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UniProtKB - O43570 (CAH12_HUMAN)
Protein
Carbonic anhydrase 12
Gene
CA12
Organism
Homo sapiens (Human)
Status
Functioni
Reversible hydration of carbon dioxide.
1 PublicationCatalytic activityi
- EC:4.2.1.11 Publication
Cofactori
Zn2+1 Publication
Activity regulationi
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).6 Publications
Kineticsi
- KM=12.0 mM for CO22 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 94 | Proton donor/acceptorBy similarity | 1 | |
Metal bindingi | 119 | Zinc; catalytic1 Publication | 1 | |
Metal bindingi | 121 | Zinc; catalytic1 Publication | 1 | |
Metal bindingi | 145 | Zinc; catalytic1 Publication | 1 |
GO - Molecular functioni
- carbonate dehydratase activity Source: GO_Central
- hydro-lyase activity Source: GO_Central
- zinc ion binding Source: ProtInc
GO - Biological processi
- chloride ion homeostasis Source: UniProtKB
- one-carbon metabolic process Source: GO_Central
Keywordsi
Molecular function | Lyase |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 4.2.1.1, 2681 |
PathwayCommonsi | O43570 |
Reactomei | R-HSA-1475029, Reversible hydration of carbon dioxide |
SignaLinki | O43570 |
Names & Taxonomyi
Protein namesi | Recommended name: Carbonic anhydrase 12Curated (EC:4.2.1.11 Publication)Alternative name(s): Carbonate dehydratase XII Carbonic anhydrase XII Short name: CA-XII Tumor antigen HOM-RCC-3.1.3 |
Gene namesi | Name:CA12Imported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1371, CA12 |
MIMi | 603263, gene |
neXtProti | NX_O43570 |
VEuPathDBi | HostDB:ENSG00000074410 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication
Other locations
Plasma Membrane
- plasma membrane Source: GO_Central
Other locations
- integral component of membrane Source: ProtInc
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 25 – 301 | ExtracellularSequence analysisAdd BLAST | 277 | |
Transmembranei | 302 – 322 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 323 – 354 | CytoplasmicSequence analysisAdd BLAST | 32 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Hyperchlorhidrosis, isolated (HYCHL)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081182 | 121 | H → Q in HYCHL; severe decrease of activity in the presence of physiological NaCl concentrations; no effect on localization to cell membrane. 1 PublicationCorresponds to variant dbSNP:rs775067652EnsemblClinVar. | 1 | |
Natural variantiVAR_065292 | 143 | E → K in HYCHL; severe decrease of activity in the presence of physiological NaCl concentrations; 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; no effect on localization to cell membrane. 3 PublicationsCorresponds to variant dbSNP:rs267606694EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 771 |
MalaCardsi | CA12 |
MIMi | 143860, phenotype |
OpenTargetsi | ENSG00000074410 |
Orphaneti | 542657, Isolated hyperchlorhidrosis |
PharmGKBi | PA25987 |
Miscellaneous databases
Pharosi | O43570, Tclin |
Chemistry databases
ChEMBLi | CHEMBL3242 |
DrugBanki | DB00819, Acetazolamide DB00562, Benzthiazide DB08846, Ellagic acid DB00774, Hydroflumethiazide DB00909, Zonisamide |
DrugCentrali | O43570 |
GuidetoPHARMACOLOGYi | 2747 |
Genetic variation databases
BioMutai | CA12 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | Sequence analysisAdd BLAST | 24 | |
