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Symbol HAS2 contributors: mct/npt/pgu - updated : 05-07-2013
HGNC name hyaluronan synthase 2
HGNC id 4819
Location 8q24.13      Physical location : 122.625.270 - 122.653.630
Synonym name
  • hyaluronic acid synthase 2
  • HA synthase 2
  • Synonym symbol(s) MGC126241, MGC126242
    TYPE functioning gene
    SPECIAL FEATURE antisens
    text natural antisense RNA for the HAS2 gene, HAS2-AS1
    STRUCTURE 28.36 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   transcription factor
    text structure
  • transcription factors Sp1 and Sp3 bound to three sites immediately upstream of the HAS2 transcription initiation site, principal mediators of HAS2 constitutive transcription augments recent findings identifying upstream promoter elements and provides further insights into the mechanism of HAS2 transcriptional activation
  • 1 cluster of 2 retinoic acid (RA) response elements , 3 discrete NF-kappaB factors, and 12 Sp1 response elements
  • first 2250 bp of the promoter contain three response elements (REs) for the transcription factor CREB1 as well as two REs for the nuclear receptor RAR
  • MAPPING cloned Y linked N status confirmed
    Map cen - D8S586 - SNTB1 - D8S45 - D8S1895 - ANXA13 - HAS2 - D8S1101 - D8S1728 - D8S514 - D8S342 - D8S1726 - D8S198 - D8S1826 - D8S44 - D8S1979 - D8S1799 - D8S1932 - D8S1832 - D8S1067 - D8S266 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3275 - 552 - 2006 16511445
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   predominantly Homo sapiens
    Skin/Tegumentskin   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  moderately
    Muscularsmoothvessel   Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • multiple transmembrane domains
  • several consensus HA (hyaluronan) binding motifs
  • mono polymer homomer , dimer
    interspecies ortholog to rattus Has2
    ortholog to murine Has2 (98.7pc)
    intraspecies paralog to HAS1
    paralog to HAS3
  • hyaluronan synthase family
  • Nodc/has family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    text integral to plasma membrane
    basic FUNCTION
  • playing a role in hyaluronan, hyaluronic acid synthesis and in hyaluronic acidic transport
  • vital because of its involvement in epithelial-mesenchymal transition during embryonic cardiac cushion morphogenesis
  • 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
  • playing an an intrinsic role in embryonic stem cells differentiation process
  • Hyaluronan production by HAS2 is essential for normal vertebral and intervertebral disc development within the spine
  • central role of HAS2 in the regulation of proliferation in fibroblasts
  • HAS2 and its natural antisense RNA (RNA HAS2-AS1)exhibit coordinated expression in the renal proximal tubular epithelial cell
  • critical role of HAS2 in the development of a prometastatic microenvironment, suggesting that HAS2 inhibitors can act as antimetastatic agents that disrupt a paracrine growth factor loop within this microenvironment
  • main synthase in aortic smooth muscle cells, that can be O-GlcNAcylated on serine 221, which strongly increased its activity and its stability
  • HAS1 is unable to secrete hyaluronan or form a hyaluronan coat, in contrast to HAS2 and HAS3
  • key enzyme for the synthesis of hyaluronan (HA), as a direct target of GLI transcriptional regulation during development
  • novel downstream target of SHH signaling required for joint patterning and chondrogenesis
  • protects skin fibroblasts against apoptosis induced by environmental stress
  • general tendency of HAS1, HAS2, HAS3 to form both homomeric and heteromeric complexes with potentially important functional consequences on hyaluronan synthesis
    metabolism carbohydrate
    hyaluronate synthesis
    a component
    small molecule metal binding,
  • Mg2+
  • protein
  • LIF-induced gene and its product, HA, modulated osteoblast differentiation similarly to LIF
  • with its binding receptor HHMR, are differentially expressed during all stages of preimplantation human embryos and embryonic stem cells
  • primary target of the cAMP activator forskolin and the nuclear hormone all-trans-retinoic acid (RA)
  • TBX2, a central intermediary of BMP-SMAD signaling, has a central part in directing HAS2 and TTGFB2 expression, facilitating endocardial cushion formation
  • has potentially a hyaluronan CD44-independent signaling property because the HAS2 isoform appears to be a trait of breast cancer cells metastasizing to bone
  • promotes breast cancer cell invasion by suppression of TIMP1
  • GLI3 strongly binds to the HAS2 promoter region, suggesting that HAS2 is a direct transcriptional target of the Shh signaling pathway
  • cell & other
    induced by by all-trans-RA and TNF-alpha (provide an example how the action of different transcription factor families can use the same cofactors)
    inhibited by LIF (inhibits osteoblast differentiation at least in part by regulation of HAS2 and its product hyaluronan)
    Other its activity is regulated by dimerization and ubiquitination
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    during muscle hypertrophy
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • mice possessing no Has2 expression in chondrocytes died near birth and displayed abnormalities throughout their skeleton