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BCL3
B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the ''BCL3'' gene. This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha- locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin repeats, which are most closely related to those found in I kappa B proteins. This protein functions as a transcriptional coactivator that activates through its association with NF-kappa B homodimers. The expression of this gene can be induced by NF-kappa B, which forms a part of the autoregulatory loop that controls the nuclear residence of p50 NF-kappa B. Like BCL2, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma. Interactions BCL3 has been shown to interact with: * BARD1, * C-Fos, * C-jun, * C22orf25, * COPS5, * EP300, * HTATIP, * NFKB1, * NFKB2, * PIR, and * NR2B1. Clinical significance Genetic variations in ''BCL3'' gene ...
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NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory. Discovery NF-κB was discovered by Ranjan Sen in the lab of Nobel laureate David Baltimore via its interaction with an 11-base pair sequence in the immunoglobulin light-chain Enhancer (genetics), enhancer in B cells. Later work ...
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EP300
Histone acetyltransferase p300 also known as p300 HAT or E1A-associated protein p300 (where E1A = adenovirus early region 1A) also known as EP300 or p300 is an enzyme that, in humans, is encoded by the ''EP300'' gene. It functions as histone acetyltransferase that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to be critical for normal development before and after birth. The EP300 gene is located on the long (q) arm of the human chromosome 22 at position 13.2. This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. EP300 is closely related to another gene, CREB binding protein, which is found on human chromosome 16. Function p300 HAT funct ...
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BCL9
B-cell CLL/lymphoma 9 protein is a protein that in humans is encoded by the ''BCL9'' gene. Function BCL9, together with its paralogue gene BCL9L (BCL9 like or BCL9.2), have been extensively studied for their role as transcriptional beta-catenin cofactors, fundamental for the transcription of Wnt target genes. Recent work, using the mouse (''Mus musculus'') and zebrafish (''Danio rerio'') as model organisms, identified an ancient role of BCL9 and BCL9L as key factors required for cardiac development. This work emphasises the tissue-specific nature of the Wnt/β-catenin mechanism of action, and implicates alterations in BCL9 and BCL9L in human congenital heart defects. BCL9 and BCL9L have been shown to take part in other tissue-specific molecular mechanisms, showing that their role in the Wnt signaling cascade is only one aspect of their mode of action. The conserved homology domain HD1 of BCL9 (and BCL9L) has recently been shown to be interacting with TBX3 in the context of ...
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COP9 Constitutive Photomorphogenic Homolog Subunit 5
COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis), also known as COPS5 or Csn5, is a gene conserved from humans to Saccharomyces cerevisiae. Function The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein is reported to be involved in the degradation of cyclin-dependent kinase inhibitor CDKN1B/p27Kip1. It is also known to be a coactivator that increases the specificity of JUN/AP1 transcription factors. Interactions COP9 constitutive photomorphogenic homolog subunit 5 has been shown to interact with Macrophage migration inhibitory factor, GFER, BCL3, Ubiquitin ...
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C22orf25
Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene. The function of C22orf25 is not currently known. It is characterized by the NRDE superfamily domain (DUF883), which is strictly known for the conserved amino acid sequence of (N)-Asparagine (R)-Arginine (D)-Aspartic Acid (E)-Glutamic Acid. This domain is found among distantly related species from the six kingdoms: Eubacteria, Archaebacteria, Protista, Fungi, Plantae, and Animalia and is known to be involved in Golgi organization and protein secretion. It is likely that it localizes in the cytoplasm but is anchored in the cell membrane by the second amino acid. C22orf25 is also xenologous to T10 like proteins in the Fowlpox Virus and Canarypox Virus. The gene coding for C22orf25 is located on chromosome 22 and the location q11.21, so it is often associated with 22q11.2 deletion syndrome. Protein ...
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C-jun
Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun (). The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ''ju-nana'', the Japanese word for 17. The human JUN encodes a protein that is highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies. Function Regulation Both Jun and its dimerization partners in AP-1 formation are subject to regulation by diverse ...
