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MAP3K7IP2
Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the ''MAP3K7IP2'' gene. The protein encoded by this gene is an activator of MAP3K7/ TAK1, which is required for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, thus serves as an adaptor linking MAP3K7 and TRAF6. This protein, TAB1, and MAP3K7 also participate in the signal transduction induced by TNFSF11/RANKL through the activation of the receptor activator of NF-kappB ( TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Mutations in MAP3K7IP2 have been associated with human congenital heart defects. Interactions MAP3K7IP2 has been shown to interact with: * HDAC3, * TAB1, * MAP3K7IP3, * MAP3K7, * NFKB1, * NUMBL, * Nuclear receptor co-repressor 1, * TRAF2, and * TRAF6 TRAF6 is a TRAF human protein. Function The protein encoded by this ...
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MAP3K7IP3
Mitogen-activated protein kinase kinase kinase 7-interacting protein 3 is an enzyme that in humans is encoded by the ''MAP3K7IP3'' gene. Function The product of this gene functions in the NF-kappaB signal transduction pathway. The encoded protein, and the similar and functionally redundant protein MAP3K7IP2/TAB2, forms a ternary complex with the protein kinase MAP3K7/TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent MAP3K7/TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor. The human genome contains a related pseudogene. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. Interactions MAP3K7IP3 has been shown to interact with MAP3K7IP2 Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the ''MAP3K7IP2'' gene. The protein ...
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TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the IAP family members cIAP1 and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively s ...
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Nuclear Receptor Co-repressor 1
The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the ''NCOR1'' gene. NCOR1 is a transcriptional coregulatory protein which contains several nuclear receptor interacting domains. In addition, NCOR1 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR1 assists nuclear receptors in the down regulation of gene expression. Loss of function of this protein significantly increases the strength and power of mouse muscles. Family It is a member of the family of nuclear receptor corepressors; the other human protein that is a member of that family is Nuclear receptor co-repressor 2.UniProNuclear receptor corepressors familyPage accessed June 26, 2016 Interactions Nuclear receptor co-repressor 1 has been shown to interact with: * Androgen receptor, * CHD1, * Calcitriol receptor * GPS2, * Glucocorticoid receptor, * HDAC3, * HDAC4, * H ...
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MAP3K7
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the ''MAP3K7'' gene. Structure TAK1 is an evolutionarily conserved kinase in the MAP3 K family and clusters with the tyrosine-like and sterile kinase families. The protein structure of TAK1 contains an N (residues 1–104)- and C (residues 111–303)-terminus connected through the hinge region (Met 104-Ser 111). The ATP binding pocket is located in the hinge region of the kinase. Additionally, TAK1 has a catalytic lysine (Lys63) in the active site. Crystal structure of TAK1-ATP have shown that ATP forms two hydrogen bonds with residues Ala 107 and Glu 105. Further hydrogen bonding is observed to Asp 175, which is the leading residue of the DFG motif. This residue is thought to interact with Lys 63 through polar interactions and is catalytically important for phosphate transfer to substrate molecules. Critical for the TAK1-TAB1 complex is a helical loop arou ...
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NUMBL
Numb-like protein is a protein that in humans is encoded by the ''NUMBL'' gene. Interactions NUMBL has been shown to interact with MAP3K7IP2 Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the ''MAP3K7IP2'' gene. The protein encoded by this gene is an activator of MAP3K7/ TAK1, which is required for the IL-1 induced act .... References Further reading

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NFKB1
Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the ''NFKB1'' gene. This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappaB (NF-κB) protein complex. NF-κB is a transcription factor that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NF-κB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions; over 200 known genes are targets of NF-κB in various cell types, under specific conditions. Inappropriate activation of NF-κB has been associated with a number of inflammatory diseases while persistent inhibition of NF-κB leads to inappropriate immune cell development ...
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TRAF6
TRAF6 is a TRAF human protein. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/TRANCE/RANKL and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been ...
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TAB1
Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the ''TAB1'' gene. Function The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinase MAP3K7/TAK1, which is known to mediate various intracellular signaling pathways, such as those induced by TGF-beta, interleukin-1, and WNT-1. This protein interacts and thus activates TAK1 kinase. It has been shown that the C-terminal portion of this protein is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF beta, suggesting that this protein may function as a mediator between TGF beta receptors and TAK1. This protein can also interact with and activate the mitogen-activated protein kinase 14 (MAPK14/p38alpha), and thus represents an alternative activation pathway, in addition to the MAPKK pathways, which contributes to the biological responses of MAPK14 to various stimu ...
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HDAC3
Histone deacetylase 3 is an enzyme encoded by the ''HDAC3'' gene in both humans and mice. Function Histones are highly alkaline proteins that package and order DNA into structural units called nucleosomes, which comprise the major protein component of chromatin. The posttranslational and enzymatically mediated lysine acetylation and deacetylation of histone tails changes the local chromatin structure through altering the electrostatic attraction between the negatively charged DNA backbone and histones. HDAC3 is a Class I member of the histone deacetylase superfamily (comprising four classes based on function and DNA sequence homology) that is recruited to enhancers to modulate both the epigenome and nearby gene expression. HDAC3 is found exclusively in the cell nucleus where it is the sole endogenous histone deacetylase biochemically purified in the nuclear-receptor corepressor complex containing NCOR and SMRT (NCOR2). Thus, HDAC3 unlike other HDACs, has a unique role in mo ...
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Osteoclasts
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as ''bone resorption''. This process also helps regulate the level of blood calcium. Osteoclasts are found on those surfaces of bone that are undergoing resorption. On such surfaces, the osteoclasts are seen to be located in shallow depressions called ''resorption bays (Howship's lacunae)''. The resorption bays are created by the erosive action of osteoclasts on the underlying bone. The border of the lower part of an osteoclast exhibits finger-like processes due to the presence of deep infoldings of the cell membrane; this border is called ''ruffled border''. The ruffled border lies in contact with the bone surface within a resorption bay. The peripher ...
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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. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ...
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