ID   CLCA1_HUMAN             Reviewed;         914 AA.
AC   A8K7I4; B2RAV5; O95151; Q5TDF4; Q9UNF6; Q9UPC6;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 3.
DT   27-MAR-2024, entry version 125.
DE   RecName: Full=Calcium-activated chloride channel regulator 1;
DE            EC=3.4.-.- {ECO:0000269|PubMed:23112050};
DE   AltName: Full=Calcium-activated chloride channel family member 1;
DE            Short=hCLCA1;
DE   AltName: Full=Calcium-activated chloride channel protein 1;
DE            Short=CaCC-1;
DE            Short=hCaCC-1;
DE   Flags: Precursor;
GN   Name=CLCA1; Synonyms=CACC1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE SPECIFICITY,
RP   GLYCOSYLATION, PROTEOLYTIC PROCESSING, AND VARIANTS PHE-65; LYS-152;
RP   SER-357; THR-524 AND ASN-760.
RC   TISSUE=Small intestine;
RX   PubMed=9828122; DOI=10.1006/geno.1998.5562;
RA   Gruber A.D., Elble R.C., Ji H.-L., Schreur K.D., Fuller C.M., Pauli B.U.;
RT   "Genomic cloning, molecular characterization, and functional analysis of
RT   human CLCA1, the first human member of the family of Ca2+-activated
RT   Cl- channel proteins.";
RL   Genomics 54:200-214(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS PHE-65;
RP   SER-357 AND THR-524.
RC   TISSUE=Small intestine;
RX   PubMed=10437792; DOI=10.1016/s0014-5793(99)00891-1;
RA   Agnel M., Vermat T., Culouscou J.-M.;
RT   "Identification of three novel members of the calcium-dependent chloride
RT   channel (CaCC) family predominantly expressed in the digestive tract and
RT   trachea.";
RL   FEBS Lett. 455:295-301(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PHE-65; SER-357 AND
RP   THR-524.
RC   TISSUE=Colon, and Small intestine;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS PHE-65; SER-357
RP   AND THR-524.
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   PROTEIN SEQUENCE OF 695-699, FUNCTION, METALLOPROTEASE DOMAIN, PROTEOLYTIC
RP   PROCESSING, AND MUTAGENESIS OF GLN-150; HIS-156; GLU-157; HIS-160; ASP-167
RP   AND GLU-168.
RX   PubMed=23112050; DOI=10.1074/jbc.m112.410282;
RA   Yurtsever Z., Sala-Rabanal M., Randolph D.T., Scheaffer S.M., Roswit W.T.,
RA   Alevy Y.G., Patel A.C., Heier R.F., Romero A.G., Nichols C.G.,
RA   Holtzman M.J., Brett T.J.;
RT   "Self-cleavage of human CLCA1 protein by a novel internal metalloprotease
RT   domain controls calcium-activated chloride channel activation.";
RL   J. Biol. Chem. 287:42138-42149(2012).
RN   [7]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=11445004; DOI=10.1089/10445490152122442;
RA   Bustin S.A., Li S.-R., Dorudi S.;
RT   "Expression of the Ca2+-activated chloride channel genes CLCA1 and CLCA2 is
RT   downregulated in human colorectal cancer.";
RL   DNA Cell Biol. 20:331-338(2001).
RN   [8]
RP   FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX   PubMed=11956057; DOI=10.1164/ajrccm.165.8.2107068;
RA   Hoshino M., Morita S., Iwashita H., Sagiya Y., Nagi T., Nakanishi A.,
RA   Ashida Y., Nishimura O., Fujisawa Y., Fujino M.;
RT   "Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1)
RT   gene in the asthmatic airway.";
RL   Am. J. Respir. Crit. Care Med. 165:1132-1136(2002).
RN   [9]
RP   FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX   PubMed=11842292; DOI=10.1067/mai.2002.121555;
RA   Toda M., Tulic M.K., Levitt R.C., Hamid Q.;
RT   "A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9
RT   expression and mucus production in bronchial epithelium of patients with
RT   asthma.";
RL   J. Allergy Clin. Immunol. 109:246-250(2002).
