Galactosidase, beta 1, also known as GLB1, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
which in humans is encoded by the ''GLB1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
The GLB1 protein is a
beta-galactosidase that cleaves the terminal beta-
galactose
Galactose (, ''wikt:galacto-, galacto-'' + ''wikt:-ose#Suffix 2, -ose'', ), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweetness, sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epime ...
from
ganglioside
A ganglioside is a molecule composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (e.g. N-acetylneuraminic acid, ''N''-acetylneuraminic acid, NANA) linked on the sugar chain. NeuNAc, an acetylated derivative ...
substrates and other glycoconjugates.
The ''GLB1'' gene also encodes an
elastin
Elastin is a protein encoded by the ''ELN'' gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates). It is highly Elasticity (physics), elastic and present in connective ...
binding protein.
In
corn
Maize (; ''Zea mays''), also known as corn in North American English, is a tall stout Poaceae, grass that produces cereal grain. It was domesticated by indigenous peoples of Mexico, indigenous peoples in southern Mexico about 9,000 years ago ...
(''
Zea mays
Maize (; ''Zea mays''), also known as corn in North American English, is a tall stout Poaceae, grass that produces cereal grain. It was domesticated by indigenous peoples of Mexico, indigenous peoples in southern Mexico about 9,000 years ago ...
''), ''Glb1'' is a gene coding for the storage protein
globulin
The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune ...
.
Clinical significance
GM1-gangliosidosis is a
lysosomal storage disease
Lysosomal storage diseases (LSDs; ) 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 ...
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 fiber
Elastic fibers (or yellow 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 ai ...
s.
Elastin receptor
The
RNA
Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
transcript
Transcript may refer to:
* Transcript (biology), a molecule of RNA transcribed from DNA
* Transcript (education), a copy of a student's permanent academic record
* Transcript (law), a written record of spoken language in court proceedings
* Transc ...
of the GLB1 gene is
alternatively spliced
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
and produces 2 mRNAs. The 2.5-
kilobase
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
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
Elastin is a protein encoded by the ''ELN'' gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates). It is highly Elasticity (physics), elastic and present in connective ...
and fragments of elastin that are generated by
proteolysis
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...
.
The S-Gal protein is a
peripheral membrane protein
Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the periph ...
that functions as part of an elastin
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
complex on the surface of cells.
The elastin receptor complex includes S-Gal,
neuraminidase
Exo-α-sialidase (, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids:
: Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycosidic linkag ...
and
Cathepsin A
Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the ''CTSA'' gene. The enzyme is also known as Human Protective Protein. It is a lysosomal serine carboxypeptidase. The enzyme ...
. When elastin-derived
peptide
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
s bind to the S-Gal protein then the associated neuraminidase
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
activity is activated and responding cells can have altered
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...
involving
extracellular signal-regulated kinases
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
and regulated
matrix metallopeptidase production. Elastin-derived peptides are
chemotactic
Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemica ...
for some
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
* Cellphone, a phone connected to a cellular network
* Clandestine cell, a penetration-resistant form of a secret or outlawed organization
* Electrochemical cell, a de ...
types
and can alter
cell cycle
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
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 acids are a class of alpha-keto acid sugars with a nine-carbon backbone.
The term "sialic acid" () was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is ''N''-acetylneuraminic acid ...
from extracellular and cell surface proteins such as
growth factor receptor
A growth factor receptor is a receptor that binds to a growth factor. Growth factor receptors are the first stop in cells where the signaling cascade for cell differentiation and proliferation begins. Growth factors, which are ligands that bind to ...
s.
The S-Gal protein functions during the normal assembly of
elastin
Elastin is a protein encoded by the ''ELN'' gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates). It is highly Elasticity (physics), elastic and present in connective ...
into
extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
elastic fiber
Elastic fibers (or yellow 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 ai ...
s. Elastin is initially present as newly synthesized
tropoelastin
Elastin is a protein encoded by the ''ELN'' gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates). It is highly elastic and present in connective tissue of the body t ...
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 is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the ''CTSA'' gene. The enzyme is also known as Human Protective Protein. It is a lysosomal serine carboxypeptidase. The enzyme ...
is also required for normal elastin biosynthesis.
References
Further reading
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{{Proteoglycan metabolism enzymes