120 PSLKGLNMTG YETQAGEFPM VNNGHTVQIS LPSTMRMTVA DGTVYIAQQM HFHWGGASSE 130 140 150 160 170 180 ISGSEHTVDG IRHVIEIHIV HYNSKYKSYD IAQDAPDGLA VLAAFVEVKN YPENTYYSNF 190 200 210 220 230 240 ISHLANIKYP GQRTTLTGLD VQDMLPRNLQ HYYTYHGSLT TPPCTENVHW FVLADFVKLS 250 260 270 280 290 300 RTQVWKLENS LLDHRNKTIH NDYRRTQPLN HRVVESNFPN QEYTLGSEFQ FYLHKIEEIL DYLRRALN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human secreted carbonic anhydrase: cDNA cloning, nucleotide sequence, and hybridization histochemistry." Aldred P., Fu P., Barrett G., Penschow J.D., Wright R., Coghlan J.P., Fernley R.T. Biochemistry 30:569-575(1991) [PubMed: 1899030] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-90.
[2]	Grubb D.J. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-90.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Saccharin inhibits carbonic anhydrases: possible explanation for its unpleasant metallic aftertaste." Koehler K., Hillebrecht A., Schulze Wischeler J., Innocenti A., Heine A., Supuran C.T., Klebe G. Angew. Chem. Int. Ed. Engl. 46:7697-7699(2007) [PubMed: 17705204] [Abstract] Cited for: ENZYME REGULATION.
[5]	"Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I." Temperini C., Innocenti A., Guerri A., Scozzafava A., Rusconi S., Supuran C.T. Bioorg. Med. Chem. Lett. 17:2210-2215(2007) [PubMed: 17314045] [Abstract] Cited for: ENZYME REGULATION.
[6]	"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: 19186056] [Abstract] Cited for: ENZYME REGULATION.
[7]	"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: 19206230] [Abstract] Cited for: ENZYME REGULATION.
[8]	"Crystal structure of human erythrocyte carbonic anhydrase C. VI. The three-dimensional structure at high resolution in relation to other mammalian carbonic anhydrases." Kannan K.K., Liljas A., Waara I., Bergsten P.C., Loevgren S., Strandberg B., Bengtsson U., Carlbom U., Fridborg K., Jaerup L., Petef M. Cold Spring Harb. Symp. Quant. Biol. 36:221-231(1972) [PubMed: 4628675] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 21-290 IN COMPLEX WITH MAGNESIUM ION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M57892 mRNA. Translation: AAA51892.1.
AF128418 , AF128411, AF128412, AF128413, AF128414, AF128415, AF128416, AF128417 Genomic DNA. Translation: AAF22565.1.
AL139415 Genomic DNA. Translation: CAC42429.1.

IPI

IPI00295105.

PIR

CRHU6. A37917.

RefSeq

NP_001206.2. NM_001215.2.

UniGene

Hs.100322.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3FE4	X-ray	1.90	A/B	21-290	[»]

ProteinModelPortal

P23280.

SMR

P23280. Positions 33-280.

ModBase

Search...

Protein-protein interaction databases

STRING

P23280.

Polymorphism databases

DMDM

116241278.

Proteomic databases

PRIDE

P23280.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377443; ENSP00000366662; ENSG00000131686.
ENST00000413627; ENSP00000388267; ENSG00000131686.

GeneID

765.

KEGG

hsa:765.

UCSC

uc001apm.1. human.

Organism-specific databases

CTD

765.

GeneCards

GC01P009005.

H-InvDB

HIX0028508.

HGNC

HGNC:1380. CA6.

HPA

HPA028550.
HPA028692.

MIM

114780. gene.

neXtProt

NX_P23280.

PharmGKB

PA25995.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04824.

GeneTree

ENSGT00570000078862.

HOVERGEN

HBG002837.

OrthoDB

EOG43FGWZ.

PhylomeDB

P23280.

Enzyme and pathway databases

BRENDA

4.2.1.1. 2681.

Gene expression databases

ArrayExpress

P23280.

Bgee

P23280.

CleanEx

HS_CA6.

Genevestigator

P23280.

GermOnline

ENSG00000131686. Homo sapiens.

Family and domain databases

InterPro

IPR001148. a_carbonic_anhydrase.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018428. Carbonic_anhydrase_CA6.
[Graphical view]

Gene3D

G3DSA:3.10.200.10. Euk_COanhd. 1 hit.

KO

K01672.

PANTHER

PTHR18952:SF17. Carbonic_anhydrase_CA6. 1 hit.
PTHR18952. Euk_COanhd. 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

NextBio

3092.

SOURCE

Search...

Entry information

Entry name

CAH6_HUMAN

Accession

Primary (citable) accession number: P23280
Secondary accession number(s): Q96QX8, Q9UF03

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	October 17, 2006
Last modified:	January 25, 2012
This is version 110 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.