| IED ID | IndEnz0005000971 |
| Enzyme Type ID | lipase000971 |
| Protein Name |
Thyroglobulin Tg |
| Gene Name | TG |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MALVLEIFTLLASICWVSANIFEYQVDAQPLRPCELQRETAFLKQADYVPQCAEDGSFQTVQCQNDGRSCWCVGANGSEVLGSRQPGRPVACLSFCQLQKQQILLSGYINSTDTSYLPQCQDSGDYAPVQCDVQQVQCWCVDAEGMEVYGTRQLGRPKRCPRSCEIRNRRLLHGVGDKSPPQCSAEGEFMPVQCKFVNTTDMMIFDLVHSYNRFPDAFVTFSSFQRRFPEVSGYCHCADSQGRELAETGLELLLDEIYDTIFAGLDLPSTFTETTLYRILQRRFLAVQSVISGRFRCPTKCEVERFTATSFGHPYVPSCRRNGDYQAVQCQTEGPCWCVDAQGKEMHGTRQQGEPPSCAEGQSCASERQQALSRLYFGTSGYFSQHDLFSSPEKRWASPRVARFATSCPPTIKELFVDSGLLRPMVEGQSQQFSVSENLLKEAIRAIFPSRGLARLALQFTTNPKRLQQNLFGGKFLVNVGQFNLSGALGTRGTFNFSQFFQQLGLASFLNGGRQEDLAKPLSVGLDSNSSTGTPEAAKKDGTMNKPTVGSFGFEINLQENQNALKFLASLLELPEFLLFLQHAISVPEDVARDLGDVMETVLSSQTCEQTPERLFVPSCTTEGSYEDVQCFSGECWCVNSWGKELPGSRVRGGQPRCPTDCEKQRARMQSLMGSQPAGSTLFVPACTSEGHFLPVQCFNSECYCVDAEGQAIPGTRSAIGKPKKCPTPCQLQSEQAFLRTVQALLSNSSMLPTLSDTYIPQCSTDGQWRQVQCNGPPEQVFELYQRWEAQNKGQDLTPAKLLVKIMSYREAASGNFSLFIQSLYEAGQQDVFPVLSQYPSLQDVPLAALEGKRPQPRENILLEPYLFWQILNGQLSQYPGSYSDFSTPLAHFDLRNCWCVDEAGQELEGMRSEPSKLPTCPGSCEEAKLRVLQFIRETEEIVSASNSSRFPLGESFLVAKGIRLRNEDLGLPPLFPPREAFAEQFLRGSDYAIRLAAQSTLSFYQRRRFSPDDSAGASALLRSGPYMPQCDAFGSWEPVQCHAGTGHCWCVDEKGGFIPGSLTARSLQIPQCPTTCEKSRTSGLLSSWKQARSQENPSPKDLFVPACLETGEYARLQASGAGTWCVDPASGEELRPGSSSSAQCPSLCNVLKSGVLSRRVSPGYVPACRAEDGGFSPVQCDQAQGSCWCVMDSGEEVPGTRVTGGQPACESPRCPLPFNASEVVGGTILCETISGPTGSAMQQCQLLCRQGSWSVFPPGPLICSLESGRWESQLPQPRACQRPQLWQTIQTQGHFQLQLPPGKMCSADYADLLQTFQVFILDELTARGFCQIQVKTFGTLVSIPVCNNSSVQVGCLTRERLGVNVTWKSRLEDIPVASLPDLHDIERALVGKDLLGRFTDLIQSGSFQLHLDSKTFPAETIRFLQGDHFGTSPRTWFGCSEGFYQVLTSEASQDGLGCVKCPEGSYSQDEECIPCPVGFYQEQAGSLACVPCPVGRTTISAGAFSQTHCVTDCQRNEAGLQCDQNGQYRASQKDRGSGKAFCVDGEGRRLPWWETEAPLEDSQCLMMQKFEKVPESKVIFDANAPVAVRSKVPDSEFPVMQCLTDCTEDEACSFFTVSTTEPEISCDFYAWTSDNVACMTSDQKRDALGNSKATSFGSLRCQVKVRSHGQDSPAVYLKKGQGSTTTLQKRFEPTGFQNMLSGLYNPIVFSASGANLTDAHLFCLLACDRDLCCDGFVLTQVQGGAIICGLLSSPSVLLCNVKDWMDPSEAWANATCPGVTYDQESHQVILRLGDQEFIKSLTPLEGTQDTFTNFQQVYLWKDSDMGSRPESMGCRKDTVPRPASPTEAGLTTELFSPVDLNQVIVNGNQSLSSQKHWLFKHLFSAQQANLWCLSRCVQEHSFCQLAEITESASLYFTCTLYPEAQVCDDIMESNAQGCRLILPQMPKALFRKKVILEDKVKNFYTRLPFQKLMGISIRNKVPMSEKSISNGFFECERRCDADPCCTGFGFLNVSQLKGGEVTCLTLNSLGIQMCSEENGGAWRILDCGSPDIEVHTYPFGWYQKPIAQNNAPSFCPLVVLPSLTEKVSLDSWQSLALSSVVVDPSIRHFDVAHVSTAATSNFSAVRDLCLSECSQHEACLITTLQTQPGAVRCMFYADTQSCTHSLQGQNCRLLLREEATHIYRKPGISLLSYEASVPSVPISTHGRLLGRSQAIQVGTSWKQVDQFLGVPYAAPPLAERRFQAPEPLNWTGSWDASKPRASCWQPGTRTSTSPGVSEDCLYLNVFIPQNVAPNASVLVFFHNTMDREESEGWPAIDGSFLAAVGNLIVVTASYRVGVFGFLSSGSGEVSGNWGLLDQVAALTWVQTHIRGFGGDPRRVSLAADRGGADVASIHLLTARATNSQLFRRAVLMGGSALSPAAVISHERAQQQAIALAKEVSCPMSSSQEVVSCLRQKPANVLNDAQTKLLAVSGPFHYWGPVIDGHFLREPPARALKRSLWVEVDLLIGSSQDDGLINRAKAVKQFEESRGRTSSKTAFYQALQNSLGGEDSDARVEAAATWYYSLEHSTDDYASFSRALENATRDYFIICPIIDMASAWAKRARGNVFMYHAPENYGHGSLELLADVQFALGLPFYPAYEGQFSLEEKSLSLKIMQYFSHFIRSGNPNYPYEFSRKVPTFATPWPDFVPRAGGENYKEFSELLPNRQGLKKADCSFWSKYISSLKTSADGAKGGQSAESEEEELTAGSGLREDLLSLQEPGSKTYSK |
| Enzyme Length | 2768 |
| Uniprot Accession Number | P01266 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3) (PubMed:32025030, PubMed:17532758). The synthesis of T3 and T4 involves iodination of selected tyrosine residues of TG/thyroglobulin followed by their oxidative coupling in the thyroid follicle lumen (PubMed:32025030). Following TG re-internalization and lysosomal-mediated proteolysis, T3 and T4 are released from the polypeptide backbone leading to their secretion into the bloodstream (PubMed:32025030). One dimer produces 7 thyroid hormone molecules (PubMed:32025030). {ECO:0000269|PubMed:17532758, ECO:0000269|PubMed:32025030}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Chain (1); Compositional bias (1); Disulfide bond (60); Domain (11); Glycosylation (21); Modified residue (36); Mutagenesis (10); Natural variant (42); Region (3); Repeat (8); Sequence conflict (8); Signal peptide (1); Site (4) |
| Keywords | 3D-structure;Alternative splicing;Congenital hypothyroidism;Direct protein sequencing;Disease variant;Disulfide bond;Glycoprotein;Hormone;Iodination;Proteoglycan;Reference proteome;Repeat;Secreted;Signal;Sulfation;Thyroid hormone;Thyroid hormones biosynthesis |
| Interact With | Q99523 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11082042, ECO:0000269|PubMed:19509106, ECO:0000269|PubMed:8626858}. Note=Secreted into the thyroid follicle lumen (PubMed:19509106). Localizes to colloid globules, a structure formed in the thyroid follicle lumen consisting of cross-linked TG arranged in concentric layers (PubMed:8626858, PubMed:11082042). {ECO:0000269|PubMed:11082042, ECO:0000269|PubMed:19509106, ECO:0000269|PubMed:8626858}. |
| Modified Residue | MOD_RES 24; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 24; /note="Sulfotyrosine; alternate"; /evidence="ECO:0000250|UniProtKB:F1RRV3"; MOD_RES 24; /note="Thyroxine; alternate"; /evidence="ECO:0000269|PubMed:2760035, ECO:0000305|PubMed:32025030"; MOD_RES 24; /note="Triiodothyronine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 108; /note="Iodotyrosine"; /evidence="ECO:0000305|PubMed:32025030"; MOD_RES 149; /note="Diiodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 149; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035, ECO:0000305|PubMed:32025030"; MOD_RES 234; /note="Iodotyrosine"; /evidence="ECO:0000305|PubMed:32025030"; MOD_RES 258; /note="Iodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 704; /note="Diiodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 704; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 704; /note="Thyroxine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 704; /note="Triiodothyronine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 785; /note="Iodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 866; /note="Diiodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 866; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 883; /note="Diiodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 992; /note="Diiodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 992; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 1310; /note="Iodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 1310; /note="Thyroxine"; /evidence="ECO:0000269|PubMed:2760035, ECO:0000305|PubMed:32025030"; MOD_RES 1467; /note="Diiodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 1467; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2184; /note="Iodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2540; /note="Iodotyrosine"; /evidence="ECO:0000305|PubMed:32025030"; MOD_RES 2573; /note="Diiodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2573; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2573; /note="Thyroxine; alternate"; /evidence="ECO:0000269|PubMed:2760035, ECO:0000305|PubMed:32025030"; MOD_RES 