GHKL Domain
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GHKL Domain
The GHKL domain ( Gyrase, Hsp90, Histidine Kinase, MutL) is an evolutionary conserved protein domain. This family represents the structurally related ATPase domains of histidine kinase, DNA gyrase B and HSP90. This domain is found in several ATP-binding proteins for example: histidine kinase, DNA gyrase B, topoisomerases, heat shock protein HSP90, phytochrome-like ATPases and DNA mismatch repair proteins. More information about this protein can be found at Protein of the Month: DNA Topoisomerase. Subfamilies * Histidine kinase related protein, C-terminal Members * BCKDK * HSP90AA1, HSP90AB1, HSP90B1 * MLH1, MLH3, MORC1, MORC2, MORC3, MORC4 * PDK1, PDK2, PDK3, PDK4 * PMS1, PMS2, PMS2L1, PMS2L11, PMS2L3, PMS4L * TOP2A, TOP2B * TRAP1 Heat shock protein 75 kDa, mitochondrial is a protein that in humans is encoded by the ''TRAP1'' gene. Interactions TRAP1 has been shown to interact with EXT2, EXT1 and Retinoblastoma protein The retinoblastoma pro ...
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DNA Gyrase
DNA gyrase, or simply gyrase, is an enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ... within the class of topoisomerase and is a subclass of Type II topoisomerases that reduces topological strain in an ATP dependent manner while double-stranded DNA is being unwound by elongating RNA polymerase, RNA-polymerase or by helicase in front of the progressing DNA replication#Replication fork, replication fork. The enzyme causes negative DNA supercoil, supercoiling of the DNA or relaxes positive supercoils. It does so by looping the template so as to form a crossing, then cutting one of the double helices and passing the other through it before releasing the break, changing the linking number by two in each enzymatic step. This process occurs in bacteria, whose single circular DNA is ...
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PDK1
Pyruvate dehydrogenase lipoamide kinase isozyme 1, mitochondrial is an enzyme that in humans is encoded by the ''PDK1'' gene. It codes for an isozyme of pyruvate dehydrogenase kinase (PDK). Pyruvate dehydrogenase (PDH) is a part of a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Structure The mature protein encoded by the PDK4 gene contains 407 amino acids in its sequence. To form the active protein, two of the polypeptide chains come together to form an open conformation. The catalytic domain of PDK1 might exist separately in cells and important for the regulation of the PDK1 substrate. The crystal structural studies suggest that the PIF-pocket is ...
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TRAP1
Heat shock protein 75 kDa, mitochondrial is a protein that in humans is encoded by the ''TRAP1'' gene. Interactions TRAP1 has been shown to interact with EXT2, EXT1 and Retinoblastoma protein The retinoblastoma protein (protein name abbreviated pRb; gene name abbreviated ''Rb'', ''RB'' or ''RB1'') is a proto-oncogenic tumor suppressor protein that is dysfunctional in several major cancers. One function of pRb is to prevent excessive .... References Further reading * * * * * * * * * * * * External links

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TOP2B
DNA topoisomerase 2-beta is an enzyme that in humans is encoded by the ''TOP2B'' gene. Function This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This nuclear enzyme is involved in processes such as chromosome condensation, chromatid separation, and the relief of torsional stress that occurs during DNA transcription and replication. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another, thus altering the topology of DNA. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, beta, is localized to chromosome 3 and the alpha form is localized to chromosome 17. The gene encoding this enzyme functions as the target for several anticancer agents, for example mitoxantrone, and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced a ...
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TOP2A
DNA topoisomerase IIα is a human enzyme encoded by the ''TOP2A'' gene. Topoisomerase IIα relives topological DNA stress during transcription, condenses chromosomes, and separates chromatids. It catalyzes the transient breaking and rejoining of two strands of duplex DNA which allows the strands to pass through one another. Two forms of this enzyme exist as likely products of a gene duplication event. The gene encoding this form, alpha, is localized to chromosome 17 and the beta gene is localized to chromosome 3. The gene encoding this enzyme functions as the target for several chemotherapy agents and a variety of mutations in this gene have been associated with the development of drug resistance. Reduced activity of this enzyme may also play a role in ataxia-telangiectasia. Interactions TOP2A has been shown to interact with SMURF2, HDAC1, CDC5L, Small ubiquitin-related modifier 1, P53, and TOPBP1. In other species In ''Drosophila'' Hadlaczky et al 1988 found DNA topoisomeras ...