RN   [10]
RP   TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=16012037; DOI=10.1080/00016480510028519;
RA   Lee S.H., Park J.H., Jung H.H., Lee S.H., Oh J.W., Lee H.M., Jun H.S.,
RA   Cho W.J., Lee J.Y.;
RT   "Expression and distribution of ion transport mRNAs in human nasal mucosa
RT   and nasal polyps.";
RL   Acta Oto-Laryngol. 125:745-752(2005).
RN   [11]
RP   INDUCTION.
RX   PubMed=15696080; DOI=10.1016/j.jaci.2004.09.039;
RA   Hauber H.-P., Daigneault P., Frenkiel S., Lavigne F., Hung H.-L.,
RA   Levitt R.C., Hamid Q.;
RT   "Niflumic acid and MSI-2216 reduce TNF-alpha-induced mucin expression in
RT   human airway mucosa.";
RL   J. Allergy Clin. Immunol. 115:266-271(2005).
RN   [12]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15919655; DOI=10.1074/jbc.m504654200;
RA   Gibson A., Lewis A.P., Affleck K., Aitken A.J., Meldrum E., Thompson N.;
RT   "hCLCA1 and mCLCA3 are secreted non-integral membrane proteins and
RT   therefore are not ion channels.";
RL   J. Biol. Chem. 280:27205-27212(2005).
RN   [13]
RP   INDUCTION.
RX   PubMed=16151054; DOI=10.1165/rcmb.2004-0220rc;
RA   Thai P., Chen Y., Dolganov G., Wu R.;
RT   "Differential regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 expression in
RT   airway epithelium.";
RL   Am. J. Respir. Cell Mol. Biol. 33:523-530(2005).
RN   [14]
RP   INDUCTION.
RX   PubMed=17622767; DOI=10.1159/000104419;
RA   Kim Y.M., Won T.-B., Kim S.W., Min Y.-G., Lee C.H., Rhee C.-S.;
RT   "Histamine induces MUC5AC expression via a hCLCA1 pathway.";
RL   Pharmacology 80:219-226(2007).
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       {ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:11842292,
CC       ECO:0000269|PubMed:11956057, ECO:0000269|PubMed:23112050,
CC       ECO:0000269|PubMed:9828122}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC       {ECO:0000269|PubMed:15919655}. Cell membrane
CC       {ECO:0000269|PubMed:15919655}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:15919655}; Extracellular side
CC       {ECO:0000269|PubMed:15919655}. Note=Protein that remains attached to
CC       the plasma membrane appeared to be predominantly localized to
CC       microvilli.
CC   -!- TISSUE SPECIFICITY: Highly expressed in small intestine and colon
CC       namely in intestinal basal crypt epithelia and goblet cells, and
CC       appendix. Weakly expressed in uterus, testis and kidney. Expressed in
CC       the airways epithelium of both asthmatic and healthy patients.
CC       Expressed in the bronchial epithelium, especially in mucus-producing
CC       goblet cells. Expressed in normal turbinate mucosa and nasal polyp.
CC       Expressed in. {ECO:0000269|PubMed:10437792,
CC       ECO:0000269|PubMed:11842292, ECO:0000269|PubMed:11956057,
CC       ECO:0000269|PubMed:16012037, ECO:0000269|PubMed:9828122}.
CC   -!- INDUCTION: By IL13/interleukin-13 in tracheobronchial epithelial cells.
CC       Up-regulated by histamine in a dose-dependent manner. Significantly
CC       down-regulated in colorectal cancer. Significantly up-regulated in the
CC       IL9-responsive mucus-producing epithelium of asthmatic patients.
CC       Significantly decreased in nasal polyp. Significantly increased by TNF
CC       in upper airway mucosa. {ECO:0000269|PubMed:11445004,
CC       ECO:0000269|PubMed:11842292, ECO:0000269|PubMed:11956057,
CC       ECO:0000269|PubMed:15696080, ECO:0000269|PubMed:16012037,
CC       ECO:0000269|PubMed:16151054, ECO:0000269|PubMed:17622767}.
