Keywords: [xander]

Phenotypic mutation: pale_fire
...domains are conserved regions that are usually involved in homotypic protein interactions, and are composed of a bundle of six α-helices. The pale_fire mutation results in a methionine (M) to leucine (L) substitution at position 838 (M838L) within the DD. Please see the record xander for more information about Nfkb2. | The NF-κB signaling pathway functions in essentially all mammalian cell types and is activated in response to injury, infection, inflammation and other stressful conditions requiring rapid reprogramming of gene expression. The non-canonical NF-&kapp...
Phenotypic mutation: Murgatroyd
... strongly predicted by Polyphen-2 to cause loss of function (score = 0.720). | Figure 3. The NF-κB and IκB families. The nuclear-κB family consists of five members: REL (c-Rel), RelA (p65), RelB, p105/p50 (NF-κB1), and p100/p52 (NF-κB2; see the record for xander). They share a conserved N-terminal Rel-homology domain (RHD), which contains the dimerization, nuclear translocation, and DNA binding motifs. c-Rel, RelA, and RelB also have non-homologous C-terminal transactivation domains, and RelB contains an additional leucine zipper (shown in orange). ...
Phenotypic mutation: kookaburra
...f lysine 128 for a premature stop codon (K128*) in the NF-κB1 protein. | Figure 7. The NF-κB and IκB families. The nuclear-κB family consists of five members: REL (c-Rel), RelA (p65), RelB, p105/p50 (NF-κB1), and p100/p52 (NF-κB2; see the record for xander). They share a conserved N-terminal Rel-homology domain (RHD), which contains the dimerization, nuclear translocation, and DNA binding motifs. c-Rel, RelA, and RelB also have non-homologous C-terminal transactivation domains, and RelB contains an additional leucine zipper (shown in orange). ...
Phenotypic mutation: Roomba
...indicated in blue lettering and the mutated nucleotide is indicated in red. | Figure 5. The NF-κB and IκB families. The nuclear-κB family consists of five members: REL (c-Rel), RelA (p65), RelB, p105/p50 (NF-κB1), and p100/p52 (NF-κB2; see the record for xander). They share a conserved N-terminal Rel-homology domain (RHD), which contains the dimerization, nuclear translocation, and DNA binding motifs. c-Rel, RelA, and RelB also have non-homologous C-terminal transactivation domains, and RelB contains an additional leucine zipper (shown in orange). ...
Phenotypic mutation: Frisbee
... strongly predicted by Polyphen-2 to cause loss of function (score = 0.934). | Figure 6. The NF-κB and IκB families. The nuclear-κB family consists of five members: REL (c-Rel), RelA (p65), RelB, p105/p50 (NF-κB1), and p100/p52 (NF-κB2; see the record for xander). They share a conserved N-terminal Rel-homology domain (RHD), which contains the dimerization, nuclear translocation, and DNA binding motifs. c-Rel, RelA, and RelB also have non-homologous C-terminal transactivation domains, and RelB contains an additional leucine zipper (shown in orange). ...
Phenotypic mutation: xander
Nfkb2 | nuclear factor of kappa light polypeptide gene enhancer in B cells 2, p49/p100 | NF kappaB2, p52 | NCBI RefSeq: NM_019408; MGI: 1099800 | xander | Autosomal Recessive | Australian PhenomeBank: 93 | The xander mutation was discovered in a screen of ethylnitrosourea (ENU)-mutagenized G3 C57BL/6 mice, which had their blood lymphocyte subsets screened by flow cytometry. Homozygous xander (xdr/xdr)mice have reduced numbers of circulating B cells in the blood as assessed by the B220 cell-surface marker, which is the B cell form of CD45 (see the record for belittle). T lymphocytes are pre...
Phenotypic mutation: Memorial
... 142 is within the first ankyrin repeat. Please see the record sunrise for more information about Bcl3. | The NF-κB family of transcription factors consists of the evolutionary conserved proteins p65/RelA, c-Rel, RelB, p50 and p52 (derived from the p100 precursor; see the record for xander). In the resting cell, NF-κB dimers are kept inactive in the cytoplasm through their association with IκB inhibitory molecules, including p105 and p100. Degradation of IκBs allows the NF-κB dimers to translocate into the nucleus, where they are able to activate the tra...
Phenotypic mutation: lolita
...s that are usually involved in homotypic protein interactions, and are composed of a bundle of six α-helices. The lolita mutation would cause an in-frame deletion of 53 amino acids beginning after amino acid 168 of the protein, which would affect the RHD. Please see the record xander for more information about Nfkb2. | The NF-κB signaling pathway functions in essentially all mammalian cell types and is activated in response to injury, infection, inflammation and other stressful conditions requiring rapid reprogramming of gene expression. The non-canonical NF-&kapp...
Phenotypic mutation: Wheelo
...tion 215 (T215I) in the NF-κB1 protein; Thr215 is within the RHD. Please see the record for Finlay for more information about Nfkb1. | NF-κB1 (p50 and p105) can form homodimers or heterodimers with c-Rel, RelA (p65), NF-κB2 (p52 and its precursor p100; see the record for xander), or RelB (11). The p105 precursor can act as an inhibitor of NF-κB dimers through both a direct dimerization to the NF-κB polypeptides as well as through interactions with preformed dimers (12). After agonist stimulation, p105 is degraded, facilitating the release of associated R...
Phenotypic mutation: bananasplit
...se see the record hulk for information about Traf3. | TRAF3 functions in several cell types including B cells, T cells, dendritic cells, macrophages, and osteoclast precursors [reviewed in (3)]. TRAF3 functions in the alternative (i.e., non-canonical) NF-κB (NF-κB2; see the record for xander) signaling pathway [(4;5); reviewed in (2)]. The NF-κB2 pathway regulates secondary lymphoid organogenesis via LTβR-associated signaling (see the record kama), thymic epithelial cell development, and iNKT cell development as well as B cell development, maintenance, and antibody pro...
Phenotypic mutation: marine_blue
...ma;t+; see the record for chestnut) (9;13;14). LIGHT is a homotrimer expressed on T lymphocytes, monocytes, granulocytes, and immature dendritic cells (13). LTβR signals through both the canonical (classical; see the record for finlay) and non-canonical (alternative; see the record for xander) nuclear factor κB (NF-κB) signaling pathways [(15-17); reviewed in (18)]. LTβR-mediated activation of the NF-κB signaling pathways results in the expression of genes that encode adhesion molecules, chemokines (e.g., CCL21 and CXCL13), and lymphokines involved in inflam...
Phenotypic mutation: sunrise2
...nhibiting p50 ubiquitination and degradation (14). During Toll-like receptor and TNF receptor signaling, Bcl-3-stabilized p50 homodimers can block NF-κB target sites in the DNA, subsequently preventing the binding of active dimers to the DNA and gene transcription (14). Please see the records xander and Finlay for additional details about NF-κB signaling. Bcl3−/− mice are overtly normal and were born at the expected Mendelian frequency (15). The Bcl3−/− mice exhibited a reduced B to T cell ratio in the spleen, blood, and lymph nodes (15). The Bcl3&mi...
Phenotypic mutation: Armitage
...ma;t+; see the record for chestnut) (9;13;14). LIGHT is a homotrimer expressed on T lymphocytes, monocytes, granulocytes, and immature dendritic cells (13). LTβR signals through both the canonical (classical; see the record for finlay) and non-canonical (alternative; see the record for xander) nuclear factor κB (NF-κB) signaling pathways [(15-17); reviewed in (18)]. LTβR-mediated activation of the NF-κB signaling pathways results in the expression of genes that encode adhesion molecules, chemokines (e.g., CCL21 and CXCL13), and lymphokines involved in inflam...
Phenotypic mutation: Nabukov
...d in homotypic protein interactions, and are composed of a bundle of six α-helices. The Nabukov mutation results in an aspartic acid to glycine substitution at position 316 (D316G); amino acid 316 is within an undefined region between the RHD and the GRR. Please see the record xander for more information about Nfkb2. | The NF-κB signaling pathway functions in essentially all mammalian cell types and is activated in response to injury, infection, inflammation and other stressful conditions requiring rapid reprogramming of gene expression. The non-canonical NF-&kapp...
Phenotypic mutation: arrested
...sted with its receptors BCMA, TACI (transmembrane activator and calcium modulator ligand (CAML) interactor), and BAFFR. Please see the record Frozen for more information about Tnfsf13b. | BAFF/BAFFR activates the alternative NF-κB (NF-κB2) signaling pathway (see the record for xander) to mediate the survival and maturation of splenic B cells (7;8). BAFF/BAFFR-induced NF-κB2 signaling promotes B cell survival by upregulating integrins that retains autoreactive B cells in the splenic marginal zone (9). In addition, ERK activation is sustained and there is an increased...
Phenotypic mutation: Pacific
...tion, Lyn phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) of the Igα/Igβ BCR subunits (6-8). These signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), NF-κB (see the records for Finlay and xander) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation, and apoptosis as well as the secretion of antigen-specific antibodies [reviewed in (9)]. Lyn has a non-redundant role in negative regulation of BCR signaling (6). Lyn phosphorylates the ...
Phenotypic mutation: water
...tion, Lyn phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) of the Igα/Igβ BCR subunits (6-8). These signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), NF-κB (see the records for Finlay and xander) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation, and apoptosis as well as the secretion of antigen-specific antibodies [reviewed in (9)]. Lyn has a non-redundant role in negative regulation of BCR signaling (6). Lyn phosphorylates the ...
Phenotypic mutation: Applecrisp
...crisp with its receptors BCMA, TACI (transmembrane activator and calcium modulator ligand (CAML) interactor), and BAFFR. Please see the Frozen entry for more information about Tnfsf13b. | BAFF/BAFFR activates the alternative NF-κB (NF-κB2) signaling pathway (see the record for xander) to mediate the survival and maturation of splenic B cells (4;5). BAFF/BAFFR-induced NF-κB2 signaling promotes B cell survival by upregulating integrins that retains autoreactive B cells in the splenic marginal zone (6). In addition, ERK activation is sustained and there is an increased...
Phenotypic mutation: bluebonnet
... in the pathway (red) and the genes affected by these mutations (black). Click on the mutations for more specific information. The members of the TNFR superfamily regulate cell survival and death through the canonical and non-canonical NF-κB [see the records for Finlay (Nfkb1) and xander (Nfkb2), respectively] signaling pathways. CD40/CD40L provides costimulatory, activating signals to antigen presenting cells (APCs) such as B cells, macrophages, and DCs. The CD40 receptor, expressed on B cells and other APCs, is engaged by CD40L that is present primarily on activated T cells...
Phenotypic mutation: Amun-ra
...eractive; click on the other mutations to view additional information. Rel encodes c-Rel, a member of the NF-κB family of transcription factors, which also includes RelA (p65), RelB, NF-κB1 (p105/p50; see the record for Finlay), and NF-κB2 (p100/p52; see the record for xander). The NF-κB protein family members are characterized by the presence of an N-terminal Rel homology domain (RHD) (Figure 9). The RHD (amino acids 8-297, UniProt) is comprised of the N-terminal domain, the dimerization domain (DimD), and a nuclear localization sequence (amino acids 291-29...
Phenotypic mutation: Teton_range
... For more information about Tnfrsf13c, please see the record for tannin. | BAFF/BAFFR signaling is essential for B cell homeostasis, differentiation, proliferation, survival, and function (3-8). BAFF/BAFFR activates the alternative NF-κB (NF-κB2) signaling pathway (see the record for xander) to mediate splenic B cell survival and maturation (9;10). BAFF/BAFFR-induced NF-κB2 signaling promotes B cell survival by upregulating integrins that retains autoreactive B cells in the splenic marginal zone (11). In addition, ERK activation is sustained and there is an increased turno...
Phenotypic mutation: Tannin
... Click on the mutations for more specific information. BAFF/BAFFR signaling is essential for B cell homeostasis, differentiation, proliferation, survival, and function (Figure 7) (3-8). BAFF/BAFFR activates the alternative NF-κB (NF-κB2) signaling pathway (see the record for xander) to mediate splenic B cell survival and maturation (9;10). The non-canonical NF-κB pathway drives the post-translational processing of p100 to mature p52 through IKK-1 and NIK, and results in the activation of p52/RelB heterodimers (11;12). TRAF2 and TRAF5 positively regulate NIK activi...
Phenotypic mutation: Dome
...he record for hulk). During cell survival, MAP3K family members associate with TRAF2, which activates JNK (Jun N-terminal kinases). NIK (NF-κB-inducing kinase; see the record for lucky) is also downstream of TRAF2 and mediates TNF-induced NF-κB activation (see the records for finlay and xander). Similar to PanR1 mice, Dome mice exhibit reduced TNF-α secretion in response to TLR agonists indicating that the Dome mutation results in a loss of TNF function. | Dome genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the ...
Phenotypic mutation: Cress
...tion, Lyn phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) of the Igα/Igβ BCR subunits (6-8). These signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), NF-κB (see the records for Finlay and xander) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation, and apoptosis as well as the secretion of antigen-specific antibodies [reviewed in (9)]. Lyn has a non-redundant role in negative regulation of BCR signaling (6). Lyn phosphorylates the ...
Phenotypic mutation: Sisyphus
... record for busy), PLCγ2 (see the record for queen), and protein kinase C β (PKCβ; see the record for Untied). BCR-associated signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), NF-κB (see the records for puff, xander and panr2) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation, and apoptosis as well as the secretion of antigen-specific antibodies [reviewed in (8)]. Syk couples pre-BCR and BCR activation to downstream signaling pathways that mediate B ...
Phenotypic mutation: giza
...ive; click on the other mutations to view additional information. Rel encodes c-Rel, a member of the NF-κB family of transcription factors, which also includes RelA (p65), RelB, NF-κB1 (p105/p50; see the record for Finlay), and NF-κB2 (p100/p52; see the record for xander). The NF-κB protein family members are characterized by the presence of an N-terminal Rel homology domain (RHD) (Figure 3). The RHD (amino acids 8-297, UniProt) is comprised of the N-terminal domain, the dimerization domain (DimD), and a nuclear localization sequence (amino acids 291-29...
Phenotypic mutation: Surface
...DAG) and inositol-1,4,5-triphosphate (IP3). Ultimately, through activation of IP3 receptors on the endoplasmic reticulum, IP3 triggers a large influx of Ca2+ to the cytoplasm. Sustained elevation of cytosolic Ca2+ regulates the activity of transcription factors including NF-AT and NF-κB (see xander and Finlay). BCR engagement also activates pathways regulated by PKCβ (see Untied), PI-3K, and Ras/MAPK, which further modulate B cell responses [see (26;27) for reviews of B cell antigen receptor signaling]. For more information about BCR-associated signaling, please see the record for...
Phenotypic mutation: sunrise
...e genes affected by these mutations (black). Click on the mutations for more specific information. The NF-κB family of transcription factors consists of the evolutionary conserved proteins p65/RelA, c-Rel, RelB, p50 and p52 (derived from the p100 precursor; see the record for xander). In the resting cell, NF-κB dimers are kept inactive in the cytoplasm through their association with IκB inhibitory molecules, including p105 and p100. In the canonical NF-κB signaling pathway, cytokines (e.g., IL-1 and TNFα) or bacterial products (e.g., LPS) facilit...
Phenotypic mutation: Finlay
...ation within ankyrin repeat two). A premature stop codon would also encode a premature stop codon within the IκBγ isoform (L220*). NF-κB1 (p50 and p105) can form homodimers or heterodimers with c-Rel, RelA (p65), NF-κB2 (p52 and its precursor p100; see the record for xander), or RelB (30). The p105 precursor can act as an inhibitor of NF-κB dimers through both a direct dimerization to the NF-κB polypeptides as well as through interactions with preformed dimers (31). After agonist stimulation, p105 is degraded, facilitating the release of associated R...
Phenotypic mutation: bonsai
...ma;t+; see the record for chestnut) (9;13;14). LIGHT is a homotrimer expressed on T lymphocytes, monocytes, granulocytes, and immature dendritic cells (13). LTβR signals through both the canonical (classical; see the record for finlay) and non-canonical (alternative; see the record for xander) nuclear factor κB (NF-κB) signaling pathways [(15-17); reviewed in (18)]. LTβR-mediated activation of the NF-κB signaling pathways results in the expression of genes that encode adhesion molecules, chemokines (e.g., CCL21 and CXCL13), and lymphokines involved in inflam...
Phenotypic mutation: tardive
...k, and Ras by BLNK to the BCR activates MAP kinase cascades such as JNK, p38 and extracellular signal regulated kinase (ERK). Together, these signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), NF-κB (see the records for puff, xander and panr2) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation, and apoptosis as well as the secretion of antigen-specific antibodies. Following BCR ligation, Blk and/or Lyn phosphorylates the ITAMs of the Igα (see the record...
Phenotypic mutation: Pillar
...to the BCR activates MAP kinase cascades such as JNK, p38 and extracellular signal regulated kinase (ERK) [reviewed in (32)]. Together, these signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), NF-κB (see the records for puff, xander and panr2) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation, and apoptosis as well as the secretion of antigen-specific antibodies [reviewed in (33)]. Other molecules that play important roles in BCR signaling include Bcl10, mucosa-assoc...
Phenotypic mutation: mousebird
...nd B cells, MALT1 functions in mast cells, dendritic cells, macrophages and natural killer (NK) cells (32-34). In marginal zone B cells, MALT1 mediates BAFF (see the record for Frozen)-dependent anti-apoptotic gene induction through the noncanonical NF-κB signaling pathway (see the record for xander) (35). In mast cells, MALT1 mediates IgE FcεRI receptor-mediated secretion of TNFα (see the record for Panr1) and IL-6 (33). Malt1-/- mice have normal skin mast cells and exhibit regular IgE-mediated immediate phase anaphylactic reactions; however, late phase anaphylactic reacti...
Phenotypic mutation: kama
...on of LTα1β2 or LIGHT with LTβR forms a connection between lymphocytes and the surrounding parenchymal and stromal cells [reviewed in (33)]. LTβR signals through both the canonical (classical; see the record for finlay) and non-canonical (alternative; see the record for xander) nuclear factor κB (NF-κB) signaling pathways [Figure 5; (34-36); reviewed in (23)]. In canonical NF-κB signaling pathway, TRAF2/5 is quickly recruited to LTβR upon ligation (12;37). The activation of the inhibitor of κB kinase (IKK) complex (NEMO/IKKγ (see ...
Phenotypic mutation: freckle
...bits osteoclast formation and survival by attenuating JNK and NF-κB signaling in response to receptor activator of NF-κB ligand (RANKL) and TNFα (see the record for Panr1) (32;53). RANKL binding to RANK stimulates the non-canonical NF-κB signaling pathway (see the record for xander). TNFα binding to TNFR-1 results in activation of the TAB2/TAK1 complex, and subsequent activation of the IKK complex to phosphorylate IκB, resulting in release of NF-κB for translocation to the nucleus and activation of gene expression. TNFR1 also activates JNK through sequ...
Phenotypic mutation: currant
...a2+-dependent signal transduction including activation of nuclear factor of activated T cells (NF-AT), and activation of protein kinase C theta (PKCθ; please see the record for Untied) and Ras, respectively. PKCθ regulates nuclear factor-κB (NF-κB; see the records for panr2, xander, and finlay) activation via the trimolecular complex composed of Bcl10, mucosa-associated lymphoid tissue translocation gene 1 (MALT1 or paracaspase), and caspase recruitment domain family, member 11 (CARMA1 or CARD11; see the record for king). In its GTP-bound active state, Ras initiates a m...
Phenotypic mutation: Hulk
...rity of TRAF3 as the mutant protein was able to assemble in its native conformation (6). In mouse 3T3 fibroblasts depleted of wild-type TRAF3 using short hairpin RNA, expression of the Phe474Glu mutant resulted in constitutive processing of the NF-κB precursor protein p100 (see the record for xander) to the active NF-κB p52 transcription factor similar to what is observed in TRAF3 knockout mouse embryonic fibroblasts (17) and cells in which TRAF3 was knocked down using shRNA (6). K63-linked ubiquitination of TRAF3 in TRIF-dependent Toll-like receptor (TLR) signaling facilit...
Phenotypic mutation: Lemon
... the BCR activates MAP kinase cascades such as JNK, p38 and extracellular signal regulated kinase (ERK) [reviewed in (56)]. Together, these signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), NF-κB (see the records for finlay, xander and panr2) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation, and apoptosis as well as the secretion of antigen-specific antibodies [reviewed in (57)]. Lyn is essential for the terminal differentiation of peripheral B cells as well as the...
Phenotypic mutation: hallasan
...(DAG) and inositol-1,4,5-triphosphate (IP3). Ultimately, through activation of IP3 receptors on the endoplasmic reticulum, IP3 triggers a large influx of Ca2+ to the cytoplasm. Sustained elevation of cytosolic Ca2+ regulates the activity of transcription factors including NF-AT and NF-κB (see xander and panr2). BCR engagement also activates pathways regulated by PKCβ (see Untied), PI-3K, and Ras/MAPK, which further modulate B cell responses [see (22;23) for reviews of B cell antigen receptor signaling]. Signal transduction following antigen binding to the BCR absolutely requires Ig&...
Phenotypic mutation: Impaired
...he B and T cell receptors (BCR and TCR, respectively). The NF-κB family of transcription factors consists of the evolutionary conserved proteins p65/RelA, c-Rel, RelB, p50 (derived from the p105 precursor; see the record for Finlay) and p52 (derived from the p100 precursor; see the record for xander). In the resting cell, NF-κB dimers are kept inactive in the cytoplasm through their association with IκB inhibitory molecules, including p105 and p100. IκBs are phosphorylated by the IKK complex at conserved serine residues in response to stimulation (3). This modification ...
Phenotypic mutation: Frozen
...AFF also functions in the induction of IL-10-producing regulatory B cell (CD1dhiCD5+) differentiation from marginal zone B cells that suppress T cell proliferation and Th1 cytokine production (39). BAFF/BAFFR activates the alternative NF-κB (NF-κB2) signaling pathway (see the record for xander) to mediate the survival and maturation of splenic B cells (40;41). The non-canonical NF-κB pathway drives the post-translational processing of p100 to mature p52 through IKK-1 and NIK, and results in the activation of p52/RelB heterodimers (42;43). TRAF2 and TRAF5 positively regulate N...
Phenotypic mutation: crab
...AG) and inositol-1,4,5-triphosphate (IP3). Ultimately, through activation of IP3 receptors on the endoplasmic reticulum, IP3 triggers a large influx of Ca2+ to the cytoplasm. Sustained elevation of cytosolic Ca2+ regulates the activity of transcription factors including NF-AT and NF-κB (see xander and panr2) (Figure 4). BCR engagement also activates pathways regulated by PKCβ (see Untied), PI-3K, and Ras/MAPK, which further modulate B cell responses [see (28;29) for reviews of B cell antigen receptor signaling]. Signal transduction following antigen binding to the BCR absolutely...
Phenotypic mutation: asilomar
...cretion through Src tyrosine kinase/mTOR/p70S6K and Src tyrosine kinase/AKT pathways. See the text for more details. This image is interactive; click on mutants to view more information. Binding of CD137L to CD137 activates the non-canonical NF-κB (NF-κB2; see the record for xander) signaling pathway (Figure 13) (4;5). The non-canonical NF-κB pathway drives the post-translational processing of p100 to mature p52 through IKK-1 and NIK, and results in the activation of p52/RelB heterodimers. The receptors involved in non-canonical signaling (e.g., lymphotoxin-β...