ChainiPRO_0000004248 | 25 – 354 | Carbonic anhydrase 12Add BLAST | 330 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 28 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 50 ↔ 230 | 1 Publication | ||
Glycosylationi | 80 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 162 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | O43570 |
jPOSTi | O43570 |
MassIVEi | O43570 |
MaxQBi | O43570 |
PaxDbi | O43570 |
PeptideAtlasi | O43570 |
PRIDEi | O43570 |
ProteomicsDBi | 49059 [O43570-1] 49060 [O43570-2] |
PTM databases
GlyConnecti | 1064, 1 N-Linked glycan (1 site) |
GlyGeni | O43570, 3 sites, 1 N-linked glycan (1 site) |
iPTMneti | O43570 |
PhosphoSitePlusi | O43570 |
Expressioni
Tissue specificityi
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. Expressed in sweat glands and bronchiolar epithelium (PubMed:26911677).1 Publication
Gene expression databases
Bgeei | ENSG00000074410, Expressed in cortex of kidney and 215 other tissues |
ExpressionAtlasi | O43570, baseline and differential |
Genevisiblei | O43570, HS |
Organism-specific databases
HPAi | ENSG00000074410, Tissue enhanced (kidney, skin) |
Interactioni
Subunit structurei
Homodimer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 107225, 22 interactors |
IntActi | O43570, 15 interactors |
MINTi | O43570 |
STRINGi | 9606.ENSP00000178638 |
Chemistry databases
BindingDBi | O43570 |
Miscellaneous databases
RNActi | O43570, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | O43570 |
SMRi | O43570 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O43570 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 30 – 289 | Alpha-carbonic anhydrasePROSITE-ProRule annotationAdd BLAST | 260 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 226 – 227 | Substrate bindingBy similarity | 2 |
Sequence similaritiesi
Belongs to the alpha-carbonic anhydrase family.Curated
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0382, Eukaryota |
GeneTreei | ENSGT00940000159282 |
HOGENOMi | CLU_039326_1_2_1 |
InParanoidi | O43570 |
OMAi | SKWSYIG |
OrthoDBi | 1377476at2759 |
PhylomeDBi | O43570 |
TreeFami | TF316425 |
Family and domain databases
Gene3Di | 3.10.200.10, 1 hit |
InterProi | View protein in InterPro IPR001148, CA_dom IPR036398, CA_dom_sf IPR023561, Carbonic_anhydrase_a-class IPR018338, Carbonic_anhydrase_a-class_CS IPR018430, Carbonic_anhydrase_CA12 |
PANTHERi | PTHR18952, PTHR18952, 1 hit PTHR18952:SF19, PTHR18952:SF19, 1 hit |
Pfami | View protein in Pfam PF00194, Carb_anhydrase, 1 hit |
SMARTi | View protein in SMART SM01057, Carb_anhydrase, 1 hit |
SUPFAMi | SSF51069, SSF51069, 1 hit |
PROSITEi | View protein in PROSITE PS00162, ALPHA_CA_1, 1 hit PS51144, ALPHA_CA_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: O43570-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPRRSLHAAA VLLLVILKEQ PSSPAPVNGS KWTYFGPDGE NSWSKKYPSC
60 70 80 90 100
GGLLQSPIDL HSDILQYDAS LTPLEFQGYN LSANKQFLLT NNGHSVKLNL
110 120 130 140 150
PSDMHIQGLQ SRYSATQLHL HWGNPNDPHG SEHTVSGQHF AAELHIVHYN
160 170 180 190 200
SDLYPDASTA SNKSEGLAVL AVLIEMGSFN PSYDKIFSHL QHVKYKGQEA
210 220 230 240 250
FVPGFNIEEL LPERTAEYYR YRGSLTTPPC NPTVLWTVFR NPVQISQEQL
260 270 280 290 300
LALETALYCT HMDDPSPREM INNFRQVQKF DERLVYTSFS QVQVCTAAGL
310 320 330 340 350
SLGIILSLAL AGILGICIVV VVSIWLFRRK SIKKGDNKGV IYKPATKMET
EAHA