CC   -!- DOMAIN: The metalloprotease region is responsible for autoproteolytic
CC       processing. It can also cross-cleave other CLCA substrates.
CC       {ECO:0000269|PubMed:23112050}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:9828122}.
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:0000269|PubMed:23112050,
CC       ECO:0000269|PubMed:9828122}.
CC   -!- SIMILARITY: Belongs to the CLCR family. {ECO:0000305}.
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DR   EMBL; AF039400; AAC95428.1; -; mRNA.
DR   EMBL; AF039401; AAC95429.1; -; Genomic_DNA.
DR   EMBL; AF127036; AAD25487.1; -; mRNA.
DR   EMBL; AK291999; BAF84688.1; -; mRNA.
DR   EMBL; AK314375; BAG37002.1; -; mRNA.
DR   EMBL; AL122002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471097; EAW73186.1; -; Genomic_DNA.
DR   CCDS; CCDS709.1; -.
DR   RefSeq; NP_001276.2; NM_001285.3.
DR   PDB; 6PYO; X-ray; 2.00 A; A/B=302-476.
DR   PDB; 6PYX; X-ray; 2.60 A; A/B=302-476.
DR   PDBsum; 6PYO; -.
DR   PDBsum; 6PYX; -.
DR   AlphaFoldDB; A8K7I4; -.
DR   SASBDB; A8K7I4; -.
DR   SMR; A8K7I4; -.
DR   BioGRID; 107593; 5.
DR   IntAct; A8K7I4; 4.
DR   STRING; 9606.ENSP00000234701; -.
DR   ChEMBL; CHEMBL2364708; -.
DR   MEROPS; M87.001; -.
DR   TCDB; 1.A.13.1.6; the epithelial chloride channel (e-clc) family.
DR   GlyCosmos; A8K7I4; 8 sites, No reported glycans.
DR   GlyGen; A8K7I4; 8 sites.
DR   iPTMnet; A8K7I4; -.
DR   PhosphoSitePlus; A8K7I4; -.
DR   BioMuta; CLCA1; -.
DR   jPOST; A8K7I4; -.
DR   MassIVE; A8K7I4; -.
DR   PaxDb; 9606-ENSP00000234701; -.
DR   PeptideAtlas; A8K7I4; -.
DR   ProteomicsDB; 1869; -.
DR   Antibodypedia; 33585; 239 antibodies from 31 providers.
DR   DNASU; 1179; -.
DR   Ensembl; ENST00000234701.7; ENSP00000234701.3; ENSG00000016490.16.
DR   Ensembl; ENST00000394711.2; ENSP00000378200.1; ENSG00000016490.16.
DR   GeneID; 1179; -.
DR   KEGG; hsa:1179; -.
DR   MANE-Select; ENST00000394711.2; ENSP00000378200.1; NM_001285.4; NP_001276.3.
DR   UCSC; uc001dlt.4; human.
DR   AGR; HGNC:2015; -.
DR   CTD; 1179; -.
DR   DisGeNET; 1179; -.
DR   GeneCards; CLCA1; -.
DR   HGNC; HGNC:2015; CLCA1.
DR   HPA; ENSG00000016490; Tissue enriched (intestine).
DR   MIM; 603906; gene.
DR   neXtProt; NX_A8K7I4; -.
DR   OpenTargets; ENSG00000016490; -.
DR   PharmGKB; PA26542; -.
DR   VEuPathDB; HostDB:ENSG00000016490; -.
DR   eggNOG; ENOG502QRRD; Eukaryota.
DR   GeneTree; ENSGT00940000154682; -.
DR   HOGENOM; CLU_005812_0_1_1; -.
DR   InParanoid; A8K7I4; -.
DR   OMA; QERVFVH; -.
DR   OrthoDB; 5479609at2759; -.
DR   PhylomeDB; A8K7I4; -.
DR   TreeFam; TF328396; -.
DR   PathwayCommons; A8K7I4; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; A8K7I4; -.
DR   BioGRID-ORCS; 1179; 6 hits in 1144 CRISPR screens.
DR   ChiTaRS; CLCA1; human.
DR   GeneWiki; CLCA1; -.
DR   GenomeRNAi; 1179; -.
DR   Pharos; A8K7I4; Tbio.
DR   PRO; PR:A8K7I4; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; A8K7I4; Protein.
DR   Bgee; ENSG00000016490; Expressed in ileal mucosa and 94 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0042589; C:zymogen granule membrane; IEA:Ensembl.
DR   GO; GO:0005254; F:chloride channel activity; TAS:ProtInc.
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:0004222; F:metalloendopeptidase activity; TAS:Reactome.
DR   GO; GO:0006816; P:calcium ion transport; IEA:UniProtKB-KW.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR   GO; GO:0034220; P:monoatomic ion transmembrane transport; TAS:Reactome.
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:SF52; CALCIUM-ACTIVATED CHLORIDE CHANNEL REGULATOR 1; 1.
DR   Pfam; PF08434; CLCA; 1.
DR   Pfam; PF13519; VWA_2; 1.
DR   SMART; SM00327; VWA; 1.
DR   SUPFAM; SSF53300; vWA-like; 1.
DR   PROSITE; PS50234; VWFA; 1.
DR   Genevisible; A8K7I4; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Autocatalytic cleavage; Calcium; Calcium transport;
KW   Cell membrane; Chloride; Direct protein sequencing; Glycoprotein;
KW   Hydrolase; Ion transport; Membrane; Metal-binding; Metalloprotease;
KW   Protease; Reference proteome; Secreted; Signal; Transport; Zinc.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..914
FT                   /note="Calcium-activated chloride channel regulator 1"
FT                   /id="PRO_0000333690"
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:0000269|PubMed:23112050"
FT   ACT_SITE        157
FT                   /evidence="ECO:0000305|PubMed:23112050"
FT   BINDING         156
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000305|PubMed:23112050"
FT   BINDING         160
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000305|PubMed:23112050"
FT   BINDING         167
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000305|PubMed:23112050"
FT   SITE            694..695
FT                   /note="Cleavage; by autolysis"
FT                   /evidence="ECO:0000269|PubMed:23112050"
FT   CARBOHYD        503
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        585
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        831
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        890
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         65
FT                   /note="L -> F (in dbSNP:rs2145412)"
FT                   /evidence="ECO:0000269|PubMed:10437792,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:9828122,
FT                   ECO:0000269|Ref.5"
FT                   /id="VAR_054654"
FT   VARIANT         152
FT                   /note="R -> K (in dbSNP:rs2753386)"
FT                   /evidence="ECO:0000269|PubMed:9828122"
FT                   /id="VAR_054655"
FT   VARIANT         357
FT                   /note="N -> S (in dbSNP:rs2734705)"
FT                   /evidence="ECO:0000269|PubMed:10437792,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:9828122,
FT                   ECO:0000269|Ref.5"
FT                   /id="VAR_043146"
FT   VARIANT         406
FT                   /note="E -> V (in dbSNP:rs1142185)"
FT                   /id="VAR_054656"
FT   VARIANT         426
FT                   /note="K -> R (in dbSNP:rs4647852)"
FT                   /id="VAR_054657"
FT   VARIANT         524
FT                   /note="M -> T (in dbSNP:rs2791494)"
FT                   /evidence="ECO:0000269|PubMed:10437792,
FT                   ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:9828122,
FT                   ECO:0000269|Ref.5"
FT                   /id="VAR_043147"
FT   VARIANT         661
FT                   /note="Y -> H (in dbSNP:rs5744409)"
FT                   /id="VAR_054658"
FT   VARIANT         760
FT                   /note="K -> N (in dbSNP:rs2791483)"
FT                   /evidence="ECO:0000269|PubMed:9828122"
FT                   /id="VAR_054659"
FT   MUTAGEN         150
FT                   /note="Q->A: Reduces proteolytic cleavage."
