CLCA1_HORSE
ID CLCA1_HORSE Reviewed; 913 AA.
AC Q2TU62; Q1RQG8; Q1RQG9;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 105.
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 Short=eCLCA1;
DE Flags: Precursor;
GN Name=CLCA1;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, GLYCOSYLATION,
RP AND VARIANTS ARG-485 AND LEU-490.
RX PubMed=15879574; DOI=10.1369/jhc.4a6599.2005;
RA Anton F., Leverkoehne I., Mundhenk L., Thoreson W.B., Gruber A.D.;
RT "Overexpression of eCLCA1 in small airways of horses with recurrent airway
RT obstruction.";
RL J. Histochem. Cytochem. 53:1011-1021(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 266-315 AND 808-894.
RA Klukowska-Roetzler J., Gerber V., Bugno M., Slota E., Robinson A.J.,
RA Guerin G., Dolf G.;
RT "Chromosomal assignment of two candidate genes for equine recurrent airway
RT obstruction (RAO).";
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in mucin-producing cells in the
CC respiratory and intestinal tracts, cutaneous sweat glands, and renal
CC mucous glands (at protein level). Strong overexpression in the airways
CC of horses with recurrent airway obstruction (at protein level).
CC {ECO:0000269|PubMed:15879574}.
CC -!- INDUCTION: Strongly up-regulated in bronchioles with recurrent airway
CC obstruction (RAO). {ECO:0000269|PubMed:15879574}.
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:15879574}.
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; AY524856; AAT01505.1; -; mRNA.
DR EMBL; AJ938085; CAI79650.1; -; Genomic_DNA.
DR EMBL; AJ938086; CAI79651.1; -; Genomic_DNA.
DR RefSeq; NP_001075268.1; NM_001081799.2.
DR AlphaFoldDB; Q2TU62; -.
DR SMR; Q2TU62; -.
DR STRING; 9796.ENSECAP00000016845; -.
DR MEROPS; M87.001; -.
DR PaxDb; Q2TU62; -.
DR PeptideAtlas; Q2TU62; -.
DR GeneID; 100009706; -.
DR KEGG; ecb:100009706; -.
DR CTD; 1179; -.
DR HOGENOM; CLU_005812_0_1_1; -.
DR InParanoid; Q2TU62; -.
DR OMA; IPQQNGA; -.
DR OrthoDB; 685640at2759; -.
DR TreeFam; TF328396; -.
DR Proteomes; UP000002281; 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 1: Evidence at protein 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..913
FT /note="Calcium-activated chloride channel regulator 1"
FT /id="PRO_0000333689"
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 694..695
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 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 770
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 804
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 810
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 836
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 885
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 485
FT /note="H -> R"
FT /evidence="ECO:0000269|PubMed:15879574"
FT VARIANT 490
FT /note="V -> L"
FT /evidence="ECO:0000269|PubMed:15879574"
FT CONFLICT 889
FT /note="A -> T (in Ref. 2; CAI79651)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 913 AA; 100134 MW; 4570EFFD53EC75FC CRC64;
MGSFKSSVFI LVLHLLEGAL SNSLIHLNNN GYEGIVIAID PNVPEDETLI QQIKDMVTQA
SPYLFEATEK RFYFKNVAIL VPENWKTKPE YERPKLETYK NADVLVAEPN PPGNDQPYTE
QMGKCGEKGE RIYFTPDFLA GKRLDEYGPQ GRVFVHEWAH LRWGLFNEYN DDQKFYLSNK
EIKPVKCSAD IAGKNVVNHC QGGSCATKPC RRDRVTGLYA QECEFIPDEQ QTEKASIMFS
QSIDSVVEFC TEENHNREAP NMQNQRCNLR STWEVIRDSE DFKKTTPMTA QPPQPTFSLL
QIGQRIVCLV LDKSGSMAIG DRLKRLTQAG KLFLLQTVEQ GSWVGMVTFD SAAYVQSALR
QIKGGTDRDA LTKSLPTVAS GGTSICSGLR SAFTVIRKKY KTDGSEIVLL TDGEDNTISS
CFNEVKQSGA IIHTVALGPS AAAELEELSK MTGGLQTYAS DQAQNNGLID AFGALSSGNG
AVSQHSIQLV SRGSTLQNSQ WMNGTVIVDS TVGNDTLFLI TWTSQPPQIL LWDPSGKKQD
GFVVDTNTKM AYLQVPGTAK VGTWTYSLQA SSQTLTLTVT SRASSATLPP VTVTSKVNKD
TGKFPSPVVV YAKIHQGGLP ILRATVTALI ESVDGKTVTL ELLDNGAGAD ATKDDGIYSR
YFTAYNTNGR YSIKVWALGG VNAARQMGIS QQNGAMYRAG RMKNGEIIWN PPRPKINIDD
LLSKQVPFSR TSSGGSFVAS NVPNAPIPDL FPPCQITDLK AKIQGDSLIN LTWTAPGDDY
DHGRADRYII RISTNILDLR DKFNDSLQVN TTDLIPKEAT SEEVFVFKPE NIAFENGTDL
FIAIQAVDEV DLESEISNIA QVSLFLPPQT PPETPSPSLP CPDSNITSAI PGIHILKVMW
KWLGELQLSV ALG
