A8K7I4 · CLCA1_HUMAN
- ProteinCalcium-activated chloride channel regulator 1
- GeneCLCA1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids914 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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.
Features
Showing features for binding site, active site, site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | microvillus | |
Cellular Component | plasma membrane | |
Cellular Component | zymogen granule membrane | |
Molecular Function | chloride channel activity | |
Molecular Function | intracellularly calcium-gated chloride channel activity | |
Molecular Function | metal ion binding | |
Molecular Function | metalloendopeptidase activity | |
Biological Process | calcium ion transport | |
Biological Process | cellular response to hypoxia | |
Biological Process | monoatomic ion transmembrane transport | |
Biological Process | proteolysis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameCalcium-activated chloride channel regulator 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionA8K7I4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Note: Protein that remains attached to the plasma membrane appeared to be predominantly localized to microvilli.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_054654 | 65 | in dbSNP:rs2145412 | |||
Sequence: L → F | ||||||
Mutagenesis | 150 | Reduces proteolytic cleavage. | ||||
Sequence: Q → A | ||||||
Natural variant | VAR_054655 | 152 | in dbSNP:rs2753386 | |||
Sequence: R → K | ||||||
Mutagenesis | 156 | Abolishes proteolytic cleavage. | ||||
Sequence: H → A | ||||||
Mutagenesis | 157 | Abolishes proteolytic cleavage. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 160 | Abolishes proteolytic cleavage. | ||||
Sequence: H → A | ||||||
Mutagenesis | 167 | Abolishes proteolytic cleavage. | ||||
Sequence: D → A | ||||||
Mutagenesis | 168 | Abolishes proteolytic cleavage. | ||||
Sequence: E → A | ||||||
Natural variant | VAR_043146 | 357 | in dbSNP:rs2734705 | |||
Sequence: N → S | ||||||
Natural variant | VAR_054656 | 406 | in dbSNP:rs1142185 | |||
Sequence: E → V | ||||||
Natural variant | VAR_054657 | 426 | in dbSNP:rs4647852 | |||
Sequence: K → R | ||||||
Natural variant | VAR_043147 | 524 | in dbSNP:rs2791494 | |||
Sequence: M → T | ||||||
Natural variant | VAR_054658 | 661 | in dbSNP:rs5744409 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_054659 | 760 | in dbSNP:rs2791483 | |||
Sequence: K → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,158 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MGPFKSSVFILILHLLEGALS | ||||||
Chain | PRO_0000333690 | 22-914 | Calcium-activated chloride channel regulator 1 | |||
Sequence: NSLIQLNNNGYEGIVVAIDPNVPEDETLIQQIKDMVTQASLYLLEATGKRFYFKNVAILIPETWKTKADYVRPKLETYKNADVLVAESTPPGNDEPYTEQMGNCGEKGERIHLTPDFIAGKKLAEYGPQGRAFVHEWAHLRWGVFDEYNNDEKFYLSNGRIQAVRCSAGITGTNVVKKCQGGSCYTKRCTFNKVTGLYEKGCEFVLQSRQTEKASIMFAQHVDSIVEFCTEQNHNKEAPNKQNQKCNLRSTWEVIRDSEDFKKTTPMTTQPPNPTFSLLQIGQRIVCLVLDKSGSMATGNRLNRLNQAGQLFLLQTVELGSWVGMVTFDSAAHVQNELIQINSGSDRDTLAKRLPAAASGGTSICSGLRSAFTVIRKKYPTDGSEIVLLTDGEDNTISGCFNEVKQSGAIIHTVALGPSAAQELEELSKMTGGLQTYASDQVQNNGLIDAFGALSSGNGAVSQRSIQLESKGLTLQNSQWMNGTVIVDSTVGKDTLFLITWTMQPPQILLWDPSGQKQGGFVVDKNTKMAYLQIPGIAKVGTWKYSLQASSQTLTLTVTSRASNATLPPITVTSKTNKDTSKFPSPLVVYANIRQGASPILRASVTALIESVNGKTVTLELLDNGAGADATKDDGVYSRYFTTYDTNGRYSVKVRALGGVNAARRRVIPQQSGALYIPGWIENDEIQWNPPRPEINKDDVQHKQVCFSRTSSGGSFVASDVPNAPIPDLFPPGQITDLKAEIHGGSLINLTWTAPGDDYDHGTAHKYIIRISTSILDLRDKFNESLQVNTTALIPKEANSEEVFLFKPENITFENGTDLFIAIQAVDKVDLKSEISNIARVSLFIPPQTPPETPSPDETSAPCPNIHINSTIPGIHILKIMWKWIGELQLSIA | ||||||
Glycosylation | 503 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 585 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 770 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 804 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 810 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 831 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 836 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 890 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Glycosylated.
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in small intestine and colon namely in intestinal basal crypt epithelia and goblet cells, and appendix. Weakly expressed in uterus, testis and kidney. Expressed in the airways epithelium of both asthmatic and healthy patients. Expressed in the bronchial epithelium, especially in mucus-producing goblet cells. Expressed in normal turbinate mucosa and nasal polyp. Expressed in.
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.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 46-199 | Metalloprotease domain | ||||
Sequence: DETLIQQIKDMVTQASLYLLEATGKRFYFKNVAILIPETWKTKADYVRPKLETYKNADVLVAESTPPGNDEPYTEQMGNCGEKGERIHLTPDFIAGKKLAEYGPQGRAFVHEWAHLRWGVFDEYNNDEKFYLSNGRIQAVRCSAGITGTNVVKK | ||||||
Domain | 306-475 | VWFA | ||||
Sequence: IVCLVLDKSGSMATGNRLNRLNQAGQLFLLQTVELGSWVGMVTFDSAAHVQNELIQINSGSDRDTLAKRLPAAASGGTSICSGLRSAFTVIRKKYPTDGSEIVLLTDGEDNTISGCFNEVKQSGAIIHTVALGPSAAQELEELSKMTGGLQTYASDQVQNNGLIDAFGAL |
Domain
The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates.
Sequence similarities
Belongs to the CLCR family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length914
- Mass (Da)100,226
- Last updated2010-11-02 v3
- Checksum8D8999E855822711
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 393 | in Ref. 3; BAF84688 | ||||
Sequence: F → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF039400 EMBL· GenBank· DDBJ | AAC95428.1 EMBL· GenBank· DDBJ | mRNA | ||
AF039401 EMBL· GenBank· DDBJ | AAC95429.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF127036 EMBL· GenBank· DDBJ | AAD25487.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291999 EMBL· GenBank· DDBJ | BAF84688.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314375 EMBL· GenBank· DDBJ | BAG37002.1 EMBL· GenBank· DDBJ | mRNA | ||
AL122002 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471097 EMBL· GenBank· DDBJ | EAW73186.1 EMBL· GenBank· DDBJ | Genomic DNA |