GLB1

Last updated
GLB1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GLB1 , EBP, ELNR1, MPS4B, galactosidase beta 1
External IDs OMIM: 611458 MGI: 88151 HomoloGene: 47922 GeneCards: GLB1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001135602
NM_000404
NM_001079811
NM_001317040
NM_001393580

Contents

NM_009752

RefSeq (protein)

NP_000395
NP_001073279
NP_001129074
NP_001303969

NP_033882

Location (UCSC) Chr 3: 33 – 33.1 Mb Chr 9: 114.23 – 114.3 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the GLB1 gene. [5] [6]

The GLB1 protein is a beta-galactosidase that cleaves the terminal beta-galactose from ganglioside substrates and other glycoconjugates. [7] The GLB1 gene also encodes an elastin binding protein. [8]

In corn ( Zea mays ), Glb1 is a gene coding for the storage protein globulin.

Clinical significance

GM1-gangliosidosis is a lysosomal storage disease that can be caused by a deficiency of β-galactosidase (GLB1). Some cases of Morquio syndrome B have been shown to be due to GLP1 mutations that cause patients to have abnormal elastic fibers. [9]

Elastin receptor

The RNA transcript of the GLB1 gene is alternatively spliced and produces 2 mRNAs. The 2.5-kilobase transcript encodes the beta-galactosidase enzyme of 677 amino acids. The alternative 2.0-kb mRNA encodes a beta-galactosidase-related protein (S-Gal) that is only 546 amino acids long and that has no enzymatic activity. The S-Gal protein does bind elastin and fragments of elastin that are generated by proteolysis. [10]

The S-Gal protein is a peripheral membrane protein that functions as part of an elastin receptor complex on the surface of cells. [11] The elastin receptor complex includes S-Gal, neuraminidase and Cathepsin A. When elastin-derived peptides bind to the S-Gal protein then the associated neuraminidase enzyme activity is activated and responding cells can have altered signal transduction involving extracellular signal-regulated kinases and regulated matrix metallopeptidase production. Elastin-derived peptides are chemotactic for some cell types [12] and can alter cell cycle progression. [13] The ability of the GLB1-derived elastin binding protein and the elastin receptor complex to influence cell proliferation appears to be indirect and involve removal of sialic acid from extracellular and cell surface proteins such as growth factor receptors.

The S-Gal protein functions during the normal assembly of elastin into extracellular elastic fibers. Elastin is initially present as newly synthesized tropoelastin which can be found in association with S-Gal. The enzymatic activity of neuraminidase in the elastin receptor complex is involved in the release of tropoelastin molecules from the S-Gal chaperone. [14] Cathepsin A is also required for normal elastin biosynthesis. [15]

Related Research Articles

β-Galactosidase Family of glycoside hydrolase enzymes

β-Galactosidase is a glycoside hydrolase enzyme that catalyzes hydrolysis of terminal non-reducing β-D-galactose residues in β-D-galactosides.

<span class="mw-page-title-main">Lysosomal storage disease</span> Medical condition

Lysosomal storage diseases are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective due to a mutation, the large molecules accumulate within the cell, eventually killing it.

<span class="mw-page-title-main">Elastic fiber</span> Type of connective tissue in animals

Elastic fibers are an essential component of the extracellular matrix composed of bundles of proteins (elastin) which are produced by a number of different cell types including fibroblasts, endothelial, smooth muscle, and airway epithelial cells. These fibers are able to stretch many times their length, and snap back to their original length when relaxed without loss of energy. Elastic fibers include elastin, elaunin and oxytalan.

<span class="mw-page-title-main">Glucocerebrosidase</span> Mammalian protein found in humans

β-Glucocerebrosidase is an enzyme with glucosylceramidase activity that cleaves by hydrolysis the β-glycosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism that is abundant in cell membranes. It is localized in the lysosome, where it remains associated with the lysosomal membrane. β-Glucocerebrosidase is 497 amino acids in length and has a molecular mass of 59,700 Da.

α-Galactosidase Enzyme

α-Galactosidase is a glycoside hydrolase enzyme that catalyses the following reaction:

The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are better known by their individual names: Tay–Sachs disease, AB variant, and Sandhoff disease.

The GM1 gangliosidoses, usually shortened to GM1, are gangliosidoses caused by mutation in the GLB1 gene resulting in a deficiency of beta-galactosidase. The deficiency causes abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells, resulting in progressive neurodegeneration. GM1 is a rare lysosomal storage disorder with a prevalence of 1 to every 100,000 to 200,000 live births worldwide, although rates are higher in some regions.

<span class="mw-page-title-main">HEXB</span> Protein-coding gene in the species Homo sapiens

Beta-hexosaminidase subunit beta is an enzyme that in humans is encoded by the HEXB gene.

<span class="mw-page-title-main">Cathepsin A</span>

Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.

<span class="mw-page-title-main">Nuclear receptor 4A2</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor 4A2 (NR4A2) also known as nuclear receptor related 1 protein (NURR1) is a protein that in humans is encoded by the NR4A2 gene. NR4A2 is a member of the nuclear receptor family of intracellular transcription factors.

<span class="mw-page-title-main">GM2A</span> Mammalian protein found in Homo sapiens

GM2 ganglioside activator also known as GM2A is a protein which in humans is encoded by the GM2A gene.

<span class="mw-page-title-main">HEXA</span> Protein-coding gene in the species Homo sapiens

Hexosaminidase A (alpha polypeptide), also known as HEXA, is an enzyme that in humans is encoded by the HEXA gene, located on the 15th chromosome.

<span class="mw-page-title-main">Frizzled-4</span> Protein-coding gene in the species Homo sapiens

Frizzled-4(Fz-4) is a protein that in humans is encoded by the FZD4 gene. Fz-4 has also been designated as CD344.

<span class="mw-page-title-main">Collagen, type IV, alpha 3</span> Protein found in humans

Collagen alpha-3(IV) chain is a protein that in humans is encoded by the COL4A3 gene.

<span class="mw-page-title-main">FBLN5</span> Protein-coding gene in the species Homo sapiens

Fibulin-5 is a protein that in humans is encoded by the FBLN5 gene.

<i>NAGA</i> (gene) Protein-coding gene in the species Homo sapiens

Alpha-N-acetylgalactosaminidase is an enzyme that in humans is encoded by the NAGA gene.

<span class="mw-page-title-main">SCARB2</span> Protein-coding gene in the species Homo sapiens

Lysosomal integral membrane protein 2 (LIMP-2) is a protein that in humans is encoded by the SCARB2 gene. LIMP-2 is expressed in brain, heart, liver, lung and kidney, mainly in the membrane of lysosome organelles; however, in cardiac muscle, LIMP-2 is also expressed at intercalated discs. LIMP-2 in a membrane protein in lysosomes that functions to regulate lysosomal/endosomal transport. Mutations in LIMP-2 have been shown to cause Gaucher disease, myoclonic epilepsy, and action myoclonus–renal failure syndrome. Abnormal levels of LIMP-2 have also been found in patients with hypertrophic cardiomyopathy.

<span class="mw-page-title-main">PTPRK</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase kappa is an enzyme that in humans is encoded by the PTPRK gene. PTPRK is also known as PTPkappa and PTPκ.

<span class="mw-page-title-main">Sialidase-1</span> Protein-coding gene in the species Homo sapiens

Sialidase-1, is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene.

<span class="mw-page-title-main">Galactosialidosis</span> Rare disease

Galactosialidosis, also known as neuraminidase deficiency with beta-galactosidase deficiency, is a genetic lysosomal storage disease. It is caused by a mutation in the CTSA gene which leads to a deficiency of enzymes β-galactosidase and neuraminidase. This deficiency inhibits the lysosomes of cells from functioning properly, resulting in the accumulation of toxic matter within the cell. Hallmark symptoms include abnormal spinal structure, vision problems, coarse facial features, hearing impairment, and intellectual disability. Because galactosialidosis involves the lysosomes of all cells, it can affect various areas of the body, including the brain, eyes, bones, and muscles. Depending on the patient's age at the onset of symptoms, the disease consists of three subtypes: early infantile, late infantile, and juvenile/adult. This condition is considered rare, with most cases having been in the juvenile/adult group of patients.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000170266 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000045594 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Shows TB, Scrafford-Wolff L, Brown JA, Meisler M (1978). "Assignment of a beta-galactosidase gene (beta GALA) to chromosome 3 in man". Cytogenetics and Cell Genetics. 22 (1–6): 219–22. doi:10.1159/000130940. PMID   110522.
  6. Oshima A, Tsuji A, Nagao Y, Sakuraba H, Suzuki Y (Nov 1988). "Cloning, sequencing, and expression of cDNA for human beta-galactosidase". Biochemical and Biophysical Research Communications. 157 (1): 238–44. doi:10.1016/S0006-291X(88)80038-X. PMID   3143362.
  7. Yoshida K, Oshima A, Shimmoto M, Fukuhara Y, Sakuraba H, Yanagisawa N, Suzuki Y (Aug 1991). "Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases". American Journal of Human Genetics. 49 (2): 435–42. PMC   1683306 . PMID   1907800.
  8. Caciotti A, Donati MA, Boneh A, d'Azzo A, Federico A, Parini R, Antuzzi D, Bardelli T, Nosi D, Kimonis V, Zammarchi E, Morrone A (Mar 2005). "Role of beta-galactosidase and elastin binding protein in lysosomal and nonlysosomal complexes of patients with GM1-gangliosidosis". Human Mutation. 25 (3): 285–92. doi:10.1002/humu.20147. hdl: 2158/312510 . PMID   15714521. S2CID   36584440.
  9. Hinek A, Zhang S, Smith AC, Callahan JW (Jul 2000). "Impaired elastic-fiber assembly by fibroblasts from patients with either Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency in the 67-kD spliced variant of beta-galactosidase". American Journal of Human Genetics. 67 (1): 23–36. doi:10.1086/302968. PMC   1287082 . PMID   10841810. Archived from the original on 2005-01-18. Retrieved 2009-05-31.
  10. Privitera S, Prody CA, Callahan JW, Hinek A (Mar 1998). "The 67-kDa enzymatically inactive alternatively spliced variant of beta-galactosidase is identical to the elastin/laminin-binding protein". The Journal of Biological Chemistry. 273 (11): 6319–26. doi: 10.1074/jbc.273.11.6319 . PMID   9497360. Archived from the original on 2005-01-18. Retrieved 2009-05-31.
  11. Duca L, Blanchevoye C, Cantarelli B, Ghoneim C, Dedieu S, Delacoux F, Hornebeck W, Hinek A, Martiny L, Debelle L (Apr 2007). "The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit". The Journal of Biological Chemistry. 282 (17): 12484–91. doi: 10.1074/jbc.M609505200 . PMID   17327233. Archived from the original on 2008-09-22. Retrieved 2009-05-31.
  12. Adair-Kirk TL, Senior RM (December 2008). "Fragments of extracellular matrix as mediators of inflammation". The International Journal of Biochemistry & Cell Biology. 40 (6–7): 1101–10. doi:10.1016/j.biocel.2007.12.005. PMC   2478752 . PMID   18243041.
  13. Hinek A, Bodnaruk TD, Bunda S, Wang Y, Liu K (Oct 2008). "Neuraminidase-1, a subunit of the cell surface elastin receptor, desialylates and functionally inactivates adjacent receptors interacting with the mitogenic growth factors PDGF-BB and IGF-2". The American Journal of Pathology. 173 (4): 1042–56. doi:10.2353/ajpath.2008.071081. PMC   2543072 . PMID   18772331.
  14. Hinek A, Pshezhetsky AV, von Itzstein M, Starcher B (Feb 2006). "Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly". The Journal of Biological Chemistry. 281 (6): 3698–710. doi: 10.1074/jbc.M508736200 . PMID   16314420. Archived from the original on 2008-09-19. Retrieved 2009-05-31.
  15. Seyrantepe V, Hinek A, Peng J, Fedjaev M, Ernest S, Kadota Y, Canuel M, Itoh K, Morales CR, Lavoie J, Tremblay J, Pshezhetsky AV (Apr 2008). "Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1". Circulation. 117 (15): 1973–81. doi: 10.1161/CIRCULATIONAHA.107.733212 . PMID   18391110. Archived from the original on 2008-09-19. Retrieved 2009-05-31.

Further reading