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB3KUB4 | B3KUB4_HUMAN | Carbonic anhydrase | CA12 hCG_2003428 | 283 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 305 | I → T in BAG38121 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081182 | 121 | H → Q in HYCHL; severe decrease of activity in the presence of physiological NaCl concentrations; no effect on localization to cell membrane. 1 PublicationCorresponds to variant dbSNP:rs775067652EnsemblClinVar. | 1 | |
Natural variantiVAR_065292 | 143 | E → K in HYCHL; severe decrease of activity in the presence of physiological NaCl concentrations; 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; no effect on localization to cell membrane. 3 PublicationsCorresponds to variant dbSNP:rs267606694EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_000772 | 292 – 302 | Missing in isoform 2. 2 PublicationsAdd BLAST | 11 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF051882 mRNA Translation: AAC39789.1 AF037335 mRNA Translation: AAC63952.1 BT006656 mRNA Translation: AAP35302.1 AK315769 mRNA Translation: BAG38121.1 BC000278 mRNA Translation: AAH00278.1 BC011691 mRNA Translation: AAH11691.1 BC023981 mRNA Translation: AAH23981.1 |
CCDSi | CCDS10185.1 [O43570-1] CCDS10186.1 [O43570-2] |
RefSeqi | NP_001209.1, NM_001218.4 [O43570-1] NP_996808.1, NM_206925.2 [O43570-2] |
Genome annotation databases
Ensembli | ENST00000178638.8; ENSP00000178638.3; ENSG00000074410.14 ENST00000344366.7; ENSP00000343088.3; ENSG00000074410.14 [O43570-2] |
GeneIDi | 771 |
KEGGi | hsa:771 |
MANE-Selecti | ENST00000178638.8; ENSP00000178638.3; NM_001218.5; NP_001209.1 |
UCSCi | uc002amc.4, human [O43570-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF051882 mRNA Translation: AAC39789.1 AF037335 mRNA Translation: AAC63952.1 BT006656 mRNA Translation: AAP35302.1 AK315769 mRNA Translation: BAG38121.1 BC000278 mRNA Translation: AAH00278.1 BC011691 mRNA Translation: AAH11691.1 BC023981 mRNA Translation: AAH23981.1 |
CCDSi | CCDS10185.1 [O43570-1] CCDS10186.1 [O43570-2] |
RefSeqi | NP_001209.1, NM_001218.4 [O43570-1] NP_996808.1, NM_206925.2 [O43570-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
4HT2 | X-ray | 1.45 | A/B/C/D | 30-291 | [»] | |
4KP5 | X-ray | 1.45 | A/B/C/D | 30-291 | [»] | |
4KP8 | X-ray | 1.80 | A/B/C/D | 30-291 | [»] | |
4Q0L | X-ray | 2.00 | A/B/C/D | 30-291 | [»] | |
4QJ0 | X-ray | 1.55 | A/B/C/D | 30-291 | [»] | |
4QJO | X-ray | 1.80 | A/B/C/D | 30-291 | [»] | |
4QJW | X-ray | 1.55 | A/B/C/D | 30-291 | [»] | |
4WW8 | X-ray | 1.42 | A/B/C/D | 30-291 | [»] | |
5LL5 | X-ray | 1.42 | A/B/C/D | 30-291 | [»] | |
5LL9 | X-ray | 1.45 | A/B/C/D | 30-291 | [»] | |
5LLO | X-ray | 1.60 | A/B/C/D | 30-291 | [»] | |
5LLP | X-ray | 1.48 | A/B/C/D | 30-291 | [»] | |
5MSA | X-ray | 1.20 | A/B/C/D | 30-291 | [»] | |
5MSB | X-ray | 1.30 | A/B/C/D | 30-291 | [»] | |
6G5L | X-ray | 1.21 | A/B/C/D | 30-291 | [»] | |
6G7A | X-ray | 1.42 | A/B/C/D | 30-291 | [»] | |
6QN0 | X-ray | 1.89 | A/B/C/D | 30-291 | [»] | |
6QNG | X-ray | 1.67 | A/B/C/D | 30-291 | [»] | |
6QNL | X-ray | 1.53 | A/B/C/D | 30-291 | [»] | |
6R6Y | X-ray | 1.38 | A/B/C/D | 30-291 | [»] | |
6R71 | X-ray | 2.00 | A/B | 30-291 | [»] | |
6RPS | X-ray | 2.79 | A/B | 31-291 | [»] | |
6T5P | X-ray | 1.50 | A/B/C/D | 30-291 | [»] | |
6T5Q | X-ray | 1.80 | A/B/C/D | 30-291 | [»] | |
7PUU | X-ray | 1.51 | A/B/C/D | 30-291 | [»] | |
7PUV | X-ray | 1.40 | A/B/C/D | 30-291 | [»] | |
7PUW | X-ray | 1.42 | A/B/C/D | 30-291 | [»] | |
AlphaFoldDBi | O43570 | |||||
SMRi | O43570 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107225, 22 interactors |
IntActi | O43570, 15 interactors |