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PMS2L3
Premenstrual syndrome (PMS) refers to emotional and physical symptoms that regularly occur in the one to two weeks before the start of each menstrual period. Symptoms resolve around the time menstrual bleeding begins. Different women experience different symptoms. Premenstrual syndrome is commonly noted by at least one physical, emotional, or behavioral symptom, that resolves with menses. The range of symptoms is wide, and most commonly are breast tenderness, bloating, headache, mood swings, depression, anxiety, anger, and irritability. They must interfere with daily living, during two menstrual cycles of prospective recording. These symptoms are nonspecific and may be seen in women without PMS. Often PMS-related symptoms are present for about six days. An individual's pattern of symptoms may change over time. Symptoms do not occur during pregnancy or following menopause.> Diagnosis requires a consistent pattern of emotional and physical symptoms occurring after ovulat ...
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PMS2L11
Premenstrual syndrome (PMS) refers to emotional and physical symptoms that regularly occur in the one to two weeks before the start of each menstrual period. Symptoms resolve around the time menstrual bleeding begins. Different women experience different symptoms. Premenstrual syndrome is commonly noted by at least one physical, emotional, or behavioral symptom, that resolves with menses. The range of symptoms is wide, and most commonly are breast tenderness, bloating, headache, mood swings, depression, anxiety, anger, and irritability. They must interfere with daily living, during two menstrual cycles of prospective recording. These symptoms are nonspecific and may be seen in women without PMS. Often PMS-related symptoms are present for about six days. An individual's pattern of symptoms may change over time. Symptoms do not occur during pregnancy or following menopause.> Diagnosis requires a consistent pattern of emotional and physical symptoms occurring after ovulat ...
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PMS2L1
Premenstrual syndrome (PMS) refers to emotional and physical symptoms that regularly occur in the one to two weeks before the start of each menstrual period. Symptoms resolve around the time menstrual bleeding begins. Different women experience different symptoms. Premenstrual syndrome is commonly noted by at least one physical, emotional, or behavioral symptom, that resolves with menses. The range of symptoms is wide, and most commonly are breast tenderness, bloating, headache, mood swings, depression, anxiety, anger, and irritability. They must interfere with daily living, during two menstrual cycles of prospective recording. These symptoms are nonspecific and may be seen in women without PMS. Often PMS-related symptoms are present for about six days. An individual's pattern of symptoms may change over time. Symptoms do not occur during pregnancy or following menopause.> Diagnosis requires a consistent pattern of emotional and physical symptoms occurring after ovulat ...
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PMS2
Mismatch repair endonuclease PMS2 is an enzyme that in humans is encoded by the ''PMS2'' gene. Function This gene is one of the PMS2 gene family members which are found in clusters on chromosome 7. Human PMS2 related genes are located at bands 7p12, 7p13, 7q11, and 7q22. Exons 1 through 5 of these homologues share high degree of identity to human PMS2 The product of this gene is involved in DNA mismatch repair. The protein forms a heterodimer with MLH1 and this complex interacts with MSH2 bound to mismatched bases. Defects in this gene are associated with hereditary nonpolyposis colorectal cancer, with Turcot syndrome, and are a cause of supratentorial primitive neuroectodermal tumors. Alternatively spliced transcript variants have been observed. Mismatch repair and endonuclease activity PMS2 is involved in mismatch repair and is known to have latent endonuclease activity that depends on the integrity of the meta-binding motif in MutL homologs. As an endonuclease, PMS2 intro ...
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PMS1
PMS1 protein homolog 1 is a protein that in humans is encoded by the ''PMS1'' gene. Function The protein encoded by this gene was identified by its homology to a yeast protein involved in DNA mismatch repair. A role for this protein in mismatch repair has not been proven. However, the protein forms heterodimers In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ... with MLH1, a DNA mismatch repair protein, and some cases of hereditary nonpolyposis colorectal cancer have been found to have mutations in this gene. References Further reading

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PDK4
Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial is an enzyme that in humans is encoded by the ''PDK4'' gene. It codes for an isozyme of pyruvate dehydrogenase kinase. This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, reducing the conversion of pyruvate, which is produced from the oxidation of glucose and amino acids, to acetyl-CoA and contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. PDK4 is increased in hibernation and helps to decrease metabolism and conserve glucose by decreasing its conversion to acetyl-CoA, which enters the citric acid cycle and is converted to ATP. Structure The mature protein encoded by the PDK4 gene contains 294 amino acids in i ...
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