ID MUC5A_HUMAN Reviewed; 5654 AA. AC P98088; A0A096LPK4; O60460; O76065; Q13792; Q14425; Q658Q1; Q7M4S5; Q8N4M9; AC Q8WWQ3; Q8WWQ4; Q8WWQ5; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-APR-2015, sequence version 4. DT 27-MAR-2024, entry version 199. DE RecName: Full=Mucin-5AC {ECO:0000305}; DE Short=MUC-5AC {ECO:0000305}; DE AltName: Full=Gastric mucin {ECO:0000303|PubMed:8948439}; DE AltName: Full=Major airway glycoprotein {ECO:0000303|PubMed:7513696}; DE AltName: Full=Mucin-5 subtype AC, tracheobronchial; DE AltName: Full=Tracheobronchial mucin {ECO:0000303|PubMed:2656675}; DE Short=TBM {ECO:0000303|PubMed:7513696}; DE Flags: Precursor; GN Name=MUC5AC {ECO:0000303|PubMed:11535137, ECO:0000312|HGNC:HGNC:7515}; GN Synonyms=MUC5 {ECO:0000303|PubMed:7513696}; 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-4589, NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF RP 3025-4373, AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 3081-4793. RX PubMed=11535137; DOI=10.1042/0264-6021:3580763; RA Escande F., Aubert J.-P., Porchet N., Buisine M.P.; RT "Human mucin gene MUC5AC: organization of its 5'-region and central RT repetitive region."; RL Biochem. J. 358:763-772(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1104. RC TISSUE=Trachea; RX PubMed=9506983; DOI=10.1074/jbc.273.12.6812; RA Li D., Gallup M., Fan N., Szymkowski D.E., Basbaum C.B.; RT "Cloning of the amino-terminal and 5'-flanking region of the human MUC5AC RT mucin gene and transcriptional up-regulation by bacterial exoproducts."; RL J. Biol. Chem. 273:6812-6820(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1005-1854. RX PubMed=8948439; DOI=10.1042/bj3080831; RA Klomp L.W., Van Rens L., Strous G.J.; RT "Cloning and analysis of human gastric mucin cDNA reveals two types of RT conserved cysteine-rich domains."; RL Biochem. J. 308:831-838(1995). RN [5] RP PROTEIN SEQUENCE OF 1752-1773; 1796-1805; 2125-2146; 2169-2178; 3231-3252; RP 3273-3284; 3529-3550; 3573-3582; 3962-3983; 4004-4015 AND 4636-4657. RC TISSUE=Tracheobronchial mucosa; RX PubMed=2656675; DOI=10.1016/s0021-9258(18)83168-4; RA Rose M.C., Kaufman B., Martin B.M.; RT "Proteolytic fragmentation and peptide mapping of human RT carboxyamidomethylated tracheobronchial mucin."; RL J. Biol. Chem. 264:8193-8199(1989). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 4574-5654. RC TISSUE=Placenta, and Trachea; RX PubMed=9620876; DOI=10.1042/bj3320729; RA Buisine M.P., Desseyn J.-L., Porchet N., Degand P., Laine A., Aubert J.-P.; RT "Genomic organization of the 3'-region of the human MUC5AC mucin gene: RT additional evidence for a common ancestral gene for the 11p15.5 mucin gene RT family."; RL Biochem. J. 332:729-738(1998). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4614-5654, PARTIAL PROTEIN SEQUENCE, TISSUE RP SPECIFICITY, AND VARIANT LEU-5521. RC TISSUE=Nasal polyp; RX PubMed=7513696; DOI=10.1016/s0021-9258(18)99965-5; RA Meerzaman D., Charles P., Daskal E., Polymeropoulos M.H., Martin B.M., RA Rose M.C.; RT "Cloning and analysis of cDNA encoding a major airway glycoprotein, human RT tracheobronchial mucin (MUC5)."; RL J. Biol. Chem. 269:12932-12939(1994). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 4705-5654, AND VARIANT LEU-5521. RX PubMed=7775418; DOI=10.1074/jbc.270.23.13665; RA Lesuffleur T., Roche F., Hill A.S., Lacasa M., Fox M., Swallow D.M., RA Zweibaum A., Real F.X.; RT "Characterization of a mucin cDNA clone isolated from HT-29 mucus secreting RT cells: the 3' end of MUC5AC?"; RL J. Biol. Chem. 270:13665-13673(1995). RN [9] RP PROTEIN SEQUENCE OF 4927-4936, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF RP ASP-4926. RX PubMed=16787389; DOI=10.1042/bj20060443; RA Lidell M.E., Hansson G.C.; RT "Cleavage in the GDPH sequence of the C-terminal cysteine-rich part of the RT human MUC5AC mucin."; RL Biochem. J. 399:121-129(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5081-5654. RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5193-5654, AND VARIANT LEU-5521. RC TISSUE=Stomach; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [12] RP STRUCTURE OF O-LINKED CARBOHYDRATES. RX PubMed=11445551; DOI=10.1093/glycob/11.6.459; RA Silverman H.S., Parry S., Sutton-Smith M., Burdick M.D., McDermott K., RA Reid C.J., Batra S.K., Morris H.R., Hollingsworth M.A., Dell A., Harris A.; RT "In vivo glycosylation of mucin tandem repeats."; RL Glycobiology 11:459-471(2001). RN [13] RP FUNCTION, TISSUE SPECIFICITY, AND GLYCOSYLATION. RX PubMed=14535999; DOI=10.1046/j.1523-5378.2003.00173.x; RA Van de Bovenkamp J.H., Mahdavi