ID MUC2_MOUSE Reviewed; 4576 AA. AC Q80Z19; A0A087WSG8; Q0P637; Q80Z17; Q8K0Q1; Q9CVG8; Q9Z2U5; DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot. DT 22-FEB-2023, sequence version 3. DT 27-MAR-2024, entry version 130. DE RecName: Full=Mucin-2 {ECO:0000303|PubMed:9886986}; DE Short=MUC-2 {ECO:0000303|PubMed:9886986}; DE AltName: Full=Colonic mucin {ECO:0000303|PubMed:9886986}; DE Short=MCM {ECO:0000303|PubMed:9886986}; DE AltName: Full=Secreted gel-forming mucin {ECO:0000312|EMBL:CAD54414.1}; DE Flags: Precursor; GN Name=Muc2 {ECO:0000303|PubMed:9886986, ECO:0000312|MGI:MGI:1339364}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] {ECO:0000305, ECO:0000312|EMBL:CAD54414.1} RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-1442 AND 3655-4576, AND TISSUE RP SPECIFICITY. RC STRAIN=C57BL/6J {ECO:0000312|EMBL:CAD54414.1}; RX PubMed=14984930; DOI=10.1016/j.bbaexp.2004.01.001; RA Escande F., Porchet N., Bernigaud A., Petitprez D., Aubert J.-P., RA Buisine M.-P.; RT "The mouse secreted gel-forming mucin gene cluster."; RL Biochim. Biophys. Acta 1676:240-250(2004). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD01593.1} RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-301, TISSUE SPECIFICITY, AND GLYCOSYLATION. RC STRAIN=129 {ECO:0000312|EMBL:AAD01593.1}; RC TISSUE=Colon {ECO:0000312|EMBL:AAD01593.1}; RX PubMed=9886986; DOI=10.1152/ajpgi.1999.276.1.g115; RA van Klinken B.J.-W., Einerhand A.W.C., Duits L.A., Makkink M.K., RA Tytgat K.M.A.J., Renes I.B., Verburg M., Bueller H.A., Dekker J.; RT "Gastrointestinal expression and partial cDNA cloning of murine Muc2."; RL Am. J. Physiol. 276:G115-G124(1999). RN [3] {ECO:0000305, ECO:0000312|EMBL:AAH30862.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2809-3654 AND 3691-4576. RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH30862.1}; RC TISSUE=Colon {ECO:0000312|EMBL:AAH30862.1}; 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 [4] {ECO:0000305, ECO:0000312|EMBL:BAB25557.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4095-4576. RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB25557.1}; RC TISSUE=Small intestine {ECO:0000312|EMBL:BAB25557.1}; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] {ECO:0000305} RP DISRUPTION PHENOTYPE. RX PubMed=11872843; DOI=10.1126/science.1069094; RA Velcich A., Yang W., Heyer J., Fragale A., Nicholas C., Viani S., RA Kucherlapati R., Lipkin M., Yang K., Augenlicht L.; RT "Colorectal cancer in mice genetically deficient in the mucin Muc2."; RL Science 295:1726-1729(2002). RN [6] {ECO:0000305} RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE. RX PubMed=18806221; DOI=10.1073/pnas.0803124105; RA Johansson M.E.V., Phillipson M., Petersson J., Velcich A., Holm L., RA Hansson G.C.; RT "The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid RT of bacteria."; RL Proc. Natl. Acad. Sci. U.S.A. 105:15064-15069(2008). RN [7] {ECO:0000305} RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH FCGBP, AND RP SUBCELLULAR LOCATION. RX PubMed=19432394; DOI=10.1021/pr9002504; RA Johansson M.E.V., Thomsson K.A., Hansson G.C.; RT "Proteomic analyses of the two mucus layers of the colon barrier reveal RT that their main component, the Muc2 mucin, is strongly bound to the Fcgbp RT protein."; RL J. Proteome Res. 8:3549-3557(2009). RN [8] RP FUNCTION, AND GLYCOSYLATION. RX PubMed=33093110; DOI=10.1126/science.aay7367; RA Bergstrom K., Shan X., Casero D., Batushansky A., Lagishetty V., RA Jacobs J.P., Hoover C., Kondo Y., Shao B., Gao L., Zandberg W., RA Noyovitz B., McDaniel J.M., Gibson D.L., Pakpour S., Kazemian N., McGee S., RA Houchen C.W., Rao C.V., Griffin T.M., Sonnenburg J.L., McEver R.P., RA Braun J., Xia L.; RT "Proximal colon-derived O-glycosylated mucus encapsulates and modulates the RT microbiota."; RL Science 370:467-472(2020). CC -!- FUNCTION: Coats the epithelia of the intestines and other mucus CC membrane-containing organs to provide a protective, lubricating barrier CC against particles and infectious agents at mucosal surfaces CC (PubMed:18806221, PubMed:19432394, PubMed:33093110). Major constituent CC of the colon mucus, which is mainly formed by large polymeric networks CC of MUC2 secreted by goblet cells that cover the exposed surfaces of CC intestine (PubMed:18806221, PubMed:19432394, PubMed:33093110). MUC2 CC networks form hydrogels that guard the underlying epithelium from CC pathogens and other hazardous matter entering from the outside world, CC while permitting nutrient absorption and gas exchange (PubMed:18806221, CC PubMed:19432394). Acts as a divalent copper chaperone that protects CC intestinal cells from copper toxicity and facilitates nutritional CC copper unptake into cells (By similarity). Binds both Cu(2+) and its CC reduced form, Cu(1+), at two juxtaposed binding sites: Cu(2+), once CC reduced to Cu(1+) by vitamin C (ascorbate) or other dietary CC antioxidants, transits to the other binding site (By similarity). MUC2- CC bound Cu(1+) is protected from oxidation in aerobic environments, and CC can be released for nutritional delivery to cells (By similarity). CC Mucin gels store antimicrobial molecules that participate in innate CC immunity (PubMed:18806221, PubMed:19432394). Mucin glycoproteins also CC house and feed the microbiome, lubricate tissue surfaces, and may CC facilitate the removal of contaminants and waste products from the body CC (PubMed:33093110). Goblet cells synthesize two forms of MUC2 mucin that CC differ in branched chain O-glycosylation and the site of production in CC the colon: a (1) 'thick' mucus that wraps the microbiota to form fecal CC pellets is produced in the proximal, ascending colon (PubMed:33093110). CC 'Thick' mucus transits along the descending colon and is lubricated by CC a (2) 'thin' MUC2 mucus produced in the distal colon which adheres to CC the 'thick' mucus (PubMed:33093110). {ECO:0000250|UniProtKB:Q02817, CC ECO:0000269|PubMed:18806221, ECO:0000269|PubMed:19432394, CC ECO:0000269|PubMed:33093110}. CC -!- SUBUNIT: Homomultimer; disulfide-linked. The N- and C-terminus mediate CC their assembly into higher order structures to form filaments (By CC similarity). The CTCK domains of two polypeptides associate in the CC endoplasmic reticulum to generate intermolecularly disulfide-bonded CC dimers (By similarity). These dimers progress to the Golgi apparatus, CC which is a more acidic environment than the endoplasmic reticulum (By CC similarity). Under acidic conditions, the N-termini form non-covalent CC intermolecular interactions that juxtapose assemblies of the third VWD CC domain (VWD3) from different CTCK-linked dimers (By similarity). The CC VWD3 assemblies then become disulfide bonded to one another to produce CC long, disulfide-linked polymers that remain highly compact until CC secretion (By similarity). Interacts with FCGBP (PubMed:19432394). CC Interacts with AGR2; disulfide-linked (By similarity). CC {ECO:0000250|UniProtKB:Q02817, ECO:0000250|UniProtKB:Q9HC84, CC ECO:0000269|PubMed:19432394}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18806221, CC ECO:0000269|PubMed:19432394}. Note=In the intestine, secreted into the CC inner and outer mucus layers (PubMed:18806221, PubMed:19432394). Before CC secretion, mucin polymers are stored in dedicated secretory vesicles CC (By similarity). {ECO:0000250|UniProtKB:Q02817, CC ECO:0000269|PubMed:18806221, ECO:0000269|PubMed:19432394}. CC -!- TISSUE SPECIFICITY: Highly expressed in goblet cells of the colon with CC lower levels in the small intestine and no expression in the stomach CC (at protein level). {ECO:0000269|PubMed:14984930, CC ECO:0000269|PubMed:9886986}. CC -!- DOMAIN: The CTCK domain mediates interchain disulfide bonds with CC another molecule of MUC2. {ECO:0000250|UniProtKB:Q9HC84}. CC -!- PTM: O-glycosylated (PubMed:9886986). O-glycosylation is required for CC mucin assembly (By similarity). Goblet cells synthesize two forms of CC mucin that differ in branched chain O-glycosylation and the site of CC production in the colon (PubMed:33093110). CC {ECO:0000250|UniProtKB:Q02817, ECO:0000269|PubMed:33093110, CC ECO:0000269|PubMed:9886986}. CC -!- PTM: May undergo proteolytic cleavage in the outer mucus layer of the CC colon, contributing to the expanded volume and loose nature of this CC layer which allows for bacterial colonization in contrast to the inner CC mucus layer which is dense and devoid of bacteria. CC {ECO:0000269|PubMed:18806221}. CC -!- PTM: At low pH of 6 and under, undergoes autocatalytic cleavage in CC vitro in the N-terminal region of the fourth VWD domain. It is likely CC that this also occurs in vivo and is triggered by the low pH of the CC late secretory pathway. {ECO:0000250|UniProtKB:Q02817}. CC -!- DISRUPTION PHENOTYPE: Aberrant intestinal crypt morphology and altered CC cell maturation and migration (PubMed:11872843). Frequent development CC of adenomas in the small intestine which progress to invasive CC adenocarcinomas, as well as rectal tumors (PubMed:11872843). Absence of CC inner and outer mucus layers in the colon so that bacteria are in CC direct contact with the colon epithelium and enter into the cells and CC crypts in contrast to wild-type animals which are devoid of bacteria in CC the inner mucus layer (PubMed:18806221). {ECO:0000269|PubMed:11872843, CC ECO:0000269|PubMed:18806221}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH30862.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Mucin database; CC URL="http://www.medkem.gu.se/mucinbiology/databases/"; 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; AJ511872; CAD54414.1; -; Genomic_DNA. DR EMBL; AJ511873; CAD54416.1; -; Genomic_DNA. DR EMBL; AJ511874; CAD54416.1; JOINED; Genomic_DNA. DR EMBL; AF016695; AAD01593.1; -; mRNA. DR EMBL; BC024540; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC030862; AAH30862.1; ALT_INIT; mRNA. DR EMBL; BC036168; AAH36168.1; -; mRNA. DR EMBL; AK008250; BAB25557.1; -; mRNA. DR AlphaFoldDB; Q80Z19; -. DR SMR; Q80Z19; -. DR STRING; 10090.ENSMUSP00000141128; -. DR MEROPS; I08.954; -. DR GlyCosmos; Q80Z19; 3 sites, No reported glycans. DR GlyGen; Q80Z19; 38 sites. DR PhosphoSitePlus; Q80Z19; -. DR SwissPalm; Q80Z19; -. DR jPOST; Q80Z19; -. DR MaxQB; Q80Z19; -. DR PaxDb; 10090-ENSMUSP00000141128; -. DR PeptideAtlas; Q80Z19; -. DR ProteomicsDB; 291459; -. DR ProteomicsDB; 363370; -. DR Ensembl; ENSMUST00000185406.8; ENSMUSP00000141040.3; ENSMUSG00000025515.17. DR UCSC; uc029wpp.2; mouse. DR AGR; MGI:1339364; -. DR MGI; MGI:1339364; Muc2. DR VEuPathDB; HostDB:ENSMUSG00000025515; -. DR eggNOG; KOG1216; Eukaryota. DR GeneTree; ENSGT00940000163661; -. DR HOGENOM; CLU_000076_6_1_1; -. DR InParanoid; Q80Z19; -. DR OMA; CYNKDQT; -. DR TreeFam; TF337106; -. DR Reactome; R-MMU-913709; O-linked glycosylation of mucins. DR Reactome; R-MMU-977068; Termination of O-glycan biosynthesis. DR ChiTaRS; Muc2; mouse. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; Q80Z19; Protein. DR Bgee; ENSMUSG00000025515; Expressed in jejunum and 47 other cell types or tissues. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0031012; C:extracellular matrix; IDA:MGI. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0070702; C:inner mucus layer; IDA:UniProtKB. DR GO; GO:0070701; C:mucus layer; IDA:UniProt. DR GO; GO:0070703; C:outer mucus layer; IDA:UniProtKB. DR GO; GO:1903135; F:cupric ion binding; ISS:UniProtKB. DR GO; GO:1903136; F:cuprous ion binding; ISS:UniProtKB. DR GO; GO:0005201; F:extracellular matrix structural constituent; IDA:UniProt. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0006915; P:apoptotic process; IMP:MGI. DR GO; GO:0010273; P:detoxification of copper ion; ISS:UniProtKB. DR GO; GO:0002068; P:glandular epithelial cell development; IMP:MGI. DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; IDA:UniProtKB. DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IDA:UniProtKB. DR GO; GO:0070254; P:mucus secretion; IDA:UniProt. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI. DR CDD; cd19941; TIL; 2. DR Gene3D; 2.10.25.10; Laminin; 3. 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:SF399; MUCIN-2; 1. DR Pfam; PF08742; C8; 4. DR Pfam; PF13330; Mucin2_WxxW; 2. DR Pfam; PF01826; TIL; 1. DR Pfam; PF00094; VWD; 4. DR PRINTS; PR01217; PRICHEXTENSN. DR SMART; SM00832; C8; 4. DR SMART; SM00041; CT; 1. DR SMART; SM00214; VWC; 4. DR SMART; SM00215; VWC_out; 2. DR SMART; SM00216; VWD; 4. DR SUPFAM; SSF57603; FnI-like domain; 3. 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. PE 1: Evidence at protein level; KW Autocatalytic cleavage; Calcium; Copper; Disulfide bond; Glycoprotein; KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Secreted; KW Signal. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..4576 FT /note="Mucin-2" FT /evidence="ECO:0000255" FT /id="PRO_5030002787" FT DOMAIN 32..205 FT /note="VWFD 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DOMAIN 293..349 FT /note="TIL" FT /evidence="ECO:0000255" FT DOMAIN 387..562 FT /note="VWFD 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DOMAIN 857..1026 FT /note="VWFD 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT REPEAT 1395..1415 FT /note="1" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1416..1427 FT /note="2" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1428..1437 FT /note="3" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1438..1453 FT /note="4" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1454..1460 FT /note="5" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1478..1497 FT /note="7B" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1498..1510 FT /note="8A" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1530..1556 FT /note="9B" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1557..1572 FT /note="10A" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1573..1588 FT /note="10B" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1589..1607 FT /note="11A" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1608..1634 FT /note="11B" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1635..1642 FT /note="12" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT REPEAT 1665..1681 FT /note="15" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DOMAIN 3880..4063 FT /note="VWFD 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DOMAIN 4213..4282 FT /note="VWFC 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 4320..4387 FT /note="VWFC 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220" FT DOMAIN 4471..4556 FT /note="CTCK" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT REGION 1395..2866 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2975..3706 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3764..3806 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3776..3806 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 46 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 143 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 151 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 153 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 168 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 170 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 177 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 275 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 322 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 324 FT /ligand="Cu(+)" FT /ligand_id="ChEBI:CHEBI:49552" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 401 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 528 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 530 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 532 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 535 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 536 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 871 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 992 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 994 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 999 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1000 