MINTi | O43570 |
STRINGi | 9606.ENSP00000178638 |
Chemistry databases
BindingDBi | O43570 |
ChEMBLi | CHEMBL3242 |
DrugBanki | DB00819, Acetazolamide DB00562, Benzthiazide DB08846, Ellagic acid DB00774, Hydroflumethiazide DB00909, Zonisamide |
DrugCentrali | O43570 |
GuidetoPHARMACOLOGYi | 2747 |
PTM databases
GlyConnecti | 1064, 1 N-Linked glycan (1 site) |
GlyGeni | O43570, 3 sites, 1 N-linked glycan (1 site) |
iPTMneti | O43570 |
PhosphoSitePlusi | O43570 |
Genetic variation databases
BioMutai | CA12 |
Proteomic databases
EPDi | O43570 |
jPOSTi | O43570 |
MassIVEi | O43570 |
MaxQBi | O43570 |
PaxDbi | O43570 |
PeptideAtlasi | O43570 |
PRIDEi | O43570 |
ProteomicsDBi | 49059 [O43570-1] 49060 [O43570-2] |
Protocols and materials databases
ABCDi | O43570, 1 sequenced antibody |
Antibodypediai | 2237, 525 antibodies from 33 providers |
DNASUi | 771 |
Genome annotation databases
Ensembli | ENST00000178638.8; ENSP00000178638.3; ENSG00000074410.14 ENST00000344366.7; ENSP00000343088.3; ENSG00000074410.14 [O43570-2] |
GeneIDi | 771 |
KEGGi | hsa:771 |
MANE-Selecti | ENST00000178638.8; ENSP00000178638.3; NM_001218.5; NP_001209.1 |
UCSCi | uc002amc.4, human [O43570-1] |
Organism-specific databases
CTDi | 771 |
DisGeNETi | 771 |
GeneCardsi | CA12 |
HGNCi | HGNC:1371, CA12 |
HPAi | ENSG00000074410, Tissue enhanced (kidney, skin) |
MalaCardsi | CA12 |
MIMi | 143860, phenotype 603263, gene |
neXtProti | NX_O43570 |
OpenTargetsi | ENSG00000074410 |
Orphaneti | 542657, Isolated hyperchlorhidrosis |
PharmGKBi | PA25987 |
VEuPathDBi | HostDB:ENSG00000074410 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0382, Eukaryota |
GeneTreei | ENSGT00940000159282 |
HOGENOMi | CLU_039326_1_2_1 |
InParanoidi | O43570 |
OMAi | SKWSYIG |
OrthoDBi | 1377476at2759 |
PhylomeDBi | O43570 |
TreeFami | TF316425 |
Enzyme and pathway databases
BRENDAi | 4.2.1.1, 2681 |
PathwayCommonsi | O43570 |
Reactomei | R-HSA-1475029, Reversible hydration of carbon dioxide |
SignaLinki | O43570 |
Miscellaneous databases
BioGRID-ORCSi | 771, 14 hits in 1073 CRISPR screens |
ChiTaRSi | CA12, human |
EvolutionaryTracei | O43570 |
GeneWikii | CA12 |
GenomeRNAii | 771 |
Pharosi | O43570, Tclin |
PROi | PR:O43570 |
RNActi | O43570, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000074410, Expressed in cortex of kidney and 215 other tissues |
ExpressionAtlasi | O43570, baseline and differential |
Genevisiblei | O43570, HS |
Family and domain databases
Gene3Di | 3.10.200.10, 1 hit |
InterProi | View protein in InterPro IPR001148, CA_dom IPR036398, CA_dom_sf IPR023561, Carbonic_anhydrase_a-class IPR018338, Carbonic_anhydrase_a-class_CS IPR018430, Carbonic_anhydrase_CA12 |
PANTHERi | PTHR18952, PTHR18952, 1 hit PTHR18952:SF19, PTHR18952:SF19, 1 hit |
Pfami | View protein in Pfam PF00194, Carb_anhydrase, 1 hit |
SMARTi | View protein in SMART SM01057, Carb_anhydrase, 1 hit |
SUPFAMi | SSF51069, SSF51069, 1 hit |
PROSITEi | View protein in PROSITE PS00162, ALPHA_CA_1, 1 hit PS51144, ALPHA_CA_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CAH12_HUMAN | |
Accessioni | O43570Primary (citable) accession number: O43570 Secondary accession number(s): B2RE24, Q53YE5, Q9BWG2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | June 1, 1998 | |
Last modified: | May 25, 2022 | |
This is version 200 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - 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