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O43570 (CAH12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 114. 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
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 12
EC=4.2.1.1
Alternative name(s):
Carbonate dehydratase XII
Carbonic anhydrase XII
Short name=CA-XII
Tumor antigen HOM-RCC-3.1.3
Gene names
Name:CA12
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length354 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.

Catalytic activity

H2CO3 = CO2 + H2O.

Cofactor

Zinc.

Enzyme regulation

Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA), benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide) and Foscarnet (phosphonoformate trisodium salt). Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Subunit structure

Homodimer. Ref.11

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Highly expressed in colon, kidney, prostate, intestine and activated lymphocytes. Expressed at much higher levels in the renal cell cancers than in surrounding normal kidney tissue. Moderately expressed in pancreas, ovary and testis.

Involvement in disease

Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:143860]. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat. Ref.12

Sequence similarities

Belongs to the alpha-carbonic anhydrase family.

Biophysicochemical properties

Kinetic parameters:

KM=12.0 mM for CO2 Ref.10

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   DomainSignal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionLyase
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological processone-carbon metabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular componentintegral to membrane

Traceable author statement. Source: ProtInc

   Molecular functioncarbonate dehydratase activity

Traceable author statement. Source: ProtInc

zinc ion binding

Traceable author statement. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43570-1)

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: O43570-2)

The sequence of this isoform differs from the canonical sequence as follows:
     292-302: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 354330Carbonic anhydrase 12
PRO_0000004248

Regions

Topological domain25 – 301277Extracellular Potential
Transmembrane302 – 32221Helical; Potential
Topological domain323 – 35432Cytoplasmic Potential
Region226 – 2272Substrate binding By similarity

Sites

Active site941Proton acceptor By similarity
Active site1541 By similarity
Metal binding1191Zinc; catalytic
Metal binding1211Zinc; catalytic
Metal binding1451Zinc; catalytic

Amino acid modifications

Glycosylation281N-linked (GlcNAc...) Potential
Glycosylation801N-linked (GlcNAc...) Potential
Glycosylation1621N-linked (GlcNAc...) Potential
Disulfide bond50 ↔ 230 Ref.11

Natural variations

Alternative sequence292 – 30211Missing in isoform 2.
VSP_000772
Natural variant1431E → K in HCHLH; mild reduction of activity; mutant enzyme is highly inhibited by acetazolamide and shows higher sensitivity to inhibition by anions compared to wild-type; the mutation affects the chloride-mediated negative feedback regulation of the enzyme leading to excessive chloride secretion in sweat. Ref.12
VAR_065292

Secondary structure

1 ................................................... 354
Helix Strand Turn

Details...

Sequences

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

Last modified June 1, 1998. Version 1.
Checksum: 9016216BF2CA6C0C

FASTA35439,451
        10         20         30         40         50         60 
MPRRSLHAAA VLLLVILKEQ PSSPAPVNGS KWTYFGPDGE NSWSKKYPSC GGLLQSPIDL 

        70         80         90        100        110        120 
HSDILQYDAS LTPLEFQGYN LSANKQFLLT NNGHSVKLNL PSDMHIQGLQ SRYSATQLHL 

       130        140        150        160        170        180 
HWGNPNDPHG SEHTVSGQHF AAELHIVHYN SDLYPDASTA SNKSEGLAVL AVLIEMGSFN 

       190        200        210        220        230        240 
PSYDKIFSHL QHVKYKGQEA FVPGFNIEEL LPERTAEYYR YRGSLTTPPC NPTVLWTVFR 

       250        260        270        280        290        300 
NPVQISQEQL LALETALYCT HMDDPSPREM INNFRQVQKF DERLVYTSFS QVQVCTAAGL 

       310        320        330        340        350 
SLGIILSLAL AGILGICIVV VVSIWLFRRK SIKKGDNKGV IYKPATKMET EAHA

« Hide

Isoform 2 [UniParc].

Checksum: 87FD35255B137D18
Show »

FASTA34338,408

References

« Hide 'large scale' references
[1]"Human carbonic anhydrase XII: cDNA cloning, expression, and chromosomal localization of a carbonic anhydrase gene that is overexpressed in some renal cell cancers."
Tuereci O., Sahin U., Vollmar E., Siemer S., Goettert E., Seitz G., Parkkila A.-K., Shah G.N., Grubb J.H., Pfreundschuh M., Sly W.S.
Proc. Natl. Acad. Sci. U.S.A. 95:7608-7613(1998) [PubMed: 9636197] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
Tissue: Renal cell carcinoma.
[2]"Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes."
Ivanov S.V., Kuzmin I., Wei M.-H., Pack S., Geil L., Johnson B.E., Stanbridge E.J., Lerman M.I.
Proc. Natl. Acad. Sci. U.S.A. 95:12596-12601(1998) [PubMed: 9770531] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Lung.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]"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] (ISOFORMS 1 AND 2).
Tissue: Eye and Kidney.
[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: 17705204] [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: 17314045] [Abstract]
Cited for: ENZYME REGULATION.
[7]"Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II."
Srivastava D.K., Jude K.M., Banerjee A.L., Haldar M., Manokaran S., Kooren J., Mallik S., Christianson D.W.
J. Am. Chem. Soc. 129:5528-5537(2007) [PubMed: 17407288] [Abstract]
Cited for: ENZYME REGULATION.
[8]"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: 19186056] [Abstract]
Cited for: ENZYME REGULATION.
[9]"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: 19206230] [Abstract]
Cited for: ENZYME REGULATION.
[10]"Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide."
Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A., Pedone C., Scozzafava A., Supuran C.T., De Simone G.
Proteins 74:164-175(2009) [PubMed: 18618712] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[11]"Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells."
Whittington D.A., Waheed A., Ulmasov B., Shah G.N., Grubb J.H., Sly W.S., Christianson D.W.
Proc. Natl. Acad. Sci. U.S.A. 98:9545-9550(2001) [PubMed: 11493685] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 30-291 IN COMPLEX WITH ZINC ION AND THE INHIBITOR ACETAZOLAMIDE, DISULFIDE BOND, SUBUNIT.
[12]"Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII."
Feldshtein M., Elkrinawi S., Yerushalmi B., Marcus B., Vullo D., Romi H., Ofir R., Landau D., Sivan S., Supuran C.T., Birk O.S.
Am. J. Hum. Genet. 87:713-720(2010) [PubMed: 21035102] [Abstract]
Cited for: VARIANT HCHLH LYS-143.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF051882 mRNA. Translation: AAC39789.1.
AF037335 mRNA. Translation: AAC63952.1.
BT006656 mRNA. Translation: AAP35302.1.
BC000278 mRNA. Translation: AAH00278.1.
BC011691 mRNA. Translation: AAH11691.1.
BC023981 mRNA. Translation: AAH23981.1.
IPIIPI00012895.
IPI00221392.
RefSeqNP_001209.1. NM_001218.3.
NP_996808.1. NM_206925.1.
UniGeneHs.210995.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JCZX-ray1.55A/B30-291[»]
1JD0X-ray1.50A/B30-291[»]
ProteinModelPortalO43570.
SMRO43570. Positions 31-290.
ModBaseSearch...

Protein-protein interaction databases

IntActO43570. 7 interactions.
MINTMINT-1392387.
STRINGO43570.

PTM databases

PhosphoSiteO43570.

Proteomic databases

PRIDEO43570.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000178638; ENSP00000178638; ENSG00000074410.
GeneID771.
KEGGhsa:771.
UCSCuc002amc.1. human.
uc002amd.1. human.

Organism-specific databases

CTD771.
GeneCardsGC15M063613.
H-InvDBHIX0012325.
HGNCHGNC:1371. CA12.
HPACAB025181.
HPA008773.
MIM143860. phenotype.
603263. gene.
neXtProtNX_O43570.
PharmGKBPA25987.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG17521.
GeneTreeENSGT00570000078862.
HOGENOMHBG717384.
HOVERGENHBG002837.
InParanoidO43570.
OMAAEYYRYR.
OrthoDBEOG4QZ7MH.
PhylomeDBO43570.

Enzyme and pathway databases

BRENDA4.2.1.1. 2681.

Gene expression databases

ArrayExpressO43570.
BgeeO43570.
CleanExHS_CA12.
GenevestigatorO43570.
GermOnlineENSG00000074410. Homo sapiens.

Family and domain databases

InterProIPR001148. a_carbonic_anhydrase.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018430. Carbonic_anhydrase_CA12.
[Graphical view]
Gene3DG3DSA:3.10.200.10. Euk_COanhd. 1 hit.
KOK01672.
PANTHERPTHR18952:SF19. Carbonic_anhydrase_CA12. 1 hit.
PTHR18952. Euk_COanhd. 1 hit.
PfamPF00194. Carb_anhydrase. 1 hit.
[Graphical view]
SMARTSM01057. Carb_anhydrase. 1 hit.
[Graphical view]
SUPFAMSSF51069. Euk_COanhd. 1 hit.
PROSITEPS00162. ALPHA_CA_1. 1 hit.
PS51144. ALPHA_CA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00819. Acetazolamide.
NextBio3114.
SOURCESearch...

Entry information

Entry nameCAH12_HUMAN
AccessionPrimary (citable) accession number: O43570
Secondary accession number(s): Q53YE5, Q9BWG2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: January 25, 2012
This is version 114 of the entry and version 1 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

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents