ID THYG_HUMAN Reviewed; 2768 AA. AC P01266; O15274; O43899; Q15593; Q15948; Q9NYR1; Q9NYR2; Q9UMZ0; AC Q9UNY3; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 5. DT 16-JAN-2019, entry version 207. DE RecName: Full=Thyroglobulin {ECO:0000305}; DE Short=Tg; DE Flags: Precursor; GN Name=TG {ECO:0000312|HGNC:HGNC:11764}; 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 [MRNA] (ISOFORM 1), AND VARIANTS ASP-604; ASP-653; RP GLN-985 DEL; TYR-1043; THR-1059; GLY-1312; ARG-1437; HIS-1463; RP THR-1936; GLU-2091; LEU-2149; ARG-2170 AND HIS-2242. RX PubMed=3595599; DOI=10.1111/j.1432-1033.1987.tb11466.x; RA Malthiery Y., Lissitzky S.; RT "Primary structure of human thyroglobulin deduced from the sequence of RT its 8448-base complementary DNA."; RL Eur. J. Biochem. 165:491-498(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLY-1312. RC TISSUE=Thyroid; RX PubMed=9186272; DOI=10.1530/eje.0.1360508; RA van de Graaf S.A.R., Pauws E., de Vijlder J.J.M., Ris-Stalpers C.; RT "The revised 8307 base pair coding sequence of human thyroglobulin RT transiently expressed in eukaryotic cells."; RL Eur. J. Endocrinol. 136:508-515(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLU-515. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., RA Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-730, AND VARIANTS ASP-604 AND ASP-653. RX PubMed=3971976; DOI=10.1111/j.1432-1033.1985.tb08717.x; RA Malthiery Y., Lissitzky S.; RT "Sequence of the 5'-end quarter of the human-thyroglobulin messenger RT ribonucleic acid and of its deduced amino-acid sequence."; RL Eur. J. Biochem. 147:53-58(1985). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-415; 640-737 AND 880-1000, AND RP VARIANT ALA-734. RX PubMed=3681978; DOI=10.1016/0022-2836(87)90403-7; RA Parma J., Christophe D., Pohl V., Vassart G.; RT "Structural organization of the 5' region of the thyroglobulin gene. RT Evidence for intron loss and 'exonization' during evolution."; RL J. Mol. Biol. 196:769-779(1987). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25. RX PubMed=2991855; DOI=10.1093/nar/13.14.5127; RA Christophe D., Cabrer B., Bacolla A., Targovnik H.M., Pohl V., RA Vassart G.; RT "An unusually long poly(purine)-poly(pyrimidine) sequence is located RT upstream from the human thyroglobulin gene."; RL Nucleic Acids Res. 13:5127-5144(1985). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1002-1566 (ISOFORM 1), AND RP VARIANT GLY-1312. RX PubMed=11124863; DOI=10.1530/eje.0.1430789; RA Moya C.M., Mendive F.M., Rivolta C.M., Vassart G., Targovnik H.M.; RT "Genomic organization of the 5' region of the human thyroglobulin RT gene."; RL Eur. J. Endocrinol. 143:789-798(2000). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1645-2768, AND VARIANTS LEU-2149 RP AND ARG-2170. RX PubMed=10524569; DOI=10.1089/thy.1999.9.903; RA Mendive F.M., Rivolta C.M., Vassart G., Targovnik H.M.; RT "Genomic organization of the 3' region of the human thyroglobulin RT gene."; RL Thyroid 9:903-912(1999). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1504-1602 (ISOFORM 2). RX PubMed=1639210; DOI=10.1016/0303-7207(92)90087-M; RA Targovnik H.M., Cochaux P., Corach D., Vassart G.; RT "Identification of a minor Tg mRNA transcript in RNA from normal and RT goitrous thyroids."; RL Mol. Cell. Endocrinol. 84:R23-R26(1992). RN [10] RP PARTIAL PROTEIN SEQUENCE. RX PubMed=2914619; DOI=10.1016/0014-5793(89)80513-7; RA Marriq C., Lejeune P.J., Venot N., Vinet L.; RT "Hormone synthesis in human thyroglobulin: possible cleavage of the RT polypeptide chain at the tyrosine donor site."; RL FEBS Lett. 242:414-418(1989). RN [11] RP PARTIAL PROTEIN SEQUENCE. RX PubMed=8269951; DOI=10.1111/j.1432-1033.1993.tb18414.x; RA Gentile F., Salvatore G.; RT "Preferential sites of proteolytic cleavage of bovine, human and rat RT thyroglobulin. The use of limited proteolysis to detect solvent- RT exposed regions of the primary structure."; RL Eur. J. Biochem. 218:603-621(1993). RN [12] RP PARTIAL PROTEIN SEQUENCE. RX PubMed=7793989; DOI=10.1006/abbi.1995.1346; RA Xiao S., Pollock H.G., Taurog A., Rawitch A.B.; RT "Characterization of hormonogenic sites in an N-terminal, cyanogen RT bromide fragment of human thyroglobulin."; RL Arch. Biochem. Biophys. 320:96-105(1995). RN [13] RP PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-76; ASN-198; ASN-484; RP ASN-529; ASN-748; ASN-816; ASN-947; ASN-1220; ASN-1348; ASN-1349; RP ASN-1365; ASN-1716; ASN-1774; ASN-2013; ASN-2250; ASN-2295 AND RP ASN-2582, AND LACK OF GLYCOSYLATION AT ASN-110; ASN-496; ASN-1869 AND RP ASN-2122. RX PubMed=8615697; DOI=10.1006/abbi.1996.0093; RA Yang S.X., Pollock H.G., Rawitch A.B.; RT "Glycosylation in human thyroglobulin: location of the N-linked RT oligosaccharide units and comparison with bovine thyroglobulin."; RL Arch. Biochem. Biophys. 327:61-70(1996). RN [14] RP PRESENCE OF A 11TH THYROGLOBULIN TYPE-1 REPEAT. RX PubMed=8797845; DOI=10.1111/j.1432-1033.1996.0125h.x; RA Molina F., Bouanani M., Pau B., Granier C.; RT "Characterization of the type-1 repeat from thyroglobulin, a cysteine- RT rich module found in proteins from different families."; RL Eur. J. Biochem. 240:125-133(1996). RN [15] RP IODINATION AT TYR-24; TYR-149; TYR-258; TYR-704; TYR-785; TYR-866; RP TYR-883; TYR-992; TYR-1310; TYR-1467; TYR-2184; TYR-2573; TYR-2587; RP TYR-2617; TYR-2697 AND TYR-2766. RX PubMed=2760035; RA Lamas L., Anderson P.C., Fox J.W., Dunn J.T.; RT "Consensus sequences for early iodination and hormonogenesis in human RT thyroglobulin."; RL J. Biol. Chem. 264:13541-13545(1989). RN [16] RP SULFATION. RX PubMed=10448091; DOI=10.1006/bbrc.1999.1173; RA Nlend M.-C., Cauvi D., Venot N., Chabaud O.; RT "Sulfated tyrosines of thyroglobulin are involved in thyroid hormone RT synthesis."; RL Biochem. Biophys. Res. Commun. 262:193-197(1999). RN [17] RP SULFATION AT TYR-24. RX PubMed=12387814; DOI=10.1016/S0006-291X(02)02425-7; RA Venot N., Nlend M.-C., Cauvi D., Chabaud O.; RT "The hormonogenic tyrosine 5 of porcine thyroglobulin is sulfated."; RL Biochem. Biophys. Res. Commun. 298:193-197(2002). RN [18] RP GLYCOSYLATION AT SER-2749. RX PubMed=16679516; DOI=10.1074/jbc.M513382200; RA Conte M., Arcaro A., D'Angelo D., Gnata A., Mamone G., Ferranti P., RA Formisano S., Gentile F.; RT "A single chondroitin 6-sulfate oligosaccharide unit at Ser-2730 of RT human thyroglobulin enhances hormone formation and limits proteolytic RT accessibility at the carboxyl terminus. Potential insights into RT thyroid homeostasis and autoimmunity."; RL J. Biol. Chem. 281:22200-22211(2006). RN [19] RP VARIANT HIS-870. RX PubMed=8094490; DOI=10.1016/0140-6736(93)90209-Y; RA Corral J., Martin C., Perez R., Sanchez I., Mories M.T., RA San Millan J.L., Miralles J.M., Gonzalez-Sarmiento R.; RT "Thyroglobulin gene point mutation associated with non-endemic simple RT goitre."; RL Lancet 341:462-464(1993). RN [20] RP VARIANTS TDH3 ARG-1264 AND SER-1996, AND VARIANTS HIS-135; ASP-604; RP ASP-653; ALA-734; GLU-830; GLN-985 DEL; VAL-1028; TYR-1043; THR-1059; RP ARG-1437; HIS-1463; ASN-1838; THR-1936; TRP-1999; GLU-2091; LEU-2149; RP ARG-2170; HIS-2242; ARG-2501 AND GLN-2530. RX PubMed=10199792; DOI=10.1210/jcem.84.4.5633; RA Hishinuma A., Takamatsu J., Ohyama Y., Yokozawa T., Kanno Y., Kuma K., RA Yoshida S., Matsuura N., Ieiri T.; RT "Two novel cysteine substitutions (C1263R and C1995S) of thyroglobulin RT cause a defect in intracellular transport of thyroglobulin in patients RT with congenital goiter and the variant type of adenomatous goiter."; RL J. Clin. Endocrinol. Metab. 84:1438-1444(1999). RN [21] RP VARIANTS ALA-734; VAL-1028 AND TRP-1979, AND INVOLVEMENT IN AITD3. RX PubMed=14657345; DOI=10.1073/pnas.2434175100; RA Ban Y., Greenberg D.A., Concepcion E., Skrabanek L., Villanueva R., RA Tomer Y.; RT "Amino acid substitutions in the thyroglobulin gene are associated RT with susceptibility to human and murine autoimmune thyroid disease."; RL Proc. Natl. Acad. Sci. U.S.A. 100:15119-15124(2003). RN [22] RP VARIANTS TDH3 TYR-1897 AND GLN-2336. RX PubMed=16477365; DOI=10.1007/s10038-006-0360-2; RA Kitanaka S., Takeda A., Sato U., Miki Y., Hishinuma A., Ieiri T., RA Igarashi T.; RT "A novel compound heterozygous mutation in the thyroglobulin gene RT resulting in congenital goitrous hypothyroidism with high serum RT triiodothyronine levels."; RL J. Hum. Genet. 51:379-382(2006). RN [23] RP VARIANTS TDH3 TYR-183 AND ASP-2234. RX PubMed=17532758; DOI=10.1111/j.1365-2265.2007.02889.x; RA Caputo M., Rivolta C.M., Esperante S.A., Gruneiro-Papendieck L., RA Chiesa A., Pellizas C.G., Gonzalez-Sarmiento R., Targovnik H.M.; RT "Congenital hypothyroidism with goitre caused by new mutations in the RT thyroglobulin gene."; RL Clin. Endocrinol. (Oxf.) 67:351-357(2007). RN [24] RP VARIANT TDH3 ARG-2375. RX PubMed=17244789; DOI=10.1210/jc.2006-1242; RA Kanou Y., Hishinuma A., Tsunekawa K., Seki K., Mizuno Y., Fujisawa H., RA Imai T., Miura Y., Nagasaka T., Yamada C., Ieiri T., Murakami M., RA Murata Y.; RT "Thyroglobulin gene mutations producing defective intracellular RT transport of thyroglobulin are associated with increased thyroidal RT type 2 iodothyronine deiodinase activity."; RL J. Clin. Endocrinol. Metab. 92:1451-1457(2007). RN [25] RP VARIANT TDH3 ASP-2234, AND CHARACTERIZATION OF VARIANT TDH3 ASP-2234. RX PubMed=19509106; DOI=10.1210/jc.2009-0150; RA Pardo V., Vono-Toniolo J., Rubio I.G., Knobel M., Possato R.F., RA Targovnik H.M., Kopp P., Medeiros-Neto G.; RT "The p.A2215D thyroglobulin gene mutation leads to deficient synthesis RT and secretion of the mutated protein and congenital hypothyroidism RT with wide phenotype variation."; RL J. Clin. Endocrinol. Metab. 94:2938-2944(2009). RN [26] RP VARIANT TDH3 2336-ARG--LYS-2768 DEL. RX PubMed=27305979; DOI=10.1038/jhg.2016.62; RA Mittal K., Rafiq M.A., Rafiullah R., Harripaul R., Ali H., Ayaz M., RA Aslam M., Naeem F., Amin-Ud-Din M., Waqas A., So J., Rappold G.A., RA Vincent J.B., Ayub M.; RT "Mutations in the genes for thyroglobulin and thyroid peroxidase cause RT thyroid dyshormonogenesis and autosomal-recessive intellectual RT disability."; RL J. Hum. Genet. 61:867-872(2016). CC -!- FUNCTION: Precursor of the iodinated thyroid hormones thyroxine CC (T4) and triiodothyronine (T3). CC -!- SUBUNIT: Homodimer. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Major; CC IsoId=P01266-1; Sequence=Displayed; CC Name=2; Synonyms=Minor; CC IsoId=P01266-2; Sequence=VSP_012655; CC -!- TISSUE SPECIFICITY: Thyroid gland specific. CC -!- PTM: Sulfated tyrosines are desulfated during iodination. CC {ECO:0000269|PubMed:10448091, ECO:0000269|PubMed:12387814}. CC -!- DISEASE: Thyroid dyshormonogenesis 3 (TDH3) [MIM:274700]: A CC disorder due to thyroid dyshormonogenesis, causing large goiters CC of elastic and soft consistency in the majority of patients. CC Although the degree of thyroid dysfunction varies considerably CC among patients with defective thyroglobulin synthesis, patients CC usually have a relatively high serum free triiodothyronine (T3) CC concentration with disproportionately low free tetraiodothyronine CC (T4) level. The maintenance of relatively high free T3 levels CC prevents profound tissue hypothyroidism except in brain and CC pituitary, which are dependent on T4 supply, resulting in CC neurologic and intellectual defects in some cases. CC {ECO:0000269|PubMed:10199792, ECO:0000269|PubMed:16477365, CC ECO:0000269|PubMed:17244789, ECO:0000269|PubMed:17532758, CC ECO:0000269|PubMed:19509106, ECO:0000269|PubMed:27305979}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Autoimmune thyroid disease 3 (AITD3) [MIM:608175]: A CC complex autoimmune disorder comprising two related diseases CC affecting the thyroid: Graves disease and Hashimoto thyroiditis. CC In both disorders, thyroid-reactive T-cells are formed and CC infiltrate the thyroid gland. In Graves disease, the majority of CC the T-cells undergo a Th2 differentiation and activate B-cells to CC produce antibodies against the TSH receptor, which stimulate the CC thyroid and cause clinical hyperthyroidism. In contrast, Hashimoto CC thyroiditis is characterized by Th1 switching of the thyroid- CC infiltrating T-cells, which induces apoptosis of thyroid CC follicular cells and clinical hypothyroidism. CC {ECO:0000269|PubMed:14657345}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the type-B carboxylesterase/lipase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Thyroglobulin entry; CC URL="https://en.wikipedia.org/wiki/Thyroglobulin"; 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; X05615; CAA29104.1; -; mRNA. DR EMBL; U93033; AAC51924.1; -; mRNA. DR EMBL; AF230667; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF235100; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF230666; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF305872; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X02154; CAA26089.1; -; mRNA. DR