CAP/Ponsin

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, respon ...

, also known as Sorbin and SH3 domain-containing protein 1 is a

that in humans is encoded by the ''SORBS1''

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 b ...

. It is part of a small family of adaptor proteins that regulate

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for r ...

signaling and

cytoskeletal The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is comp ...

formation. It is mainly expressed in

heart The heart is a muscular organ found 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 diox ...

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 m ...

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

adipose Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

tissue, and macrophages; in striated muscle tissue, it is localized to

costamere The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331 Costameres are sub-sarcolemmal protein assemblies circumferentially a ...

structures.

Structure

CAP/Ponsin may exist as thirteen alternatively-spliced isoforms, ranging from 81 kDa to 142 kDa. It is part of an adaptor protein family, of which ArgBP2 and vinexin are also a part. These proteins contain a conserved sorbin homology (SOHO) domain 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 phosp ...

s, and CAP/Ponsin is expressed in

tissue, and

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

Function

In muscle, CAP/Ponsin plays a role in the formation of mature

s from

focal adhesion In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More ...

-like contacts during assembly of the contractile apparatus, as overexpression of CAP/Ponsin disrupted normal cell-matrix contact morphology. In a mouse model of viral

myocarditis Myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The ...

due to

Coxsackievirus Coxsackieviruses are a few related enteroviruses that belong to the ''Picornaviridae'' family of nonenveloped, linear, positive-sense single-stranded RNA viruses, as well as its genus ''Enterovirus'', which also includes poliovirus and echoviru ...

infection, CAP/Ponsin stabilized antiviral type I

interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten t ...

production and was protective against apoptosis and cytotoxicity. It has also been shown to be a major regulator of

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabol ...

-stimulated signaling and regulation of

glucose uptake Method of glucose uptake differs throughout tissues depending on two factors; the metabolic needs of the tissue and availability of glucose. The two ways in which glucose uptake can take place are facilitated diffusion (a passive process) and seco ...

, by potentiating

-induced

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, ...

and recruitment of

CBL CBL may refer to: CBC Radio * CBL-FM, a CBC Radio Two radio station in Toronto, Ontario * CBLA-FM in Toronto had the call sign CBL for much of the period when it was on the AM band (1937–99) Sports leagues and associations * Canadian Basebal ...

to a

lipid raft The cell membrane, plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein Receptor (biochemistry), receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular mem ...

signaling complex involving

flotillin 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 pr ...

. A role for it in macrophage function was illuminated by the finding that, in mice harboring ''SORBS1''-deficient macrophages in

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoieti ...

, it was protective against high-fat diet-induced

insulin resistance Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood suga ...

and showed reduced

inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

. In non-muscle cells, it inhibits cell spreading and

turnover, as its

siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating ...

-mediated knockdown resulted in enhanced

PAK Pak or PAK may refer to: Places * Pakistan (country code PAK) * Pak, Afghanistan * Pak Island, in the Admiralty Islands group of Papua New Guinea * Pak Tea House, a café in Lahore, Punjab, Pakistan Arts and entertainment * PAK (band), an Amer ...

/ MEK/ ERK activation and cell migration.

Clinical Significance

CAP/Ponsin was demonstrated to be down-regulated in end-stage

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...

patients; an effect that was restored upon mechanical unloading. A single nucleotide polymorphism in ''SORBS1'' was found to be associated with

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinati ...

and

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

Interactions

SORBS1 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 organizat ...

with: *

, *

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 pro ...

, *

INPPL1 SH2-domain containing Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 is an enzyme that in humans is encoded by the ''INPPL1'' gene. INPPL1 encodes inositol polyphosphate-5 phosphatase-like 1, a protein that in addition to the phosphatase ...

, *

INSM1 Insulinoma-associated protein 1 is a protein that in humans is encoded by the ''INSM1'' gene. Function Insulinoma-associated 1 (INSM1) gene is intronless and encodes a protein containing both a zinc finger DNA-binding domain and a putative pro ...

, *

MLLT4 Afadin is a protein that in humans is encoded by the ''AFDN'' gene. Function Afadin is a Ras (see HRAS; MIM 190020) target that regulates cell–cell adhesions downstream of Ras activation. It is fused with MLL (MIM 159555) in leukemias caused ...

, *

PXN 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 ...

, and *

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 cel ...

Structure

Function

Clinical Significance

Interactions

References

Further reading