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Protein

Carbonic anhydrase 9

Gene

CA9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

H2CO3 = CO2 + H2O.

Cofactori

Zn2+1 Publication

Enzyme regulationi

Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA) and Foscarnet (phosphonoformate trisodium salt).4 Publications

pH dependencei

Optimum pH is 6.5.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei200Proton acceptorBy similarity1
Metal bindingi226Zinc; catalytic1 Publication1
Metal bindingi228Zinc; catalytic1 Publication1
Metal bindingi251Zinc; catalytic1 Publication1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS02974-MONOMER.
BRENDAi4.2.1.1. 2681.
ReactomeiR-HSA-1234158. Regulation of gene expression by Hypoxia-inducible Factor.
R-HSA-1475029. Reversible hydration of carbon dioxide.
SIGNORiQ16790.

Names & Taxonomyi

Protein namesi
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 namesi
Name:CA9
Synonyms:G250, MN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:1383. CA9.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini38 – 414ExtracellularAdd BLAST377
Transmembranei415 – 435HelicalSequence analysisAdd BLAST21
Topological domaini436 – 459CytoplasmicAdd BLAST24

GO - Cellular componenti

  • basolateral plasma membrane Source: Ensembl
  • integral component of membrane Source: ProtInc
  • microvillus membrane Source: UniProtKB-SubCell
  • nucleolus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi768.
OpenTargetsiENSG00000107159.
PharmGKBiPA25998.

Chemistry databases

ChEMBLiCHEMBL3594.
DrugBankiDB00562. Benzthiazide.
DB00999. Hydrochlorothiazide.
DB00774. Hydroflumethiazide.
DB00909. Zonisamide.

Polymorphism and mutation databases

BioMutaiCA9.
DMDMi83300925.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 371 PublicationAdd BLAST37
ChainiPRO_000000424338 – 459Carbonic anhydrase 9Add BLAST422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi115O-linked (GlcNAc...)1 Publication1
Disulfide bondi156 ↔ 3361 Publication
Disulfide bondi174Interchain1 Publication
Glycosylationi346N-linked (GlcNAc...)2 Publications1
Modified residuei449Phosphotyrosine1 Publication1

Post-translational modificationi

Asn-346 bears high-mannose type glycan structures.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ16790.
PaxDbiQ16790.
PeptideAtlasiQ16790.
PRIDEiQ16790.

PTM databases

iPTMnetiQ16790.
PhosphoSitePlusiQ16790.

Expressioni

Tissue specificityi

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.

Inductioni

By hypoxia.1 Publication

Gene expression databases

BgeeiENSG00000107159.
CleanExiHS_CA9.
ExpressionAtlasiQ16790. baseline and differential.
GenevisibleiQ16790. HS.

Organism-specific databases

HPAiCAB005100.
CAB017107.
HPA055207.

Interactioni

Subunit structurei

Forms oligomers linked by disulfide bonds.3 Publications

Protein-protein interaction databases

BioGridi107223. 30 interactors.
DIPiDIP-48973N.
IntActiQ16790. 1 interactor.
STRINGi9606.ENSP00000367608.

Chemistry databases

BindingDBiQ16790.

