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Literature summary extracted from

  • Siiskonen, H.; Oikari, S.; Pasonen-Seppaenen, S.; Rilla, K.
    Hyaluronan synthase 1: a mysterious enzyme with unexpected functions (2015), Front. Immunol., 6, 43.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.4.1.212 medicine the role of HAS1 as a poor predictor in breast cancer, and is correlated with high relapse rate and short overall survival Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.4.1.212 gene HAS1, in addition to the full-length form, HAS1 has multiple transcript variants resulting from alternative splicing Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.4.1.212 additional information both COS-1 and MCF-7 cell lines have negligible endogenous hyaluronan production, and even overexpression of HAS1 enzymes does not cause prominent changes in it. Upon treatment with glucose or glucosamine, compounds that increase the amounts of hyaluronan substrates, the HAS1 enzyme is able to produce significant amounts of hyaluronan Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.4.1.212 additional information
-
 additional information availability of substrate UDP-GlcNAc does not considerably influence the Km of Has1 toward UDP-GlcUA, whereas levels of UDP-GlcUA have a significant effect of the Km toward UDP-GlcNAc Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.4.1.212 cytoplasm
-
 Homo sapiens 5737
-
2.4.1.212 cytoskeleton
-
 Homo sapiens 5856
-
2.4.1.212 endoplasmic reticulum
-
 Homo sapiens 5783
-
2.4.1.212 Golgi apparatus
-
 Homo sapiens 5794
-
2.4.1.212 membrane are integral membrane proteins with transmembrane domains in addition to membrane-associated domains Homo sapiens 16020
-
2.4.1.212 microtubule
-
 Homo sapiens 5874
-
2.4.1.212 additional information the intracellular distribution pattern of HAS1 is distinct from other isoenzymes. In all cell types studied so far, a high proportion of HAS1 is accumulated intracellularly, with a faint signal detected on the plasma membrane and its protrusions. The recombinant GFP-HAS1 signal is mainly cytoplasmic, rather than on the plasma membrane, being distributed either diffusely or in cytoplasmic patches, and partially co-localizing with the Golgi apparatus. Transfected HAS1V-GFP constructs localize with cytoskeletal structures like microtubules Homo sapiens
-
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.4.1.212 Mg2+ the enzyme requires Mg2+ or Mn2+ for activity Homo sapiens
2.4.1.212 Mn2+ the enzyme requires Mg2+ or Mn2+ for activity Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
2.4.1.212 Homo sapiens Q92839 gene HAS1
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.4.1.212 breast cancer cell
-
 Homo sapiens
-
2.4.1.212 fibroblast
-
 Homo sapiens
-
2.4.1.212 MCF-7 cell
-
 Homo sapiens
-
2.4.1.212 mesothelioma cell
-
 Homo sapiens
-
2.4.1.212 additional information both full length and splice variants of HAS1 are expressed in malignancies like bladder and prostate cancers, multiple myeloma, and malignant mesothelioma Homo sapiens
-
2.4.1.212 myeloma cell
-
 Homo sapiens
-
2.4.1.212 prostate cancer cell
-
 Homo sapiens
-
2.4.1.212 synoviocyte
-
 Homo sapiens
-
2.4.1.212 urinary bladder cancer cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.4.1.212 UDP-alpha-D-glucuronate + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
-
 Homo sapiens UDP + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-[nascent hyaluronan]
-
 ?
2.4.1.212 UDP-alpha-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
 Homo sapiens UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-[nascent hyaluronan]
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.4.1.212 HAS1
-
 Homo sapiens
2.4.1.212 hyaluronan synthase 1
-
 Homo sapiens

Expression

EC Number Organism Comment Expression
2.4.1.212 Homo sapiens the enzyme expression is decreased in transcriptional regulation by estradiol, 4-methylumbelliferone, and TGF-beta1 down
2.4.1.212 Homo sapiens Has1 is upregulated in states associated with inflammation, like atherosclerosis, osteoarthritis, and infectious lung disease. The enzyme expression is increased in transcriptional regulation by factors EGF, FGF2, FGF, forskolin, IGF, IL-1beta, PDGF, progesterone, prostaglandin D2, prostaglandin E2, and TGF-beta up

General Information

EC Number General Information Comment Organism
2.4.1.212 additional information An important factor affecting activity of all HAS enzymes is the cytoplasmic availability of substrates, namely, UDP-GlcUA and UDP-GlcNAc. This role of substrates is particularly interesting in regulation of HAS1 as its activity of hyaluronan production in many cell models is low or absent unless stimulated Homo sapiens
2.4.1.212 physiological function hyaluronan synthase 1 (HAS1) is one of three isoenzymes responsible for cellular hyaluronan synthesis. The role of HAS1 in hyaluronan production seems to be insignificant compared to the two other isoenzymes, HAS2 and HAS3, which have higher enzymatic activity. Isozyme Has1 is upregulated in states associated with inflammation, like atherosclerosis, osteoarthritis, and infectious lung disease. Both full length and splice variants of HAS1 are expressed in malignancies like bladder and prostate cancers, multiple myeloma, and malignant mesothelioma. The pericellular hyaluronan coat produced by HAS1 is usually thin without induction by inflammatory agents or glycemic stress and depends on CD44–HA interactions. These specific interactions regulate the organization of hyaluronan into a leukocyte recruiting matrix during inflammatory responses. 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. HAS1 expression is transcriptionally regulated by transforming growth factor-beta in synoviocytes and by the pro-inflammatory cytokine interleukin-1beta in fibroblasts, while these factors may have similar or opposite effects on other HASs, depending on the cell type. Has1 is associated with breast tumor and with estrogen receptor negativity, HER2 positivity, high relapse rate, and short overall survival Homo sapiens