ArgBP2
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
, also referred to as Sorbin and SH3 domain-containing protein 2 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''SORBS2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains. ArgBP2 is highly abundant in
cardiac muscle
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...
cells at
sarcomeric Z-disc structures, and is expressed in other cells at
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
stress fiber
Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin II (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated ...
s and the
nucleus
Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to:
*Atomic nucleus, the very dense central region of an atom
* Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA
Nucl ...
.
Structure
ArgBP2 may exist in as many as 9 unique isoforms ranging from 52 kDa to 117 kDa (492 to 1100 amino acids).
ArgBP2 belongs to the a small family of adaptor proteins having sorbin homology (SOHO) domains and three
SH3 domain
The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phos ...
s, which regulate cell adhesion, cytoskeletal organization and growth factor signaling; other members include
CAP/ponsin and
vinexin.
The three
SH3 domain
The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phos ...
s are
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
, a serine-threonine rich domain
resides in the middle, and the sorbin homology (SoHo) domain is
N-terminal. The SH3 domains interact with Arg/Abl, vinculin.
The SOHO domain interacts with
flotillin found in lipid rafts.
Function
The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that ArgBP2 functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. ArgBP2 contains several potential Abl phosphorylation sites;
Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. In non-muscle cells, ArgBP2 bids
Cbl which enhances the degradation of
c-Abl; and also
Pyk2
Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the ''PTK2B'' gene.
Function
This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the ...
which promotes cytoskeletal remodeling. ArgBP2 binding with
flotillin at lipid rafts may indicate a role for ArgBP2 in vesicle trafficking and signal transduction.
flotillin in
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
cells exhibits a striated pattern suggesting localization to
T-tubule
T-tubules (transverse tubules) are extensions of the cell membrane that penetrate into the center of skeletal and cardiac muscle cells. With membranes that contain large concentrations of ion channels, transporters, and pumps, T-tubules permi ...
s or
sarcoplasmic reticular cisternae, though no precise role has been determined in
cardiac
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
cells. In cardiac muscle cells, pull-down experiments discovered ArgBP2 in complex with
alpha actinin-2,
vinculin
In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cell ...
,
spectrin
Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membr ...
,
paxillin
Paxillin is a protein that in humans is encoded by the ''PXN'' gene. Paxillin is expressed at focal adhesions of non-striated cells and at costameres of striated muscle cells, and it functions to adhere cells to the extracellular matrix. Mutation ...
,
Pyk2
Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the ''PTK2B'' gene.
Function
This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the ...
and
flotillin, suggesting that ArgBP2 may be involved in
myofibril
A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myo ...
assembly and
Z-band signaling in cardiomyocytes,
though functional studies are necessary to elucidate specific mechanisms. ArgBP2 has been linked to hyertrophic signaling, as a potent paracrine-acting RNA molecule shown to induce
cardiac hypertrophy in mice, miR-21, acts on both ArgBP2 and
PDLIM5
PDZ and LIM domain protein 5 is a protein that in humans is encoded by the ''PDLIM5'' gene.
The protein encoded by this gene is a LIM domain protein. LIM domains are cysteine-rich double zinc fingers composed of 50 to 60 amino acids that are invol ...
to trigger the
hypertrophic
Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number.Updated by Linda J. ...
response.
Clinical Significance
Elevated levels of serum ArgBP2 and coordinate decreases in ArgBP2 in
myocardial
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...
tissue were detected in the very early phase from patients post-
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
who died within 7 hours of the insult. Chromosome 4
pericentric inversion has been observed in 10 patients, with associated
cardiac
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
defects linked to terminal 4q35.1 deletions, which may affect ''SORBS2''.
Interactions
ArgBP2 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
ABL,
[
* ]ABL2
Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ''ABL2'' gene.
Function
ABL2 is a cytoplasmic tyrosine kinase which is closely related to but distinct from ABL1. The simila ...
,
* ACTC1,
* CBL,[
* ]FLOT1
Flotillin-1 is a protein that in humans is encoded by the ''FLOT1'' gene.
Caveolae are small domains on the inner cell membrane involved in vesicular trafficking and signal transduction. FLOT1 encodes a caveolae-associated, integral membrane prot ...
,
* PTK2B
Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the ''PTK2B'' gene.
Function
This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the ...
,
* PLDN
Pallidin is a protein that in humans is encoded by the ''PLDN'' gene.
Function
The protein encoded by this gene may play a role in intracellular vesicle trafficking. It interacts with Syntaxin 13 which mediates intracellular membrane fusion. Se ...
, and
* VCL.
References
Further reading
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