DegronMD - P19838(NFKB1)

FUNCTION: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. {ECO:0000269|PubMed:15485931}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S893P	TCGA-19-1388	GBM	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.7222
p.S893Y	TCGA-19-1388	GBM	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.7222
p.D927N	TCGA-A5-A0G9	UCEC	TCGA	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation altering degron motif	0.6932
p.S908L	TCGA-A5-A2K3	UCEC	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.0833
p.S908L	TCGA-FS-A1ZZ	SKCM	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.0833
p.S904L	TCGA-AG-A002	READ	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.1944
p.S893F	TCGA-AO-A0JD	BRCA	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.7222
p.P909H	TCGA-AX-A06F	UCEC	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.0556
p.R935C	TCGA-EE-A17X	SKCM	TCGA	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation substituting flanking lysine	0.3611
p.A902D	TCGA-UF-A7JO	HNSC	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.25
p.Q901E	TCGA-VS-A9UR	CESC	TCGA	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.2778
p.S892F	DO2860	BRCA	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.6944
p.Q900E	DO219739	CESC	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.3056
p.S892Y	DO13797	GBM	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.6944
p.S892P	DO13797	GBM	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.6944
p.S892P	DO229245	THCA	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.6944
p.A901D	DO219088	HNSC	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.2778
p.A891S	DO228952	LICA	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.2222
p.R934L	DO229029	LICA	ICGC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.2778
p.S921I	DO231104	LUSC	ICGC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.1944
p.P894L	DO220852	MELA	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.3056
p.S907L	DO37412	SKCM	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.5556
p.S907L	DO43899	UCEC	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.5556
p.R934C	DO37931	SKCM	ICGC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.2778
p.D926N	DO42304	UCEC	ICGC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation altering degron motif	0.6932
p.P908H	DO41752	UCEC	ICGC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.0833
p.F939L	SIDM00946	T-Lymphoblastic Leukemia	GDSC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation blocking phosphorylation signal	0.5833
p.F939L	ACH-000981	Leukemia	CCLE	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation blocking phosphorylation signal	0.5833
p.F939L	DND-41	haematopoietic and lymphoid tissue	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation blocking phosphorylation signal	0.5833
p.E941Q	SIDM00393	Gastric Carcinoma	GDSC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation blocking phosphorylation signal	0.5278
p.E941Q	ACH-001653	Gastric Cancer	CCLE	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation blocking phosphorylation signal	0.5278
p.E941Q	SK-GT-2	stomach	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation blocking phosphorylation signal	0.5278
p.V930M	SIDM00596	Endometrial Carcinoma	GDSC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation altering degron motif	0.7208
p.V930M	ACH-000954	Endometrial/Uterine Cancer	CCLE	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation altering degron motif	0.7208
p.V930M	ACH-001517	Endometrial/Uterine Cancer	CCLE	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation altering degron motif	0.7208
p.V930M	HEC-1	endometrium	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation altering degron motif	0.7208
p.E918K	SIDM00220	Ovarian Carcinoma	GDSC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.1111
p.E918K	ACH-000962	Ovarian Cancer	CCLE	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.1111
p.E918K	ACH-001145	Ovarian Cancer	CCLE	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.1111
p.E918K	OC-314	ovary	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.1111
p.A885G	SIDM01368	Gastric Carcinoma	GDSC	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.0556
p.A885G	ACH-000255	Gastric Cancer	CCLE	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation rewiring degron network	0.0556
p.S893N	ACH-000999	Colon/Colorectal Cancer	CCLE	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation blocking phosphorylation signal	0.7222
p.V896M	ACH-001377	Pancreatic Cancer	CCLE	VKTTS	DEG_SPOP_SBC_1	895:899	Mutation altering degron motif	0.7208
p.F938L	DND-41	haematopoietic and lymphoid tissue	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.1667
p.E940Q	SK-GT-2	stomach	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.1111
p.V929M	HEC-1	endometrium	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation altering degron motif	0.6097
p.E917K	OC-314	ovary	COSMIC	DSGVETS	DEG_SCF_TRCP1_1	926:932	Mutation rewiring degron network	0.0833

Kaplan plot for NFKB1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

NFKB1

UniProt ID: P19838

Entrez ID: 4790

Protein name: Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 subunit]

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for NFKB1 in