J., Korteland-Van Male A.M., Bueller H.A., RA Einerhand A.W., Boren T., Dekker J.; RT "The MUC5AC glycoprotein is the primary receptor for Helicobacter pylori in RT the human stomach."; RL Helicobacter 8:521-532(2003). RN [14] RP GLYCOSYLATION AT TRP-2122, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP TRP-2122. RX PubMed=14718370; DOI=10.1093/glycob/cwh041; RA Perez-Vilar J., Randell S.H., Boucher R.C.; RT "C-Mannosylation of MUC5AC and MUC5B Cys subdomains."; RL Glycobiology 14:325-337(2004). RN [15] RP GLYCOSYLATION. RX PubMed=22186971; DOI=10.1093/glycob/cwr183; RA Raman J., Guan Y., Perrine C.L., Gerken T.A., Tabak L.A.; RT "UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- RT acetylgalactosaminyltransferases: completion of the family tree."; RL Glycobiology 22:768-777(2012). RN [16] RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INDUCTION. RX PubMed=31732694; DOI=10.26508/lsa.201900462; RA Simoes F.B., Quaresma M.C., Clarke L.A., Silva I.A., Pankonien I., RA Railean V., Kmit A., Amaral M.D.; RT "TMEM16A chloride channel does not drive mucus production."; RL Life. Sci Alliance 2:0-0(2019). RN [17] {ECO:0007744|PDB:5AJN, ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP} RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF GLYCOPEPTIDE REPEAT IN COMPLEX RP WITH GALNT2, AND GLYCOSYLATION AT THR-2395; THR-2405; THR-2451; THR-2461; RP THR-2531; THR-2541; THR-2571; THR-2581; THR-2699; THR-2709; THR-2883; RP THR-2893; THR-2979; THR-2989; THR-3067; THR-3077; THR-4224; THR-4234; RP THR-4296; THR-4306; THR-4320; THR-4330; THR-4376; THR-4386; THR-4440; RP THR-4450; THR-4480; THR-4490; THR-4512; THR-4522; THR-4568 AND THR-4578. RX PubMed=25939779; DOI=10.1038/ncomms7937; RA Lira-Navarrete E., de Las Rivas M., Companon I., Pallares M.C., Kong Y., RA Iglesias-Fernandez J., Bernardes G.J., Peregrina J.M., Rovira C., RA Bernado P., Bruscolini P., Clausen H., Lostao A., Corzana F., RA Hurtado-Guerrero R.; RT "Dynamic interplay between catalytic and lectin domains of GalNAc- RT transferases modulates protein O-glycosylation."; RL Nat. Commun. 6:6937-6937(2015). CC -!- FUNCTION: Gel-forming glycoprotein of gastric and respiratory tract CC epithelia that protects the mucosa from infection and chemical damage CC by binding to inhaled microorganisms and particles that are CC subsequently removed by the mucociliary system (PubMed:14535999, CC PubMed:14718370). Interacts with H.pylori in the gastric epithelium, CC Barrett's esophagus as well as in gastric metaplasia of the duodenum CC (GMD) (PubMed:14535999). {ECO:0000269|PubMed:14535999, CC ECO:0000303|PubMed:14535999, ECO:0000303|PubMed:14718370}. CC -!- SUBUNIT: Homomultimer; disulfide-linked (PubMed:14718370). The N- and CC C-terminus mediate their assembly into higher order structures to form CC filaments (By similarity). The CTCK domains of two polypeptides CC associate in the endoplasmic reticulum to generate intermolecularly CC disulfide-bonded dimers (By similarity). These dimers progress to the CC Golgi apparatus, which is a more acidic environment than the CC endoplasmic reticulum. Under acidic conditions, the N-termini form non- CC covalent intermolecular interactions that juxtapose assemblies from CC different CTCK-linked dimers to produce long, disulfide-linked polymers CC that remain highly compact until secretion (By similarity). CC {ECO:0000250|UniProtKB:Q02817, ECO:0000250|UniProtKB:Q9HC84, CC ECO:0000269|PubMed:14718370}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14718370, CC ECO:0000269|PubMed:31732694}. CC -!- TISSUE SPECIFICITY: Highly expressed in surface mucosal cells of CC respiratory tract and stomach epithelia. Overexpressed in a number of CC carcinomas. Also expressed in Barrett's esophagus epithelium and in the CC proximal duodenum. {ECO:0000269|PubMed:14535999, CC ECO:0000269|PubMed:7513696}. CC -!- DEVELOPMENTAL STAGE: In airway epithelial cells, expression increases CC significantly during cell differentiation (at protein level). CC {ECO:0000269|PubMed:31732694}. CC -!- INDUCTION: By IL4. {ECO:0000269|PubMed:31732694}. CC -!- DOMAIN: The cysteine residues in the Cys-rich subdomain repeats are not CC involved in disulfide bonding. CC -!- DOMAIN: The CTCK domain mediates interchain disulfide bonds with CC another molecule of MUC5AC. {ECO:0000250|UniProtKB:Q9HC84}. CC -!