Gram Domain-containing 2A
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Gram Domain-containing 2A
GRAM domain-containing 2A protein (GRAMD2A; formerly GRAMD2) is a protein encoded by the GRAMD2A gene. Like GRAMD2B, the protein consists of a GRAM domain and a transmembrane domain that anchors it to the endoplasmic reticulum. GRAMD2A is a mammalian representative of the yeast lipid transfer proteins anchored at a membrane contact site (LAM) family. It has four paralogs: GRAMD1A, GRAMD1B, GRAMD1C and GRAMD2B. Unlike LAM and its paralogs except GRAMD2B, GRAMD2A lacks a VASt domain. The protein localizes to sites where membranes from different organelles are in close apposition. There, it tethers the endoplasmic reticulum to the plasma membrane through its GRAM domain binding phosphatidylinositol 4,5-bisphosphate in the plasma membrane at sites enriched for the phospholipid. The protein ensures proper stromal interaction molecule 1 (STIM1) recruitment to these sites of membrane contact as part of the store-operated calcium entry pathway – a component of intracellular ...
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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 resid ...
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Gram Domain Containing 1b
GRAM domain containing 1B, also known as GRAMD1B, Aster-B and KIAA1201, is a cholesterol transport protein that is encoded by the GRAMD1B gene. It contains a transmembrane region and two domains of known function; the GRAM domain and a VASt domain. It is anchored to the endoplasmic reticulum. This highly conserved gene is found in a variety of vertebrates and invertebrates. Homologs (Lam/Ltc proteins) are found in yeast. Gene GRAMD1B, also known as KIAA1201, is located in the human genome at 11q24.1. It is located on the + strand and is flanked by a variety of other genes. It spans 269,347 bases. mRNA The most verified isoform, isoform 1, contains 21 exons. There are four validated isoform variants of human GRAMD1B. These consist of truncated 5’ and 3’ regions, resulting in the loss of an exon. One prominent analysis of the mouse gene predicts one form of Gramd1b that is 699 amino acids long. Protein GRAMD1B is an integral membrane protein that contains several ...
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Stromal Interaction Molecule 1
Stromal interaction molecule 1 is a protein that in humans is encoded by the ''STIM1'' gene. STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane. Even though the protein has been identified earlier, its function was unknown until recently. In 2005, it was discovered that STIM1 functions as a calcium sensor in the endoplasmic reticulum. Upon activation of the IP3 receptor, the calcium concentration in the endoplasmic reticulum decreases, which is sensed by STIM1, via its EF hand domain. STIM1 activates the "store-operated" ORAI1 calcium ion channels in the plasma membrane, via intracellular STIM1 movement, clustering under plasma membrane and protein interaction with ORAI isoforms. STIM1-mediated calcium entry is required for thrombin-induced disassembly of VE-cadherin adherens junctions. 2-Aminoethoxydiphenyl borate (2-APB) and 4-chloro-3-ethylphenol (4-CEP) cause STIM1 clustering in a cell and prevent ...
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Phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typically have omega-3 fatty acids EPA and DHA integrated as part of the phospholipid molecule. The phosphate group can be modified with simple organic molecules such as choline, ethanolamine or serine. Phospholipids are a key component of all cell membranes. They can form lipid bilayers because of their amphiphilic characteristic. In eukaryotes, cell membranes also contain another class of lipid, sterol, interspersed among the phospholipids. The combination provides fluidity in two dimensions combined with mechanical strength against rupture. Purified phospholipids are produced commercially and have found applications in nanotechnology and materials science. The first phospholipid identified in 1847 as such in biological tissues wa ...
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Phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins. PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P. The fatty acids of PIP2 are variable in different species and tissues, but the most common fatty acids are stearic in position 1 and arachidonic in 2. Signaling pathways PIP2 is a part of many cellular signaling pathways, including PIP2 cycle, PI3K signalling, and PI5P metabolism. Recently, it has been found in the nucleus with unknown function. Functions Cytoskeleton dynamics near membranes PIP2 regulates the organization, polymerization, and bra ...
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Plasma Membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to io ...
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Organelles
In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the suffix ''-elle'' being a diminutive. Organelles are either separately enclosed within their own lipid bilayers (also called membrane-bound organelles) or are spatially distinct functional units without a surrounding lipid bilayer (non-membrane bound organelles). Although most organelles are functional units within cells, some function units that extend outside of cells are often termed organelles, such as cilia, the flagellum and archaellum, and the trichocyst. Organelles are identified by microscopy, and can also be purified by cell fractionation. There are many types of organelles, particularly in eukaryotic cells. They include structures that make up the endomembrane system (such as the nuclear envelope, endoplasmic reticulum, a ...
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VAD1 Analog Of StAR-related Lipid Transfer
VAD1 analog of StAR-related lipid transfer (VASt) is a steroidogenic acute regulatory protein‐related lipid transfer (StART)-like lipid-binding domain first identified in the vad1 (vascular associated death1) protein in ''Arabidopsis thaliana'' (mouse-ear cress ). Proteins containing these domains are found in eukaryotes and usually contain another lipid-binding domain, typically the GRAM domain and sometimes the C2 domain in plants and the integral peroxisomal membrane peroxin Pex24p domain in oomycetes. Structure The VASt domain structurally resembles a truncated form of a START domain, but with limited sequence similarity. While VASt is a member of the Bet v1-like superfamily, it is unclear if it evolved from the same ancestral domain as the START domain or is an example of convergent evolution. The domain is highly conserved across all eukaryotes and is typically present in only one copy in VASt domain-containing proteins. Like the START domain, the VASt domain consists ...
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GRAMD1C
GRAM domain containing 1C also known as Aster-C is a cholesterol transport protein that is encoded by the GRAMD1C gene. It contains a transmembrane region, a GRAM domain and a VASt domain. It is anchored to the endoplasmic reticulum through its transmembrane domain. GRAMD1C has four paralogs: GRAMD1B and GRAMD1A and two without VASt domains, GRAMD2A and GRAMD2B. Homologs of GramD proteins (Lam/Ltc proteins) are found in yeast. The protein is expressed in the liver and testes. Function When the plasma membrane contains high levels of cholesterol, GRAMD1c as well as GRAMD1a and GRAMD1b move to sites of contact between the plasma membrane and the endoplasmic reticulum. GRAMD1 proteins then facilitate the transport of cholesterol into the endoplasmic reticulum. Reduction of GRAMD1B and GRAMD1C suppresses the onset of a form of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (NASH) in mice. The VASt domain is responsible for binding cholesterol while th ...
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Gram Domain Containing 1a
GRAM domain containing 1A also known as Aster-A is a protein that is encoded by the GRAMD1A gene. It contains a transmembrane region, a GRAM domain and a VASt domain that can bind cholesterol. GRAMD1A has four paralogs: GRAMD1B and GRAMD1C and two without VASt domains, GRAMD2A and GRAMD2B. These proteins are mammalian representatives of the yeast lipid transfer proteins anchored at a membrane contact site (LAM) family. The protein is expressed ubiquitously with higher levels in the central nervous system. Function GRAMD1A localizes to the endoplasmic reticulum. Its GRAM domain tethers it to the plasma membrane where it can bind phosphatidylinositol phosphate in areas enriched for it. When the plasma membrane contains high levels of cholesterol, GRAMD1a like GRAMD1b and GRAMD1c moves to sites of contact between the plasma membrane and the endoplasmic reticulum. The VASt domain of GRAMD1A then binds cholesterol and cholesterol is moved from the plasma membrane to the e ...
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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 basic unit of heredity and 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: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as g ...
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Paralog
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal (or lateral) gene transfer event (xenologs). Homology among DNA, RNA, or proteins is typically inferred from their nucleotide or amino acid sequence similarity. Significant similarity is strong evidence that two sequences are related by evolutionary changes from a common ancestral sequence. Alignments of multiple sequences are used to indicate which regions of each sequence are homologous. Identity, similarity, and conservation The term "percent homology" is often used to mean "sequence similarity”, that is the percentage of identical residues (''percent identity''), or the percentage of residues conserved with similar physicochemical properties ( ...
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