2573; /note="Triiodothyronine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2587; /note="Iodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2617; /note="Iodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2697; /note="Diiodotyrosine"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2766; /note="Diiodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2766; /note="Iodotyrosine; alternate"; /evidence="ECO:0000269|PubMed:2760035"; MOD_RES 2766; /note="Thyroxine; alternate"; /evidence="ECO:0000269|PubMed:2760035, ECO:0000305|PubMed:32025030"; MOD_RES 2766; /note="Triiodothyronine; alternate"; /evidence="ECO:0000269|PubMed:2760035" |
| Post Translational Modification | PTM: Iodinated on tyrosine residues by TPO (PubMed:2760035, PubMed:32025030). There are 4 pairs of iodinated tyrosines used for coupling: acceptor Tyr-24 is coupled to donor Tyr-149 or Tyr-234, acceptor Tyr-2573 is coupled to donor Tyr-2540, acceptor Tyr-2766 in monomer 1 is coupled to donor Tyr-2766 in monomer 2 and acceptor Tyr-1310 in monomer 1 is coupled to donor Tyr-108 in monomer 2 (PubMed:32025030). {ECO:0000269|PubMed:2760035, ECO:0000269|PubMed:32025030}.; PTM: Sulfated tyrosines are desulfated during iodination. {ECO:0000269|PubMed:10448091}.; PTM: Undergoes sequential proteolysis by cathepsins to release thyroxine (T4) and triiodothyronine (T3) hormones. In the thyroid follicle lumen, cross-linked TG (storage form) is solubilized by limited proteolysis mediated by cathepsins CTSB and/or CTSL. Partially cleaved TG is further processed by CTSK/cathepsin K and/or CTSL resulting in the release of T4. Following endocytosis, further processing occurs leading to the release of T3 and more T4 hormones. {ECO:0000250|UniProtKB:O08710}. |
| Signal Peptide | SIGNAL 1..19; /evidence=ECO:0000250|UniProtKB:F1RRV3 |
| Structure 3D | Electron microscopy (1) |
| Cross Reference PDB | 6SCJ; |
| Mapped Pubmed ID | 11935320; 12022704; 12804099; 12819023; 14557492; 14633662; 14764582; 15070908; 15272924; 15562032; 15579752; 15579800; 15769978; 15785246; 16230285; 16260629; 16271015; 16403815; 16646680; 17278897; 17526951; 17550957; 17644307; 17671725; 17854396; 17902201; 17911408; 18166820; 18243140; 18271683; 18385936; 18514160; 18566446; 18631008; 18636294; 18656705; 18755875; 19034705; 19194833; 19404338; 19416000; 19438904; 19438905; 19633549; 19730683; 19776016; 19837936; 20089614; 20173019; 20182447; 20215770; 20353937; 20379614; 20486066; 20573721; 20711500; 20864102; 20960158; 20972722; 20972728; 21039721; 21372558; 21476894; 21636579; 21646855; 21958696; 22098450; 22136265; 22136267; 22170797; 22259066; 22265031; 22517745; 22662162; 22784463; 23164529; 23190420; 23242039; 23345097; 23360821; 23455760; 23489940; 23826916; 23886742; 23900865; 23933148; 23949896; 24064687; 24341425; 24460082; 24565964; 24599957; 24762031; 25213012; 25536321; 25607926; 25633667; 25893415; 25895485; 26099577; 26595189; 26777470; 26851767; 26896794; 26963610; 27236916; 27525530; 28137736; 28396984; 28454525; 28493284; 28558632; 28675712; 28743746; 28855631; 28942902; 29275168; 29720101; 29953410; 30139952; 31352718; 31421134; 31444962; 31525728; 31585887; 31867598; 32633627; 33689781; 33964321; 34003526; 34119605; |
| Motif | |
| Gene Encoded By | |
| Mass | 304,790 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |