Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
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
    EC.number 2.4.1.212
    DNA
    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
    motif
    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
    Physical map
    COLEC10 8q24.13 collectin sub-family member 10 (C-type lectin) MAL2 8q23 mal, T-cell differentiation protein 2 NOV 8q24.1 nephroblastoma overexpressed gene LOC392264 8 hypothetical gene supported by AK122835 ENPP2 8q24.13 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin) HCP23 8q24.12 cytochrome c, somatic pseudogene TAF2 8q24.12 TAF2 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 150kDa MGC5528 8q24.12 defective in sister chromatid cohesion homolog 1 (S. cerevisiae) MGC14407 8q24.12 hypothetical protein MGC14407 FLJ12428 8q24.12 hypothetical protein FLJ12428 LOC389682 8 similar to collagen type XIV COL14A1 8q24.13 collagen, type XIV, alpha 1 (undulin) MRPL13 8q22.1-q22.3 mitochondrial ribosomal protein L13 MTBP 8q24.1-q24.2 Mdm2, transformed 3T3 cell double minute 2, p53 binding protein (mouse) binding protein, 104kDa SNTB1 8q24.13 syntrophin, beta 1 (dystrophin-associated protein A1, 59kDa, basic component 1) HAS2 8q24.13 hyaluronan synthase 2 MRPS36P3 8q24.13 mitochondrial ribosomal protein S36 pseudogene LOC389683 8 LOC389683 LOC392265 8 similar to Cell division protein kinase 5 (Tau protein kinase II catalytic subunit) (TPKII catalytic subunit) (Serine/threonine protein kinase PSSALRE) LOC389684 8 LOC389684 ZHX2 8q24.13 zinc fingers and homeoboxes 2 MGC3067 8q24.13 hypothetical protein MGC3067 MGC21654 8q24.13 unknown MGC21654 product MGC14128 8q24.13 hypothetical protein MGC14128 FLJ14825 8q24.13 hypothetical protein FLJ14825 ZHX1 8q zinc-fingers and homeoboxes 1 LOC392266 8 similar to Peroxisomal multifunctional enzyme type 2 (MFE-2) (D-bifunctional protein) (DBP) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) PRO2000 8p22 similar to Peroxisomal multifunctional enzyme type 2 (MFE-2) (D-bifunctional protein) (DBP) (17-beta-hydroxysteroid dehydrogenase 4) (17-beta-HSD 4) LOC392267 8 similar to inosine monophosphate dehydrogenase 1 isoform b; sWSS2608 FLJ10204 8q24.13 hypothetical protein FLJ10204 FBXO32 8q24.13 F-box only protein 32 LOC340359 8q24.13 similar to hypothetical protein 8230402K04 ANXA13 8q24.13-q24.2 annexin A13 FLJ23790 8q24.13 hypothetical protein FLJ23790 FLJ35721 8q24.13 hypothetical protein FLJ35721 FLJ32770 8q24.13 hypothetical protein FLJ32770
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3275 - 552 - 2006 16511445
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   predominantly Homo sapiens
    Skin/Tegumentskin   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  moderately
    Muscularsmoothvessel   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    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 rattus Has2
    ortholog to murine Has2 (98.7pc)
    intraspecies paralog to HAS1
    paralog to HAS3
    Homologene
    FAMILY
  • 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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    hyaluronate synthesis
    a component
    INTERACTION
    DNA
    RNA
    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
    REGULATION
    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
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    during muscle hypertrophy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice possessing no Has2 expression in chondrocytes died near birth and displayed abnormalities throughout their skeleton