GLB1
Encyclopedia
Galactosidase, beta 1, also known as GLB1, is a protein
which in humans is encoded by the GLB1 gene
.
The GLB1 protein is a beta-galactosidase
that cleaves the terminal beta-galactose
from ganglioside
substrates and other glycoconjugates. The GLB1 gene also encodes an elastin
binding protein.
In corn
(Zea mays), Glb1 is a gene coding for the storage protein globulin
.
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.
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
.
The S-Gal protein is a peripheral membrane protein
that functions as part of an elastin receptor
complex on the surface of cells. The elastin receptor complex includes S-Gal, neuraminidase
and Cathepsin A
. When elastin-derived peptide
s 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 and can alter cell cycle
progression. 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 receptor
s.
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. Cathepsin A
is also required for normal elastin biosynthesis.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the GLB1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
The GLB1 protein is a beta-galactosidase
Beta-galactosidase
β-galactosidase, also called beta-gal or β-gal, is a hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides. Substrates of different β-galactosidases include ganglioside GM1, lactosylceramides, lactose, and various glycoproteins...
that cleaves the terminal beta-galactose
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
from ganglioside
Ganglioside
Ganglioside is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. The 60+ known gangliosides differ mainly in the position and number of NANA residues.It is a component of the cell plasma membrane that modulates cell signal transduction events...
substrates and other glycoconjugates. The GLB1 gene also encodes an elastin
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
binding protein.
In corn
Maize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...
(Zea mays), Glb1 is a gene coding for the storage protein globulin
Globulin
Globulin is one of the three types of serum proteins, the others being albumin and fibrinogen. Some globulins are produced in the liver, while others are made by the immune system. The term globulin encompasses a heterogeneous group of proteins with typical high molecular weight, and both...
.
Clinical significance
GM1-gangliosidosisGM1 gangliosidoses
The GM1 gangliosidoses are caused by a deficiency of beta-galactosidase, with resulting abnormal storage of acidic lipid materials in cells of the central and peripheral nervous systems, but particularly in the nerve cells.-Early infantile GM1:...
is a lysosomal storage disease
Lysosomal storage disease
Lysosomal storage diseases are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function...
that can be caused by a deficiency of β-galactosidase (GLB1). Some cases of Morquio syndrome B
Morquio syndrome
Morquio's syndrome is an autosomal recessive mucopolysaccharide storage disease , usually inherited. It is a rare type of birth defect with serious consequences...
have been shown to be due to GLP1 mutations that cause patients to have abnormal elastic fibers.
Elastin receptor
The RNARNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
transcript
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
of the GLB1 gene is alternatively spliced
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
and produces 2 mRNAs. The 2.5-kilobase transcript encodes
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
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
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
and fragments of elastin that are generated by proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
.
The S-Gal protein is a peripheral membrane protein
Peripheral membrane protein
Peripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. These molecules attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and...
that functions as part of an elastin receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
complex on the surface of cells. The elastin receptor complex includes S-Gal, neuraminidase
NEU1
Sialidase 1 , also known as NEU1 is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the NEU1 gene.- Function :...
and Cathepsin A
Cathepsin A
Cathepsin A is an enzyme which is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.- Function :...
. When elastin-derived peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s bind to the S-Gal protein then the associated neuraminidase enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
activity is activated and responding cells can have altered signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
involving extracellular signal-regulated kinases
Extracellular signal-regulated kinases
In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...
and regulated matrix metallopeptidase
MMP1
Interstitial collagenase also known as matrix metalloproteinase-1 and fibroblast collagenase is an enzyme that in humans is encoded by the MMP1 gene.- Function :...
production. Elastin-derived peptides are chemotactic
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
for some cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
types and can alter cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...
progression. 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
Sialic acid
Sialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
from extracellular and cell surface proteins such as growth factor receptor
Growth factor receptor
A growth factor receptor is a receptor which binds to growth factor.These receptors may use the JAK/STAT, MAP kinase, and PI3 kinase pathways....
s.
The S-Gal protein functions during the normal assembly of elastin
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...
into extracellular
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
elastic fibers. Elastin is initially present as newly synthesized tropoelastin
Tropoelastin
Tropoelastin is a water-soluble molecule with a molecular weight of approximately 72,000 daltons. Multiple tropoelastin molecules covalently bind together with crosslinks to form the protein elastin that is very prevalent in the body. There is only one gene for this molecule and so only one protein...
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. Cathepsin A
Cathepsin A
Cathepsin A is an enzyme which is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.- Function :...
is also required for normal elastin biosynthesis.