Reviewed, UniProtKB/Swiss-Prot Q16790 (CAH9_HUMAN)

Names and origin

Protein names

Recommended name:
    Carbonic anhydrase 9
    EC=4.2.1.1
Alternative name(s):
    Carbonic anhydrase IX
      Short name=CA-IX
      Short name=CAIX
    Carbonate dehydratase IX
    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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.10
Catalytic activity	H2CO3 = CO2 + H2O.
Cofactor	Zinc By similarity.
Subunit structure	Forms oligomers linked by disulfide bonds. Ref.10
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
Post-translational modification	Asn-346 bears high-mannose type glycan structures.
Sequence similarities	Belongs to the alpha-carbonic anhydrase family.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	one-carbon metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	cell projection Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Traceable author statement. Source: ProtInc nucleolus 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: UniProtKB-KW
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

Potential

Topological domain

436 – 459

24

Cytoplasmic

Region

38 – 112

75

Proteoglycan-like (PG)

Region

113 – 414

302

Catalytic

Sites

Metal binding

226

1

Zinc; catalytic By similarity

Metal binding

228

1

Zinc; catalytic By similarity

Metal binding

251

1

Zinc; catalytic By similarity

Amino acid modifications

Modified residue

449

1

Phosphotyrosine Ref.9

Glycosylation

115

1

O-linked (GlcNAc...) Ref.10

Glycosylation

346

1

N-linked (GlcNAc...) Ref.10

Disulfide bond

156 ↔ 336

Ref.10

Disulfide bond

174

Interchain Probable

Natural variations

Natural variant

33

1

V → M: dbSNP rs2071676. Ref.1 Ref.5

VAR_010787

Natural variant

326

1

Q → R: dbSNP rs3829078.

VAR_020049

Secondary structure

1

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459

Helix Strand Turn

Details...

Helix

149 – 152

4

Helix

154 – 156

3

Helix

168 – 170

3

Beta strand

171 – 173

3

Beta strand

181 – 183

3

Beta strand

193 – 197

5

Beta strand

202 – 205

4

Beta strand

211 – 213

3

Beta strand

219 – 228

10

Beta strand

239 – 241

3

Beta strand

247 – 256

10

Helix

262 – 265

4

Beta strand

273 – 280

8

Helix

287 – 293

7

Helix

294 – 299

6

Beta strand

305 – 308

4

Helix

313 – 316

4

Beta strand

324 – 327

4

Beta strand

341 – 347

7

Helix

353 – 361

9

Beta strand

387 – 389

3

Sequences

	Sequence		Length	Mass (Da)
	Q16790-1 [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: 8084592] [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: 10709109] [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: 15164053] [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: 15489334] [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: 15340161] [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: 1312272] [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: 8486430] [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: 16310354] [Abstract] Cited for: PHOSPHORYLATION AT TYR-449.
[10]	"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: 18703501] [Abstract] Cited for: FUNCTION, SUBUNIT, INDUCTION, GLYCOSYLATION AT THR-115 AND ASN-346, DISULFIDE BONDS.
+	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.

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	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q16790.

PTM databases

PhosphoSite

Q16790.

Proteomic databases

PRIDE

Q16790.

Genome annotation databases

Ensembl

ENST00000378357; ENSP00000367608; ENSG00000107159; Homo sapiens. [Genome view]

GeneID

768.

KEGG

hsa:768.

UCSC

uc003zxo.2. human.

Organism-specific databases

CTD

768.

GeneCards

GC09P035663.

HGNC

HGNC:1383. CA9.

HPA

CAB005100.
CAB017107.

MIM

603179. gene.

PharmGKB

PA24384.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG717384.

HOVERGEN

Q16790.

InParanoid

Q16790.

OMA

FRATQPL.

OrthoDB

EOG92FW3C.

PhylomeDB

Q16790.

Enzyme and pathway databases

BRENDA

4.2.1.1. 247.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Gene expression databases

ArrayExpress

Q16790.

Bgee

Q16790.

CleanEx

HS_CA9.

Genevestigator

Q16790.

GermOnline

ENSG00000107159. Homo sapiens.

Family and domain databases

InterPro

IPR001148. Carbonic_anhydrase_a-class_cat.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018429. Carbonic_anhydrase_CA9.
[Graphical view]

Gene3D

G3DSA:3.10.200.10. Euk_COanhd. 1 hit.

PANTHER

PTHR18952:SF18. Carbonic_anhydrase_CA9. 1 hit.
PTHR18952. Euk_COanhd. 1 hit.

Pfam

PF00194. Carb_anhydrase. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

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:	January 19, 2010
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.