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C-Fos
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkins murine osteogenic sarcoma virus) (Curran and Tech, 1982). It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun (part of Jun family of transcription factors), resulting in the formation of AP-1 (Activator Protein-1) complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers. Structure and function c-Fos is a 380 amino acid protein wit ...
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BARD1
BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the ''BARD1'' gene. The human BARD1 protein is 777 amino acids long and contains a RING finger domain (residues 46-90), four ankyrin repeats (residues 420-555), and a tandem BRCT domain (residues 568-777). Function Most, if not all, BRCA1 heterodimerizes with BARD1 in vivo. BARD1 and BRCA1 form a heterodimer via their N-terminal RING finger domains. The BARD1-BRCA1 interaction is observed in vivo and in vitro and is essential for BRCA1 stability. BARD1 shares homology with the two most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes, and developmentally important genes such as the polycomb group of genes. The BARD1 protein also contains three tandem ankyrin repeats. The BARD1/BRCA1 i ...
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NFKB2
Nuclear factor NF-kappa-B p100 subunit is a protein that in humans is encoded by the ''NFKB2'' gene. Function NF-κB has been detected in numerous cell types that express cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in health and in various disease states. NF-κB is activated by a wide variety of stimuli such as cytokines, oxidant-free radicals, inhaled particles, ultraviolet irradiation, and bacterial or viral products. Inappropriate activation of NF-kappa-B has been linked to inflammatory events associated with autoimmune arthritis, asthma, septic shock, lung fibrosis, glomerulonephritis, atherosclerosis, and AIDS. In contrast, complete and persistent inhibition of NF-kappa-B has been linked directly to apoptosis, inappropriate immune cell development, and delayed cell growth. For reviews, see Chen et al. (1999) and Baldwin (1996). upplied by OMIM Clinical significance Mutation of the NFKB2 gene has been linked to Common vari ...
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PIR (gene)
Pirin is a protein that in humans is encoded by the ''PIR'' gene. This gene encodes a member of the cupin superfamily. The encoded protein is a Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein suggest the encoded protein may act as a transcriptional cofactor and be involved in the regulation of DNA transcription and replication. Alternatively spliced transcript variants have been described. Interactions PIR (gene) has been shown to interact with BCL3. Pirin in Bacteria The ''pir'' gene is conserved in both bacteria and eukaryotes. In '' Pseudomonas stutzeri'' this protein exhibited quercetinase activity. In '' Streptomyces ambofaciens'', a strain known to produce the antibiotic spiramycin Spiramycin is a macrolide antibiotic and antiparasitic. It is used to treat toxoplasmosis and v ...
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BCL10
B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the ''BCL10'' gene. Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma. Function Bcl10 was identified by its translocation in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. The protein encoded by this gene contains a caspase recruitment domain (CARD), and has been shown to activate NF-κB. This protein is reported to interact with other CARD and coiled coil domain containing proteins including CARD9, -10, -11 and -14, which are thought to function as upstream regulators in NF-κB signaling. This protein is found to form a complex with the paracaspase MALT1, a protein encoded by another gene known to be translocated in MALT lymphoma. MALT1 and Bcl10 thought to synergize in the activation of NF-κB, and the deregulation of either of them may contribute to the same pathogenetic process that leads to the malignancy. Bcl10 is evolutionary conserved since ...
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BCL2
Bcl-2, encoded in humans by the ''BCL2'' gene, is the founding member of the apoptosis regulator proteins, Bcl-2 family, Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first apoptosis regulator identified in any organism. Bcl-2 derives its name from ''B-cell lymphoma 2'', as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes Chromosome 14, 14 and Chromosome 18, 18 in follicular lymphomas. Orthologs (such as ''Bcl2'' in mice) have been identified in numerous mammals for which complete genome data are available. Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma. Isoforms The two isoforms of Bcl-2, Isoform 1, and Isoform 2, exhibit a similar fold. However, results in the ability of these isoforms to bind to the Bcl-2-associated death promoter, BAD and Bcl-2 homolo ...
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