- PTM: C-, O- and N-glycosylated (PubMed:14718370). O-glycosylated on the CC second and last Thr of the Thr-/Ser-rich tandem repeats TTPSPVPTTSTTSA CC (PubMed:25939779, PubMed:14718370, PubMed:22186971). One form of CC glycosylation is also known as Lewis B (LeB) blood group antigen, a CC tetrasaccharide consisting of N-acetylglucosamine having a fucosyl CC residue attached (PubMed:14535999). It has a role as an epitope and CC antigen and functions as a receptor for H.pylori binding and CC facilitates infection (PubMed:14535999). C-mannosylation in the Cys- CC rich subdomains may be required for proper folding of these regions and CC for export from the endoplasmic reticulum during biosynthesis CC (PubMed:14718370). {ECO:0000269|PubMed:14535999, CC ECO:0000269|PubMed:14718370, ECO:0000269|PubMed:25939779}. CC -!- PTM: Proteolytic cleavage in the C-terminal is initiated early in the CC secretory pathway and does not involve a serine protease. The extent of CC cleavage is increased in the acidic parts of the secretory pathway. CC Cleavage generates a reactive group which could link the protein to a CC primary amide. {ECO:0000269|PubMed:16787389}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA18431.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA18431.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAC15950.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAA88307.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAH56330.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Mucin database; CC URL="http://www.medkem.gu.se/mucinbiology/databases/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41460/MUC5AC"; 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; FO680660; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; FP326773; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KC800812; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJ298317; CAC83674.1; -; mRNA. DR EMBL; AJ298318; CAC83675.1; -; Genomic_DNA. DR EMBL; AJ298319; CAC83676.1; -; Genomic_DNA. DR EMBL; AF015521; AAC15950.1; ALT_FRAME; mRNA. DR EMBL; X81649; CAA57309.1; -; mRNA. DR EMBL; AJ001402; CAA04737.1; -; mRNA. DR EMBL; AJ001403; CAA04738.1; -; Genomic_DNA. DR EMBL; U06711; AAA18431.1; ALT_SEQ; mRNA. DR EMBL; Z48314; CAA88307.1; ALT_FRAME; mRNA. DR EMBL; BC033831; AAH33831.1; -; mRNA. DR EMBL; AL833060; CAH56330.1; ALT_FRAME; mRNA. DR CCDS; CCDS76369.1; -. DR PIR; A33811; A33811. DR PIR; JE0095; JE0095. DR RefSeq; NP_001291288.1; NM_001304359.1. DR PDB; 5AJN; X-ray; 1.67 A; P=4254-4268. DR PDB; 5AJO; X-ray; 1.48 A; B=2528-2543. DR PDB; 5AJP; X-ray; 1.65 A; B=2528-2543. DR PDB; 8OV0; X-ray; 1.70 A; A=3518-3626. DR PDBsum; 5AJN; -. DR PDBsum; 5AJO; -. DR PDBsum; 5AJP; -. DR PDBsum; 8OV0; -. DR SMR; P98088; -. DR IntAct; P98088; 3. DR STRING; 9606.ENSP00000485659; -. DR ChEMBL; CHEMBL3713020; -. DR MEROPS; I08.951; -. DR GlyConnect; 375; 10 O-Linked glycans. DR GlyCosmos; P98088; 58 sites, 17 glycans. DR GlyGen; P98088; 63 sites, 17 O-linked glycans (1 site). DR iPTMnet; P98088; -. DR PhosphoSitePlus; P98088; -. DR SwissPalm; P98088; -. DR BioMuta; MUC5AC; -. DR DMDM; 160370004; -. DR jPOST; P98088; -. DR MassIVE; P98088; -. DR PaxDb; 9606-ENSP00000485659; -. DR PeptideAtlas; P98088; -. DR ProteomicsDB; 57789; -. DR Pumba; P98088; -. DR ABCD; P98088; 1 sequenced antibody. DR Antibodypedia; 3457; 1150 antibodies from 35 providers. DR DNASU; 4586; -. DR Ensembl; ENST00000621226.2; ENSP00000485659.1; ENSG00000215182.8. DR Ensembl; ENST00000707307.1; ENSP00000516835.1; ENSG00000291363.1. DR GeneID; 4586; -. DR KEGG; hsa:4586; -. DR MANE-Select; ENST00000621226.2; ENSP00000485659.1; NM_001304359.2; NP_001291288.1. DR UCSC; uc031xcx.2; human. DR AGR; HGNC:7515; -. DR CTD; 4586; -. DR DisGeNET; 4586; -. DR GeneCards; MUC5AC; -. DR HGNC; HGNC:7515; MUC5AC. DR HPA; ENSG00000215182; Tissue enriched (stomach). DR MIM; 158373; gene. DR neXtProt; NX_P98088; -. DR OpenTargets; ENSG00000215182; -. DR VEuPathDB; HostDB:ENSG00000215182; -. DR eggNOG; KOG1216; Eukaryota. DR GeneTree; ENSGT00940000156076; -. DR HOGENOM; CLU_000076_3_1_1; -. DR InParanoid; P98088; -. DR OMA; CRAKSHP; -. DR OrthoDB; 4662957at2759; -. DR PathwayCommons; P98088; -. DR Reactome; R-HSA-5083625; Defective GALNT3 causes HFTC. DR Reactome; R-HSA-5083632; Defective C1GALT1C1 causes TNPS. DR Reactome; R-HSA-5083636; Defective GALNT12 causes CRCS1. DR Reactome; R-HSA-5621480; Dectin-2 family. DR Reactome; R-HSA-913709; O-linked glycosylation of mucins. DR Reactome; R-HSA-977068; Termination of O-glycan biosynthesis. DR SignaLink; P98088; -. DR BioGRID-ORCS; 4586; 5 hits in 198 CRISPR screens. DR GenomeRNAi; 4586; -. DR Pharos; P98088; Tbio. DR PRO; PR:P98088; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P98088; Protein. DR Bgee; ENSG00000215182; Expressed in olfactory segment of nasal mucosa and 41 other cell types or tissues. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0070701; C:mucus layer; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005201; F:extracellular matrix structural constituent; TAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR CDD; cd19941; TIL; 3. DR Gene3D; 2.10.25.10; Laminin; 4. DR InterPro; IPR006207; Cys_knot_C. DR InterPro; IPR036084; Ser_inhib-like_sf. DR InterPro; IPR002919; TIL_dom. DR InterPro; IPR014853; VWF/SSPO/ZAN-like_Cys-rich_dom. DR InterPro; IPR001007; VWF_dom. DR InterPro; IPR001846; VWF_type-D. DR InterPro; IPR025155; WxxW_domain. DR PANTHER; PTHR11339; EXTRACELLULAR MATRIX GLYCOPROTEIN RELATED; 1. DR PANTHER; PTHR11339:SF404; MUCIN-5AC; 1. DR Pfam; PF08742; C8; 4. DR Pfam; PF13330; Mucin2_WxxW; 9. DR Pfam; PF01826; TIL; 2. DR Pfam; PF00094; VWD; 4. DR SMART; SM00832; C8; 4. DR SMART; SM00041; CT; 1. DR SMART; SM00214; VWC; 6. DR SMART; SM00215; VWC_out; 2. DR SMART; SM00216; VWD; 4. DR SUPFAM; SSF57603; FnI-like domain; 1. DR SUPFAM; SSF57567; Serine protease inhibitors; 4. DR PROSITE; PS01185; CTCK_1; 1. DR PROSITE; PS01225; CTCK_2; 1. DR PROSITE; PS01208; VWFC_1; 2. DR PROSITE; PS50184; VWFC_2; 2. DR PROSITE; PS51233; VWFD; 4. DR Genevisible; P98088; HS. PE 1: Evidence at protein level; KW 3D-structure; Copper; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Metal-binding; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT CHAIN 28..5654 FT /note="Mucin-5AC" FT /evidence="ECO:0000255" FT /id="PRO_0000158957" FT DOMAIN 79..249 FT /note="VWFD 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DOMAIN 338..394 FT /note="TIL 1" FT /evidence="ECO:0000255" FT DOMAIN 394..465 FT /note="VWFC 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 432..607 FT /note="VWFD 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DOMAIN 704..761 FT /note="TIL 2" FT /evidence="ECO:0000255" FT DOMAIN 818..863 FT /note="TIL 3" FT /evidence="ECO:0000255" FT DOMAIN 901..1072 FT /note="VWFD 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT REPEAT 1383..1481 FT /note="Cys-rich subdomain 1" FT REPEAT 1577..1677 FT /note="Cys-rich subdomain 2" FT REPEAT 1743..1847 FT /note="Cys-rich subdomain 3" FT REPEAT 1950..2050 FT /note="Cys-rich subdomain 4" FT REPEAT 2116..2220 FT /note="Cys-rich subdomain 5" FT REPEAT 3222..3326 FT /note="Cys-rich subdomain 6" FT REPEAT 3520..3660 FT /note="Cys-rich subdomain 7" FT REPEAT 3953..4057 FT /note="Cys-rich subdomain 8" FT REPEAT 4627..4731 FT /note="Cys-rich subdomain 9" FT DOMAIN 4852..4918 FT /note="VWFC 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 4919..5103 FT /note="VWFD 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DOMAIN 5276..5345 FT /note="VWFC 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 5381..5448 FT /note="VWFC 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 5532..5620 FT /note="CTCK" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT REGION 27..49 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1336..1377 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1383..4731 FT /note="9 X Cys-rich subdomain repeats" FT REGION 1483..1575 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1688..1733 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1849..1948 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2059..2110 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2224..3214 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2257..3200 FT /note="107 X 8 AA approximate tandem repeats of T-T-S-T-T- FT S-A-P" FT REGION 3329..3515 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3363..3498 FT /note="17 X 8 AA approximate tandem repeats of T-T-S-T-T-S- FT A-P" FT REGION 3628..3951 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3661..3931 FT /note="34 X 8 AA approximate tandem repeats of T-T-S-T-T-S- FT A-P" FT REGION 4060..4625 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 4093..4595 FT /note="58 X 8 AA approximate tandem repeats of T-T-S-T-T-S- FT A-P" FT REGION 4830..4849 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 5622..5654 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1336..1374 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1483..1538 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1548..1575 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1849..1911 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1921..1948 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 4835..4849 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 198 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 320 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 367 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT SITE 4926..4927 FT /note="Cleavage" FT CARBOHYD 205 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 258 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 415 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 524 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1308 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1389 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 1584 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 1749 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 1957 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 2122 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000269|PubMed:14718370" FT CARBOHYD 2395 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 2405 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 2451 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 2461 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 2531 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 2541 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 2571 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 2581 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 2699 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 2709 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 2883 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 2893 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 2979 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 2989 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 3067 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 3077 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 3228 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 3526 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 3774 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 3959 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 4224 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4234 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4296 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4306 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4320 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4330 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4376 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4386 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4440 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4450 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4480 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4490 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4512 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4522 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4568 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO" FT CARBOHYD 4578 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:25939779, FT ECO:0007744|PDB:5AJO, ECO:0007744|PDB:5AJP" FT CARBOHYD 4633 FT /note="C-linked (Man) tryptophan" FT /evidence="ECO:0000305" FT CARBOHYD 4869 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 4942 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5057 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5093 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5236 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5347 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5377 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5386 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5455 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5528 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 5591 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 81..211 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 103..248 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 434..571 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 456..606 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 478..486 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 903..1036 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 925..1071 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 934..1033 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 953..960 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 4921..5063 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 4943..5102 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 4967..4975 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 5532..5582 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT DISULFID 5546..5596 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT DISULFID 5557..5612 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT DISULFID 5561..5614 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT VARIANT 5521 FT /note="P -> L (in dbSNP:rs1132436)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9620876" FT /id="VAR_036832" FT MUTAGEN 2122 FT /note="W->A: No binding to mannose-specific lectin. Loss of FT secretion from the endoplasmic reticulum." FT /evidence="ECO:0000269|PubMed:14718370" FT MUTAGEN 4926 FT /note="D->A,E: Abolishes cleavage." FT /evidence="ECO:0000269|PubMed:16787389" FT CONFLICT 25 FT /note="G -> S (in Ref. 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 221 FT /note="S -> R (in Ref. 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 246 FT /note="D -> E (in Ref. 2; CAC83674 and 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 432 FT /note="G -> D (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 549 FT /note="L -> P (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 658 FT /note="M -> V (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 702 FT /note="T -> I (in Ref. 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 716 FT /note="T -> A (in Ref. 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 817..818 FT /note="GD -> RG (in Ref. 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 869 FT /note="E -> K (in Ref. 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 978 FT /note="G -> R (in Ref. 3; AAC15950)" FT /evidence="ECO:0000305" FT CONFLICT 996 FT /note="R -> Q (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 1141 FT /note="A -> R (in Ref. 4; CAA57309)" FT /evidence="ECO:0000305" FT CONFLICT 1151..1155 FT /note="LCVSW -> TCVCL (in Ref. 4; CAA57309)" FT /evidence="ECO:0000305" FT CONFLICT 1154..1155 FT /note="SW -> CL (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 1480 FT /note="P -> A (in Ref. 4; CAA57309)" FT /evidence="ECO:0000305" FT CONFLICT 1683 FT /note="L -> P (in Ref. 4; CAA57309)" FT /evidence="ECO:0000305" FT CONFLICT 1738 FT /note="L -> P (in Ref. 4; CAA57309)" FT /evidence="ECO:0000305" FT CONFLICT 1790 FT /note="L -> V (in Ref. 2; CAC83674 and 4; CAA57309)" FT /evidence="ECO:0000305" FT CONFLICT 1803 FT /note="E -> N (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 1874 FT /note="T -> I (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 2008..2009 FT /note="AD -> GR (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 2176 FT /note="E -> N (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 2207 FT /note="Y -> I (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 2238 FT /note="T -> I (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 2289..4237 FT /note="Missing (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 3047 FT /note="S -> T (in Ref. 2; CAC83675)" FT /evidence="ECO:0000305" FT CONFLICT 3088 FT /note="A -> S (in Ref. 2; CAC83676)" FT /evidence="ECO:0000305" FT CONFLICT 3095..3096 FT /note="AP -> PL (in Ref. 2; CAC83676)" FT /evidence="ECO:0000305" FT CONFLICT 3105 FT /note="T -> I (in Ref. 2; CAC83676)" FT /evidence="ECO:0000305" FT CONFLICT 3107..4287 FT /note="Missing (in Ref. 2; CAC83676)" FT /evidence="ECO:0000305" FT CONFLICT 3234 FT /note="I -> V (in Ref. 2; CAC83675)" FT /evidence="ECO:0000305" FT CONFLICT 3481 FT /note="G -> S (in Ref. 2; CAC83675)" FT /evidence="ECO:0000305" FT CONFLICT 3562 FT /note="E -> Q (in Ref. 2; CAC83675)" FT /evidence="ECO:0000305" FT CONFLICT 3580 FT /note="E -> N (in Ref. 5; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 3636..3644 FT /note="TPSGRATSP -> PLVGEPPAQ (in Ref. 2; CAC83675)" FT /evidence="ECO:0000305" FT CONFLICT 3817 FT /note="S -> P (in Ref. 2; CAC83675)" FT /evidence="ECO:0000305" FT CONFLICT 4244 FT /note="A -> V (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4250..4254 FT /note="TSGPG -> ISGPK (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4262 FT /note="S -> T (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4265 FT /note="T -> I (in Ref. 2; CAC83675)" FT /evidence="ECO:0000305" FT CONFLICT 4274 FT /note="T -> I (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4280..4284 FT /note="RTTSA -> STTSV (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4286..4373 FT /note="Missing (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4290 FT /note="T -> P (in Ref. 2; CAC83676)" FT /evidence="ECO:0000305" FT CONFLICT 4314..4473 FT /note="Missing (in Ref. 2; CAC83676)" FT /evidence="ECO:0000305" FT CONFLICT 4381 FT /note="P -> L (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4398..4400 FT /note="TAS -> PAG (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4407 FT /note="S -> N (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4418 FT /note="T -> I (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4421..4484 FT /note="Missing (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4489 FT /note="T -> I (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4501..4503 FT /note="STA -> PTS (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4521 FT /note="T -> I (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4533..4572 FT /note="Missing (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4588 FT /note="G -> A (in Ref. 2; CAC83674)" FT /evidence="ECO:0000305" FT CONFLICT 4614..4615 FT /note="VS -> HE (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 4827 FT /note="P -> R (in Ref. 8; CAA88307)" FT /evidence="ECO:0000305" FT CONFLICT 4884 FT /note="R -> S (in Ref. 6; CAA04737/CAA04738 and 8; FT CAA88307)" FT /evidence="ECO:0000305" FT CONFLICT 4886 FT /note="R -> P (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 4899 FT /note="G -> A (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 4946..4947 FT /note="VL -> AW (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5013 FT /note="G -> A (in Ref. 8; CAA88307)" FT /evidence="ECO:0000305" FT CONFLICT 5081..5084 FT /note="VVAS -> HASA (in Ref. 10; AAH33831)" FT /evidence="ECO:0000305" FT CONFLICT 5148 FT /note="Q -> H (in Ref. 8; CAA88307 and 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5209..5210 FT /note="GH -> RD (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5245 FT /note="P -> R (in Ref. 6; CAA04737/CAA04738 and 7; FT AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5264 FT /note="S -> T (in Ref. 6; CAA04737/CAA04738)" FT /evidence="ECO:0000305" FT CONFLICT 5356 FT /note="G -> R (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5363 FT /note="A -> R (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5433 FT /note="G -> R (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5441 FT /note="G -> A (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5546 FT /note="C -> S (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT CONFLICT 5622 FT /note="P -> A (in Ref. 7; AAA18431)" FT /evidence="ECO:0000305" FT STRAND 3523..3526 FT /evidence="ECO:0007829|PDB:8OV0" FT STRAND 3542..3546 FT /evidence="ECO:0007829|PDB:8OV0" FT HELIX 3547..3552 FT /evidence="ECO:0007829|PDB:8OV0" FT STRAND 3563..3571 FT /evidence="ECO:0007829|PDB:8OV0" FT HELIX 3579..3582 FT /evidence="ECO:0007829|PDB:8OV0" FT STRAND 3586..3589 FT /evidence="ECO:0007829|PDB:8OV0" FT TURN 3590..3592 FT /evidence="ECO:0007829|PDB:8OV0" FT STRAND 3593..3597 FT /evidence="ECO:0007829|PDB:8OV0" FT HELIX 3598..3600 FT /evidence="ECO:0007829|PDB:8OV0" FT STRAND 3603..3605 FT /evidence="ECO:0007829|PDB:8OV0" FT STRAND 3611..3619 FT /evidence="ECO:0007829|PDB:8OV0" SQ SEQUENCE 5654 AA; 585570 MW; 13217A8257E8E2DE CRC64; MSVGRRKLAL LWALALALAC TRHTGHAQDG SSESSYKHHP ALSPIARGPS GVPLRGATVF PSLRTIPVVR ASNPAHNGRV CSTWGSFHYK TFDGDVFRFP GLCNYVFSEH CGAAYEDFNI QLRRSQESAA PTLSRVLMKV DGVVIQLTKG SVLVNGHPVL LPFSQSGVLI QQSSSYTKVE ARLGLVLMWN HDDSLLLELD TKYANKTCGL CGDFNGMPVV SELLSHNTKL TPMEFGNLQK MDDPTDQCQD PVPEPPRNCS TGFGICEELL HGQLFSGCVA LVDVGSYLEA CRQDLCFCED TDLLSCVCHT LAEYSRQCTH AGGLPQDWRG PDFCPQKCPN NMQYHECRSP CADTCSNQEH SRACEDHCVA GCFCPEGTVL DDIGQTGCVP VSKCACVYNG AAYAPGATYS TDCTNCTCSG GRWSCQEVPC PGTCSVLGGA HFSTFDGKQY TVHGDCSYVL TKPCDSSAFT VLAELRRCGL TDSETCLKSV TLSLDGAQTV VVIKASGEVF LNQIYTQLPI SAANVTIFRP STFFIIAQTS LGLQLNLQLV PTMQLFMQLA PKLRGQTCGL CGNFNSIQAD DFRTLSGVVE ATAAAFFNTF KTQAACPNIR NSFEDPCSLS VENEKYAQHW CSQLTDADGP FGRCHAAVKP GTYYSNCMFD TCNCERSEDC LCAALSSYVH ACAAKGVQLG GWRDGVCTKP MTTCPKSMTY HYHVSTCQPT CRSLSEGDIT CSVGFIPVDG CICPKGTFLD DTGKCVQASN CPCYHRGSMI PNGESVHDSG AICTCTHGKL SCIGGQAPAP VCAAPMVFFD CRNATPGDTG AGCQKSCHTL DMTCYSPQCV PGCVCPDGLV ADGEGGCITA EDCPCVHNEA SYRAGQTIRV GCNTCTCDSR MWRCTDDPCL ATCAVYGDGH YLTFDGQSYS FNGDCEYTLV QNHCGGKDST QDSFRVVTEN VPCGTTGTTC SKAIKIFLGG FELKLSHGKV EVIGTDESQE VPYTIRQMGI YLVVDTDIGL VLLWDKKTSI FINLSPEFKG RVCGLCGNFD DIAVNDFATR SRSVVGDVLE FGNSWKLSPS CPDALAPKDP CTANPFRKSW AQKQCSILHG PTFAACHAHV EPARYYEACV NDACACDSGG DCECFCTAVA AYAQACHEVG LCVSWRTPSI CPLFCDYYNP EGQCEWHYQP CGVPCLRTCR NPRGDCLRDV RGLEGCYPKC PPEAPIFDED KMQCVATCPT PPLPPRCHVH GKSYRPGAVV PSDKNCQSCL CTERGVECTY KAEACVCTYN GQRFHPGDVI YHTTDGTGGC ISARCGANGT IERRVYPCSP TTPVPPTTFS FSTPPLVVSS THTPSNGPSS AHTGPPSSAW PTTAGTSPRT RLPTASASLP PVCGEKCLWS PWMDVSRPGR GTDSGDFDTL ENLRAHGYRV CESPRSVECR AEDAPGVPLR ALGQRVQCSP DVGLTCRNRE QASGLCYNYQ IRVQCCTPLP CSTSSSPAQT