Structurei

Secondary structure

1459
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni137 – 139Combined sources3
Beta strandi145 – 147Combined sources3
Helixi149 – 152Combined sources4
Helixi154 – 157Combined sources4
Helixi168 – 170Combined sources3
Beta strandi171 – 173Combined sources3
Beta strandi181 – 184Combined sources4
Beta strandi193 – 197Combined sources5
Beta strandi202 – 205Combined sources4
Beta strandi211 – 215Combined sources5
Beta strandi218 – 229Combined sources12
Beta strandi238 – 241Combined sources4
Beta strandi247 – 256Combined sources10
Helixi262 – 265Combined sources4
Beta strandi271 – 281Combined sources11
Helixi287 – 293Combined sources7
Turni294 – 296Combined sources3
Helixi297 – 299Combined sources3
Beta strandi305 – 308Combined sources4
Helixi313 – 316Combined sources4
Beta strandi324 – 330Combined sources7
Beta strandi338 – 347Combined sources10
Beta strandi349 – 351Combined sources3
Helixi353 – 361Combined sources9
Beta strandi387 – 390Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HKFX-ray2.01P83-91[»]
3IAIX-ray2.20A/B/C/D137-391[»]
5DVXX-ray1.60A/B140-399[»]
5FL4X-ray1.82A/B/C/D137-391[»]
5FL5X-ray2.05A/B/C/D137-391[»]
5FL6X-ray1.95A/B/C/D137-391[»]
ProteinModelPortaliQ16790.
SMRiQ16790.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16790.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini139 – 390Alpha-carbonic anhydrasePROSITE-ProRule annotationAdd BLAST252

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni38 – 112Proteoglycan-like (PG)Add BLAST75
Regioni113 – 414CatalyticAdd BLAST302
Regioni332 – 333Substrate bindingBy similarity2

Sequence similaritiesi

Belongs to the alpha-carbonic anhydrase family.Curated
Contains 1 alpha-carbonic anhydrase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0382. Eukaryota.
COG3338. LUCA.
GeneTreeiENSGT00760000118915.
HOGENOMiHOG000112637.
HOVERGENiHBG002837.
InParanoidiQ16790.
KOiK01672.
OMAiSRYFRYE.
OrthoDBiEOG091G0XFM.
PhylomeDBiQ16790.
TreeFamiTF316425.

Family and domain databases

Gene3Di3.10.200.10. 1 hit.
InterProiIPR018429. CA9.
IPR001148. Carbonic_anhydrase_a.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
[Graphical view]
PANTHERiPTHR18952. PTHR18952. 1 hit.
PTHR18952:SF18. PTHR18952:SF18. 1 hit.
PfamiPF00194. Carb_anhydrase. 1 hit.
[Graphical view]
SMARTiSM01057. Carb_anhydrase. 1 hit.
[Graphical view]
SUPFAMiSSF51069. SSF51069. 1 hit.
PROSITEiPS00162. ALPHA_CA_1. 1 hit.
PS51144. ALPHA_CA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q16790-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPLCPSPWL PLLIPAPAPG LTVQLLLSLL LLVPVHPQRL PRMQEDSPLG
60 70 80 90 100
GGSSGEDDPL GEEDLPSEED SPREEDPPGE EDLPGEEDLP GEEDLPEVKP
110 120 130 140 150
KSEEEGSLKL EDLPTVEAPG DPQEPQNNAH RDKEGDDQSH WRYGGDPPWP
160 170 180 190 200
RVSPACAGRF QSPVDIRPQL AAFCPALRPL ELLGFQLPPL PELRLRNNGH
210 220 230 240 250
SVQLTLPPGL EMALGPGREY RALQLHLHWG AAGRPGSEHT VEGHRFPAEI
260 270 280 290 300
HVVHLSTAFA RVDEALGRPG GLAVLAAFLE EGPEENSAYE QLLSRLEEIA
310 320 330 340 350
EEGSETQVPG LDISALLPSD FSRYFQYEGS LTTPPCAQGV IWTVFNQTVM
360 370 380 390 400
LSAKQLHTLS DTLWGPGDSR LQLNFRATQP LNGRVIEASF PAGVDSSPRA
410 420 430 440 450
AEPVQLNSCL AAGDILALVF GLLFAVTSVA FLVQMRRQHR RGTKGGVSYR

PAEVAETGA
Length:459
Mass (Da):49,698
Last modified:December 6, 2005 - v2
Checksum:iBA67195483F0F5CE
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01078733V → M.2 PublicationsCorresponds to variant rs2071676dbSNPEnsembl.1
Natural variantiVAR_020049326Q → R.Corresponds to variant rs3829078dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6585.1.
PIRiI38013.
RefSeqiNP_001207.2. NM_001216.2.
UniGeneiHs.63287.

