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FLASH GENE
Symbol PTHLH contributors: mct/npt/pgu - updated : 21-10-2013
HGNC name parathyroid hormone-like hormone
HGNC id 9607
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a nuclear localization signal (NLS) sequence within 87-107 AA, with two acidic glutamate AAs at 99 and 101 within the basic amino acid stretch, that is a useful carrier peptide for delivery and expression of cargo molecules in the cytoplasm
    • isoforms Precursor precursor sequence of 36 AA followed by mature peptide of 141 AA
    HOMOLOGY
    Homologene
    FAMILY
  • parathyroid hormone family
    • CATEGORY signaling growth factor , receptor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    basic FUNCTION
  • putatively involved in the regulation of insulin secretion
  • regulator of chondrocytes proliferation/differentiation during endochondrial ossification
  • playing a physiological role in lactation, possibly as a hormone for the mobilization and/or transfer of calcium to the milk
  • play a role in tumorigenesis in prostate cancer, and is a key mediator for communication and interactions between prostate cancer and the bone microenvironment
  • key survival factor for cells subjected to apoptotic stimuli
  • inhibits mitochondrial-dependent apoptosis through casein kinase CK2
  • ADAMTS12, a downstream molecule of PTHLH signaling, is a novel regulator of chondrogenesis
  • plays a critical role in bone invasion by oral squamous cell carcinoma
  • represses the induction of human decidualization, stimulates stromal cell apoptosis, and limits the extent of uterine stromal cell differentiation
  • plays an autocrine/paracrine neoplastic role in GCT (Giant Cell Tumor of Bone) by allowing the proliferating stromal cells to evade apoptosis, possibly through non-traditional caspase-independent pathways
  • direct functions of PTHLH in metastasis, particularly from tumors with strong bone tropism
  • potential roles of PTHLH in the premetastatic niche, and tumor dormancy
  • regulates periosteal/intramembranous bone cell activity on cortical bone surfaces
  • serves as a load-induced modeling tool
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling hormonal
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FGFR3
  • IHH
  • interacting with ARRB1 isoform b for a novel function of PTHLH in the cytoplasm
  • interaction with PTHR modified by mutation of PTH and PTHLH (induce a conformational change in the PTH1R that promotes arrestin binding and dissociates SlC9A3R1 from PTH1R internalization)
  • regulate EFNBB2 to act in a paracrine or autocrine manner on EEPHB4 or EPHB2 in the osteoblast
  • steroid hormones negatively regulate PTHLH expression
  • HTR2A, HTR2B, HTR2C are implicated as being critical for induction of PTHLH and RUNX2
  • regulates chondrocyte differentiation and GLI activity in a SUFU-dependent manner, with SUFU acting as a molecular switch in its regulation of differentiation
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ECDMM2 , BDE2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene occurrence of PTHLH may be an indication of developing oral malignant carcinomas
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    targeting PTHLH in prostate cancer, thereby reversing the effect on caspase activity and alpha6beta4 levels, may thus prove therapeutically beneficial
    cancerbone 
    PTHLH neutralizing immunotherapy is an intriguing potential therapeutic strategy for Giant Cell Tumor of Bone.
    ANIMAL & CELL MODELS