FT                   /evidence="ECO:0000269|PubMed:23112050"
FT   MUTAGEN         156
FT                   /note="H->A: Abolishes proteolytic cleavage."
FT                   /evidence="ECO:0000269|PubMed:23112050"
FT   MUTAGEN         157
FT                   /note="E->Q: Abolishes proteolytic cleavage."
FT                   /evidence="ECO:0000269|PubMed:23112050"
FT   MUTAGEN         160
FT                   /note="H->A: Abolishes proteolytic cleavage."
FT                   /evidence="ECO:0000269|PubMed:23112050"
FT   MUTAGEN         167
FT                   /note="D->A: Abolishes proteolytic cleavage."
FT                   /evidence="ECO:0000269|PubMed:23112050"
FT   MUTAGEN         168
FT                   /note="E->A: Abolishes proteolytic cleavage."
FT                   /evidence="ECO:0000269|PubMed:23112050"
FT   CONFLICT        393
FT                   /note="F -> S (in Ref. 3; BAF84688)"
FT                   /evidence="ECO:0000305"
FT   STRAND          306..312
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   HELIX           315..318
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   HELIX           322..335
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   STRAND          343..361
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   HELIX           365..372
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   HELIX           385..397
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   STRAND          406..411
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   HELIX           418..421
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   HELIX           422..428
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   STRAND          431..436
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   HELIX           443..450
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   TURN            451..453
FT                   /evidence="ECO:0007829|PDB:6PYO"
FT   STRAND          456..458
FT                   /evidence="ECO:0007829|PDB:6PYX"
SQ   SEQUENCE   914 AA;  100226 MW;  8D8999E855822711 CRC64;
     MGPFKSSVFI LILHLLEGAL SNSLIQLNNN GYEGIVVAID PNVPEDETLI QQIKDMVTQA
     SLYLLEATGK RFYFKNVAIL IPETWKTKAD YVRPKLETYK NADVLVAEST PPGNDEPYTE
     QMGNCGEKGE RIHLTPDFIA GKKLAEYGPQ GRAFVHEWAH LRWGVFDEYN NDEKFYLSNG
     RIQAVRCSAG ITGTNVVKKC QGGSCYTKRC TFNKVTGLYE KGCEFVLQSR QTEKASIMFA
     QHVDSIVEFC TEQNHNKEAP NKQNQKCNLR STWEVIRDSE DFKKTTPMTT QPPNPTFSLL
     QIGQRIVCLV LDKSGSMATG NRLNRLNQAG QLFLLQTVEL GSWVGMVTFD SAAHVQNELI
     QINSGSDRDT LAKRLPAAAS GGTSICSGLR SAFTVIRKKY PTDGSEIVLL TDGEDNTISG
     CFNEVKQSGA IIHTVALGPS AAQELEELSK MTGGLQTYAS DQVQNNGLID AFGALSSGNG
     AVSQRSIQLE SKGLTLQNSQ WMNGTVIVDS TVGKDTLFLI TWTMQPPQIL LWDPSGQKQG
     GFVVDKNTKM AYLQIPGIAK VGTWKYSLQA SSQTLTLTVT SRASNATLPP ITVTSKTNKD
     TSKFPSPLVV YANIRQGASP ILRASVTALI ESVNGKTVTL ELLDNGAGAD ATKDDGVYSR
     YFTTYDTNGR YSVKVRALGG VNAARRRVIP QQSGALYIPG WIENDEIQWN PPRPEINKDD
     VQHKQVCFSR TSSGGSFVAS DVPNAPIPDL FPPGQITDLK AEIHGGSLIN LTWTAPGDDY
     DHGTAHKYII RISTSILDLR DKFNESLQVN TTALIPKEAN SEEVFLFKPE NITFENGTDL
     FIAIQAVDKV DLKSEISNIA RVSLFIPPQT PPETPSPDET SAPCPNIHIN STIPGIHILK
     IMWKWIGELQ LSIA
//