Protein:THRB |
Protein Summary |
 Gene summary |
| Gene name: THRB | ASpdb.0 ID: 7068 | Gene | Gene symbol | THRB | Gene ID | 7068 |
| Gene name | thyroid hormone receptor beta |
| Synonyms | C-ERBA-2|C-ERBA-BETA|ERBA2|GRTH|NR1A2|PRTH|THR1|THRB1|THRB2|THRbeta|THRbeta1|TRb|TRbeta|TRbeta1|Thrbeta2 |
| Cytomap | 3p24.2 |
| Type of gene | protein-coding |
| Description | thyroid hormone receptor betanuclear receptor subfamily 1 group A member 2oncogene ERBA2thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian) |
| Modification date | 20240411 |
| UniProtAcc | P10828 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | THRB | GO:0002157 | positive regulation of thyroid hormone mediated signaling pathway | 26289479 |
| Gene | THRB | GO:0004879 | nuclear receptor activity | 15466465 |
| Gene | THRB | GO:0016604 | nuclear body | - |
| Gene | THRB | GO:0042789 | mRNA transcription by RNA polymerase II | 26289479 |
| Gene | THRB | GO:0045944 | positive regulation of transcription by RNA polymerase II | 26289479 |
| Gene | THRB | GO:0070324 | thyroid hormone binding | 15466465 |
| Gene | THRB | GO:0090575 | RNA polymerase II transcription regulator complex | 26289479 |
| Gene | THRB | GO:0097067 | cellular response to thyroid hormone stimulus | 9368056 |
| Gene | THRB | GO:1990837 | sequence-specific double-stranded DNA binding | 28473536 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P10828-1 | P10828-1_1nq0_A.pdb | 1NQ0 | X-ray | 2.4 | A | 202 | 461 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P10828 | THRB | P10828-1 | P10828-2 | 461 | 476 | 1 | 93 | Substitution | MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEEKKC | MNYCMQEIYEVHPAAGSNCYMQSTDYYAYFEDSPGYSGCDAQAVPSNNIYMEQAWAVNQPYTCSYPGNMFKSKDSDLDMALNQYSQPEYFTEEKPTFSQVQSPSYSQK | 1 | 108 |
| Multiple sequence alignment of our canonical and alternatively spliced THRB |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of THRB |
| UniProt-id | ENSG | ENST | ENSP |
| P10828-1 | ENSG00000151090.20 | ENST00000356447.9 | ENSP00000348827.4 |
| P10828-1 | ENSG00000151090.20 | ENST00000396671.7 | ENSP00000379904.2 |
| P10828-1 | ENSG00000151090.20 | ENST00000416420.5 | ENSP00000414444.1 |
| P10828-1 | ENSG00000151090.20 | ENST00000642307.1 | ENSP00000494618.1 |
| P10828-1 | ENSG00000151090.20 | ENST00000643772.1 | ENSP00000496029.1 |
| P10828-1 | ENSG00000151090.20 | ENST00000644321.1 | ENSP00000496616.1 |
| P10828-1 | ENSG00000151090.20 | ENST00000645139.1 | ENSP00000493709.1 |
| P10828-1 | ENSG00000151090.20 | ENST00000646209.2 | ENSP00000496686.2 |
| P10828-1 | ENSG00000151090.20 | ENST00000646432.1 | ENSP00000496509.1 |
| P10828-2 | ENSG00000151090.20 | ENST00000280696.9 | ENSP00000280696.5 |
| UniProt-id | NM ID | NP ID |
| P10828-1 | NM_000461.4 | NP_000452.2 |
| P10828-1 | NM_001128176.2 | NP_001121648.1 |
| P10828-1 | NM_001128177.1 | NP_001121649.1 |
| P10828-1 | NM_001252634.1 | NP_001239563.1 |
| P10828-1 | XM_011534047.2 | XP_011532349.1 |
| P10828-1 | XM_011534050.2 | XP_011532352.1 |
| Amino acid sequences of our canonical and alternatively spliced THRB |
| accession_id | Protein sequence |
| P10828-1 | MTPNSMTENGLTAWDKPKHCPDREHDWKLVGMSEACLHRKSHSERRSTLKNEQSSPHLIQTTWTSSIFHLDHDDVNDQSVSSAQTFQTEE KKCKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECRFKKCIYVGMATDLVL DDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLPEDIGQAPIVNAPEGGKVDLEAFS HFTKIITPAITRVVDFAKKLPMFCELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAVTRGQLKNGGLGVVSDAIFDLGMSL SSFNLDDTEVALLQAVLLMSSDRPGLACVERIEKYQDSFLLAFEHYINYRKHHVTHFWPKLLMKVTDLRMIGACHASRFLHMKVECPTEL |
| P10828-2 | MNYCMQEIYEVHPAAGSNCYMQSTDYYAYFEDSPGYSGCDAQAVPSNNIYMEQAWAVNQPYTCSYPGNMFKSKDSDLDMALNQYSQPEYF TEEKPTFSQVQSPSYSQKKGYIPSYLDKDELCVVCGDKATGYHYRCITCEGCKGFFRRTIQKNLHPSYSCKYEGKCVIDKVTRNQCQECR FKKCIYVGMATDLVLDDSKRLAKRKLIEENREKRRREELQKSIGHKPEPTDEEWELIKTVTEAHVATNAQGSHWKQKRKFLPEDIGQAPI VNAPEGGKVDLEAFSHFTKIITPAITRVVDFAKKLPMFCELPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAVTRGQLKNGG LGVVSDAIFDLGMSLSSFNLDDTEVALLQAVLLMSSDRPGLACVERIEKYQDSFLLAFEHYINYRKHHVTHFWPKLLMKVTDLRMIGACH |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| THRB (go to UniProt):P10828 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P10828 | Region | 1 | 106 | Note=Modulating | Type=Substitution;Start=1;End=93 |
Gene Isoform Structures and Expression Levels for THRB |
| Gene structures of our canonical and alternative spliced genes of THRB * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P10828-1 |
| 3D view using mol* of P10828-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P10828-1 |
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| pLDDT distribution across the protein length of P10828-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P10828-1 |
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| Ramachandran plot of P10828-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P10828-1 | 1.249 | 141 | 1.29 | 156.408 | 0.208 | 0.981 | 1.333 | 3.485 | 0.73 | 4.771 | 0.305 | 232,233,234,269,272,273,275,276,279,282,310,313,31 4,316,317,320,330,331,341,344,345,346,353,442,451, 452,455 |
| P10828-2 | 1.274 | 156 | 1.335 | 181.79 | 0.2 | 0.976 | 1.285 | 4.049 | 0.584 | 6.933 | 0.319 | 247,248,249,284,287,288,290,291,294,297,298,325,32 8,329,331,332,335,344,345,346,347,356,359,360,361, 368,457,466,470 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P10828-1_P10828-1_1nq0_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P10828-1_1nq0_A_P10828-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P10828-1_P10828-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P10828-1_vs_P10828-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P10828-1_vs_P10828-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to THRB |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P10828 | THRB | DB02106 | [3,5-Dibromo-4-(4-Hydroxy-3-Phenethylcarbamoyl-Phenoxy)-Phenyl]-Acetic Acid | experimental | |
| P10828 | THRB | DB03181 | 2-[4-(4-Hydroxy-3-Isopropyl-Phenoxy)-3,5-Dimethyl-Phenyl]-2h-[1,2,4]Triazine-3,5-Dione | experimental | |
| P10828 | THRB | DB00451 | Levothyroxine | approved | agonist |
| P10828 | THRB | DB03604 | Tiratricol | investigational | |
| P10828 | THRB | DB05035 | Eprotirome | investigational | |
| P10828 | THRB | DB08085 | 1-(4-HEXYLPHENYL)PROP-2-EN-1-ONE | experimental | |
| P10828 | THRB | DB07425 | Sobetirome | investigational | |
| P10828 | THRB | DB03176 | KB-141 | experimental | |
| P10828 | THRB | DB00509 | Dextrothyroxine | approved, investigational | agonist |
| P10828 | THRB | DB01583 | Liotrix | approved | agonist |
| P10828 | THRB | DB03788 | GC-24 | experimental | |
| P10828 | THRB | DB05192 | MB07811 | investigational | |
| P10828 | THRB | DB09100 | Thyroid, porcine | approved | substrate |
| P10828 | THRB | DB00279 | Liothyronine | approved, vet_approved | agonist |
Related Diseases to THRB |
| Previous studies relating to the alternative splicing of THRB and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| THRB | 11518802 | Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance. | Patients with TSH-secreting pituitary tumors (TSHomas) have high serum TSH levels despite elevated thyroid hormone levels. The mechanism for this defect in the negative regulation of TSH secretion is not known. We performed RT-PCR to detect mutations in TRbeta from a surgically resected TSHoma. Analyses of the RT-PCR products revealed a 135-bp deletion within the sixth exon that encodes the ligand-binding domain of TRbeta2. This deletion was caused by alternative splicing of TRbeta2 mRNA, as near-consensus splice sequences were found at the junction site and no deletion or mutations were detected in the tumoral genomic DNA. This TRbeta variant (TRbeta2spl) lacked thyroid hormone binding and had impaired T3-dependent negative regulation of both TSHbeta and glycoprotein hormone alpha-subunit genes in cotransfection studies. Furthermore, TRbeta2spl showed dominant negative activity against the wild-type TRbeta2. These findings strongly suggest that aberrant alternative splicing of TRbeta2 mRNA generated an abnormal TR protein that accounted for the defective negative regulation of TSH in the TSHoma. This is the first example of aberrant alternative splicing of a nuclear hormone receptor causing hormonal dysregulation. This novel posttranscriptional mechanism for generating abnormal receptors may occur in other hormone-resistant states or tumors in which no receptor mutation is detected in genomic DNA. | D000236 | Adenoma |
| THRB | 11518802 | Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance. | Patients with TSH-secreting pituitary tumors (TSHomas) have high serum TSH levels despite elevated thyroid hormone levels. The mechanism for this defect in the negative regulation of TSH secretion is not known. We performed RT-PCR to detect mutations in TRbeta from a surgically resected TSHoma. Analyses of the RT-PCR products revealed a 135-bp deletion within the sixth exon that encodes the ligand-binding domain of TRbeta2. This deletion was caused by alternative splicing of TRbeta2 mRNA, as near-consensus splice sequences were found at the junction site and no deletion or mutations were detected in the tumoral genomic DNA. This TRbeta variant (TRbeta2spl) lacked thyroid hormone binding and had impaired T3-dependent negative regulation of both TSHbeta and glycoprotein hormone alpha-subunit genes in cotransfection studies. Furthermore, TRbeta2spl showed dominant negative activity against the wild-type TRbeta2. These findings strongly suggest that aberrant alternative splicing of TRbeta2 mRNA generated an abnormal TR protein that accounted for the defective negative regulation of TSH in the TSHoma. This is the first example of aberrant alternative splicing of a nuclear hormone receptor causing hormonal dysregulation. This novel posttranscriptional mechanism for generating abnormal receptors may occur in other hormone-resistant states or tumors in which no receptor mutation is detected in genomic DNA. | D010911 | Pituitary Neoplasms |
| THRB | 20691260 | Untranslated regions of thyroid hormone receptor beta 1 mRNA are impaired in human clear cell renal cell carcinoma. | Thyroid hormone receptor β1 (TRβ1) is a hormone-dependent transcription factor activated by 3,5,3'-l-triiodothyronine (T3). TRβ1 functions as a tumor suppressor and disturbances of the THRB gene are frequent findings in cancer. Translational control mediated by untranslated regions (UTRs) regulates cell proliferation, metabolism and responses to cellular stress, processes that are involved in carcinogenesis. We hypothesized that reduced TRβ1 expression in clear cell renal cell cancer (ccRCC) results from regulatory effects of TRβ1 5' and 3'UTRs on protein translation. We determined TRβ1 expression and alternative splicing of TRβ1 5' and 3'UTRs in ccRCC and control tissue together with expression of the type 1 deiodinase enzyme (coded by DIO1, a TRβ1 target gene). Tissue concentrations of T3 (which are generated in part by D1) and expression of miRNA-204 (an mRNA inhibitor for which a putative interaction site was identified in the TRβ1 3'UTR) were also determined. TRβ1 mRNA and protein levels were reduced by 70% and 91% in ccRCC and accompanied by absent D1 protein, a 58% reduction in tissue T3 concentration and 2-fold increase in miRNA-204. Structural analysis of TRβ1 UTR variants indicated that reduced TRβ1 expression may be maintained in ccRCC by posttranscriptional mechanisms involving 5'UTRs and miRNA-204. The tumor suppressor activity of TRβ1 indicates that reduced TRβ1 expression and tissue hypothyroidism in ccRCC tumors is likely to be involved in the process of carcinogenesis or in maintaining a proliferative advantage to malignant cells. | D002292 | Carcinoma, Renal Cell |
| THRB | 20691260 | Untranslated regions of thyroid hormone receptor beta 1 mRNA are impaired in human clear cell renal cell carcinoma. | Thyroid hormone receptor β1 (TRβ1) is a hormone-dependent transcription factor activated by 3,5,3'-l-triiodothyronine (T3). TRβ1 functions as a tumor suppressor and disturbances of the THRB gene are frequent findings in cancer. Translational control mediated by untranslated regions (UTRs) regulates cell proliferation, metabolism and responses to cellular stress, processes that are involved in carcinogenesis. We hypothesized that reduced TRβ1 expression in clear cell renal cell cancer (ccRCC) results from regulatory effects of TRβ1 5' and 3'UTRs on protein translation. We determined TRβ1 expression and alternative splicing of TRβ1 5' and 3'UTRs in ccRCC and control tissue together with expression of the type 1 deiodinase enzyme (coded by DIO1, a TRβ1 target gene). Tissue concentrations of T3 (which are generated in part by D1) and expression of miRNA-204 (an mRNA inhibitor for which a putative interaction site was identified in the TRβ1 3'UTR) were also determined. TRβ1 mRNA and protein levels were reduced by 70% and 91% in ccRCC and accompanied by absent D1 protein, a 58% reduction in tissue T3 concentration and 2-fold increase in miRNA-204. Structural analysis of TRβ1 UTR variants indicated that reduced TRβ1 expression may be maintained in ccRCC by posttranscriptional mechanisms involving 5'UTRs and miRNA-204. The tumor suppressor activity of TRβ1 indicates that reduced TRβ1 expression and tissue hypothyroidism in ccRCC tumors is likely to be involved in the process of carcinogenesis or in maintaining a proliferative advantage to malignant cells. | D007680 | Kidney Neoplasms |
Clinically important variants in THRB |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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