TRIB1
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TRIB1
Tribbles homolog 1 is a protein kinase that in humans is encoded by the ''TRIB1'' gene. Orthologs of this protein pseudokinase (pseudoenzyme) can be found almost ubiquitously throughout the animal kingdom. It exerts its biological functions through binding to signalling proteins of the MAPKK level of the MAPK pathway, therefore eliciting a regulatory role in the function of this pathway which mediates proliferation, apoptosis and differentiation in cells. Tribbles-1 is encoded by the trib1 gene, which in humans can be found on chromosome 8 at position 24.13 on the longest arm (q). Recent crystal structures show that Tribbles 1 has an unusual 3D structure, containing a 'broken' C-helix region, a binding site for ubiquitinated substrates such as C/EBPalpha and a key regulatory C-tail region. Like TRIB2 and TRIB3, TRIB1 has recently been considered as a potential allosteric drug target. Function Tribbles-1 is one of three members of the Tribbles subfamily, which is a part of the ...
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TRIB2
Tribbles homolog 2 is an atypical protein kinase that is encoded in human by the ''TRIB2'' gene. TRIB2 is a pseudokinase member of the (pseudoenzyme) class of signaling/scaffold proteins, possessing little vestigial catalytic output in vitro. It is known to signal to canonical MAPK pathways and to regulate the ubiquitination of substrates with important functions in the immune system. It has also been associated with various diseases, especially in vertebrate leukaemia models. Like TRIB1 and TRIB3 Tribbles homolog 3 is a protein that in humans is encoded by the ''TRIB3'' gene. Function The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. It is a pseudoenzyme that is though ..., TRIB2 has recently been considered as a potential allosteric drug target, and is a putative regulator of cancer-associated signalling and survival through AKT pSer473 modulation References Further reading * * * * * * * EC 2.7.11 ...
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TRIB3
Tribbles homolog 3 is a protein that in humans is encoded by the ''TRIB3'' gene. Function The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. It is a pseudoenzyme that is thought to be a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein has been reported to negatively regulate the cell survival serine-threonine kinase AKT1. TRIB3 has recently been associated with neuronal signalling, and like TRIB1 and TRIB2, could be considered as a potential allosteric drug target Interactions TRIB3 has been shown to interact with: * AKT1, * CSNK2B, * Fibronectin * MCM3AP, * RELA, * SIAH1 E3 ubiquitin-protein ligase SIAH1 is an enzyme that in humans is encoded by the ''SIAH1'' gene. Function This gene encodes for a polypeptide structure that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase ..., and * TIAF1 ...
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Protein Kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein ( substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets and most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction. Chemical ac ...
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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 gen ...
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Ortholog
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 similarityā€¯, that is the percentage of identical residues (''percent identity''), or the percentage of residues conserved with similar physicochemical properties ('' ...
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Pseudoenzyme
Pseudoenzymes are variants of enzymes (usually proteins) that are catalytically-deficient (usually inactive), meaning that they perform little or no enzyme catalysis. They are believed to be represented in all major enzyme families in the kingdoms of life, where they have important signaling and metabolic functions, many of which are only now coming to light. Pseudoenzymes are becoming increasingly important to analyse, especially as the bioinformatic analysis of genomes reveals their ubiquity. Their important regulatory and sometimes disease-associated functions in metabolic and signalling pathways are also shedding new light on the non-catalytic functions of active enzymes, of moonlighting proteins, the re-purposing of proteins in distinct cellular roles (Protein moonlighting). They are also suggesting new ways to target and interpret cellular signalling mechanisms using small molecules and drugs. The most intensively analyzed, and certainly the best understood pseudoenzymes in ...
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Positive Feedback
Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the magnitude of the perturbation. That is, ''A produces more of B which in turn produces more of A''.Keesing, R.M. (1981). Cultural anthropology: A contemporary perspective (2nd ed.) p.149. Sydney: Holt, Rinehard & Winston, Inc. In contrast, a system in which the results of a change act to reduce or counteract it has negative feedback. Both concepts play an important role in science and engineering, including biology, chemistry, and cybernetics. Mathematically, positive feedback is defined as a positive loop gain around a closed loop of cause and effect. That is, positive feedback is Phase (waves), in phase with the input, in the sense that it adds to make the input larger. Positive feedback tends to cause Control theory#Stability, system i ...
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