Detail Information for IndEnz0002018298
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