PTM in Sequence
Summary
| Uniprot ID | P10828 |
| Organism | Human |
| NRNC Symbol | NR1A2 |
| Gene | THRB |
| Sub-family | Thyroid Hormone Receptor-like |
| Group | a) Thyroid hormone receptor |
| Chromosome | 3 |
| Position | 24117153-24495756 |
| HGNC | 11799 |
| Subcellular Location | Nuclear bodies |
| Disease Involvement | Cancer-related genes; Deafness; Disease variant; FDA approved drug targets |
| RNA Tissue/Cell Type | Liver - Hepatocytes; Pituitary gland - Lactotropes; Thyroid gland - Fibroblasts |
| Pathway Name | Nuclear Receptor transcription pathway. SUMOylation of intracellular receptors. SUMO E3 ligases SUMOylate target proteins. SUMOylation. Gene expression (Transcription). Generic Transcription Pathway. RNA Polymerase II Transcription. Post-translational protein modification. Metabolism of proteins |
| RNA Seq Expression Plot | Visualize Heatmap |
| sRNA Seq Expression Plot | Visualize Heatmap |
Domain Distribution
Gene Ontology
Link Outs
| AlphaFold | AF-P10828-F1-v4 |
| STRING | 9606.ENSP00000379904 |
| DisGeNET | 7068 |
| NCBI | 7068 |
| GeneCards | THRB |
| Protein Atlas | ENSG00000151090 |
| Expression Atlas | ENSG00000151090 |
PTM in Structure
NOTE: Use your mouse to drag, rotate, and zoom in and out of the structure
Legend
Shape: Spheres (Circles)- Acetylation
- Methylation
- Phosphorylation
- Sumoylation
Modification & Variant Details
| Sr. No. | Isoform | PTM | Domain | Site of PTM (Uniprot) | Modifier 1 | Modifier 1 (Uniprot) | Modifier 2 | Modifier 2 (Uniprot) | Effect | Sequence Fragment |
|---|---|---|---|---|---|---|---|---|---|---|
| TRβ-1 | Acetylation | Hinge Domain | K184 | NA | NA | NA | NA | Enhanced gene transactivation and cytosolic localization of thyroid hormone receptor | VLDDSKRLAKR | |
| TRβ-1 | Acetylation | Hinge Domain | K188 | NA | NA | NA | NA | Enhanced gene transactivation and cytosolic localization of thyroid hormone receptor | SKRLAKRKLIE | |
| TRβ-1 | Acetylation | Hinge Domain | K190 | NA | NA | NA | NA | Enhanced gene transactivation and cytosolic localization of thyroid hormone receptor | RLAKRKLIEEN | |
| TRβ-1 | Methylation | DNA-binding Domain | K137 | NA | NA | NA | NA | NA | RRTIQKNLHPS | |
| TRβ-1 | Methylation | DNA-binding Domain | K155 | NA | NA | NA | NA | NA | KCVIDKVTRNQ | |
| TRβ-1 | Methylation | Hinge Domain | K206 | NA | NA | NA | NA | NA | REELQKSIGHK | |
| TRβ-1 | Methylation | Hinge Domain | K223 | NA | NA | NA | NA | NA | EWELIKTVTEA | |
| TRβ-1 | Methylation | Ligand-binding Domain | K306 | NA | NA | NA | NA | NA | QIILLKGCCME | |
| TRβ-1 | Phosphorylation | DNA-binding Domain | K128 | Mitogen-activated protein kinase 1 | P28482 | NA | NA | L-thyroxine -conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor; and they altered transcriptional activity of TR in a thyroid hormone response element-luciferase reporter assay. | TCEGCKGFFRR | |
| TRβ-1 | Phosphorylation | DNA-binding Domain | R132 | Mitogen-activated protein kinase 1 | P28482 | NA | NA | L-thyroxine -conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor; and they altered transcriptional activity of TR in a thyroid hormone response element-luciferase reporter assay. | CKGFFRRTIQK | |
| TRβ-1 | Phosphorylation | DNA-binding Domain | R133 | Mitogen-activated protein kinase 1 | P28482 | NA | NA | L-thyroxine -conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor; and they altered transcriptional activity of TR in a thyroid hormone response element-luciferase reporter assay. | KGFFRRTIQKN | |
| TRβ-1 | Phosphorylation | DNA-binding Domain | S142 | Mitogen-activated protein kinase 1 | P28482 | NA | NA | L-thyroxine -conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor; and they altered transcriptional activity of TR in a thyroid hormone response element-luciferase reporter assay. | KNLHPSYSCKY | |
| TRβ-1 | Phosphorylation | Ligand-binding Domain | S270 | NA | NA | NA | NA | NA | DLEAFSHFTKI | |
| TRβ-1 | Phosphorylation | Ligand-binding Domain | T273 | NA | NA | NA | NA | NA | AFSHFTKIITP | |
| TRβ-1 | Phosphorylation | Ligand-binding Domain | Y406 | NA | NA | NA | NA | NA | LAFEHYINYRK | |
| TRβ-1 | Phosphorylation | N-terminal Domain | S5 | NA | NA | NA | NA | NA | -MTPNSMTENG | |
| TRβ-1 | Phosphorylation | N-terminal Domain | S55 | NA | NA | NA | NA | NA | KNEQSSPHLIQ | |
| TRβ-1 | Phosphorylation | N-terminal Domain | S99 | NA | NA | NA | NA | NA | KGYIPSYLDKD | |
| TRβ-1 | Phosphorylation | N-terminal Domain | T12 | NA | NA | NA | NA | NA | TENGLTAWDKP | |
| TRβ-1 | Phosphorylation | N-terminal Domain | T2 | NA | NA | NA | NA | NA | ----MTPNSMT | |
| TRβ-1 | Phosphorylation | N-terminal Domain | Y100 | NA | NA | NA | NA | NA | GYIPSYLDKDE | |
| TRβ-1 | Sumoylation | DNA-binding Domain | K146 | E3 SUMO-protein ligase PIAS1 | O75925 | NA | NA | SUMO1 was required for T3-mediated recruitment of NCoR and release of CBP from the TSHβ-negative TRE. SUMO3 was required for T3-stimulated TR binding to the TSHβ-negative TRE and recruitment of NCoR. Conjugation of SUMO to TR has a TR-isoform preference and is important for T3-dependent gene induction and repression. | PSYSCKYEGKC | |
| TRβ-1 | Sumoylation | Hinge Domain | K211 | NA | NA | NA | NA | NA | KSIGHKPEPTD | |
| TRβ-1 | Sumoylation | Ligand-binding Domain | K443 | E3 SUMO-protein ligase PIAS1 | O75925 | NA | NA | SUMO1 was required for T3-mediated recruitment of NCoR and release of CBP from the TSHβ-negative TRE. SUMO3 was required for T3-stimulated TR binding to the TSHβ-negative TRE and recruitment of NCoR. Conjugation of SUMO to TR has a TR-isoform preference and is important for T3-dependent gene induction and repression. | RFLHMKVECPT | |
| TRβ-1 | Sumoylation | N-terminal Domain | K50 | E3 SUMO-protein ligase PIAS1 | O75925 | NA | NA | SUMO1 was required for T3-mediated recruitment of NCoR and release of CBP from the TSHβ-negative TRE. SUMO3 was required for T3-stimulated TR binding to the TSHβ-negative TRE and recruitment of NCoR. Conjugation of SUMO to TR has a TR-isoform preference and is important for T3-dependent gene induction and repression. | RRSTLKNEQSS | |
| TRβ-2 | NA | NA | NA | NA | NA | NA | NA | NA | NA |
ClinVar Variant
| Sr. No. | Member | Variant Type | Variant Name | Clinical Significance | Phenotype List | Review Status |
|---|---|---|---|---|---|---|
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1020G>C (p.Gln340His) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | Deletion | NM_001354712.2(THRB):c.1010_1012del (p.Thr337del) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|Thyroid hormone resistance; generalized; autosomal recessive | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.949G>A (p.Ala317Thr) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|Thyroid hormone resistance syndrome | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1034G>T (p.Gly345Val) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1324A>G (p.Met442Val) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|THRB-related disorder | criteria provided; multiple submitters; no conflicts | |
| TRβ | Duplication | NM_001354712.2(THRB):c.1341dup (p.Thr448fs) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1357C>A (p.Pro453Thr) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|THRB-related disorder | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1033G>A (p.Gly345Ser) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.959G>A (p.Arg320His) | Pathogenic/Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|Inborn genetic diseases|THRB-related disorder | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.700G>A (p.Ala234Thr) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|Thyroid hormone resistance syndrome|not provided | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.947G>A (p.Arg316His) | Pathogenic | Selective pituitary resistance to thyroid hormone|Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.958C>T (p.Arg320Cys) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|Thyroid hormone resistance; generalized; autosomal recessive;Thyroid hormone resistance; generalized; autosomal dominant;Selective pituitary resistance to thyroid hormone|THRB-related disorder|not provided | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1012C>T (p.Arg338Trp) | Pathogenic | Selective pituitary resistance to thyroid hormone|Thyroid hormone resistance; generalized; autosomal dominant|not provided|Thyroid hormone resistance; generalized; autosomal recessive;Thyroid hormone resistance; generalized; autosomal dominant;Selective pituitary resistance to thyroid hormone | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1313G>A (p.Arg438His) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|not specified | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1336T>C (p.Cys446Arg) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1373T>C (p.Val458Ala) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1302C>A (p.Cys434Ter) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.728G>A (p.Arg243Gln) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|Selective pituitary resistance to thyroid hormone;Thyroid hormone resistance; generalized; autosomal recessive;Thyroid hormone resistance; generalized; autosomal dominant|THRB-related disorder | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.727C>T (p.Arg243Trp) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|THRB-related disorder | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.67C>T (p.Arg23Ter) | Pathogenic | not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1351T>G (p.Phe451Val) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1021C>G (p.Leu341Val) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1305T>G (p.His435Gln) | Pathogenic | Thyroid hormone resistance syndrome|Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1357C>T (p.Pro453Ser) | Pathogenic | not provided|Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1345G>T (p.Glu449Ter) | Likely pathogenic | not provided|Inborn genetic diseases | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.751G>C (p.Gly251Arg) | Likely pathogenic | not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1378G>A (p.Glu460Lys) | Pathogenic/Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta | criteria provided; multiple submitters; no conflicts | |
| TRβ | Duplication | NM_001354712.2(THRB):c.1358dup (p.Leu454fs) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|THRB-related disorder|not provided | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1357C>G (p.Pro453Ala) | Pathogenic/Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.938T>C (p.Met313Thr) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.803C>G (p.Ala268Gly) | Pathogenic/Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|Thyroid hormone resistance; generalized; autosomal recessive|not provided|THRB-related disorder|Thyroid hormone resistance syndrome | criteria provided; multiple submitters; no conflicts | |
| TRβ | Indel | NM_001354712.2(THRB):c.1326_1327delinsAT (p.Met442_Lys443delinsIleTer) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1286G>A (p.Arg429Gln) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant|not provided|THRB-related disorder | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.749T>C (p.Ile250Thr) | Likely pathogenic | not provided|resistance to thyroid hormone (RTH) | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.928A>T (p.Met310Leu) | Pathogenic | not provided | criteria provided; single submitter | |
| TRβ | Microsatellite | NM_001354712.2(THRB):c.1287GAT[1] (p.Met430del) | Likely pathogenic | not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.949G>T (p.Ala317Ser) | Likely pathogenic | not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.917A>C (p.Lys306Thr) | Likely pathogenic | not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.830C>T (p.Thr277Ile) | Pathogenic | not provided | criteria provided; single submitter | |
| TRβ | Indel | NM_001354712.2(THRB):c.1357_1358delinsAA (p.Pro453Asn) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.283+1G>A | Pathogenic | Macular dystrophy | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1292T>C (p.Ile431Thr) | Likely pathogenic | not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1358C>T (p.Pro453Leu) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1304A>G (p.His435Arg) | Likely pathogenic | THRB-related disorder | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1144+1G>T | Likely pathogenic | THRB-related disorder | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.740C>T (p.Pro247Leu) | Likely pathogenic | THRB-related disorder | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1045G>A (p.Val349Met) | Likely pathogenic | not provided|Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; multiple submitters; no conflicts | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1058T>C (p.Ile353Thr) | Pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | Microsatellite | NM_001354712.2(THRB):c.824TCA[1] (p.Ile276del) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | Duplication | NM_001354712.2(THRB):c.1347dup (p.Leu450fs) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1377C>G (p.Phe459Leu) | Likely pathogenic | not provided | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1325T>C (p.Met442Thr) | Likely pathogenic | Thyroid hormone resistance; generalized; autosomal dominant | criteria provided; single submitter | |
| TRβ | single nucleotide variant | NM_001354712.2(THRB):c.1025A>T (p.Lys342Ile) | Pathogenic | not provided | criteria provided; single submitter |
DisGeNET Variant
| Sr. No. | Member | Disease Name | Disease Class | Score |
|---|---|---|---|---|
| TRβ | Thyroid Hormone Resistance Syndrome | Endocrine System Diseases (C19) | 1 | |
| TRβ | THYROID HORMONE RESISTANCE; SELECTIVE PITUITARY | Endocrine System Diseases (C19) | 1 | |
| TRβ | Generalized Thyroid Hormone Resistance | Endocrine System Diseases (C19) | 0.9 | |
| TRβ | Breast Carcinoma | Neoplasms (C04); Skin and Connective Tissue Diseases (C17) | 0.8 | |
| TRβ | Follicular thyroid carcinoma | Neoplasms (C04) | 0.8 | |
| TRβ | Atrial Fibrillation | Cardiovascular Diseases (C14); Pathological Conditions; Signs and Symptoms (C23) | 0.65 | |
| TRβ | Malignant neoplasm of prostate | Neoplasms (C04); Urogenital Diseases (C12) | 0.65 | |
| TRβ | Prostatic Neoplasms | Neoplasms (C04); Urogenital Diseases (C12) | 0.65 | |
| TRβ | Renal Cell Carcinoma | Urogenital Diseases (C12); Neoplasms (C04) | 0.65 | |
| TRβ | THYROID HORMONE RESISTANCE; GENERALIZED; AUTOSOMAL DOMINANT | Endocrine System Diseases (C19) | 0.55 | |
| TRβ | Thyroid Hormone Resistance; Generalized; Autosomal Recessive | Endocrine System Diseases (C19) | 0.5 | |
| TRβ | Macular dystrophy | Eye Diseases (C11) | 0.5 | |
| TRβ | Carcinoma in situ of uterine cervix | Urogenital Diseases (C12); Neoplasms (C04) | 0.45 | |
| TRβ | Craniofacial Abnormalities | Musculoskeletal Diseases (C05); Congenital; Hereditary; and Neonatal Diseases and Abnormalities (C16) | 0.4 | |
| TRβ | Diaphragmatic Hernia | Pathological Conditions; Signs and Symptoms (C23) | 0.4 | |
| TRβ | Neurodevelopmental Disorders | Mental Disorders (F03) | 0.4 |