VPR
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Vpr
Vpr is a Human immunodeficiency virus gene and protein product. Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for virus replication and enhanced gene expression from provirus in dividing or non-dividing cells such as T cells or macrophages. Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction. Vpr is also immunosuppressive due to its ability to sequester a proinflammatory transcriptional activator in the cytoplasm. HIV-2 contains both a Vpr protein and a related (by sequence homology) Vpx protein (Viral Protein X). Two functions of Vpr in HIV-1 are split between Vpr and Vpx in HIV-2, with the HIV-2 Vpr protein inducing cell cycle arrest and the Vpx protein required for nuclear import. __TOC__ Vpr-binding protein Vpr-binding protein (VprBP) is a 1,507-amino-acid human protein that contains ...
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CUL4A
Cullin-4A is a protein that in humans is encoded by the ''CUL4A'' gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide. Structure CUL4A protein is 759 amino acids long and forms an extended, rigid structure primarily consisting of alpha-helices. At the N-terminus, CUL4A binds to the beta-propeller of the DDB1 adaptor protein which interacts with numerous DDB1-CUL4-Associated Factors (DCAFs). As a result, the N-terminus is crucial for the recruitment of substrates for the ubiquitin ligase complex. At the C-terminal end, CUL4A interacts with the RBX1/RO ...
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HIV-1 Pre-integration Complex
The pre-integration complex (PIC) is a nucleoprotein complex of viral genetic material and associated viral and host proteins which is capable of inserting a viral genome into a host genome. The PIC forms after uncoating of a viral particle after entry into the host cell. In the case of the human immunodeficiency virus (HIV), the PIC forms after the Reverse Transcription Complex (RTC) has reverse transcribed the viral RNA into DNA. The PIC consists of viral proteins (including Vpr, matrix and integrase), host proteins (including Barrier to autointegration factor 1) and the viral DNA. The PIC enters the cellular nucleus through the nuclear pore complex without disrupting the nuclear envelope, thus allowing HIV and related retroviruses to replicate in non-dividing cells. Following nuclear entry, the PIC's DNA payload may be integrated into the host DNA as a " provirus". See also *HIV *Barrier to autointegration factor 1 Barrier-to-autointegration factor is a protein that in h ...
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DDB1
DNA damage-binding protein 1 is a protein that in humans is encoded by the ''DDB1'' gene. Gene The gene's position is on chromosome 11q12-q13. Protein The DDB1 gene encodes the large subunit of DNA damage-binding protein, a heterodimer composed of a large and a small ( DDB2) subunit. DDB1 contains 1140 amino acids, amounting to a mass of 127 kDa. Function As its name suggests, DDB1 was initially implicated in the process of a specific type of DNA repair known as nucleotide excision repair. Since then, researchers have found that DDB1 primarily functions as a core component of the CUL4A- and CUL4B-based E3 ubiquitin ligase complexes. DDB1 serves as a bridge or adaptor protein which interacts with dozens of proteins known as DDB1 and CUL4-associated factors (DCAFs). These DCAFs are often ubiquitin ligase substrates and regulate numerous essential processes in the cell including DNA repair (DDB2), DNA replication, chromatin remodeling ( Cdt2) and more. Interactions DDB1 has be ...
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Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ...
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G2 Phase
G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the onset of prophase, the first phase of mitosis in which the cell’s chromatin condenses into chromosomes. G2 phase is a period of rapid cell growth and protein synthesis during which the cell prepares itself for mitosis. Curiously, G2 phase is not a necessary part of the cell cycle, as some cell types (particularly young ''Xenopus'' embryos and some cancers)) proceed directly from DNA replication to mitosis. Though much is known about the genetic network which regulates G2 phase and subsequent entry into mitosis, there is still much to be discovered concerning its significance and regulation, particularly in regards to cancer. One hypothesis is that the growth in G2 phase is regulated as a method of cell size control. Fission yeast (''Schi ...
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Immunosuppressive
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. In general, deliberately induced immunosuppression is performed to prevent the body from rejecting an organ transplant. Additionally, it is used for treating graft-versus-host disease after a bone marrow transplant, or for the treatment of auto-immune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, or Crohn's disease. This is typically done using medications, but may involve surgery (splenectomy), plasmapheresis, or radiation. A person who is undergoing immunosuppression, or whose immune system is weak for some other reasons (such as chemotherapy or HIV), is said to be ''immunocompromised''. Deliberately induced Administration of immunosuppressive medica ...
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Proinflammatory
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''dolor'', ''rubor'', ''tumor'', and ''functio laesa''). Inflammation is a generic response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, which is specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. In contrast, too much inflammation, in the ...
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Sequence Homology
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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HIV-2
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey, a vulnerable West African primate. HIV-1 viruses can be further divided into groups M, N, O and P. The HIV-1 group M viruses predominate and are responsible for the AIDS pandemic. Group M can be further subdivided into subtypes based on genetic sequence data. Some of the subtypes are known to be more virulent or are resistant to different medications. Likewise, HIV-2 viruses are thought to be less virulent and transmissible than HIV-1 M group viruses, although HIV-2 is also known to cause AIDS. One of the obstacles to treatment of the human immunodeficiency virus (HIV) is its high genetic variability. Major types HIV-1 HIV-1 is the most common and pathogenic strain of the virus. Over 2 million such infections occur annually. Scientists ...
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LisH Domain
In molecular biology, the LisH domain (lis homology domain) is a protein domain found in a large number of eukaryotic proteins, from metazoa, fungi and plants that have a wide range of functions. The recently solved structure of the LisH domain in the N-terminal region of LIS1 depicted it as a novel dimerisation motif, and that other structural elements are likely to play an important role in dimerisation. The LisH domain is found in the ''Saccharomyces cerevisiae'' SIF2 protein, a component of the SET3 complex which is responsible for repressing meiotic genes 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 ba ... In SIF2 the LisH domain has been shown to mediate dimer and tetramer formation. It has been shown that the LisH domain helps mediate interaction with components of the SET3 co ...
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WD40 Repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain. Structure WD40 domain-containing proteins have 4 to 16 repeating units, all of which are thought to form a circularised beta-propeller structure (see figure to the right). The WD40 domain is composed of several repeats, a variable region of around 20 residues at the beginning followed by a more common repeated set of residues. These repeats typically form a four stranded anti-parallel beta sheet or blade. These blades come together to form a propeller with the most common being a 7 bladed beta propeller. The blades interlock so that the last beta strand of one repeat forms with the first three of the next repeat to form the 3D blade structure. Function WD40-repe ...
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E3 Ubiquitin Ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another thing (the substrate) by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases regu ...
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