EMBL; X06059; CAA29454.1; -; Genomic_DNA. DR EMBL; X06060; CAA29454.1; JOINED; Genomic_DNA. DR EMBL; X06061; CAA29454.1; JOINED; Genomic_DNA. DR EMBL; X06062; CAA29454.1; JOINED; Genomic_DNA. DR EMBL; X06063; CAA29454.1; JOINED; Genomic_DNA. DR EMBL; X06064; CAA29454.1; JOINED; Genomic_DNA. DR EMBL; X06065; CAA29454.1; JOINED; Genomic_DNA. DR EMBL; X06066; CAA29454.1; JOINED; Genomic_DNA. DR EMBL; X06067; CAA29455.1; -; Genomic_DNA. DR EMBL; X06068; CAA29455.1; JOINED; Genomic_DNA. DR EMBL; X06069; CAA29456.1; -; Genomic_DNA. DR EMBL; X06070; CAA29456.1; JOINED; Genomic_DNA. DR EMBL; X02749; CAA26527.1; -; Genomic_DNA. DR EMBL; AH008122; AAD51647.1; -; Genomic_DNA. DR EMBL; AH007064; AAC95473.1; -; Genomic_DNA. DR EMBL; AF080484; AAD50912.2; -; Genomic_DNA. DR EMBL; AF169654; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169655; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169656; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169657; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169658; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169659; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169661; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169662; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169663; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF169664; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080472; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080473; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080474; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080475; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080476; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080477; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080478; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080479; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080480; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080481; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080482; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; AF080483; AAD50912.2; JOINED; Genomic_DNA. DR EMBL; S40807; AAB22685.1; -; mRNA. DR CCDS; CCDS34944.1; -. [P01266-1] DR PIR; A59110; UIHU. DR RefSeq; NP_003226.4; NM_003235.4. [P01266-1] DR RefSeq; XP_016869284.1; XM_017013795.1. [P01266-2] DR UniGene; Hs.654591; -. DR ProteinModelPortal; P01266; -. DR SMR; P01266; -. DR BioGrid; 112896; 3. DR ELM; P01266; -. DR IntAct; P01266; 2. DR STRING; 9606.ENSP00000220616; -. DR ESTHER; human-TG; Thyroglobulin. DR MEROPS; I31.950; -. DR CarbonylDB; P01266; -. DR GlyConnect; 600; -. DR iPTMnet; P01266; -. DR PhosphoSitePlus; P01266; -. DR UniCarbKB; P01266; -. DR BioMuta; TG; -. DR DMDM; 126302607; -. DR PaxDb; P01266; -. DR PeptideAtlas; P01266; -. DR PRIDE; P01266; -. DR ProteomicsDB; 51364; -. DR ProteomicsDB; 51365; -. [P01266-2] DR Ensembl; ENST00000220616; ENSP00000220616; ENSG00000042832. [P01266-1] DR GeneID; 7038; -. DR KEGG; hsa:7038; -. DR UCSC; uc003ytw.4; human. [P01266-1] DR CTD; 7038; -. DR DisGeNET; 7038; -. DR EuPathDB; HostDB:ENSG00000042832.11; -. DR GeneCards; TG; -. DR H-InvDB; HIX0034371; -. DR HGNC; HGNC:11764; TG. DR HPA; CAB000077; -. DR HPA; CAB056155; -. DR HPA; HPA002740; -. DR MalaCards; TG; -. DR MIM; 188450; gene. DR MIM; 274700; phenotype. DR MIM; 608175; phenotype. DR neXtProt; NX_P01266; -. DR OpenTargets; ENSG00000042832; -. DR Orphanet; 95716; Familial thyroid dyshormonogenesis. DR PharmGKB; PA36479; -. DR eggNOG; ENOG410IG6K; Eukaryota. DR eggNOG; COG2272; LUCA. DR GeneTree; ENSGT00940000159300; -. DR HOVERGEN; HBG017929; -. DR InParanoid; P01266; -. DR KO; K10809; -. DR OMA; LRSCWCV; -. DR OrthoDB; 754103at2759; -. DR PhylomeDB; P01266; -. DR TreeFam; TF351833; -. DR BioCyc; MetaCyc:ENSG00000042832-MONOMER; -. DR SIGNOR; P01266; -. DR ChiTaRS; TG; human. DR GeneWiki; Thyroglobulin; -. DR GenomeRNAi; 7038; -. DR PRO; PR:P01266; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; ENSG00000042832; Expressed in 103 organ(s), highest expression level in thyroid gland. DR ExpressionAtlas; P01266; baseline and differential. DR Genevisible; P01266; HS. DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB. DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW. DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0015705; P:iodide transport; IEA:Ensembl. DR GO; GO:0031641; P:regulation of myelination; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR GO; GO:0030878; P:thyroid gland development; IEP:UniProtKB. DR GO; GO:0042403; P:thyroid hormone metabolic process; IEA:Ensembl. DR CDD; cd00191; TY; 7. DR Gene3D; 3.40.50.1820; -; 1. DR Gene3D; 4.10.800.10; -; 8. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR002018; CarbesteraseB. DR InterPro; IPR019819; Carboxylesterase_B_CS. DR InterPro; IPR016324; Thyroglobulin. DR InterPro; IPR000716; Thyroglobulin_1. DR InterPro; IPR036857; Thyroglobulin_1_sf. DR InterPro; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like. DR Pfam; PF00135; COesterase; 1. DR Pfam; PF07699; Ephrin_rec_like; 1. DR Pfam; PF00086; Thyroglobulin_1; 10. DR PIRSF; PIRSF001831; Thyroglobulin; 1. DR SMART; SM01411; Ephrin_rec_like; 1. DR SMART; SM00211; TY; 10. DR SUPFAM; SSF53474; SSF53474; 1. DR SUPFAM; SSF57610; SSF57610; 11. DR PROSITE; PS00941; CARBOXYLESTERASE_B_2; 1. DR PROSITE; PS00484; THYROGLOBULIN_1_1; 9. DR PROSITE; PS51162; THYROGLOBULIN_1_2; 11. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Congenital hypothyroidism; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Glycoprotein; Hormone; Iodination; Polymorphism; Proteoglycan; KW Reference proteome; Repeat; Secreted; Signal; Sulfation; KW Thyroid hormone; Thyroid hormones biosynthesis. FT SIGNAL 1 19 FT CHAIN 20 2768 Thyroglobulin. FT /FTId=PRO_0000008636. FT DOMAIN 31 92 Thyroglobulin type-1 1. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 93 160 Thyroglobulin type-1 2. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 161 297 Thyroglobulin type-1 3. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 298 358 Thyroglobulin type-1 4. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 605 658 Thyroglobulin type-1 5. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 659 726 Thyroglobulin type-1 6. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 727 921 Thyroglobulin type-1 7. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 922 1073 Thyroglobulin type-1 8. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 1074 1145 Thyroglobulin type-1 9. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DOMAIN 1146 1210 Thyroglobulin type-1 10. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT REPEAT 1456 1469 Type II. {ECO:0000269|PubMed:8797845}. FT REPEAT 1470 1486 Type II. {ECO:0000269|PubMed:8797845}. FT REPEAT 1487 1503 Type II. {ECO:0000269|PubMed:8797845}. FT DOMAIN 1511 1565 Thyroglobulin type-1 11. FT {ECO:0000255|PROSITE-ProRule:PRU00500}. FT REPEAT 1603 1723 Type IIIA. {ECO:0000269|PubMed:8797845}. FT REPEAT 1724 1892 Type IIIB. {ECO:0000269|PubMed:8797845}. FT REPEAT 1893 1995 Type IIIA. {ECO:0000269|PubMed:8797845}. FT REPEAT 1996 2129 Type IIIB. {ECO:0000269|PubMed:8797845}. FT REPEAT 2130 2187 Type IIIA. {ECO:0000269|PubMed:8797845}. FT SITE 110 110 Not glycosylated. FT {ECO:0000269|PubMed:8615697}. FT SITE 496 496 Not glycosylated. FT {ECO:0000269|PubMed:8615697}. FT SITE 1869 1869 Not glycosylated. FT {ECO:0000269|PubMed:8615697}. FT SITE 2122 2122 Not glycosylated. FT {ECO:0000269|PubMed:8615697}. FT MOD_RES 24 24 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 24 24 Sulfotyrosine; alternate. {ECO:0000250}. FT MOD_RES 24 24 Thyroxine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 24 24 Triiodothyronine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 149 149 Diiodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 149 149 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 258 258 Iodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 704 704 Diiodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 704 704 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 704 704 Thyroxine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 704 704 Triiodothyronine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 785 785 Iodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 866 866 Diiodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 866 866 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 883 883 Diiodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 992 992 Diiodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 992 992 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 1310 1310 Iodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 1467 1467 Diiodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 1467 1467 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2184 2184 Iodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2573 2573 Diiodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2573 2573 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2573 2573 Thyroxine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2573 2573 Triiodothyronine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2587 2587 Iodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2617 2617 Iodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2697 2697 Diiodotyrosine. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2766 2766 Diiodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2766 2766 Iodotyrosine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2766 2766 Thyroxine; alternate. FT {ECO:0000269|PubMed:2760035}. FT MOD_RES 2766 2766 Triiodothyronine; alternate. FT {ECO:0000269|PubMed:2760035}. FT CARBOHYD 76 76 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 198 198 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 484 484 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 529 529 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 748 748 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 816 816 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 947 947 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 1220 1220 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 1348 1348 N-linked (GlcNAc...) asparagine. FT {ECO:0000305|PubMed:8615697}. FT CARBOHYD 1349 1349 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 1365 1365 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 1716 1716 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 1774 1774 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 2013 2013 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 2250 2250 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 2295 2295 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 2582 2582 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:8615697}. FT CARBOHYD 2749 2749 O-linked (Xyl...) (chondroitin sulfate) FT serine. {ECO:0000269|PubMed:16679516}. FT DISULFID 34 52 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 63 70 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 72 92 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 96 120 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 131 138 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 140 160 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 164 183 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 194 235 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 301 319 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 330 336 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 338 358 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 608 620 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 631 636 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 638 658 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 662 687 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 698 703 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 705 726 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 730 763 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 774 898 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 900 921 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1042 1049 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1051 1073 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1077 1108 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1126 1145 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1149 1169 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1181 1188 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1190 1210 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1514 1523 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 1543 1565 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT DISULFID 2264 2281 {ECO:0000255|PROSITE-ProRule:PRU00500}. FT VAR_SEQ 1510 1567 CVTDCQRNEAGLQCDQNGQYRASQKDRGSGKAFCVDGEGRR FT LPWWETEAPLEDSQCLM -> L (in isoform 2). FT {ECO:0000303|PubMed:1639210}. FT /FTId=VSP_012655. FT VARIANT 135 135 Q -> H (in dbSNP:rs2069546). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010212. FT VARIANT 183 183 C -> Y (in TDH3). FT {ECO:0000269|PubMed:17532758}. FT /FTId=VAR_063034. FT VARIANT 515 515 Q -> E (in dbSNP:rs180222). FT {ECO:0000269|PubMed:16421571}. FT /FTId=VAR_016190. FT VARIANT 604 604 S -> D (requires 2 nucleotide FT substitutions; dbSNP:rs2069547). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599, FT ECO:0000269|PubMed:3971976}. FT /FTId=VAR_016852. FT VARIANT 653 653 G -> D (in dbSNP:rs2069548). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599, FT ECO:0000269|PubMed:3971976}. FT /FTId=VAR_016853. FT VARIANT 734 734 S -> A (polymorphism associated with FT AITD3; dbSNP:rs180223). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:14657345, FT ECO:0000269|PubMed:3681978}. FT /FTId=VAR_010213. FT VARIANT 777 777 P -> L (in dbSNP:rs3739274). FT /FTId=VAR_049077. FT VARIANT 815 815 G -> R (in dbSNP:rs16904774). FT /FTId=VAR_049078. FT VARIANT 830 830 Q -> E (in dbSNP:rs2076737). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010214. FT VARIANT 870 870 Q -> H (in dbSNP:rs2229843). FT {ECO:0000269|PubMed:8094490}. FT /FTId=VAR_002365. FT VARIANT 985 985 Missing. {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016854. FT VARIANT 988 988 R -> P (in dbSNP:rs16893332). FT /FTId=VAR_049079. FT VARIANT 1028 1028 M -> V (polymorphism associated with FT AITD3; dbSNP:rs853326). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:14657345}. FT /FTId=VAR_010215. FT VARIANT 1043 1043 H -> Y (in dbSNP:rs143983705). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016855. FT VARIANT 1059 1059 I -> T (in dbSNP:rs1016185504). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016856. FT VARIANT 1063 1063 L -> M (in dbSNP:rs11992497). FT /FTId=VAR_049080. FT VARIANT 1222 1222 S -> L (in dbSNP:rs12549018). FT /FTId=VAR_049081. FT VARIANT 1264 1264 C -> R (in TDH3; autosomal recessive; FT dbSNP:rs2076738). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010216. FT VARIANT 1312 1312 D -> G (in dbSNP:rs2069556). FT {ECO:0000269|PubMed:11124863, FT ECO:0000269|PubMed:3595599, FT ECO:0000269|PubMed:9186272}. FT /FTId=VAR_010217. FT VARIANT 1437 1437 W -> R (in dbSNP:rs2069558). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016857. FT VARIANT 1463 1463 P -> H. {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016858. FT VARIANT 1740 1740 T -> K (in dbSNP:rs16904791). FT /FTId=VAR_049082. FT VARIANT 1838 1838 D -> N (in dbSNP:rs2069561). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010218. FT VARIANT 1897 1897 C -> Y (in TDH3; dbSNP:rs121912649). FT {ECO:0000269|PubMed:16477365}. FT /FTId=VAR_063035. FT VARIANT 1936 1936 A -> T (in dbSNP:rs2069562). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016859. FT VARIANT 1974 1974 M -> T (in dbSNP:rs56230101). FT /FTId=VAR_061173. FT VARIANT 1979 1979 R -> W (polymorphism associated with FT AITD3). {ECO:0000269|PubMed:14657345}. FT /FTId=VAR_032013. FT VARIANT 1996 1996 C -> S (in TDH3; autosomal recessive; FT dbSNP:rs2076739). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010219. FT VARIANT 1999 1999 R -> W (in dbSNP:rs2076740). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010220. FT VARIANT 2091 2091 D -> E. {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016860. FT VARIANT 2149 2149 P -> L (in dbSNP:rs2069564). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:10524569, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016861. FT VARIANT 2170 2170 Q -> R (in dbSNP:rs2069565). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:10524569, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016862. FT VARIANT 2234 2234 A -> D (in TDH3; reduces thyroglobulin FT synthesis and secretion; promotes FT thyroglobulin retention within the FT endoplasmic reticulum; FT dbSNP:rs370991693). FT {ECO:0000269|PubMed:17532758, FT ECO:0000269|PubMed:19509106}. FT /FTId=VAR_063036. FT VARIANT 2242 2242 R -> H (in dbSNP:rs2069566). FT {ECO:0000269|PubMed:10199792, FT ECO:0000269|PubMed:3595599}. FT /FTId=VAR_016863. FT VARIANT 2336 2768 Missing (in TDH3; unknown pathological FT significance). FT {ECO:0000269|PubMed:27305979}. FT /FTId=VAR_078338. FT VARIANT 2336 2336 R -> Q (in TDH3; dbSNP:rs121912650). FT {ECO:0000269|PubMed:16477365}. FT /FTId=VAR_063037. FT VARIANT 2375 2375 G -> R (in TDH3; dbSNP:rs137854434). FT {ECO:0000269|PubMed:17244789}. FT /FTId=VAR_063038. FT VARIANT 2455 2455 R -> H (in dbSNP:rs2272707). FT /FTId=VAR_049083. FT VARIANT 2469 2469 L -> P (in dbSNP:rs2069568). FT /FTId=VAR_049084. FT VARIANT 2501 2501 W -> R (in dbSNP:rs2069569). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010221. FT VARIANT 2526 2526 F -> L (in dbSNP:rs12114109). FT /FTId=VAR_049085. FT VARIANT 2530 2530 R -> Q (in dbSNP:rs1133076). FT {ECO:0000269|PubMed:10199792}. FT /FTId=VAR_010222. FT VARIANT 2616 2616 N -> S (in dbSNP:rs10091530). FT /FTId=VAR_049086. FT CONFLICT 23 25 EYQ -> GKF (in Ref. 6; CAA26527). FT {ECO:0000305}. FT CONFLICT 848 848 Missing (in Ref. 13; AA sequence). FT {ECO:0000305}. FT CONFLICT 984 985 EQ -> DR (in Ref. 5; CAA29456). FT {ECO:0000305}. FT CONFLICT 1359 1360 Missing (in Ref. 13; AA sequence). FT {ECO:0000305}. FT CONFLICT 1717 1717 L -> A (in Ref. 13; AA sequence). FT {ECO:0000305}. FT CONFLICT 1776 1776 T -> S (in Ref. 13; AA sequence). FT {ECO:0000305}. FT CONFLICT 2019 2019 G -> H (in Ref. 13; AA sequence). FT {ECO:0000305}. FT CONFLICT 2287 2287 F -> P (in Ref. 13; AA sequence). FT {ECO:0000305}. SQ SEQUENCE 2768 AA; 304790 MW; 69A87D935F1BAA72 CRC64; MALVLEIFTL LASICWVSAN IFEYQVDAQP LRPCELQRET AFLKQADYVP QCAEDGSFQT VQCQNDGRSC WCVGANGSEV LGSRQPGRPV ACLSFCQLQK QQILLSGYIN STDTSYLPQC QDSGDYAPVQ CDVQQVQCWC VDAEGMEVYG TRQLGRPKRC PRSCEIRNRR LLHGVGDKSP PQCSAEGEFM PVQCKFVNTT DMMIFDLVHS YNRFPDAFVT FSSFQRRFPE VSGYCHCADS QGRELAETGL ELLLDEIYDT IFAGLDLPST FTETTLYRIL QRRFLAVQSV ISGRFRCPTK CEVERFTATS FGHPYVPSCR RNGDYQAVQC QTEGPCWCVD AQGKEMHGTR QQGEPPSCAE GQSCASERQQ ALSRLYFGTS GYFSQHDLFS SPEKRWASPR VARFATSCPP TIKELFVDSG LLRPMVEGQS QQFSVSENLL KEAIRAIFPS RGLARLALQF TTNPKRLQQN LFGGKFLVNV GQFNLSGALG TRGTFNFSQF FQQLGLASFL NGGRQEDLAK PLSVGLDSNS STGTPEAAKK DGTMNKPTVG SFGFEINLQE NQNALKFLAS LLELPEFLLF LQHAISVPED VARDLGDVME TVLSSQTCEQ TPERLFVPSC TTEGSYEDVQ CFSGECWCVN SWGKELPGSR VRGGQPRCPT DCEKQRARMQ SLMGSQPAGS TLFVPACTSE GHFLPVQCFN SECYCVDAEG QAIPGTRSAI GKPKKCPTPC QLQSEQAFLR TVQALLSNSS MLPTLSDTYI PQCSTDGQWR QVQCNGPPEQ VFELYQRWEA QNKGQDLTPA KLLVKIMSYR EAASGNFSLF IQSLYEAGQQ DVFPVLSQYP SLQDVPLAAL EGKRPQPREN ILLEPYLFWQ ILNGQLSQYP GSYSDFSTPL AHFDLRNCWC VDEAGQELEG MRSEPSKLPT CPGSCEEAKL RVLQFIRETE EIVSASNSSR FPLGESFLVA KGIRLRNEDL GLPPLFPPRE AFAEQFLRGS DYAIRLAAQS TLSFYQRRRF SPDDSAGASA LLRSGPYMPQ CDAFGSWEPV QCHAGTGHCW CVDEKGGFIP GSLTARSLQI PQCPTTCEKS RTSGLLSSWK QARSQENPSP KDLFVPACLE TGEYARLQAS GAGTWCVDPA SGEELRPGSS SSAQCPSLCN VLKSGVLSRR VSPGYVPACR AEDGGFSPVQ CDQAQGSCWC VMDSGEEVPG TRVTGGQPAC ESPRCPLPFN ASEVVGGTIL CETISGPTGS AMQQCQLLCR QGSWSVFPPG PLICSLESGR WESQLPQPRA CQRPQLWQTI QTQGHFQLQL PPGKMCSADY ADLLQTFQVF ILDELTARGF CQIQVKTFGT LVSIPVCNNS SVQVGCLTRE RLGVNVTWKS RLEDIPVASL PDLHDIERAL VGKDLLGRFT DLIQSGSFQL HLDSKTFPAE TIRFLQGDHF GTSPRTWFGC SEGFYQVLTS EASQDGLGCV KCPEGSYSQD EECIPCPVGF YQEQAGSLAC VPCPVGRTTI SAGAFSQTHC VTDCQRNEAG LQCDQNGQYR ASQKDRGSGK AFCVDGEGRR LPWWETEAPL EDSQCLMMQK FEKVPESKVI FDANAPVAVR SKVPDSEFPV MQCLTDCTED EACSFFTVST TEPEISCDFY AWTSDNVACM TSDQKRDALG NSKATSFGSL RCQVKVRSHG QDSPAVYLKK GQGSTTTLQK RFEPTGFQNM LSGLYNPIVF SASGANLTDA HLFCLLACDR DLCCDGFVLT QVQGGAIICG LLSSPSVLLC NVKDWMDPSE AWANATCPGV TYDQESHQVI LRLGDQEFIK SLTPLEGTQD TFTNFQQVYL WKDSDMGSRP ESMGCRKDTV PRPASPTEAG LTTELFSPVD LNQVIVNGNQ SLSSQKHWLF KHLFSAQQAN LWCLSRCVQE HSFCQLAEIT ESASLYFTCT LYPEAQVCDD IMESNAQGCR LILPQMPKAL FRKKVILEDK VKNFYTRLPF QKLMGISIRN KVPMSEKSIS NGFFECERRC DADPCCTGFG FLNVSQLKGG EVTCLTLNSL GIQMCSEENG GAWRILDCGS PDIEVHTYPF GWYQKPIAQN NAPSFCPLVV LPSLTEKVSL DSWQSLALSS VVVDPSIRHF DVAHVSTAAT SNFSAVRDLC LSECSQHEAC LITTLQTQPG AVRCMFYADT QSCTHSLQGQ NCRLLLREEA THIYRKPGIS LLSYEASVPS VPISTHGRLL GRSQAIQVGT SWKQVDQFLG VPYAAPPLAE RRFQAPEPLN WTGSWDASKP RASCWQPGTR TSTSPGVSED CLYLNVFIPQ NVAPNASVLV FFHNTMDREE SEGWPAIDGS FLAAVGNLIV VTASYRVGVF GFLSSGSGEV SGNWGLLDQV AALTWVQTHI RGFGGDPRRV SLAADRGGAD VASIHLLTAR ATNSQLFRRA VLMGGSALSP AAVISHERAQ QQAIALAKEV SCPMSSSQEV VSCLRQKPAN VLNDAQTKLL AVSGPFHYWG PVIDGHFLRE PPARALKRSL WVEVDLLIGS SQDDGLINRA KAVKQFEESR GRTSSKTAFY QALQNSLGGE DSDARVEAAA TWYYSLEHST DDYASFSRAL ENATRDYFII CPIIDMASAW AKRARGNVFM YHAPENYGHG SLELLADVQF ALGLPFYPAY EGQFSLEEKS LSLKIMQYFS HFIRSGNPNY PYEFSRKVPT FATPWPDFVP RAGGENYKEF SELLPNRQGL KKADCSFWSK YISSLKTSAD GAKGGQSAES EEEELTAGSG LREDLLSLQE PGSKTYSK //