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FLASH GENE
Symbol HMMR contributors: mct/ - updated : 09-10-2013
HGNC name hyaluronan-mediated motility receptor (RHAMM)
HGNC id 5012
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
cell lineage
cell lines breast cancer cells
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an acidic coiled coil domain
  • N-terminal motif overlapping the defined hyaluronan binding domain
  • two microtubule-binding regions
  • C-terminal 728LKDENSQLKSEVSKL742 microtubule-binding site
  • HOMOLOGY
    interspecies homolog to C.elegans c14h10.2
    Homologene
    FAMILY
  • ACC family
  • CATEGORY adhesion , protooncogene , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • the N-terminus interacts with microtubules and a separate carboxy-terminal domain is required for centrosomal targeting
  • associated with the cytoskeleton, microtubules, centrosomes and the mitotic spindle
  • found in the cell nucleus, on interphase microtubules, mitotic spindles, centrosomes, and within mitochondria
  • distributed in both the cytoplasm and nucleus
  • localized to the microtubule cytoskeleton and along mitotic spindles
  • basic FUNCTION
  • cell surface receptor for hyaluronan, and a microtubule-associated intracellular hyaluronan binding protein involved in signal transduction via Src tyrosine kinase family
  • functioning in the maintenance of spindle integrity
  • playing an important role in maintenance of embryonic stem cells pluripotency, viability, and cell cycle control
  • playing a role already in S phase
  • oncogenic protein implicated in the progression of many cancers, including breast, acute myeloid leukemia, multiple myeloma, gastric, and prostate cancers
  • required for regulating stability of interphase and mitotic microtubules and this function resided in the C-terminal 728LKDENSQLKSEVSKL742 microtubule-binding site
  • control the structure of interphase and mitotic spindle microtubules and these effects are driven by MEK1/ERK1/2 kinase activity
  • has a predominant role in the cell cycle in immortalized cells (HCF)
  • ARPC5 and HMMR, in addition to PRKCA, were required for migration of neointimal smooth muscle cells
  • centrosomal protein that contributes to the stability of the mitotic spindle
  • may play a key role in the osteoblastic differentiation process
  • ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenesis
  • cell-surface receptor for hyaluronan that regulates embryonic stem cell pluripotency and differentiation
  • required to maintain pluripotency and its dominant mechanism of action is through the modulation of signal transduction pathways at microtubules
  • CELLULAR PROCESS cell cycle
    cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • subunit of the HARC complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • hayluronic acid
  • a direct interaction with microtubules and an association with dynein
  • interacting with CD44 (HMMR and CD44 act together in a hyaluronan-dependent autocrine mechanism to coordinate sustained signaling through ERK1,2, leading to high basal motility of invasive breast cancer cells)
  • interacts with the spindle assembly factors dynein and TPX2 (like TPX2, its expression is up-regulated during mitosis)
  • associates with both interphase and mitotic spindle microtubules by directly binding to alpha- and beta-tubulin through a highly conserved leucine zipper in its C- terminus
  • MTA1 transcriptionally stimulates expression of the hyaluronan-mediated motility receptor (HMMR) and consequently regulates cancer invasion and migratory function
  • DYNLL1 interacted with a spindle-microtubule-associated adaptor formed by FAM83D and HMMR via TQT motifs in FAM83D)
  • cell & other
    REGULATION
    repressed by TP53
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    correlate with the malignant condition and might be linked to the increased or abnormal cell proliferation in human oral squamous cell carcinomas
    tumoral     --over  
    in breast cancer is predictive of poor clinical outcome
    constitutional     --low  
    HMMR loss resulted in a high percentage of multi-pole spindles in mitotic cells
    tumoral     --over  
    may contribute to the development of hormonal resistance in PCa (prostate adenocarcinoma)
    tumoral     --over  
    in the ossifying fibroma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • RHAMM&
  • 8722;/&
    8722; mouse embryonic fibroblasts exhibit strongly acetylated interphase microtubules, multi-pole mitotic spindles, aberrant chromosome segregation, and inappropriate cytokinesis during mitosis