Q16790 (CAH9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	459 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. 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. Nucleus › nucleolus. Cell membrane; Single-pass type I membrane protein. Cell projection › microvillus 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 component	Cell membrane Cell projection Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	bicarbonate transport Traceable author statement. Source: Reactome morphogenesis of an epithelium Inferred from electronic annotation. Source: Compara 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 secretion Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to 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_function	carbonate 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 37

37

Ref.6

Chain

38 – 459

422

Carbonic anhydrase 9

PRO_0000004243

Regions

Topological domain

38 – 414

377

Extracellular

Transmembrane

415 – 435

21

Helical; Potential

Topological domain

436 – 459

24

Cytoplasmic

Region

38 – 112

75

Proteoglycan-like (PG)

Region

113 – 414

302

Catalytic

Region

332 – 333

2

Substrate binding By similarity

Sites

Active site

200

1

Proton acceptor By similarity

Metal binding

226

1

Zinc; catalytic

Metal binding

228

1

Zinc; catalytic

Metal binding

251

1

Zinc; catalytic

Amino acid modifications

Modified residue

449

1

Phosphotyrosine Ref.9

Glycosylation

115

1

O-linked (GlcNAc...) Ref.12

Glycosylation

346

1

N-linked (GlcNAc...) Ref.12 Ref.17

Disulfide bond

156 ↔ 336

Ref.12 Ref.17

Disulfide bond

174

Interchain Probable

Natural variations

Natural variant

33

1

V → M. Ref.1 Ref.5
Corresponds to variant rs2071676 [ dbSNP | Ensembl ].

VAR_010787

Natural variant

326

1

Q → R.
Corresponds to variant rs3829078 [ dbSNP | Ensembl ].

VAR_020049

Secondary structure

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459

Helix Strand Turn

Details...

Turn

137 – 139

3

Beta strand

143 – 147

5

Helix

149 – 152

4

Helix

154 – 157

4

Helix

168 – 170

3

Beta strand

171 – 173

3

Beta strand

181 – 184

4

Beta strand

193 – 197

5

Beta strand

202 – 205

4

Beta strand

211 – 215

5

Beta strand

218 – 229

12

Beta strand

238 – 241

4

Beta strand

247 – 256

10

Helix

262 – 265

4

Beta strand

271 – 281

11

Helix

287 – 293

7

Helix

294 – 299

6

Beta strand

305 – 308

4

Helix

313 – 316

4

Beta strand

324 – 330

7

Beta strand

338 – 347

10

Beta strand

349 – 351

3

Helix

353 – 361

9

Beta strand

387 – 389

3

Sequences

	Sequence		Length	Mass (Da)
	Q16790 [UniParc]. Last modified December 6, 2005. Version 2. Checksum: BA67195483F0F5CE	FASTA	459	49,698
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00003966.

PIR

I38013.

RefSeq

NP_001207.2. NM_001216.2.

UniGene

Hs.63287.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HKF	X-ray	2.01	P	83-91	[»]
3IAI	X-ray	2.20	A/B/C/D	137-391	[»]

ProteinModelPortal

Q16790.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48973N.

STRING

9606.ENSP00000367608.

PTM databases

PhosphoSite

Q16790.

Polymorphism databases

DMDM

83300925.

Proteomic databases

PaxDb

Q16790.

PRIDE

Q16790.

Protocols and materials databases

DNASU

768.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000378357; ENSP00000367608; ENSG00000107159.

GeneID

768.

KEGG

hsa:768.

UCSC

uc003zxo.4. human.

Organism-specific databases

CTD

768.

GeneCards

GC09P035673.

H-InvDB

HIX0008019.

HGNC

HGNC:1383. CA9.

HPA

CAB005100.
CAB017107.

MIM

603179. gene.

neXtProt

NX_Q16790.

PharmGKB

PA25998.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3338.

HOGENOM

HOG000112637.

HOVERGEN

HBG002837.

InParanoid

Q16790.

KO

K01672.

OMA

SRYFRYE.

OrthoDB

EOG4KH2V6.

PhylomeDB

Q16790.

Enzyme and pathway databases

BRENDA

4.2.1.1. 2681.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_111217. Metabolism.
REACT_120956. Cellular responses to stress.

Gene expression databases

Bgee

Q16790.

CleanEx

HS_CA9.

Genevestigator

Q16790.

GermOnline

ENSG00000107159. 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.
IPR018429. Carbonic_anhydrase_CA9.
[Graphical view]

PANTHER

PTHR18952. PTHR18952. 1 hit.
PTHR18952:SF18. PTHR18952:SF18. 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

Q16790.

ChEMBL

CHEMBL3594.

EvolutionaryTrace

Q16790.

GenomeRNAi

768.

NextBio

3106.

SOURCE

Search...

Entry information

Entry name

CAH9_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 130 of the entry and version 2 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.