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FLASH GENE
Symbol HAS1 contributors: mct/npt - updated : 28-04-2015
HGNC name hyaluronan synthase 1
HGNC id 4818
Location 19q13.41      Physical location : 52.216.364 - 52.227.221
Synonym name
  • HA synthase 1
  • human fetal brain mRNA for hyaluronan synthase
    • Synonym symbol(s) HAS
    EC.number 2.4.1.212
    DNA
    TYPE functioning gene
    STRUCTURE 10.88 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • TGFB1 up-regulation of HAS1 transcription was mediated via SMAD3, while HAS1 induction by IL1&
    • 61472;B was Sp3- dependent
    MAPPING cloned Y linked N status provisional
    Map cen - KLK1 - SIGLEC6 - ETFB ETFB - HAS1 - FPR1 - qter
    Authors Spicer (97)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2116 64.9 578 diffusely expressed in the cell 2009 19451652
  • HAS1-FL
  • interacting with HAS1-Vs (altered distribution and half-life of HAS1-FL, coupled with the characteristics of the HAS1-Vs suggest possible mechanisms whereby the aberrant splicing observed in human cancer may contribute to oncogenesis and disease progression)
    • - splicing - - - concentrated in the cytoplasm and/or Golgi apparatus 2009 19451652
  • comprising HAS1-Va, HAS1-Vb, HAS1-Vc
  • able to relocalize HAS1-FL protein from diffuse cytoskeleton-anchored locations to deeper cytoplasmic space
    • 4 - - - - - 2009 19451652
    4 - - 38 - - 2009 19451652
    59-base intronic sequence
    4 - - - - - 2009 19451652
  • having oncogenic properties
    • 5 - 2137 - 577 - 2009 19451652
    EXPRESSION
    Type restricted
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Digestiveintestinelarge intestine   
    Reproductivefemale systemplacenta   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • multiple transmembrane domains
  • several consensus HA (hyaluronan) binding motifs
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Has1
    homolog to C.elegans t27e9.5
    intraspecies paralog to HAS2,HAS3
    Homologene
    FAMILY
  • hyaluronan synthase family
  • modc/has family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • playing a role in hyaluroman, hyaluronic acid synthesis
  • involved in glycosaminoglycan biosynthesis
  • regulates bladder cancer growth and progression by modulating HA synthesis and HA receptor levels
  • HAS1, HAS2, HAS3 act on the inner face of plasma membrane and simultaneously translocate the growing polysaccharide through plasma membrane into extracellular space
  • may mediate cellular invasion via changes in MMP7 expression (Dunn 2009)
  • almost unable to secrete hyaluronan or form a hyaluronan coat, in contrast to HAS2 and HAS3
  • HAS1 activity requires a relatively high concentration for UDP-GlcNAc
  • is capable of creating a hyaluronan coat but only in the presence of generous amounts of the UDP-sugars
  • important role for HAS1 in conditions associated with abnormal glucose metabolism
  • HAS1-dependent coat is potentially induced by inflammatory agents and glycemic stress, mediated by altered presentation of either CD44 or hyaluronan, and can offer a rapid cellular response to injury and inflammation
  • HAS1 is the main enzyme responsible for Hyaluronan (HA) production by normal keratinocytes and thus, must be considered as an actor of normal keratinocyte differentiation
  • despite the apparently minor enzymatic activity of HAS1 under normal conditions, it may be an important factor under conditions associated with glycemic stress like metabolic syndrome, inflammation, and cancer
  • general tendency of HAS1, HAS2, HAS3 to form both homomeric and heteromeric complexes with potentially important functional consequences on hyaluronan synthesis
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
    cell & other
    REGULATION
    induced by pro-inflammatory factors, and expression and activity of HAS1 are induced by pro-inflammatory factors like interleukins and cytokines, suggesting its involvement in inflammatory conditions
    repressed by estradiol that inhibits HAS1 expression in human vascular smooth muscle cells
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    increase in serum hyaluronan in endometrial cancer may be associated with disease progression through myometrial invasion and lymph-vascular space involvement
    tumoral     --other  
    aberrant HAS1 splicing in multiple myeloma, bladder cancer and Waldenstrom macroglobulinemia (Ghosh (2009)
    tumoral     --over  
    in colon, ovarian, endometrial, mesothelioma and bladder cancers (Ghosh 2009)
    constitutional       gain of function
    during muscle hypertrophy
    constitutional       gain of function
    in states associated with inflammation, like atherosclerosis, osteoarthritis, and infectious lung disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS