DNAJA3
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DNAJA3
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the ''DNAJA3'' gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers. Structure As a member of the DNAJ/Hsp40 protein family, DNAJA3 contains a conserved DnaJ domain, which includes an HPD motif that interacts with Hsp70 to perform its cochaperone function. The DnaJ domain is composed of tetrahelical regions containing a tripeptide of histidine, proline and aspartic acid ...
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Hsp40
In molecular biology, chaperone DnaJ, also known as Hsp40 (heat shock protein 40 kD), is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans. Function Molecular chaperones are a diverse family of proteins that function to protect proteins from irreversible aggregation during synthesis and in times of cellular stress. The bacterial molecular chaperone DnaK is an enzyme that couples cycles of ATP binding, hydrolysis, and ADP release by an N-terminal ATP-hydrolyzing domain to cycles of sequestration and release of unfolded proteins by a C-terminal substrate binding domain. Dimeric GrpE is the co-chaperone for DnaK, and acts as a nucleotide exchange factor, stimulating the rate of ADP release 5000-fold. DnaK is itself a weak ATPase; ATP hydrolysis by DnaK is stimulated by its interaction with another co-chaperone, DnaJ. Thus the co-chaperones DnaJ and GrpE are capable of tightly regulating the nucleotide-bound and substrate-bound st ...
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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, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. (For that, see Proteoforms.) Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments ( exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein. The discovery of isoforms could explain the discrepancy between the small number of protein coding regions genes revealed by the human genome project and the large diversity of proteins seen in an organism: different ...
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Caspase
Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cysteine protease activity – a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. As of 2009, there are 12 confirmed caspases in humans and 10 in mice, carrying out a variety of cellular functions. The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues. Caspases have other identified roles in programmed cell ...
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Cytochrome C
The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is highly water-soluble, unlike other cytochromes, and is an essential component of the respiratory electron transport chain, where it carries one electron. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It transfers electrons between Complexes III (Coenzyme Q – Cyt c reductase) and IV (Cyt c oxidase). In humans, cytochrome c is encoded by the ''CYCS'' gene. Species distribution Cytochrome c is a highly conserved protein across the spectrum of eukaryotic species, found in plants, animals, fungi, and many unicellular organisms. This, along with its small size (molecular weight about 12,000 daltons), makes it useful in studies of cladistics. Cyt ...
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Senescence
Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle. Senescence is the inevitable fate of almost all multicellular organisms with germ-soma separation, but it can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal organisms such as '' Hydra'', have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases. Environmental factors may affect aging – for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body ...
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Cellular Differentiation
Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Although metabolic composition does get altered quite dramaticall ...
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Cell Growth
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis (production of biomolecules or anabolism) is greater than the overall rate of cellular degradation (the destruction of biomolecules via the proteasome, lysosome or autophagy, or catabolism). Cell growth is not to be confused with cell division or the cell cycle, which are distinct processes that can occur alongside cell growth during the process of cell proliferation, where a cell, known as the mother cell, grows and divides to produce two daughter cells. Importantly, cell growth and cell division can also occur independently of one another. During early embryonic development ( cleavage of the zygote to form a morula and blastoderm), cell divisions occur repeatedly without cell growth. Conversely, some cells can grow without cell division or without any progression of the cell cycle, such as g ...
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Cell Migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations. Cells often migrate in response to specific external signals, including chemical signals and mechanical signals. Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis. An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for controlling, for example, invasive tumour cells. Due to the highly viscous environment (low Reynolds number), cells need to continuously produce forces in order to move. Cells achieve active movement by very different mechanisms. Many less complex prokaryotic organisms (and sperm cells) use flagella or cilia to propel themselves. Eukaryot ...
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DNM1L
Dynamin-1-like protein is a GTPase that regulates mitochondrial fission. In humans, dynamin-1-like protein, which is typically referred to as dynamin-related protein 1 (Drp1), is encoded by the ''DNM1L'' gene and is part of the dynamin superfamily (DSP) family of proteins. Structure Drp1, which is a member of the dynamin superfamily of proteins, consists of a GTPase and GTPase effector domain that are separated from each other by a helical segment of amino acids. There are 3 mouse and 6 human isoforms of Drp1, including a brain-specific variant. Drp1 exists as homooligomers and its function relies on its oligomerization ability. Function Mitochondria routinely undergo fission and fusion events that maintain a dynamic reticular network. Drp1 is a fundamental component of mitochondrial fission. Indeed, Drp1 deficient neurons have large, strongly interconnected mitochondria due to dysfunctional fission machinery. Fission helps facilitate mitophagy, which is the breakdown and r ...
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Mitochondrial Fission
Mitochondrial fission is the process where mitochondria divide or segregate into two separate mitochondrial organelles. Mitochondrial fission is counteracted by the process of mitochondrial fusion, whereby two separate mitochondria can fuse together to form a large one. Mitochondrial fusion in turn can result in elongated mitochondrial networks. Both mitochondrial fission and fusion are balanced in the cell, and mutations interfering with either processes are associated with a variety of diseases. Mitochondria can divide by prokaryotic binary fission and since they require mitochondrial DNA for their function, fission is coordinated with DNA replication. Some of the proteins that are involved in mitochondrial fission have been identified and some of them are associated with mitochondrial diseases. Mitochondrial fission has significant implications in stress response and apoptosis. Mechanism FtsZ Localization The FtsZ protein (a homologue to eukaryotic tubulin), found in many bacte ...
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HSPA9
Mitochondrial 70kDa heat shock protein (mtHsp70), also known as mortalin, is a protein that in humans is encoded by the ''HSPA9'' gene. Function The product encoded by this gene belongs to the heat shock protein 70 family which contains both heat-inducible and constitutively expressed members. The latter are called heat-shock cognate proteins. This gene encodes a heat-shock cognate protein. This protein plays a role in the control of cell proliferation. It may also act as a chaperone. Interactions HSPA9 has been shown to interact with FGF1 and P53. Clinical relevance and genetic deficiency In 2015, a group around Andrea Superti-Furga showed that biallelic variants in the ''HSPA9'' gene may result in a combination of congenital malformation A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The ...
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