Phenotypic mutation: murdock
...dependent signal transduction including activation of nuclear factor of activated T cells (NF-AT), and activation of protein kinase Cθ (PKCθ; please see the record for Untied) and Ras, respectively. PKCθ regulates nuclear factor-κB (NF-κB; see the records for panr2 and xander) activation via the trimolecular complex composed of Bcl10, mucosa-associated lymphoid tissue translocation gene 1 (MALT1 or paracaspase), and caspase recruitment domain family, member 11 (CARMA1 or CARD11; see the record for king). In its GTP-bound active state, Ras initiates a mitogen-assoc...
Phenotypic mutation: bumble
...κBε, which inhibit the NF-κB pathway by sequestering NF-κB proteins in the cytoplasm, and the novel or nuclear IκBs; Bcl3 (B cell CLL/lymphoma 3), IκBζ (also known as MAIL and INAP) and IκBNS (4). In addition, the p100/NFκB2 (see the record for xander) and p105/NFκB1 NF-κB precursor proteins, which are cleaved into p52 and p50 respectively, share common structural features with this family of proteins that allow them to function as IκBs. Lastly, an alternative transcript of the Nfkb1 gene in the mouse encodes an IκB...
Phenotypic mutation: busy
...activates MAP kinase cascades such as JNK, p38 and extracellular signal regulated kinase (ERK) [reviewed by (5)]. Together, these signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), nuclear factor (NF)-κB (see the records for xander and panr2) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation and apoptosis, as well as the secretion of antigen-specific antibodies [reviewed by (41)]. Other molecules that play important roles in BCR signaling include Bcl10, mucosa-assoc...
Phenotypic mutation: queen
...or PI3K (BCAP), are also important in stabilizing the interactions of molecules within the BCR signalosome (62;63).Together, these signals allow the activation of multiple transcription factors, including nuclear factor of activated T cells (NF-AT), nuclear factor (NF)-κB (see the records for xander and panr2) and AP-1, which subsequently regulate biological responses including cell proliferation, differentiation and apoptosis, as well as the secretion of antigen-specific antibodies [reviewed by (64)]. Other molecules that play important roles in BCR signaling include Bcl10, mucosa-asso...
Phenotypic mutation: honey
...es IFN-α and IL-12 strongly upregulated IRF4 mRNA and protein expression (40). A number of transcription factors are implicated in directly regulating Irf4 gene transcription downstream of these signaling pathways. These include nuclear factor (NF)-κB family members (see the record for xander) (42;43), the Treg master regulator Foxp3 (17), and NFAT (4;43;44). The Irf4 promoter also contains IFN-γ-activated sequence (GAS) elements, which can be bound by STAT proteins (see the records for domino and poison) (40). Interestingly, many of these factors can also physically interac...
Phenotypic mutation: lucky
...tressful conditions requiring rapid reprogramming of gene expression (Figure 3). The NF-κB family of transcription factors consists of the evolutionary conserved proteins p65/RelA, c-Rel, RelB, p50 (derived from the p105 precursor) and p52 (derived from the p100 precursor; see the record for xander). Typically, the rapid and transient activation of NF-κB complexes in response to a wide range of stimuli such as proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and CD40L (see the record for walla), DNA damaging agents, Toll-like receptor ...
Phenotypic mutation: Horus
...n c-Rel are noted in red. Click on each mutation for more information. Rel encodes c-Rel, a member of the NF-κB family of transcription factors, which also includes RelA (p65), RelB, NF-κB1 (p105/p50; see the record for Finlay), and NF-κB2 (p100/p52; see the record for xander). In contrast to the p50 and p52 subunits, which are encoded as the precursor proteins p105 and p100, respectively, RelA, RelB, and c-Rel are synthesized in an active form. The NF-κB protein family members are characterized by the presence of an N-terminal Rel homology domain (R...