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P23280 (CAH6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length308 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.5 Ref.6 Ref.7 Ref.8

Subcellular location

Secreted.

Tissue specificity

Major constituent of saliva.

Sequence similarities

Belongs to the alpha-carbonic anhydrase family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P23280-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P23280-2)

The sequence of this isoform differs from the canonical sequence as follows:
     282-308: EYTLGSEFQFYLHKIEEILDYLRRALN → GKGHGGHRGRSQNPRVQPTSTRHPLALGSLEA
Note: No experimental confirmation available.
Isoform 3 (identifier: P23280-3)

The sequence of this isoform differs from the canonical sequence as follows:
     27-86: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 308291Carbonic anhydrase 6
PRO_0000004241

Regions

Region220 – 2212Substrate binding By similarity

Sites

Active site851Proton acceptor By similarity
Active site1461 By similarity
Metal binding1111Zinc; catalytic
Metal binding1131Zinc; catalytic
Metal binding1381Zinc; catalytic

Amino acid modifications

Glycosylation671N-linked (GlcNAc...) Potential
Glycosylation2561N-linked (GlcNAc...) Potential
Disulfide bond42 ↔ 224 Potential

Natural variations

Alternative sequence27 – 8660Missing in isoform 3.
VSP_046668
Alternative sequence282 – 30827EYTLG…RRALN → GKGHGGHRGRSQNPRVQPTS TRHPLALGSLEA in isoform 2.
VSP_045435
Natural variant371Q → L.
Corresponds to variant rs34265054 [ dbSNP | Ensembl ].
VAR_033712
Natural variant551T → M.
Corresponds to variant rs2274327 [ dbSNP | Ensembl ].
VAR_028268
Natural variant581R → W.
Corresponds to variant rs58800854 [ dbSNP | Ensembl ].
VAR_061093
Natural variant681M → L.
Corresponds to variant rs2274328 [ dbSNP | Ensembl ].
VAR_028269
Natural variant701G → A.
Corresponds to variant rs2274329 [ dbSNP | Ensembl ].
VAR_028270
Natural variant901S → G. Ref.1 Ref.2 Ref.3
Corresponds to variant rs2274333 [ dbSNP | Ensembl ].
VAR_028271

Experimental info

Sequence conflict1031T → I in AAA51892. Ref.1
Sequence conflict1031T → I in BAD89434. Ref.4
Sequence conflict1481S → T in AAA51892. Ref.1
Sequence conflict1481S → T in AAF22565. Ref.2
Sequence conflict1481S → T in BAD89434. Ref.4
Sequence conflict2701N → K in AAA51892. Ref.1
Sequence conflict2701N → K in AAF22565. Ref.2
Sequence conflict2701N → K in BAD89434. Ref.4

Secondary structure

............................................. 308
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: 6EBFF15085E7112D

FASTA30835,367
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 1CF67B5ED1BD9384
Show »

FASTA31335,365
Isoform 3 [UniParc].

Checksum: 39A6223C958A3029
Show »

FASTA24828,687

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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]"CA6 mRNA, nirs splice variant 1."
Tabata Y., Hayashi A., Sameshima E., Iida K., Mitsuyama M., Kanai S., Furuya T., Saito T.
Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), VARIANT GLY-90.
[4]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[6]"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] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[7]"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.
[8]"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.
[9]"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] [Europe PMC] [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 expand/collapse EMBL AC list , AF128411, AF128412, AF128413, AF128414, AF128415, AF128416, AF128417 Genomic DNA. Translation: AAF22565.1.
AB102863 mRNA. Translation: BAD89397.1.
AB103091 mRNA. Translation: BAD89434.1.
AL139415 Genomic DNA. Translation: CAC42429.1.
PIRCRHU6. A37917.
RefSeqNP_001206.2. NM_001215.3.
NP_001257429.1. NM_001270500.1.
NP_001257430.1. NM_001270501.1.
UniGeneHs.100322.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3FE4X-ray1.90A/B21-290[»]
ProteinModelPortalP23280.
SMRP23280. Positions 33-280.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000366662.

Chemistry

BindingDBP23280.
ChEMBLCHEMBL3025.

Polymorphism databases

DMDM116241278.

Proteomic databases

PaxDbP23280.
PRIDEP23280.

Protocols and materials databases

DNASU765.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000377436; ENSP00000366654; ENSG00000131686. [P23280-2]
ENST00000377442; ENSP00000366661; ENSG00000131686. [P23280-3]
ENST00000377443; ENSP00000366662; ENSG00000131686. [P23280-1]
GeneID765.
KEGGhsa:765.
UCSCuc001apm.4. human. [P23280-1]
uc031plc.1. human.

Organism-specific databases

CTD765.
GeneCardsGC01P009005.
H-InvDBHIX0028508.
HIX0116265.
HGNCHGNC:1380. CA6.
HPAHPA028550.
HPA028692.
MIM114780. gene.
neXtProtNX_P23280.
PharmGKBPA25995.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3338.
HOGENOMHOG000112637.
HOVERGENHBG002837.
KOK01672.
OMAPDGTEYI.
PhylomeDBP23280.
TreeFamTF316425.

Enzyme and pathway databases

BRENDA4.2.1.1. 2681.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP23280.
BgeeP23280.
CleanExHS_CA6.
GenevestigatorP23280.

Family and domain databases

Gene3D3.10.200.10. 1 hit.
InterProIPR001148. Carbonic_anhydrase_a.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018428. Carbonic_anhydrase_CA6.
[Graphical view]
PANTHERPTHR18952. PTHR18952. 1 hit.
PTHR18952:SF37. PTHR18952:SF37. 1 hit.
PfamPF00194. Carb_anhydrase. 1 hit.
[Graphical view]
SMARTSM01057. Carb_anhydrase. 1 hit.
[Graphical view]
SUPFAMSSF51069. SSF51069. 1 hit.
PROSITEPS00162. ALPHA_CA_1. 1 hit.
PS51144. ALPHA_CA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP23280.
GeneWikiCarbonic_anhydrase_VI.
GenomeRNAi765.
NextBio3092.
PROP23280.
SOURCESearch...

Entry information

Entry nameCAH6_HUMAN
AccessionPrimary (citable) accession number: P23280
Secondary accession number(s): E7EMQ1 expand/collapse secondary AC list , Q5FBW3, Q5FC00, Q96QX8, Q9UF03
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM