CLCA1_HUMAN
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 03-AUG-2022, entry version 116.
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; 4.
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 GlyGen; A8K7I4; 8 sites.
DR iPTMnet; A8K7I4; -.
DR PhosphoSitePlus; A8K7I4; -.
DR BioMuta; CLCA1; -.
DR jPOST; A8K7I4; -.
DR MassIVE; A8K7I4; -.
DR PaxDb; A8K7I4; -.
DR PeptideAtlas; A8K7I4; -.
DR PRIDE; A8K7I4; -.
DR ProteomicsDB; 1869; -.
DR Antibodypedia; 33585; 216 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 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; IPQQNGA; -.
DR OrthoDB; 685640at2759; -.
DR PhylomeDB; A8K7I4; -.
DR TreeFam; TF328396; -.
DR PathwayCommons; A8K7I4; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; A8K7I4; -.
DR BioGRID-ORCS; 1179; 5 hits in 1064 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 tissues.
DR Genevisible; A8K7I4; HS.
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:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:ion transmembrane transport; TAS:Reactome.
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 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
