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FLASH GENE
Symbol TSHR contributors: mct/npt - updated : 25-08-2009
HGNC name thyroid stimulating hormone receptor
HGNC id 12373
Corresponding disease
GHTF gestational hyperthyroidism, familial
HFTA hyperfunctioning thyroid adenoma
TSHR hypothyroidism, congenital, due to TSH resistance
Location 14q31.1      Physical location : 81.421.868 - 81.612.646
Synonym name
  • thyrotropin receptor
  • thyroid stimulating hormone receptor, isoform 2
  • seven transmembrane helix receptor
  • Synonym symbol(s) GHTF, LGR3, TSHR-I, HTSHR-I, MGC75129, CHNG1
    DNA
    TYPE functioning gene
    STRUCTURE 190.80 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer   transcription factor
    text structure SSBP1, binding on the noncoding strand, within the promoter and contributing to TSHR maximal expression
    MAPPING cloned Y linked Y status confirmed
    Physical map
    LOC388001 14 LOC388001 DIO2 14q24.3 deiodinase, iodothyronine, type II C14orf145 14q31.1 chromosome 14 open reading frame 145 HMGN2P2 14 high-mobility group nucleosomal binding domain 2 pseudogene 2 C14orf61 14q31.1 chromosome 14 open reading frame 61 TSHR 14q31 thyroid stimulating hormone receptor RPL17P3 14 ribosomal protein L17 pseudogene 3 NMNATP 14q21.3 nicotinamide nucleotide adenylyltransferase pseudogene GTF2A1 14q31.1 general transcription factor IIA, 1, 19/37kDa LOC246720 14q31.1 dynein, cytoplasmic, light polypeptide pseudogene UNGP3 14 uracil-DNA glycosylase pseudogene 3 STN2 14q31.1 stonin 2 RPS24P3 14 ribosomal protein S24 pseudogene 3 LOC390498 14 similar to dynein, cytoplasmic, light peptide LOC388002 14 LOC388002 SEL1L 14q24.3-q31.1 sel-1 suppressor of lin-12-like (C. elegans) EEF1A1P2 14q31.1 eukaryotic translation elongation factor 1 alpha 1 pseudogene 2 RPL9P6 14 ribosomal protein L9 pseudogene 6 EIF3S6IPP 14 eukaryotic translation initiation factor 3, subunit 6 interacting protein pseudogene
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 4410 86 764 - -
  • a 10 exons variant
  • lacking exon 9
  • encoding for the longer product
  • 9 - 1183 28 253 - -
  • a 9 exons variant
  • lacking exons 10 & 11
  • encoding for a shorter product with a distinct C-terminus, compared to isoform 1
  • 9 - 1246 - 274 - Takeshita (1992)
    EXPRESSION
    Type
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid   predominantly
    Lymphoid/Immunethymus   highly
    Nervousbrain   lowly
     nervecranial nerve  moderately
    Reproductivefemale systemovary  highly
     female systembreastmammary gland lowly
     female systemuterus  lowly
    Respiratorylung   lowly
    Visualeye   lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  lowly
    Connectivebone  lowly
    Epithelialsecretoryglandularendocrinemoderately
    Muscular   lowly
    Nervouscentral  moderately
    Nervousperipherous  moderately
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymhoid/Immunelymphocyte
    Nervousastrocyte
    Nervousneuron
    Skeletonosteoblast
    Skeletonosteoclast
    cell lineage
    cell lines orbital fibroblasts, after adipocytic differentiation, from thyroid-associated ophthalmopathy patients
    fluid/secretion
    at STAGE
    physiological period embryo
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a large N terminal extracytoplasmic ectodomain
  • six leucine-rich repeat motifs
  • a signal peptide of 21 AA
  • seven transmembrane segments (7TM)
  • a C terminal cytoplasmic tail
  • conjugated GlycoP
    mono polymer homomer , heteromer , dimer
    isoforms Precursor of extracellular alpha and membrane spanning beta chains
    HOMOLOGY
    interspecies homolog to rattus Tshr (85.86 pc)
    homolog to murine Tshr (86.78 pc)
    Homologene
    FAMILY
  • G protein coupled receptor 1 superfamily
  • FSH/LSH/TSH subfamily
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    text upon thyrotropin binding the thyrotropin receptor is internalized and localized to endosome
    basic FUNCTION
  • activating adenylate cyclase in response to TSH, and activating phosphoinositide turnover to
  • involved in thyroid hormone synthesis and metabolism pathway
  • also acting as a receptor for thyrostimulin
  • CELLULAR PROCESS cell life, proliferation/growth
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism hormone
    signaling hormonal
    signaling through JAK/STAT3 pathways
    a component
  • forming homodimers or heterodimers with lutropin (LH/CGr) receptor
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with autoantibodies against the TSH receptor, (thyroid-stimulating immunoglobulins) TSI
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) TSHR , GHTF , HFTA
    related resource TSH Receptor mutation database
    Susceptibility to Graves disease (GD)
    Variant & Polymorphism SNP SNPs within a 40 kb region of TSHR intron 1 are highly associated with GD (Brand 2009)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    in a mouse model of Graves disease, goiter and hyperthyroidism occurred to a significantly greater extent when the adenovirus expressed the free alpha subunit as opposed to a genetically modified TSHR that cleaves minimally into subunits
  • in conclusion, shed alpha subunits induce or amplify the immune response leading to hyperthyroidism in Graves disease