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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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IRAK1
Interleukin-1 receptor-associated kinase 1 (IRAK-1) is an enzyme in humans encoded by the ''IRAK1'' gene. IRAK-1 plays an important role in the regulation of the expression of inflammatory genes by immune cells, such as monocytes and macrophages, which in turn help the immune system in eliminating bacteria, viruses, and other pathogens. IRAK-1 is part of the IRAK family consisting of IRAK-1, IRAK-2, IRAK-3, and IRAK-4, and is activated by inflammatory molecules released by signaling pathways during pathogenic attack. IRAK-1 is classified as a kinase enzyme, which regulates pathways in both innate and adaptive immune systems. Structure IRAK-1 contains an N-terminal death domain ( DD), a ProST domain, a centrally located kinase domain, and a C-terminal domain. The DD on IRAK-1 acts as an interaction platform for other DD-containing protein, most notably the adaptor protein myeloid differentiation factor 88, MyD88. The proST domain contains serine, proline, and threonine amino aci ...
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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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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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UBE2N
Ubiquitin-conjugating enzyme E2 N is a protein that in humans is encoded by the ''UBE2N'' gene. Function The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Studies in mouse suggest that this protein plays a role in DNA postreplication repair. Interactions UBE2N has been shown to interact with: * AURKA, * HLTF, * TRAF2, * TRAF6, and * UBE2V1 Ubiquitin-conjugating enzyme E2 variant 1 is a protein that in humans is encoded by the ''UBE2V1'' gene. Function Ubiquitin-conjugating E2 enzyme variant proteins constitute a distinct subfamily within the E2 protein family. They have sequence .... References Further reading

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TNFAIP3
Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the ''TNFAIP3'' gene. This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded by this gene is a zinc finger protein and a deubiquitinating enzyme, and has been shown to inhibit NF-kappa B activation as well as TNF-mediated apoptosis. The A20 protein is ancient, and protein homolog can be found as far back as cnidaria (corals, jellyfish, anemones) with a conserved protein domain composition. Using knockout mouse models of TNFAIP3 and its transcriptional repressor (i.e. KCHIP3), TNFAIP3 has been shown to be critical for limiting inflammation by terminating endotoxin- and TNF-induced NF-kappa B responses. In brief, deubiquitinase function of TNFAIP3 was shown to remove ubiquitin chains from VE-cadherin to prevent loss of VE-cadherin at the endothelial adherens junctions. Interactions TNFAIP3 has been shown to intera ...
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TAX1BP1
Tax1-binding protein 1 is a protein that in humans is encoded by the ''TAX1BP1'' gene. Interactions TAX1BP1 has been shown to interact with TNFAIP3 and TRAF6. TAX1BP1 binds to TNFAIP3 or 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 recept ... and suppresses NF-kappaB transcriptional activation. References Further reading

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Sequestosome 1
Sequestosome-1 is a protein that in humans is encoded by the ''SQSTM1'' gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype. Model organisms Model organisms have been used in the study of SQSTM1 function. A conditional knockout mouse line, called ''Sqstm1tm1a(KOMP)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: females had abnormal complete blood count paramete ...
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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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IKBKG
NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the ''IKBKG'' gene. NEMO is a subunit of the IκB kinase complex that activates NF-κB. The human gene for IKBKG is located on chromosome Xq28. Multiple transcript variants encoding different isoforms have been found for this gene. Function NEMO (IKK-γ) is the regulatory subunit of the inhibitor of IκB kinase (IKK) complex, which activates NF-κB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Clinical significance Mutations in the IKBKG gene results in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. Incontinentia Pigmenti (IP) is an X-linked dominant disease caused by a mutation in the IKBKG gene. Since IKBKG helps activate NF-κB, which protects cells against TNF-alpha induced apoptosis, a lack of ...
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Ubiquitin C
Polyubiquitin-C is a protein encoded by the ''UBC'' gene in humans. Polyubiquitin-C is one of the sources of ubiquitin, along with UBB, UBA52, and RPS27A. ''UBC'' gene is one of the two stress-regulated polyubiquitin genes (''UBB'' and ''UBC'') in mammals. It plays a key role in maintaining cellular ubiquitin levels under stress conditions. Defects of ''UBC'' gene could lead to mid-gestation embryonic lethality. Structure Gene ''UBC'' gene is located at chromosome 12q24.3, consisting of 2 exons. The promoter of the ''UBC'' gene contains putative heat shock elements ( HSEs), which mediates UBC induction upon stress. ''UBC'' gene differs from ''UBB'' gene in the number of Ub coding units they contain. Nine to ten Ub units were in the ''UBC'' gene. Protein In polyubiquitin-C, the C-terminus of a given ubiquitin molecule is covalently conjugated to either the N-terminal residue or one of seven lysine residues of another ubiquitin molecule. Different linking of ubiquitin chains r ...
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ASK1
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases. ''MAP3K5'' gene coding for the protein is located on chromosome 6 at locus 6q22.33. and the transcribed protein contains 1,374 amino acids with 11 kinase subdomains. Northern blot analysis shows that MAP3K5 transcript is abundant in human heart and pancreas. Mechanism of activation Under nonstress conditions ASK1 is oligomerized (a requirement for its activation) through its C-terminal coiled-coil domain (CCC), but remains in an inactive ...
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HSPB2
Heat shock protein beta-2 is a protein that in humans is encoded by the ''HSPB2'' gene. Interactions HSPB2 has been shown to interact with: * CRYAB, * HSPB8, * Myotonic dystrophy protein kinase and * 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 recep .... References Further reading

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