| IED ID | IndEnz0002018317 |
| Enzyme Type ID | protease018317 |
| Protein Name |
Calcium-activated chloride channel regulator 2 EC 3.4.-.- Calcium-activated chloride channel family member 2 hCLCA2 Calcium-activated chloride channel protein 3 CaCC-3 hCaCC-3 Cleaved into: Calcium-activated chloride channel regulator 2, 109 kDa form; Calcium-activated chloride channel regulator 2, 35 kDa form |
| Gene Name | CLCA2 CACC3 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MTQRSIAGPICNLKFVTLLVALSSELPFLGAGVQLQDNGYNGLLIAINPQVPENQNLISNIKEMITEASFYLFNATKRRVFFRNIKILIPATWKANNNSKIKQESYEKANVIVTDWYGAHGDDPYTLQYRGCGKEGKYIHFTPNFLLNDNLTAGYGSRGRVFVHEWAHLRWGVFDEYNNDKPFYINGQNQIKVTRCSSDITGIFVCEKGPCPQENCIISKLFKEGCTFIYNSTQNATASIMFMQSLSSVVEFCNASTHNQEAPNLQNQMCSLRSAWDVITDSADFHHSFPMNGTELPPPPTFSLVQAGDKVVCLVLDVSSKMAEADRLLQLQQAAEFYLMQIVEIHTFVGIASFDSKGEIRAQLHQINSNDDRKLLVSYLPTTVSAKTDISICSGLKKGFEVVEKLNGKAYGSVMILVTSGDDKLLGNCLPTVLSSGSTIHSIALGSSAAPNLEELSRLTGGLKFFVPDISNSNSMIDAFSRISSGTGDIFQQHIQLESTGENVKPHHQLKNTVTVDNTVGNDTMFLVTWQASGPPEIILFDPDGRKYYTNNFITNLTFRTASLWIPGTAKPGHWTYTLNNTHHSLQALKVTVTSRASNSAVPPATVEAFVERDSLHFPHPVMIYANVKQGFYPILNATVTATVEPETGDPVTLRLLDDGAGADVIKNDGIYSRYFFSFAANGRYSLKVHVNHSPSISTPAHSIPGSHAMYVPGYTANGNIQMNAPRKSVGRNEEERKWGFSRVSSGGSFSVLGVPAGPHPDVFPPCKIIDLEAVKVEEELTLSWTAPGEDFDQGQATSYEIRMSKSLQNIQDDFNNAILVNTSKRNPQQAGIREIFTFSPQISTNGPEHQPNGETHESHRIYVAIRAMDRNSLQSAVSNIAQAPLFIPPNSDPVPARDYLILKGVLTAMGLIGIICLIIVVTHHTLSRKKRADKKENGTKLL |
| Enzyme Length | 943 |
| Uniprot Accession Number | Q9UQC9 |
| Absorption | |
| Active Site | ACT_SITE 165; /evidence=ECO:0000250|UniProtKB:A8K7I4 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.-.- |
| Enzyme Function | FUNCTION: Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner, and cell adhesion. Involved in basal cell adhesion and/or stratification of squamous epithelia. May act as a tumor suppressor in breast and colorectal cancer. Plays a key role for cell adhesion in the beginning stages of lung metastasis via the binding to ITGB4. {ECO:0000269|PubMed:10554024, ECO:0000269|PubMed:11320086, ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:15707651, ECO:0000269|PubMed:16158324}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (3); Domain (1); Glycosylation (5); Metal binding (3); Mutagenesis (6); Natural variant (4); Region (1); Sequence conflict (2); Signal peptide (1); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | Autocatalytic cleavage;Calcium;Cell adhesion;Cell junction;Cell membrane;Chloride;Glycoprotein;Hydrolase;Ion transport;Membrane;Metal-binding;Metalloprotease;Protease;Reference proteome;Secreted;Signal;Transmembrane;Transmembrane helix;Transport;Zinc |
| Interact With | |
| Induction | INDUCTION: Significantly down-regulated in breast and colorectal cancer. {ECO:0000269|PubMed:10554024, ECO:0000269|PubMed:11445004}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. Basal cell membrane; Single-pass type I membrane protein. Cell junction.; SUBCELLULAR LOCATION: [Calcium-activated chloride channel regulator 2, 109 kDa form]: Secreted. Note=Remains associated to the 35 kDa form until an unidentified event triggers the release. |
| Modified Residue | |
| Post Translational Modification | PTM: The 141 kDa mature form is autoproteolytically cleaved by the metalloprotease domain, producing a 109 kDa form and a 35 kDa form. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity. {ECO:0000250|UniProtKB:A8K7I4}.; PTM: N-glycosylated. {ECO:0000269|PubMed:10362588, ECO:0000269|PubMed:16873362}. |
| Signal Peptide | SIGNAL 1..31; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 11842292; 11904445; 11956057; 12612194; 12907679; 15010458; 15174051; 15318163; 15919655; 16219661; 18724360; 18950845; 19307298; 19423540; 19654313; 20406964; 20438785; 21909135; 21984732; 22431922; 22946059; 22990203; 23112050; 25548429; 25557950; 26930581; 29463274; 29536528; 29743348; 29758025; 31326550; 32131869; 32298355; 33966732; 9662395; 9700209; |
| Motif | |
| Gene Encoded By | |
| Mass | 103,941 |
| Kinetics | |
| Metal Binding | METAL 164; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:A8K7I4; METAL 168; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:A8K7I4; METAL 175; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:A8K7I4 |
| Rhea ID | |
| Cross Reference Brenda |