Carbonic anhydrase 12 precursor - Homo sapiens (Human)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Preferred order of sections

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

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O43570 (CAH12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 128. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Sequence length	354 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

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	Hyperchlorhidrosis, isolated (HCHLH) [MIM:143860]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12
Sequence similarities	Belongs to the alpha-carbonic anhydrase family.
Biophysicochemical properties	Kinetic parameters: K_M=12.0 mM for CO₂ Ref.10

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Lyase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bicarbonate transport Traceable author statement. Source: Reactome one-carbon metabolic process Inferred from electronic annotation. Source: InterPro small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Traceable author statement Ref.1. Source: ProtInc plasma membrane Traceable author statement. Source: Reactome
Molecular_function	carbonate dehydratase activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Signal peptide

1 – 24

Potential

Chain

25 – 354

330

Carbonic anhydrase 12

PRO_0000004248

Topological domain

25 – 301

277

Extracellular Potential

Transmembrane

302 – 322

Helical; Potential

Topological domain

323 – 354

Cytoplasmic Potential

Region

226 – 227

Substrate binding By similarity

Active site

Proton acceptor By similarity

Active site

154

By similarity

Metal binding

119

Zinc; catalytic

Metal binding

121

Zinc; catalytic

Metal binding

145

Zinc; catalytic

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

162

N-linked (GlcNAc...) Potential

Disulfide bond

50 ↔ 230

Ref.11

Alternative sequence

292 – 302

Missing in isoform 2.

VSP_000772

Natural variant

143

E → 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

354

Helix Strand Turn

Details...

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 9016216BF2CA6C0C Show »	FASTA	354	39,451
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 »	FASTA	343	38,408
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 QGIILSLALA 310 320 330 340 GILGICIVVV VSIWLFRRKS IKKGDNKGVI YKPATKMETE AHA « Hide

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: VARIANT HCHLH LYS-143.
+	Additional computationally mapped references.

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.

IPI

IPI00012895.
IPI00221392.

RefSeq

NP_001209.1. NM_001218.3.
NP_996808.1. NM_206925.1.

UniGene

Hs.210995.

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JCZ	X-ray	1.55	A/B	30-291	[»]
1JD0	X-ray	1.50	A/B	30-291	[»]

ProteinModelPortal

O43570.

ModBase

Search...

IntAct

O43570. 7 interactions.

MINT

MINT-1392387.

STRING

9606.ENSP00000178638.

PhosphoSite

O43570.

PaxDb

O43570.

PRIDE

O43570.

DNASU

771.

StructuralBiologyKnowledgebase

Search...

Ensembl

ENST00000178638; ENSP00000178638; ENSG00000074410.
ENST00000344366; ENSP00000343088; ENSG00000074410.

GeneID

771.

KEGG

hsa:771.

UCSC

uc002amc.3. human.
uc002amd.3. human.

CTD

771.

GeneCards

GC15M063613.

HGNC

HGNC:1371. CA12.

HPA

CAB025181.
HPA008773.

MIM

143860. phenotype.
603263. gene.

neXtProt

NX_O43570.

PharmGKB

PA25987.

GenAtlas

Search...

eggNOG

COG3338.

HOGENOM

HOG000112637.

HOVERGEN

HBG002837.

InParanoid

O43570.

K01672.

OMA

APLNGSK.

OrthoDB

EOG4QZ7MH.

PhylomeDB

O43570.

BRENDA

4.2.1.1. 2681.

Reactome

REACT_111217. Metabolism.

ArrayExpress

O43570.

Bgee

O43570.

CleanEx

HS_CA12.

Genevestigator

O43570.

GermOnline

ENSG00000074410. Homo sapiens.

Gene3D

3.10.200.10. 1 hit.

InterPro

IPR001148. Carbonic_anhydrase_a.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018430. Carbonic_anhydrase_CA12.
[Graphical view]

PANTHER

PTHR18952. PTHR18952. 1 hit.
PTHR18952:SF19. PTHR18952:SF19. 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...

BindingDB

O43570.

ChEMBL

CHEMBL3242.

ChiTaRS

CA12. human.

DrugBank

DB00819. Acetazolamide.

EvolutionaryTrace

O43570.

GenomeRNAi

771.

NextBio

3114.

SOURCE

Search...

Entry name

CAH12_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 128 of the entry and version 1 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.

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

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

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.