CLCA1_PIG
ID CLCA1_PIG Reviewed; 917 AA.
AC Q9TUB5;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Calcium-activated chloride channel regulator 1;
DE EC=3.4.-.- {ECO:0000250|UniProtKB:A8K7I4};
DE AltName: Full=Calcium-activated chloride channel family member 1;
DE AltName: Full=pCLCA1;
DE Flags: Precursor;
GN Name=CLCA1; Synonyms=AECC;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Ileal mucosa;
RX PubMed=11015605; DOI=10.1152/physiolgenomics.2000.3.2.101;
RA Gaspar K.J., Racette K.J., Gordon J.R., Loewen M.E., Forsyth G.W.;
RT "Cloning a chloride conductance mediator from the apical membrane of
RT porcine ileal enterocytes.";
RL Physiol. Genomics 3:101-111(2000).
RN [2]
RP FUNCTION.
RX PubMed=12107050; DOI=10.1152/ajpcell.00477.2001;
RA Loewen M.E., Gabriel S.E., Forsyth G.W.;
RT "The calcium-dependent chloride conductance mediator pCLCA1.";
RL Am. J. Physiol. 283:C412-C421(2002).
RN [3]
RP FUNCTION.
RX PubMed=12408984; DOI=10.1016/s0006-291x(02)02498-1;
RA Loewen M.E., Bekar L.K., Gabriel S.E., Walz W., Forsyth G.W.;
RT "pCLCA1 becomes a cAMP-dependent chloride conductance mediator in Caco-2
RT cells.";
RL Biochem. Biophys. Res. Commun. 298:531-536(2002).
RN [4]
RP FUNCTION.
RX PubMed=14988065; DOI=10.1152/ajpgi.00023.2004;
RA Loewen M.E., Bekar L.K., Walz W., Forsyth G.W., Gabriel S.E.;
RT "pCLCA1 lacks inherent chloride channel activity in an epithelial colon
RT carcinoma cell line.";
RL Am. J. Physiol. 287:G33-G41(2004).
CC -!- FUNCTION: May be involved in mediating calcium-activated chloride
CC conductance. May play critical roles in goblet cell metaplasia, mucus
CC hypersecretion, cystic fibrosis and AHR. May be involved in the
CC regulation of mucus production and/or secretion by goblet cells.
CC Involved in the regulation of tissue inflammation in the innate immune
CC response. May play a role as a tumor suppressor. Induces MUC5AC.
CC Induces a cAMP-dependent chloride conductance possibly through effects
CC on CFTR in colon carcinoma cells. {ECO:0000269|PubMed:11015605,
CC ECO:0000269|PubMed:12107050, ECO:0000269|PubMed:12408984,
CC ECO:0000269|PubMed:14988065}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in ileum, trachea, and the major salivary
CC glands. In ileum, expressed to the crypt and villus epithelia, whereas
CC in trachea expressed in both surface epithelium and submucosal glands.
CC {ECO:0000269|PubMed:11015605}.
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:0000250}.
CC -!- PTM: The translation product is autoproteolytically cleaved by the
CC metalloprotease domain in the endoplasmic reticulum into a N-terminal
CC and a C-terminal products that remain physically associated with each
CC other. The cleavage is necessary for calcium-activated chloride channel
CC (CaCC) activation activity. {ECO:0000250|UniProtKB:A8K7I4}.
CC -!- SIMILARITY: Belongs to the CLCR family. {ECO:0000305}.
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DR EMBL; AF095584; AAF00077.1; -; mRNA.
DR RefSeq; NP_999313.1; NM_214148.1.
DR AlphaFoldDB; Q9TUB5; -.
DR SMR; Q9TUB5; -.
DR STRING; 9823.ENSSSCP00000007392; -.
DR MEROPS; M87.001; -.
DR PaxDb; Q9TUB5; -.
DR PeptideAtlas; Q9TUB5; -.
DR PRIDE; Q9TUB5; -.
DR GeneID; 397284; -.
DR KEGG; ssc:397284; -.
DR CTD; 1179; -.
DR eggNOG; ENOG502QRRD; Eukaryota.
DR InParanoid; Q9TUB5; -.
DR OrthoDB; 685640at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005615; C:extracellular space; 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; PF13519; VWA_2; 1.
DR SMART; SM00327; VWA; 1.
DR SUPFAM; SSF53300; SSF53300; 1.
DR TIGRFAMs; TIGR00868; hCaCC; 1.
DR PROSITE; PS50234; VWFA; 1.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Calcium; Calcium transport; Chloride; Glycoprotein;
KW Hydrolase; Ion transport; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Secreted; Signal; Transport; Zinc.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..917
FT /note="Calcium-activated chloride channel regulator 1"
FT /id="PRO_0000333693"
FT DOMAIN 306..475
FT /note="VWFA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219"
FT REGION 46..199
FT /note="Metalloprotease domain"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT ACT_SITE 157
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT SITE 696..697
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:A8K7I4"
FT CARBOHYD 503
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 772
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 806
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 812
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 838
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 893
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 917 AA; 100736 MW; 649F41944F7EAD19 CRC64;
MGSFRSSLFI LVLHLLEGAQ SNSLIQLNGN GYEGIVIAID PNVPEDERLI QNIKDMVTKA
SPYLFEATEK RFYFKNVAIL IPASWKAKPE YVKPKLETYK NADVVVTEPN PPENDGPYTE
QMGNCGEKGE KIYFTPDFVA GKKVLQYGPQ GRVFVHEWAH LRWGVFNEYN NEQKFYLSNK
KEQPVICSAA IRGTNVLPQC QGGSCVTKPC RADRVTGLFQ KECEFIPDPQ QSEKASIMFA
QSIDTVVEFC KEKNHNKEAP NDQNQKCNLR STWEVIQDSE DFKKTTPMTT QPPAPTFSLL
QIGQRIVCLV LDKSGSMTVG GRLKRLNQAG KLFLLQTVEQ GAWVGMVAFD SAAYVKSELV
QINSAAERDA LARSLPTAAS GGTSICSGLR SAFTVIKKKY PTDGSEIVLL TDGEDNTISA
CFPEVKQNGA IIHTVALGPS AAKELEELSQ MTGGLQTYAS DQAENNGLID AFGALSSGNR
AASQRSIQLE SQGLTLQNNE WMNGTVVVDS TVGKDTLFLI TLERKFLSPI PFFGVPSGRS
QDSFLVGKHN KMAYFQVPGT AKVGMWKYSL QASSQTLTLT VSSRRSSATL PPVTVTSKMN
KDTGKFPSPM VVYTKIHQGT LPILRAKVTA LIESENGKTV TLELLDNGAG ADATKNDGIY
SRYFTAYDAN GRYSVKVWAL GGVNTPRRRA PPLWSGAMYI RGWIENGEIK WNPPRPDINK
DDLQGKQVCF SRTASGGSFV ASDVPKSPIP DLFPPCKITD LKAGIQGDNL INLTWTAPGD
DYDHGRADRY IIRISTNILD LRDKFNDSVQ VNTTDLIPKE ANSEEVFVFK PEGIPFTNGT
DLFIAVQAVD KTNLKSEISN IAQVSLFLPP EAPPETPPET PAPSLPCPEI QVNSTIPGIH
ILKIMWKWLG ELQLSIA
