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 13-FEB-2019, entry version 99. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE RP SPECIFICITY, GLYCOSYLATION, PROTEOLYTIC PROCESSING, AND VARIANTS RP PHE-65; LYS-152; 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., RA Pauli B.U.; RT "Genomic cloning, molecular characterization, and functional analysis RT of 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 RT chloride channel (CaCC) family predominantly expressed in the RT digestive tract and trachea."; RL FEBS Lett. 455:295-301(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PHE-65; SER-357 RP AND 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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; RP SER-357 AND THR-524. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP PROTEIN SEQUENCE OF 695-699, FUNCTION, METALLOPROTEASE DOMAIN, RP PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF GLN-150; HIS-156; GLU-157; RP HIS-160; ASP-167 AND GLU-168. RX PubMed=23112050; DOI=10.1074/jbc.M112.410282; RA Yurtsever Z., Sala-Rabanal M., Randolph D.T., Scheaffer S.M., RA Roswit W.T., Alevy Y.G., Patel A.C., Heier R.F., Romero A.G., RA Nichols C.G., Holtzman M.J., Brett T.J.; RT "Self-cleavage of human CLCA1 protein by a novel internal RT metalloprotease domain controls calcium-activated chloride channel RT 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 RT CLCA2 is 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 RT (CaCC1) 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 RT IL-9 expression and mucus production in bronchial epithelium of RT patients with 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 RT mucosa 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 RT in 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., RA 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 RT expression in 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, CC mucus hypersecretion, cystic fibrosis and AHR. May be involved in CC the regulation of mucus production and/or secretion by goblet CC cells. Involved in the regulation of tissue inflammation in the CC innate immune response. May play a role as a tumor suppressor. CC Induces MUC5AC. {ECO:0000269|PubMed:11445004, CC ECO:0000269|PubMed:11842292, ECO:0000269|PubMed:11956057, CC ECO:0000269|PubMed:23112050, 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 CC to 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 CC in the airways epithelium of both asthmatic and healthy patients. CC Expressed in the bronchial epithelium, especially in mucus- CC producing goblet cells. Expressed in normal turbinate mucosa and CC nasal polyp. 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 CC cells. Up-regulated by histamine in a dose-dependent manner. CC Significantly down-regulated in colorectal cancer. Significantly CC up-regulated in the IL9-responsive mucus-producing epithelium of CC asthmatic patients. Significantly decreased in nasal polyp. CC Significantly increased by TNF in upper airway mucosa. CC {ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:11842292, CC ECO:0000269|PubMed:11956057, ECO:0000269|PubMed:15696080, CC ECO:0000269|PubMed:16012037, ECO:0000269|PubMed:16151054, CC ECO:0000269|PubMed:17622767}. CC -!- DOMAIN: The metalloprotease region is responsible for CC autoproteolytic processing. It can also cross-cleave other CLCA CC substrates. {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. CC The cleavage is necessary for calcium-activated chloride channel CC (CaCC) activation activity. {ECO:0000269|PubMed:23112050, CC ECO:0000269|PubMed:9828122}. CC -!- SIMILARITY: Belongs to the CLCR family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 UniGene; Hs.194659; -. DR ProteinModelPortal; A8K7I4; -. DR SMR; A8K7I4; -. DR BioGrid; 107593; 2. DR IntAct; A8K7I4; 1. 