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Q16790 (CAH9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carbonic anhydrase 9

EC=4.2.1.1
Alternative name(s):
Carbonate dehydratase IX
Carbonic anhydrase IX
Short name=CA-IX
Short name=CAIX
Membrane antigen MN
P54/58N
Renal cell carcinoma-associated antigen G250
Short name=RCC-associated antigen G250
pMW1
Gene names
Name:CA9
Synonyms:G250, MN
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length459 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. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia. Ref.12

Catalytic activity

H2CO3 = CO2 + H2O.

Cofactor

Zinc.

Enzyme regulation

Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA) and Foscarnet (phosphonoformate trisodium salt). Ref.10 Ref.11 Ref.14 Ref.15

Subunit structure

Forms oligomers linked by disulfide bonds. Ref.12 Ref.17

Subcellular location

Nucleus. Nucleusnucleolus. Cell membrane; Single-pass type I membrane protein. Cell projectionmicrovillus membrane; Single-pass type I membrane protein. Note: Found on the surface microvilli and in the nucleus, particularly in nucleolus. Ref.8

Tissue specificity

Expressed primarily in carcinoma cells lines. Expression is restricted to very few normal tissues and the most abundant expression is found in the epithelial cells of gastric mucosa.

Induction

By hypoxia. Ref.10 Ref.11 Ref.12 Ref.14 Ref.15

Post-translational modification

Asn-346 bears high-mannose type glycan structures.

Sequence similarities

Belongs to the alpha-carbonic anhydrase family.

Biophysicochemical properties

pH dependence:

Optimum pH is 6.5. Ref.17

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionLyase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbicarbonate transport

Traceable author statement. Source: Reactome

cellular response to hypoxia

Traceable author statement. Source: Reactome

morphogenesis of an epithelium

Inferred from electronic annotation. Source: Ensembl

one-carbon metabolic process

Inferred from electronic annotation. Source: InterPro

regulation of transcription from RNA polymerase II promoter in response to hypoxia

Traceable author statement. Source: Reactome

response to drug

Inferred from electronic annotation. Source: Ensembl

response to testosterone

Inferred from electronic annotation. Source: Ensembl

secretion

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentbasolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Traceable author statement PubMed 8661007. Source: ProtInc

microvillus membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 22087255. Source: UniProtKB

   Molecular_functioncarbonate dehydratase activity

Traceable author statement PubMed 8661007. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3737 Ref.6
Chain38 – 459422Carbonic anhydrase 9
PRO_0000004243

Regions

Topological domain38 – 414377Extracellular
Transmembrane415 – 43521Helical; Potential
Topological domain436 – 45924Cytoplasmic
Region38 – 11275Proteoglycan-like (PG)
Region113 – 414302Catalytic
Region332 – 3332Substrate binding By similarity

Sites

Active site2001Proton acceptor By similarity
Metal binding2261Zinc; catalytic
Metal binding2281Zinc; catalytic
Metal binding2511Zinc; catalytic

Amino acid modifications

Modified residue4491Phosphotyrosine Ref.9
Glycosylation1151O-linked (GlcNAc...) Ref.12
Glycosylation3461N-linked (GlcNAc...) Ref.12 Ref.17
Disulfide bond156 ↔ 336 Ref.12 Ref.17
Disulfide bond174Interchain Probable

Natural variations

Natural variant331V → M. Ref.1 Ref.5
Corresponds to variant rs2071676 [ dbSNP | Ensembl ].
VAR_010787
Natural variant3261Q → R.
Corresponds to variant rs3829078 [ dbSNP | Ensembl ].
VAR_020049

Secondary structure

............................................... 459
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16790 [UniParc].

Last modified December 6, 2005. Version 2.
Checksum: BA67195483F0F5CE

FASTA45949,698
        10         20         30         40         50         60 
MAPLCPSPWL PLLIPAPAPG LTVQLLLSLL LLVPVHPQRL PRMQEDSPLG GGSSGEDDPL 

        70         80         90        100        110        120 
GEEDLPSEED SPREEDPPGE EDLPGEEDLP GEEDLPEVKP KSEEEGSLKL EDLPTVEAPG 

       130        140        150        160        170        180 
DPQEPQNNAH RDKEGDDQSH WRYGGDPPWP RVSPACAGRF QSPVDIRPQL AAFCPALRPL 

       190        200        210        220        230        240 
ELLGFQLPPL PELRLRNNGH SVQLTLPPGL EMALGPGREY RALQLHLHWG AAGRPGSEHT 

       250        260        270        280        290        300 
VEGHRFPAEI HVVHLSTAFA RVDEALGRPG GLAVLAAFLE EGPEENSAYE QLLSRLEEIA 

       310        320        330        340        350        360 
EEGSETQVPG LDISALLPSD FSRYFQYEGS LTTPPCAQGV IWTVFNQTVM LSAKQLHTLS 

       370        380        390        400        410        420 
DTLWGPGDSR LQLNFRATQP LNGRVIEASF PAGVDSSPRA AEPVQLNSCL AAGDILALVF 

       430        440        450 
GLLFAVTSVA FLVQMRRQHR RGTKGGVSYR PAEVAETGA 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment."
Pastorek J., Pastorekova S., Callebaut I., Mornon J.-P., Zelnik V., Opavsky R., Zat'Ovicova M., Liao S., Portetelle D., Stanbridge E.J., Zavada J., Burny A., Kettmann R.
Oncogene 9:2877-2888(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, VARIANT MET-33.
Tissue: Carcinoma.
[2]"Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250."
Grabmaier K., Vissers J.L.M., De Weijert M.C.A., Oosterwijk-Wakka J.C., Van Bokhoven A., Brakenhoff R.H., Noessner E., Mulders P.A., Merkx G., Figdor C.G., Adema G.J., Oosterwijk E.
Int. J. Cancer 85:865-870(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Renal cell carcinoma.
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 MET-33.
Tissue: Colon.
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 38-52.
[7]"A novel quasi-viral agent, MaTu, is a two-component system."
Pastorekova S., Zavadova Z., Kostal M., Babusikova O., Zavada J.
Virology 187:620-626(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[8]"Expression of MaTu-MN protein in human tumor cultures and in clinical specimens."
Zavada J., Zavadova Z., Pastorekova S., Ciampor F., Pastorek J., Zelnik V.
Int. J. Cancer 54:268-274(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[9]"The role of carbonic anhydrase IX overexpression in kidney cancer."
Dorai T., Sawczuk I.S., Pastorek J., Wiernik P.H., Dutcher J.P.
Eur. J. Cancer 41:2935-2947(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-449.
[10]"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.
[11]"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.
[12]"Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes."
Hilvo M., Baranauskiene L., Salzano A.M., Scaloni A., Matulis D., Innocenti A., Scozzafava A., Monti S.M., Di Fiore A., De Simone G., Lindfors M., Janis J., Valjakka J., Pastorekova S., Pastorek J., Kulomaa M.S., Nordlund H.R., Supuran C.T., Parkkila S.
J. Biol. Chem. 283:27799-27809(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, INDUCTION, GLYCOSYLATION AT THR-115 AND ASN-346, DISULFIDE BONDS.
[13]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"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.
[15]"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.
[16]"Stabilization of antibody structure upon association to a human carbonic anhydrase IX epitope studied by X-ray crystallography, microcalorimetry, and molecular dynamics simulations."
Kral V., Mader P., Collard R., Fabry M., Horejsi M., Rezacova P., Kozisek M., Zavada J., Sedlacek J., Rulisek L., Brynda J.
Proteins 71:1275-1287(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 83-91 IN COMPLEX WITH SPECIFIC ANTIBODIES.
[17]"Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX."
Alterio V., Hilvo M., Di Fiore A., Supuran C.T., Pan P., Parkkila S., Scaloni A., Pastorek J., Pastorekova S., Pedone C., Scozzafava A., Monti S.M., De Simone G.
Proc. Natl. Acad. Sci. U.S.A. 106:16233-16238(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 137-391 IN COMPLEX WITH ZINC ION AND THE INHIBITOR ACETAZOLAMIDE, GLYCOSYLATION AT ASN-346, DISULFIDE BOND, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X66839 mRNA. Translation: CAA47315.1.
AJ010588 mRNA. Translation: CAB82444.1.
AL133410, AL357874 Genomic DNA. Translation: CAI10985.1.
AL357874, AL133410 Genomic DNA. Translation: CAI13455.1.
CH471071 Genomic DNA. Translation: EAW58359.1.
BC014950 mRNA. Translation: AAH14950.1.
CCDSCCDS6585.1.
PIRI38013.
RefSeqNP_001207.2. NM_001216.2.
UniGeneHs.63287.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2HKFX-ray2.01P83-91[»]
3IAIX-ray2.20A/B/C/D137-391[»]
ProteinModelPortalQ16790.
SMRQ16790. Positions 139-391.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107223. 31 interactions.
DIPDIP-48973N.
STRING9606.ENSP00000367608.

Chemistry

BindingDBQ16790.
ChEMBLCHEMBL3594.

PTM databases

PhosphoSiteQ16790.

Polymorphism databases

DMDM83300925.

Proteomic databases

MaxQBQ16790.
PaxDbQ16790.
PRIDEQ16790.

Protocols and materials databases

DNASU768.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000378357; ENSP00000367608; ENSG00000107159.
GeneID768.
KEGGhsa:768.
UCSCuc003zxo.4. human.

Organism-specific databases

CTD768.
GeneCardsGC09P035673.
H-InvDBHIX0008019.
HGNCHGNC:1383. CA9.
HPACAB005100.
CAB017107.
MIM603179. gene.
neXtProtNX_Q16790.
PharmGKBPA25998.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3338.
HOGENOMHOG000112637.
HOVERGENHBG002837.
InParanoidQ16790.
KOK01672.
OMASRYFRYE.
OrthoDBEOG7WMCK7.
PhylomeDBQ16790.
TreeFamTF316425.

Enzyme and pathway databases

BRENDA4.2.1.1. 2681.
ReactomeREACT_111217. Metabolism.
REACT_120956. Cellular responses to stress.

Gene expression databases

BgeeQ16790.
CleanExHS_CA9.
GenevestigatorQ16790.

Family and domain databases

Gene3D3.10.200.10. 1 hit.
InterProIPR018429. CA9.
IPR001148. Carbonic_anhydrase_a.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
[Graphical view]
PANTHERPTHR18952. PTHR18952. 1 hit.
PTHR18952:SF18. PTHR18952:SF18. 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

EvolutionaryTraceQ16790.
GeneWikiCarbonic_anhydrase_9.
GenomeRNAi768.
NextBio3106.
PROQ16790.
SOURCESearch...

Entry information

Entry nameCAH9_HUMAN
AccessionPrimary (citable) accession number: Q16790
Secondary accession number(s): Q5T4R1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: December 6, 2005
Last modified: July 9, 2014
This is version 140 of the entry and version 2 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 9

Human chromosome 9: entries, gene names and cross-references to MIM