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Literature summary for 2.4.1.212 extracted from
- Hyaluronan synthase 1: a mysterious enzyme with unexpected functions (2015), Front. Immunol., 6, 43.
Application
| Application | Comment | Organism |
|---|---|---|
| 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)
| Cloned (Comment) | Organism |
|---|---|
| gene HAS1, in addition to the full-length form, HAS1 has multiple transcript variants resulting from alternative splicing | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| 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]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 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
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Homo sapiens | 5737 | - |
| cytoskeleton | - |
Homo sapiens | 5856 | - |
| endoplasmic reticulum | - |
Homo sapiens | 5783 | - |
| Golgi apparatus | - |
Homo sapiens | 5794 | - |
| membrane | are integral membrane proteins with transmembrane domains in addition to membrane-associated domains | Homo sapiens | 16020 | - |
| microtubule | - |
Homo sapiens | 5874 | - |
| 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
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | the enzyme requires Mg2+ or Mn2+ for activity | Homo sapiens |  |
| Mn2+ | the enzyme requires Mg2+ or Mn2+ for activity | Homo sapiens | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q92839 | gene HAS1 | - |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| breast cancer cell | - |
Homo sapiens | - |
| fibroblast | - |
Homo sapiens | - |
| MCF-7 cell | - |
Homo sapiens | - |
| mesothelioma cell | - |
Homo sapiens | - |
| 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 | - |
| myeloma cell | - |
Homo sapiens | - |
| prostate cancer cell | - |
Homo sapiens | - |
| synoviocyte | - |
Homo sapiens | - |
| urinary bladder cancer cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 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] | - |
? | |
| 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
| Synonyms | Comment | Organism |
|---|---|---|
| HAS1 | - |
Homo sapiens |
| hyaluronan synthase 1 | - |
Homo sapiens |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | the enzyme expression is decreased in transcriptional regulation by estradiol, 4-methylumbelliferone, and TGF-beta1 | down |
| 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
| General Information | Comment | Organism |
|---|---|---|
| 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 |
| 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 CD44HA 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 |
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Release 2023.1 (January 2023)
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