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 iPTMnet; A8K7I4; -. DR PhosphoSitePlus; A8K7I4; -. DR BioMuta; CLCA1; -. DR jPOST; A8K7I4; -. DR PaxDb; A8K7I4; -. DR PRIDE; A8K7I4; -. DR ProteomicsDB; 1869; -. DR DNASU; 1179; -. DR Ensembl; ENST00000234701; ENSP00000234701; ENSG00000016490. DR Ensembl; ENST00000394711; ENSP00000378200; ENSG00000016490. DR GeneID; 1179; -. DR KEGG; hsa:1179; -. DR UCSC; uc001dlt.4; human. DR CTD; 1179; -. DR DisGeNET; 1179; -. DR EuPathDB; HostDB:ENSG00000016490.15; -. DR GeneCards; CLCA1; -. DR HGNC; HGNC:2015; CLCA1. DR HPA; HPA052787; -. DR HPA; HPA059301; -. DR MIM; 603906; gene. DR neXtProt; NX_A8K7I4; -. DR OpenTargets; ENSG00000016490; -. DR PharmGKB; PA26542; -. DR eggNOG; ENOG410IEPS; Eukaryota. DR eggNOG; ENOG410XPSZ; LUCA. DR GeneTree; ENSGT00940000154682; -. DR HOGENOM; HOG000015107; -. DR HOVERGEN; HBG005560; -. DR InParanoid; A8K7I4; -. DR KO; K05027; -. DR OMA; LFPPCQI; -. DR OrthoDB; 685640at2759; -. DR PhylomeDB; A8K7I4; -. DR TreeFam; TF328396; -. DR Reactome; R-HSA-2672351; Stimuli-sensing channels. DR ChiTaRS; CLCA1; human. DR GeneWiki; CLCA1; -. DR GenomeRNAi; 1179; -. DR PRO; PR:A8K7I4; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000016490; Expressed in 65 organ(s), highest expression level in sigmoid colon. 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 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; Cell membrane; KW Chloride; Complete proteome; Direct protein sequencing; Glycoprotein; KW Hydrolase; Ion transport; Membrane; Metal-binding; Metalloprotease; KW Polymorphism; Protease; Reference proteome; Secreted; Signal; KW Transport; Zinc. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 914 Calcium-activated chloride channel FT regulator 1. FT /FTId=PRO_0000333690. FT DOMAIN 306 475 VWFA. {ECO:0000255|PROSITE- FT ProRule:PRU00219}. FT REGION 46 199 Metalloprotease domain. FT {ECO:0000269|PubMed:23112050}. FT ACT_SITE 157 157 {ECO:0000305|PubMed:23112050}. FT METAL 156 156 Zinc; catalytic. FT {ECO:0000305|PubMed:23112050}. FT METAL 160 160 Zinc; catalytic. FT {ECO:0000305|PubMed:23112050}. FT METAL 167 167 Zinc; catalytic. FT {ECO:0000305|PubMed:23112050}. FT SITE 694 695 Cleavage; by autolysis. FT {ECO:0000269|PubMed:23112050}. FT CARBOHYD 503 503 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 585 585 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 770 770 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 804 804 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 810 810 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 831 831 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 836 836 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 890 890 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VARIANT 65 65 L -> F (in dbSNP:rs2145412). FT {ECO:0000269|PubMed:10437792, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:9828122, FT ECO:0000269|Ref.5}. FT /FTId=VAR_054654. FT VARIANT 152 152 R -> K (in dbSNP:rs2753386). FT {ECO:0000269|PubMed:9828122}. FT /FTId=VAR_054655. FT VARIANT 357 357 N -> S (in dbSNP:rs2734705). FT {ECO:0000269|PubMed:10437792, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:9828122, FT ECO:0000269|Ref.5}. FT /FTId=VAR_043146. FT VARIANT 406 406 E -> V (in dbSNP:rs1142185). FT /FTId=VAR_054656. FT VARIANT 426 426 K -> R (in dbSNP:rs4647852). FT /FTId=VAR_054657. FT VARIANT 524 524 M -> T (in dbSNP:rs2791494). FT {ECO:0000269|PubMed:10437792, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:9828122, FT ECO:0000269|Ref.5}. FT /FTId=VAR_043147. FT VARIANT 661 661 Y -> H (in dbSNP:rs5744409). FT /FTId=VAR_054658. FT VARIANT 760 760 K -> N (in dbSNP:rs2791483). FT {ECO:0000269|PubMed:9828122}. FT /FTId=VAR_054659. FT MUTAGEN 150 150 Q->A: Reduces proteolytic cleavage. FT {ECO:0000269|PubMed:23112050}. FT MUTAGEN 156 156 H->A: Abolishes proteolytic cleavage. FT {ECO:0000269|PubMed:23112050}. FT MUTAGEN 157 157 E->Q: Abolishes proteolytic cleavage. FT {ECO:0000269|PubMed:23112050}. FT MUTAGEN 160 160 H->A: Abolishes proteolytic cleavage. FT {ECO:0000269|PubMed:23112050}. FT MUTAGEN 167 167 D->A: Abolishes proteolytic cleavage. FT {ECO:0000269|PubMed:23112050}. FT MUTAGEN 168 168 E->A: Abolishes proteolytic cleavage. FT {ECO:0000269|PubMed:23112050}. FT CONFLICT 393 393 F -> S (in Ref. 3; BAF84688). FT {ECO:0000305}. 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 //