Genome annotation databases

EnsembliENST00000378357; ENSP00000367608; ENSG00000107159.
GeneIDi768.
KEGGihsa:768.
UCSCiuc003zxo.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6585.1.
PIRiI38013.
RefSeqiNP_001207.2. NM_001216.2.
UniGeneiHs.63287.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2HKFX-ray2.01P83-91[»]
3IAIX-ray2.20A/B/C/D137-391[»]
5DVXX-ray1.60A/B140-399[»]
5FL4X-ray1.82A/B/C/D137-391[»]
5FL5X-ray2.05A/B/C/D137-391[»]
5FL6X-ray1.95A/B/C/D137-391[»]
ProteinModelPortaliQ16790.
SMRiQ16790.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107223. 30 interactors.
DIPiDIP-48973N.
IntActiQ16790. 1 interactor.
STRINGi9606.ENSP00000367608.

Chemistry databases

BindingDBiQ16790.
ChEMBLiCHEMBL3594.
DrugBankiDB00562. Benzthiazide.
DB00999. Hydrochlorothiazide.
DB00774. Hydroflumethiazide.
DB00909. Zonisamide.

PTM databases

iPTMnetiQ16790.
PhosphoSitePlusiQ16790.

Polymorphism and mutation databases

BioMutaiCA9.
DMDMi83300925.

Proteomic databases

MaxQBiQ16790.
PaxDbiQ16790.
PeptideAtlasiQ16790.
PRIDEiQ16790.

Protocols and materials databases

DNASUi768.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378357; ENSP00000367608; ENSG00000107159.
GeneIDi768.
KEGGihsa:768.
UCSCiuc003zxo.5. human.

Organism-specific databases

CTDi768.
DisGeNETi768.
GeneCardsiCA9.
H-InvDBHIX0008019.
HGNCiHGNC:1383. CA9.
HPAiCAB005100.
CAB017107.
HPA055207.
MIMi603179. gene.
neXtProtiNX_Q16790.
OpenTargetsiENSG00000107159.
PharmGKBiPA25998.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0382. Eukaryota.
COG3338. LUCA.
GeneTreeiENSGT00760000118915.
HOGENOMiHOG000112637.
HOVERGENiHBG002837.
InParanoidiQ16790.
KOiK01672.
OMAiSRYFRYE.
OrthoDBiEOG091G0XFM.
PhylomeDBiQ16790.
TreeFamiTF316425.

Enzyme and pathway databases

BioCyciZFISH:HS02974-MONOMER.
BRENDAi4.2.1.1. 2681.
ReactomeiR-HSA-1234158. Regulation of gene expression by Hypoxia-inducible Factor.
R-HSA-1475029. Reversible hydration of carbon dioxide.
SIGNORiQ16790.

Miscellaneous databases

EvolutionaryTraceiQ16790.
GeneWikiiCarbonic_anhydrase_9.
GenomeRNAii768.
PROiQ16790.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107159.
CleanExiHS_CA9.
ExpressionAtlasiQ16790. baseline and differential.
GenevisibleiQ16790. HS.

Family and domain databases

Gene3Di3.10.200.10. 1 hit.
InterProiIPR018429. CA9.
IPR001148. Carbonic_anhydrase_a.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
[Graphical view]
PANTHERiPTHR18952. PTHR18952. 1 hit.
PTHR18952:SF18. PTHR18952:SF18. 1 hit.
PfamiPF00194. Carb_anhydrase. 1 hit.
[Graphical view]
SMARTiSM01057. Carb_anhydrase. 1 hit.
[Graphical view]
SUPFAMiSSF51069. SSF51069. 1 hit.
PROSITEiPS00162. ALPHA_CA_1. 1 hit.
PS51144. ALPHA_CA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCAH9_HUMAN
AccessioniPrimary (citable) accession number: Q16790
Secondary accession number(s): Q5T4R1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: December 6, 2005
Last modified: November 30, 2016
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.