| IED ID | IndEnz0002018298 |
| Enzyme Type ID | protease018298 |
| Protein Name |
Calcium-activated chloride channel regulator 1 EC 3.4.-.- Calcium-activated chloride channel family member 1 hCLCA1 Calcium-activated chloride channel protein 1 CaCC-1 hCaCC-1 |
| Gene Name | CLCA1 CACC1 |
| 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 | MGPFKSSVFILILHLLEGALSNSLIQLNNNGYEGIVVAIDPNVPEDETLIQQIKDMVTQASLYLLEATGKRFYFKNVAILIPETWKTKADYVRPKLETYKNADVLVAESTPPGNDEPYTEQMGNCGEKGERIHLTPDFIAGKKLAEYGPQGRAFVHEWAHLRWGVFDEYNNDEKFYLSNGRIQAVRCSAGITGTNVVKKCQGGSCYTKRCTFNKVTGLYEKGCEFVLQSRQTEKASIMFAQHVDSIVEFCTEQNHNKEAPNKQNQKCNLRSTWEVIRDSEDFKKTTPMTTQPPNPTFSLLQIGQRIVCLVLDKSGSMATGNRLNRLNQAGQLFLLQTVELGSWVGMVTFDSAAHVQNELIQINSGSDRDTLAKRLPAAASGGTSICSGLRSAFTVIRKKYPTDGSEIVLLTDGEDNTISGCFNEVKQSGAIIHTVALGPSAAQELEELSKMTGGLQTYASDQVQNNGLIDAFGALSSGNGAVSQRSIQLESKGLTLQNSQWMNGTVIVDSTVGKDTLFLITWTMQPPQILLWDPSGQKQGGFVVDKNTKMAYLQIPGIAKVGTWKYSLQASSQTLTLTVTSRASNATLPPITVTSKTNKDTSKFPSPLVVYANIRQGASPILRASVTALIESVNGKTVTLELLDNGAGADATKDDGVYSRYFTTYDTNGRYSVKVRALGGVNAARRRVIPQQSGALYIPGWIENDEIQWNPPRPEINKDDVQHKQVCFSRTSSGGSFVASDVPNAPIPDLFPPGQITDLKAEIHGGSLINLTWTAPGDDYDHGTAHKYIIRISTSILDLRDKFNESLQVNTTALIPKEANSEEVFLFKPENITFENGTDLFIAIQAVDKVDLKSEISNIARVSLFIPPQTPPETPSPDETSAPCPNIHINSTIPGIHILKIMWKWIGELQLSIA |
| Enzyme Length | 914 |
| Uniprot Accession Number | A8K7I4 |
| Absorption | |
| Active Site | ACT_SITE 157; /evidence=ECO:0000305|PubMed:23112050 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.-.- |
| Enzyme Function | FUNCTION: May be involved in mediating calcium-activated chloride conductance. May play critical roles in goblet cell metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be involved in the regulation of mucus production and/or secretion by goblet cells. Involved in the regulation of tissue inflammation in the innate immune response. May play a role as a tumor suppressor. Induces MUC5AC. {ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:11842292, ECO:0000269|PubMed:11956057, ECO:0000269|PubMed:23112050, ECO:0000269|PubMed:9828122}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Beta strand (5); Chain (1); Domain (1); Glycosylation (8); Helix (7); Metal binding (3); Mutagenesis (6); Natural variant (8); Region (1); Sequence conflict (1); Signal peptide (1); Site (1); Turn (1) |
| Keywords | 3D-structure;Autocatalytic cleavage;Calcium;Calcium transport;Cell membrane;Chloride;Direct protein sequencing;Glycoprotein;Hydrolase;Ion transport;Membrane;Metal-binding;Metalloprotease;Protease;Reference proteome;Secreted;Signal;Transport;Zinc |
| Interact With | |
| Induction | INDUCTION: By IL13/interleukin-13 in tracheobronchial epithelial cells. Up-regulated by histamine in a dose-dependent manner. Significantly down-regulated in colorectal cancer. Significantly up-regulated in the IL9-responsive mucus-producing epithelium of asthmatic patients. Significantly decreased in nasal polyp. Significantly increased by TNF in upper airway mucosa. {ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:11842292, ECO:0000269|PubMed:11956057, ECO:0000269|PubMed:15696080, ECO:0000269|PubMed:16012037, ECO:0000269|PubMed:16151054, ECO:0000269|PubMed:17622767}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000269|PubMed:15919655}. Cell membrane {ECO:0000269|PubMed:15919655}; Peripheral membrane protein {ECO:0000269|PubMed:15919655}; Extracellular side {ECO:0000269|PubMed:15919655}. Note=Protein that remains attached to the plasma membrane appeared to be predominantly localized to microvilli. |
| Modified Residue | |
| Post Translational Modification | PTM: Glycosylated. {ECO:0000269|PubMed:9828122}.; PTM: The 125-kDa product is autoproteolytically processed by the metalloprotease domain and yields to two cell-surface-associated subunits, a 90-kDa protein and a group of 37- to 41-kDa proteins. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity. {ECO:0000269|PubMed:23112050, ECO:0000269|PubMed:9828122}. |
| Signal Peptide | SIGNAL 1..21; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 6PYO; 6PYX; |
| Mapped Pubmed ID | 11904445; 12408984; 12568493; 12907679; 14985398; 15010458; 15318163; 15490240; 16023076; 16148052; 16219661; 16465045; 16470849; 17110338; 17426222; 17621552; 17698377; 18724360; 19307298; 19423540; 19530997; 19834535; 19913121; 20179644; 20406964; 20438785; 20464982; 20542744; 20628086; 21984732; 22731784; 22946059; 23593331; 24349445; 25603912; 25781344; 26004777; 28420732; 28974231; 29885864; 31570526; 31995732; 9662395; 9700209; |
| Motif | |
| Gene Encoded By | |
| Mass | 100,226 |
| Kinetics | |
| Metal Binding | METAL 156; /note=Zinc; catalytic; /evidence=ECO:0000305|PubMed:23112050; METAL 160; /note=Zinc; catalytic; /evidence=ECO:0000305|PubMed:23112050; METAL 167; /note=Zinc; catalytic; /evidence=ECO:0000305|PubMed:23112050 |
| Rhea ID | |
| Cross Reference Brenda |