ID CLCA1_BOVIN Reviewed; 903 AA. AC P54281; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 27-MAR-2024, entry version 140. DE RecName: Full=Calcium-activated chloride channel regulator 1 {ECO:0000305}; DE EC=3.4.-.- {ECO:0000250|UniProtKB:A8K7I4}; DE AltName: Full=Calcium-activated chloride channel; DE AltName: Full=Epithelial chloride channel protein {ECO:0000303|PubMed:8537359}; DE Flags: Precursor; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND GLYCOSYLATION. RC TISSUE=Trachea; RX PubMed=8537359; DOI=10.1074/jbc.270.52.31016; RA Cunningham S.A., Awayda M.S., Bubien J.K., Ismailov I.I., Arrate M.P., RA Berdiev B.K., Benos D.J., Fuller C.M.; RT "Cloning of an epithelial chloride channel from bovine trachea."; RL J. Biol. Chem. 270:31016-31026(1995). CC -!- FUNCTION: May be involved in mediating calcium-activated chloride CC conductance (PubMed:8537359). May play critical roles in goblet cell CC metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be CC involved in the regulation of mucus production and/or secretion by CC goblet cells. Involved in the regulation of tissue inflammation in the CC innate immune response. May play a role as a tumor suppressor. Induces CC MUC5AC. {ECO:0000250|UniProtKB:A8K7I4, ECO:0000269|PubMed:8537359}. CC -!- SUBCELLULAR LOCATION: Apical cell membrane CC {ECO:0000269|PubMed:8537359}; Single-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Trachea. {ECO:0000269|PubMed:8537359}. CC -!- DOMAIN: The metalloprotease region is responsible for autoproteolytic CC processing. It can also cross-cleave other CLCA substrates. CC {ECO:0000250|UniProtKB:A8K7I4}. CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:8537359}. CC -!- PTM: The 125-kDa product is autoproteolytically processed by the CC metalloprotease domain and yields to two cell-surface-associated CC subunits, a 90-kDa protein and a group of 37- to 41-kDa proteins. The CC cleavage is necessary for calcium-activated chloride channel (CaCC) CC activation activity. {ECO:0000250|UniProtKB:A8K7I4}. CC -!- SIMILARITY: Belongs to the CLCR family. {ECO:0000305}. CC -!- CAUTION: Was initially characterized as chloride channel, but such a CC function is difficult to reconcile with the single predicted CC transmembrane region. Other family members have been shown to stimulate CC channel activity. {ECO:0000269|PubMed:8537359, ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U36445; AAC48511.1; -; mRNA. DR RefSeq; NP_001229512.1; NM_001242583.1. DR AlphaFoldDB; P54281; -. DR SMR; P54281; -. DR STRING; 9913.ENSBTAP00000028657; -. DR MEROPS; M87.005; -. DR TCDB; 1.A.13.1.1; the epithelial chloride channel (e-clc) family. DR PaxDb; 9913-ENSBTAP00000028657; -. DR GeneID; 784768; -. DR KEGG; bta:784768; -. DR eggNOG; ENOG502QRRD; Eukaryota. DR InParanoid; P54281; -. DR OrthoDB; 5479609at2759; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005229; F:intracellular calcium activated chloride channel activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW. DR GO; GO:0006816; P:calcium ion transport; IEA:UniProtKB-KW. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR CDD; cd00198; vWFA; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 1. DR InterPro; IPR004727; CLCA_chordata. DR InterPro; IPR013642; CLCA_N. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR002035; VWF_A. DR InterPro; IPR036465; vWFA_dom_sf. DR NCBIfam; NF041940; choice_anch_X; 1. DR NCBIfam; TIGR00868; hCaCC; 1. DR PANTHER; PTHR10579; CALCIUM-ACTIVATED CHLORIDE CHANNEL REGULATOR; 1. DR PANTHER; PTHR10579:SF42; CALCIUM-ACTIVATED CHLORIDE CHANNEL REGULATOR 3A-1-RELATED; 1. DR Pfam; PF08434; CLCA; 1. DR Pfam; PF00092; VWA; 1. DR SMART; SM00327; VWA; 1. DR SUPFAM; SSF53300; vWA-like; 1. DR PROSITE; PS50234; VWFA; 1. PE 1: Evidence at protein level; KW Calcium; Calcium transport; Cell membrane; Chloride; Glycoprotein; KW Hydrolase; Ion transport; Membrane; Metal-binding; Metalloprotease; KW Protease; Reference proteome; Signal; Transmembrane; Transmembrane helix; KW Transport; Zinc. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..903 FT /note="Calcium-activated chloride channel regulator 1" FT /id="PRO_0000054105" FT TRANSMEM 883..903 FT /note="Helical" FT /evidence="ECO:0000255" FT DOMAIN 308..476 FT /note="VWFA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219" FT REGION 45..199 FT /note="Metalloprotease domain" FT /evidence="ECO:0000250|UniProtKB:A8K7I4" FT ACT_SITE 156 FT /evidence="ECO:0000250|UniProtKB:A8K7I4" FT BINDING 155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:A8K7I4" FT BINDING 159 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:A8K7I4" FT BINDING 166 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:A8K7I4" FT CARBOHYD 360 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 372 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 504 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 842 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" SQ SEQUENCE 903 AA; 100306 MW; 9742AB1590908AEC CRC64; MVPRLTVILF LTLHLLPGMK SSMVNLINNG YDGIVIAINP SVPEDEKLIQ NIKEMVTEAS TYLFHATKRR VYFRNVSILI PMTWKSKSEY LMPKQESYDQ AEVIVANPYL KHGDDPYTLQ YGRCGEKGQY IHFTPNFLLT NNLPIYGSRG RAFVHEWAHL RWGIFDEYNG DQPFYISRRN TIEATRCSTH ITGTNVIVKC QGGSCITRPC RRDSQTGLYE AKCTFIPEKS QTARESIMFM QSLHSVTEFC TEKTHNVEAP NLQNKMCNGK STWDVIMNST DFQNTSPMTE MNPPTQPTFS LLKSKQRVVC LVLDKSGSMS SEDRLFRMNQ AAELFLIQII EKGSLVGMVT FDSVAEIRNN LTKITDDNVY ENITANLPQE ANGGTSICRG LKAGFQAIIQ SQQSTSGSEI ILLTDGEDNE IHSCIEEVKQ SGVIIHTIAL GPSAAKELET LSDMTGGHRF YANKDINGLT NAFSRISSRS GSITQQTIQL ESKALAITEK KWVNGTVPVD STIGNDTFFV VTWTIKKPEI LLQDPKGKKY KTSDFKEDKL NIHSARLRIP GIAETGTWTY SLLNNHASPQ ILTVTVTTRA RSPTTPPVTA TAHMSQNTAH YPSPVIVYAQ VSQGFLPVLG INVTAIIETE DGHQVTLELW DNGAGADTVK NDGIYSRYFT DYRGNGRYSL KVHAEARNNT ARLSLRQPQN KALYIPGYIE NGKIILNPPR PEVKDDLAKA EIEDFSRLTS GGSFTVSGAP PGNHPSVLPP NKIIDLEAKF KEDHIQLSWT APANVLDKGK ANSYIIRISK SFLDLQKDFD NATLVNTSSL KPKEAGSDEN FEFKPEPFRI ENGTNFYIAV QAINEANLTS EVSNIAQAIK FIPMPEDSVP ALGTKISAIN LAIFALAMIL SIV //