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1305 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1308 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1315 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1316 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1318 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1375 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT BINDING 1376 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT SITE 3887..3888 FT /note="Cleavage; by autolysis; in vitro" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT MOD_RES 21 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 421 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 668 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 768 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 838 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 893 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 1137 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 1152 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 1213 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 1228 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 1244 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 1265 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT CARBOHYD 1268 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT CARBOHYD 1269 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT CARBOHYD 1281 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT CARBOHYD 1292 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT CARBOHYD 1352 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 2529 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 2910 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 3734 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 3745 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 3756 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 3823 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 3830 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 3903 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 3991 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4017 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4028 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4083 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4149 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4183 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4254 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4277 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4351 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4366 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4434 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4465 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT CARBOHYD 4488 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498" FT DISULFID 34..166 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 56..204 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 64..163 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 216..253 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 223..248 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 235..273 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 255..261 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 263..289 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 293..327 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 306..319 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 310..349 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 329..343 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 351..373 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 368..385 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 371..380 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 389..526 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 411..561 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 433..441 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 572..617 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 586..612 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 599..637 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 619..625 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 627..652 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 659..696 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 672..686 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 676..716 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 698..710 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 718..740 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 738..747 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 782..818 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 800..812 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 820..843 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 837..855 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 841..850 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 859..990 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 881..1025 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 890..987 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 907..914 FT /evidence="ECO:0000250|UniProtKB:Q02817, FT ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 1035..1078 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1049..1073 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1060..1100 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1080..1088 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1086 FT /note="Interchain" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1090..1115 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1106..1135 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1119..1161 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1128 FT /note="Interchain" FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1143..1185 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1165..1179 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1187..1211 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1206..1236 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 1209..1219 FT /evidence="ECO:0000250|UniProtKB:Q02817" FT DISULFID 3882..4023 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 3904..4062 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 3928..3936 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00580" FT DISULFID 4471..4518 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT DISULFID 4485..4532 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT DISULFID 4494..4548 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT DISULFID 4498..4550 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039" FT CONFLICT 301 FT /note="E -> G (in Ref. 2; AAD01593)" FT /evidence="ECO:0000305" FT CONFLICT 4294 FT /note="T -> P (in Ref. 3; AAH36168)" FT /evidence="ECO:0000305" SQ SEQUENCE 4576 AA; 479290 MW; A7FF1C6456439021 CRC64; MGLPLARLVA ACLVLALAKG SELQKEARSR NHVCSTWGDF HYKTFDGDVY RFPGLCDYNF ASDCRDSYKE FAVHLKRGLG EAGGHSQIES ILITIKDDTI YLTHKLAVVN GAMVSTPHYS SGLLIEKNDA YTKVYSRAGL SLMWNREDAL MVELDSRFQN HTCGLCGDFN GMQTNYEFLS EEGIQFSAIE FGNMQKINKP EVQCEDPEAV QEPESCSEHR AECERLLTSA AFEDCQTRVP VESYVRACMH DRCQCPKGGA CECSTLAEFS RQCSHAGGRP ENWRTASLCP KKCPNNMVYL ESSSPCVDTC SHLEVSSLCE EHYMDGCFCP EGTVYDDITG SGCIPVSQCH CKLHGHLYMP GQEFTNDCEQ CVCNAGRWVC KDLPCPETCA LEGGSHITTF DGKKFTFHGD CYYVLTKSEH NDSYALLGEL ASCGSTDKQT CLKTVVLLTD DKKNVVAFKS GGSVLLNEME VTLPHVAASF SIFQPSSYHI VVNTKFGLRL QIQLLPVMQL FVTLDQAAQG QVQGLCGNFN GLESDDFMTS GGMVEATGAG FANTWKAQSS CHDKLDWLDD PCSLNIESAN YAEHWCSLLK RSETPFARCH LAVDPTEYYK RCKYDTCNCQ NNEDCMCAAL SSYARACAAK GVMLWGWRER VCNKDVHACP SSQIFMYNLT TCQQTCRSLS EGDSHCLKGF APVEGCGCPD HTFMDEKGRC VPLAKCSCYH HGLYLEAGDV ILRQEERCIC RNGRLQCTQV KLIGHTCQYP KILVDCNNLT ALAVRKPRPT SCQTLVAGYY HTECISGCVC PDGLLDDGRG GCVEEDKCPC IHNKDLYSSG ESIKLDCNNT CTCQKGRWEC TRYACHSTCS IYGSGHYITF DGKHYDFDGH CSYVAVQDYC GQNSTGSFSI ITENVPCGTT GVTCSKAIKI FIGGTELKLV DKHRVVKQLE EGHHVPYITR EVGQYLVVEA SSGIIVIWDK KTTIFIKLDP SYKGTVCGLC GNFDDQTKND FTTRDHMVVT SELDFGNSWK EASTCPDVSH NPDPCSLNPH RRSWAEKQCS IIKSRVFKVC HSKVDPTVFY EACVHDSCSC DTGGDCDCFC SAVASYAQEC TKAEACVFWR TPDLCPIFCD YYNPPDECEW HYEPCGNRSF ETCRTLNGIH SNISVSYLEG CYPRCPEDRP IYDEDLKKCV TGDKCGCYIE DTRYPPGGSV PTDEICKSCT CTNTSKIECH PDEGKILNMT QDGIFCYWEF CGPNGTVGQH FNICGSSTAI PSTTTSFTTI STPISTTPIS TTITTTTVTM TTEQVPCCFW SDWINKYHPT KENGGDRETF THVCSAPEDI ECRAATDPKL SWEELGQKVQ CNVSTGLICN NEDQYGIGEF ELCYDYEIRV NCCYPMEYCT PSTISPTTST TTLSTTPPTS SPTTLPTSSP VTSSATLPTT SSITSTISPT TSPTTPLTTS PTTSPTTSPT TPSTTSPTTP TTTSPTTPST TSPTTPSTTP STTSPTTPST TSPTTPTSTS PNTQSTTSPT TSPTTPSTTS PTTSPTTPST TSPTISTTTS TISPTTPSTT SPNTPSTTSS TIPSTTSPTT PSTTSPTIST TTSTTSPTTP STTSPTTPST TSPTTPSTTS PTISTTTLTT SPTTPSTTSP TTPSTTSPTT PSTTSPTISI TTSTISPTTP STTSPTTLST TSPTTPSTTS PTISTTTSTS PTTPSTTSPT TPSTPSSTTP STTSPTTPST TSPTISTTSS TISPTTPSTT SPTTPSTTSP TTPSTTSPTI STTTSTISPT TPSTTSPTTP STTSPTTPST TSPTISTTTS TISPTTPSTT SPTTPSTTSP NTPSTTSTTT STTSPTTPST TSPTISTTTS TTSPTTPSTT SPTISTTTST TSPTTPSTTS PTTPSTTSPT TPSTTSPTTP STTSPTISTT SSTISPTTPS TTSPTTPSTT SPTTPSTTSP TISTTTSTTS PTTPSTTSPT ISTTTSTISP TTPSTSSPTT PSTTSPTTPS TTSPTISTTT STTSPTTPST TSPTTPSTTS PTISTTTSTT SPTTPSTTSP TISTTTSTTS PTTPSTTSPT TPSTTSPTTP STTSPTTPST TSPTISTTSS TISPTTPSTT SPTTPSTTSP TTPSTTSPTI STTTSTTSPT TPSTTSPTIS TTTSTTSPTT PSTTSPTTPS TTSPTTPSTT SPTTPSTTSP TISTTSSTIS PTTPSTTSPT TPSTTSPTTP STTSPTISTT TSTTSPTTPS TTSPTISTTT STISPTTPST TSPITPSTTS PTTPSTTSPT ISTTTSTTSP TTPSTTSPTI STTTSTISPT TPSTTSPITP STTSPTTPST TSPTISTTTS TISPTTPSTT SPTTPSTTSP TTLSTTSPTI STTTSTISPT TPSTTSPTTP STTSPTTPST TSPTTPSTTS PTISTTTSTI SPTTSPTTPS TTSPTTHSTT SPTTPSTTSP TISTTTSTIS PTTPSTTSLT TPSTTSPTTP STTSPTTPST TSPTISTTTS TISPTTPSTT SPTTPSTTSP TTPSTTSPNI STTTSTISPT TPSTTSPTTP STTSPTTPST TSPTISTTTS TISPTTPSTT SPTTPSTTSP TTPSTTSPTT PSTTSPTIST TTSTISPTTP STTSPTTPST TSPTTQSTTS PTISTNTPST TSPTTPSTTS PTISTTTSTI SPTTPSTTSP TTPSTTSPTT SSTTSPTIST TTSTISPTTP STTSPTTPST TSPTTPLTTS PTISTTTSTI SPTTPSTTSP TTPSTTSPTT PSTTSPTTPS TTSPTISTTT STISPTTPST TSPTTSPTTP STTSPTTSST ATQTISVTTS QTSSSATPPN SSPTSSATTS PTTSSGTSTA TSPSTSPTTS STFTTPPSTT CIDDCKWTGW LDSGKPTYDI KSGDFELIKG VCEPHWEVQN ISCRAVMHSN IPLDQLGQIV VCNKEVGLVC KNEDQEIGGI IPMRMCLNYE INVYCCNPIC FTSTPSSTTT ETPTTTSTTK TSILTSTTTQ TPSPSPTTTV TPTPAPTTTQ IPTSTSTTTQ TTTPTPITET STPTSTISQT PSPASTTTVT PATTSTTTET STSTSTTTQT TSPTPTVTET STPRSTTTQT PSPVPTTTVT STPTPTIGET TTPTTTITET FTPRSTTTQT SSPVPSTTVT PTPTPITTET STSTPTTTQT TTPTPITETS TPISTTTHTP SPSSTTSTTS TQTPTPTTTG PSTSTSTTIQ TTTPTPITET FTPTSTTTQT PSSTPTTTVT PTPTTTETST STSTTTQTTT PTPITETFTP TSTTTQTPSP TPTTTVNPTP TPTTIGPSTS TSTTTQTTTP TPTGTETSTP TSTTTQTPSP TPTTTVTPTP SPTTTETSTS TTTQTTTPTP TGTETSTPTS TTTQTPSPTP TTTVTPTPSP TTTETSTSTT TQTTTPTPIT ETSTPTSTTT QTPSPTPTTT VTPTSTPTTT GTSTSTSTTT QTTTPTPTGT ETFTPRSTTT QTPSSSSTTS GTPTPTPTTT HTSTLTSTTE ASTPTPIIET STPKSTTIQT PSPSPTTTVT SPTTPTTTVK ETSTPTNTVP TTGSTSSKPP TESSTPVTSQ STPSPPTEST TLSSTPVTTA TSSTASSPGT TSPFVTSSAG STPSSPPGST PGPTTSSGMP TSSKTTTGPT SPTTRPPSTS TPTSFTVPTE TTTQTRPLST TPTTLETTRT SSWGTFSSTS PITSPSTVWT HTETQVTCCV LNEMFYGPGE LVYNSTHGGT CFYVNCSLDC HLQFFNWSCP STPSTPTPST PTPTPSQTTT PSTTSSKSTP STPQSTSPKS TLSTPTKTTP YGCPDFDPPR QVNETWWLCN CTMAICNHDN VVEIVPLKCD PPPMPTCANG LKPVRVPDAD NCCWHWECDC YCTGWGDPHF VTFDGLYYSY QGNCTYVLVE EITPTVDNFG VYIDNYHCDA NDKVSCPRTL IVRHETQEVQ IKTVRMMPIE VEVQVNKQLV ALPYKKYGLE VYESGINIVV NISRLEAKIS YNGLSFSIRL PYKLFGNNTK GQCGTCTNNT ADDCILPSGK IISDCEIAAD EWLVNDPSKP HCPHKGLTTK RPATTTPGLS LNNCTVSPVC HLIMDSLFSQ CHAFVPPKHY YEACLFDSCY VPGSNMECAS VQAYATLCAK EGVCIDWRNH TQGVCSVKCP PHKQYQACGP EEEPTCQPSS SQNSTLLVEG CFCPEGTTKF APGYDVCVKT CGCVGPDNVP REFGEHFEFD CKDCVCREGG SGIVCQPKKC SGGNQTTCEE DGTYLVVETN PDDKCCNITS CKCDTKRCKA ERPTCLLGFE VKTEIVPGKC CPVYSCVPKG VCVHQNAEYQ PGSPVYSNKC QDCVCTNILD NSTQLNVISC THVPCNISCS SGFELVDVPG ECCKKCQQTH CIIEGPKQQY IILKPGEIHK NPSNKCTFFS CMKINNQLIS SVSNITCPDF NPSDCVSGSI TYMPNGCCKT CIPQNQTRVP CSAVSVMKEI SYNGCTKNIS MNYCFGSCGT FAMYSAQVQG LDHRCSCCKE EKTSVRSVTL ECPDGSELSH TYTHIESCLC QDTVCGLPQA QQVRTRRSSP RFLGRK //