TPPTTSKTTE TRASGSSAPS STPGTVSLST ARTTPAPGTA TSVKKTFSTP SPPPVPATST SSMSTTAPGT SVVSSKPTPT EPSTSSCLQE LCTWTEWIDG SYPAPGINGG DFDTFQNLRD EGYTFCESPR SVQCRAESFP NTPLADLGQD VICSHTEGLI CLNKNQLPPI CYNYEIRIQC CETVNVCRDI TRLPKTVATT RPTPHPTGAQ TQTTFTTHMP SASTEQPTAT SRGGPTATSV TQGTHTTLVT RNCHPRCTWT KWFDVDFPSP GPHGGDKETY NNIIRSGEKI CRRPEEITRL QCRAKSHPEV SIEHLGQVVQ CSREEGLVCR NQDQQGPFKM CLNYEVRVLC CETPRGCHMT STPGSTSSSP AQTTPSTTSK TTETQASGSS APSSTPGTVS LSTARTTPAP GTATSVKKTF STPSPPPVPA TSTSSMSTTA PGTSVVSSKP TPTEPSTSSC LQELCTWTEW IDGSYPAPGI NGGDFDTFQN LRDEGYTFCE SPRSVQCRAE SFPNTPLADL GQDVICSHTE GLICLNKNQL PPICYNYEIR IQCCETVNVC RDITRPPKTV ATTRPTPHPT GAQTQTTFTT HMPSASTEQP TATSRGGPTA TSVTQGTHTT PVTRNCHPRC TWTTWFDVDF PSPGPHGGDK ETYNNIIRSG EKICRRPEEI TRLQCRAKSH PEVSIEHLGQ VVQCSREEGL VCRNQDQQGP FKMCLNYEVR VLCCETPKGC PVTSTPVTAP STPSGRATSP TQSTSSWQKS RTTTLVTTST TSTPQTSTTY AHTTSTTSAP TARTTSAPTT RTTSASPAST TSGPGNTPSP VPTTSTISAP TTSITSAPTT STTSAPTSST TSGPGTTPSP VPTTSITSAP TTSTTSAPTT STTSARTSST TSATTTSRIS GPETTPSPVP TTSTTSATTT STTSAPTTST TSAPTSSTTS SPQTSTTSAP TTSTTSGPGT TPSPVPTTST TSAPTTRTTS APKSSTTSAA TTSTTSGPET TPRPVPTTST TSSPTTSTTS APTTSTTSAS TTSTTSGAGT TPSPVPTTST TSAPTTSTTS APISSTTSAT TTSTTSGPGT TPSPVPTTST TSAPTTSTTS GPGTTPSAVP TTSITSAPTT STNSAPISST TSATTTSRIS GPETTPSPVP TASTTSASTT STTSGPGTTP SPVPTTSTIS VPTTSTTSAS TTSTTSASTT STTSGPGTTP SPVPTTSTTS APTTSTTSAP TTSTISAPTT STTSATTTST TSAPTPRRTS APTTSTISAS TTSTTSATTT STTSATTTST ISAPTTSTTL SPTTSTTSTT ITSTTSAPIS STTSTPQTST TSAPTTSTTS GPGTTSSPVP TTSTTSAPTT STTSAPTTRT TSVPTSSTTS TATTSTTSGP GTTPSPVPTT STTSAPTTRT TSAPTTSTTS APTTSTTSAP TSSTTSATTT STISVPTTST TSVPGTTPSP VPTTSTISVP TTSTTSASTT STTSGPGTTP SPVPTTSTTS APTTSTTSAP TTSTISAPTT STPSAPTTST TLAPTTSTTS APTTSTTSTP TSSTTSSPQT STTSASTTSI TSGPGTTPSP VPTTSTTSAP TTSTTSAATT STISAPTTST TSAPTTSTTS ASTASKTSGL GTTPSPIPTT STTSPPTTST TSASTASKTS GPGTTPSPVP TTSTIFAPRT STTSASTTST TPGPGTTPSP VPTTSTASVS KTSTSHVSIS KTTHSQPVTR DCHLRCTWTK WFDIDFPSPG PHGGDKETYN NIIRSGEKIC RRPEEITRLQ CRAESHPEVS IEHLGQVVQC SREEGLVCRN QDQQGPFKMC LNYEVRVLCC ETPKGCPVTS TPVTAPSTPS GRATSPTQST SSWQKSRTTT LVTTSTTSTP QTSTTSAPTT STTSAPTTST TSAPTTSTTS TPQTSISSAP TSSTTSAPTS STISARTTSI ISAPTTSTTS SPTTSTTSAT TTSTTSAPTS STTSTPQTSK TSAATSSTTS GSGTTPSPVT TTSTASVSKT STSHVSVSKT THSQPVTRDC HPRCTWTKWF DVDFPSPGPH GGDKETYNNI IRSGEKICRR PEEITRLQCR AKSHPEVSIE HLGQVVQCSR EEGLVCRNQD QQGPFKMCLN YEVRVLCCET PKGCPVTSTS VTAPSTPSGR ATSPTQSTSS WQKSRTTTLV TSSITSTTQT STTSAPTTST TPASIPSTTS APTTSTTSAP TTSTTSAPTT STTSTPQTTT SSAPTSSTTS APTTSTISAP TTSTISAPTT STTSAPTAST TSAPTSTSSA PTTNTTSAPT TSTTSAPITS TISAPTTSTT STPQTSTISS PTTSTTSTPQ TSTTSSPTTS TTSAPTTSTT SAPTTSTTST PQTSISSAPT SSTTSAPTAS TISAPTTSTT SFHTTSTTSP PTSSTSSTPQ TSKTSAATSS TTSGSGTTPS PVPTTSTASV SKTSTSHVSV SKTTHSQPVT RDCHPRCTWT KWFDVDFPSP GPHGGDKETY NNIIRSGEKI CRRPEEITRL QCRAESHPEV SIEHLGQVVQ CSREEGLVCR NQDQQGPFKM CLNYEVRVLC CETPKGCPVT STPVTAPSTP SGRATSPTQS TSSWQKSRTT TLVTTSTTST PQTSTTSAPT TSTIPASTPS TTSAPTTSTT SAPTTSTTSA PTHRTTSGPT TSTTLAPTTS TTSAPTTSTN SAPTTSTISA STTSTISAPT TSTISSPTSS TTSTPQTSKT SAATSSTTSG SGTTPSPVPT TSTTSASTTS TTSAPTTSTT SGPGTTPSPV PSTSTTSAAT TSTTSAPTTR TTSAPTSSMT SGPGTTPSPV PTTSTTSAPT TSTTSGPGTT PSPVPTTSTT SAPITSTTSG PGSTPSPVPT TSTTSAPTTS TTSASTASTT SGPGTTPSPV PTTSTTSAPT TRTTSASTAS TTSGPGSTPS PVPTTSTTSA PTTRTTPAST ASTTSGPGTT PSPVPTTSTT SASTTSTISL PTTSTTSAPI TSMTSGPGTT PSPVPTTSTT SAPTTSTTSA STASTTSGPG TTPSPVPTTS TTSAPTTSTT SASTASTTSG PGTSLSPVPT TSTTSAPTTS TTSGPGTTPS PVPTTSTTSA PTTSTTSGPG TTPSPVPTTS TTPVSKTSTS HLSVSKTTHS QPVTSDCHPL CAWTKWFDVD FPSPGPHGGD KETYNNIIRS GEKICRRPEE ITRLQCRAES HPEVNIEHLG QVVQCSREEG LVCRNQDQQG PFKMCLNYEV RVLCCETPRG CPVTSVTPYG TSPTNALYPS LSTSMVSASV ASTSVASSSV ASSSVAYSTQ TCFCNVADRL YPAGSTIYRH RDLAGHCYYA LCSQDCQVVR GVDSDCPSTT LPPAPATSPS ISTSEPVTEL GCPNAVPPRK KGETWATPNC SEATCEGNNV ISLRPRTCPR VEKPTCANGY PAVKVADQDG CCHHYQCQCV CSGWGDPHYI TFDGTYYTFL DNCTYVLVQQ IVPVYGHFRV LVDNYFCGAE DGLSCPRSII LEYHQDRVVL TRKPVHGVMT NEIIFNNKVV SPGFRKNGIV VSRIGVKMYA TIPELGVQVM FSGLIFSVEV PFSKFANNTE GQCGTCTNDR KDECRTPRGT VVASCSEMSG LWNVSIPDQP ACHRPHPTPT TVGPTTVGST TVGPTTVGST TVGPTTPPAP CLPSPICQLI LSKVFEPCHT VIPPLLFYEG CVFDRCHMTD LDVVCSSLEL YAALCASHDI CIDWRGRTGH MCPFTCPADK VYQPCGPSNP SYCYGNDSAS LGALPEAGPI TEGCFCPEGM TLFSTSAQVC VPTGCPRCLG PHGEPVKVGH TVGMDCQECT CEAATWTLTC RPKLCPLPPA CPLPGFVPVP AAPQAGQCCP QYSCACNTSR CPAPVGCPEG ARAIPTYQEG ACCPVQNCSW TVCSINGTLY QPGAVVSSSL CETCRCELPG GPPSDAFVVS CETQICNTHC PVGFEYQEQS GQCCGTCVQV ACVTNTSKSP AHLFYPGETW SDAGNHCVTH QCEKHQDGLV VVTTKKACPP LSCSLDEARM SKDGCCRFCP PPPPPYQNQS TCAVYHRSLI IQQQGCSSSE PVRLAYCRGN CGDSSSMYSL EGNTVEHRCQ CCQELRTSLR NVTLHCTDGS SRAFSYTEVE ECGCMGRRCP APGDTQHSEE AEPEPSQEAE SGSWERGVPV SPMH //