CLCA1_BOVIN
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 03-AUG-2022, entry version 132.
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}.
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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; P54281; -.
DR PRIDE; P54281; -.
DR GeneID; 784768; -.
DR KEGG; bta:784768; -.
DR eggNOG; ENOG502QRRD; Eukaryota.
DR OrthoDB; 685640at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of 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 Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.40.50.410; -; 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 Pfam; PF08434; CLCA; 1.
DR Pfam; PF00092; VWA; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR TIGRFAMs; TIGR00868; hCaCC; 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
