DegronMD - Q14494(NFE2L1)

FUNCTION: [Endoplasmic reticulum membrane sensor NFE2L1]: Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor (PubMed:20932482, PubMed:24448410). Constitutes a precursor of the transcription factor NRF1 (By similarity). Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (PubMed:20932482). In response to stress, it is released from the endoplasmic reticulum membrane following cleavage by the protease DDI2 and translocates into the nucleus to form the transcription factor NRF1 (By similarity). Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal, such as CD36 (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits (PubMed:20932482). {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:24448410}.; FUNCTION: [Transcription factor NRF1]: CNC-type bZIP family transcription factor that translocates to the nucleus and regulates expression of target genes in response to various stresses (PubMed:8932385, PubMed:9421508). Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the antioxidant response elements (AREs), which regulate expression of genes involved in oxidative stress response (PubMed:8932385, PubMed:9421508). Activates or represses expression of target genes, depending on the context (PubMed:8932385, PubMed:9421508). Plays a key role in cholesterol homeostasis by acting as a sensor of cholesterol excess: in low cholesterol conditions, translocates into the nucleus and represses expression of genes involved in defense against cholesterol excess, such as CD36 (By similarity). In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal (By similarity). Critical for redox balance in response to oxidative stress: acts by binding the AREs motifs on promoters and mediating activation of oxidative stress response genes, such as GCLC, GCLM, GSS, MT1 and MT2 (By similarity). Plays an essential role during fetal liver hematopoiesis: probably has a protective function against oxidative stress and is involved in lipid homeostasis in the liver (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, mediates the 'bounce-back' of proteasome subunits by translocating into the nucleus and activating expression of genes encoding proteasome subunits (PubMed:20932482). Also involved in regulating glucose flux (By similarity). Together with CEBPB; represses expression of DSPP during odontoblast differentiation (PubMed:15308669). In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts. {ECO:0000250|UniProtKB:Q61985, ECO:0000269|PubMed:15308669, ECO:0000269|PubMed:20932482, ECO:0000269|PubMed:8932385, ECO:0000269|PubMed:9421508}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P398H	TCGA-AP-A0LM	UCEC	TCGA	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.1389
p.L377V	TCGA-CJ-6030	KIRC	TCGA	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.0556
p.L377F	TCGA-EK-A2PM	CESC	TCGA	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.0556
p.A388S	TCGA-EP-A26S	LIHC	TCGA	VASSS	DEG_SPOP_SBC_1	387:391	Mutation altering degron motif	0.6477
p.S337F	DO218986	BLCA	ICGC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation rewiring degron network	0.1667
p.S345F	DO5452	BRCA	ICGC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.7982
p.L221F	DO49941	CESC	ICGC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.0556
p.P239L	DO234274	ESAD	ICGC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.25
p.A385T	DO233944	GACA	ICGC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.2778
p.F362I	DO11878	GBM	ICGC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.7415
p.F362C	DO11878	GBM	ICGC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.7108
p.L221V	DO19058	KIRC	ICGC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.0556
p.S343P	DO51563	KIRP	ICGC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.6752
p.Q389H	DO228952	LICA	ICGC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation altering degron motif	0.7582
p.A231S	DO229022	LICA	ICGC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation altering degron motif	0.7588
p.S400I	DO229045	LICA	ICGC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.0833
p.A232S	DO22854	LIHC	ICGC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation altering degron motif	0.7588
p.A358T	DO45299	LIRI	ICGC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.7139
p.E383K	DO38707	STAD	ICGC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.2222
p.P242H	DO43306	UCEC	ICGC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.1667
p.P390L	DO42033	UCEC	ICGC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation altering degron motif	0.7582
p.Q401K	DO41518	UCEC	ICGC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.0556
p.V382M	SIDM01021	Glioblastoma	GDSC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.1944
p.V382M	D-245MG	central nervous system	COSMIC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.1944
p.E334G	SIDM00048	Non-Small Cell Lung Carcinoma	GDSC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation rewiring degron network	0.0833
p.P356S	SIDM00807	Bladder Carcinoma	GDSC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.5641
p.P356S	5637	urinary tract	COSMIC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.5641
p.G369E	SIDM00655	Other Solid Cancers	GDSC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation rewiring degron network	0.1667
p.G369E	NCCIT	testis	COSMIC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation rewiring degron network	0.1667
p.S346N	SIDM00217	Colorectal Carcinoma	GDSC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.5958
p.S346N	SNU-1040	large intestine	COSMIC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.5958
p.R226Q	SIDM01343	Gastric Carcinoma	GDSC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.1944
p.A366V	SIDM01729	Endometrial Carcinoma	GDSC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation rewiring degron network	0.25
p.S392R	ACH-000491	Colon/Colorectal Cancer	CCLE	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.3056
p.P345S	ACH-000905	Bladder Cancer	CCLE	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.6752
p.P345S	5637	urinary tract	COSMIC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.6752
p.A355V	ACH-000909	Endometrial/Uterine Cancer	CCLE	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.6936
p.V387M	ACH-000938	Leukemia	CCLE	VASSS	DEG_SPOP_SBC_1	387:391	Mutation altering degron motif	0.7208
p.S335N	ACH-000999	Colon/Colorectal Cancer	CCLE	DPLSTNYSLAP	CBL_PTK	343:353	Mutation rewiring degron network	0.1111
p.S335N	SNU-1040	large intestine	COSMIC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation rewiring degron network	0.1111
p.P333Q	ACH-001033	Unknown	CCLE	DPLSTNYSLAP	CBL_PTK	343:353	Mutation rewiring degron network	0.0556
p.G358E	ACH-001578	Embryonal Cancer	CCLE	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.7199
p.G358E	NCCIT	testis	COSMIC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.7199
p.V371M	ACH-002223	Brain Cancer	CCLE	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation rewiring degron network	0.1111
p.V371M	D-245MG	central nervous system	COSMIC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation rewiring degron network	0.1111
p.P232R	JIMT-1	breast	COSMIC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation altering degron motif	0.7512
p.V352M	D-245MG	central nervous system	COSMIC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.7208
p.V352M	D-245MG	central nervous system	COSMIC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.7208
p.S347F	NCI-H847	lung	COSMIC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation altering degron motif	0.7982
p.L225M	FADU	upper aerodigestive tract	COSMIC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.1667
p.P221R	JIMT-1	breast	COSMIC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.0556
p.P390R	JIMT-1	breast	COSMIC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation altering degron motif	0.7512
p.V226M	D-245MG	central nervous system	COSMIC	DGETGE	DEG_Kelch_Keap1_1	231:236	Mutation rewiring degron network	0.1944
p.L363R	PF-382	haematopoietic and lymphoid tissue	COSMIC	LAPNTPINQNVSL	DEG_ODPH_VHL_1	351:363	Mutation altering degron motif	0.8428
p.L383M	FADU	upper aerodigestive tract	COSMIC	VASSS	DEG_SPOP_SBC_1	387:391	Mutation rewiring degron network	0.2222
p.G339E	NCCIT	testis	COSMIC	DPLSTNYSLAP	CBL_PTK	343:353	Mutation rewiring degron network	0.2222

Kaplan plot for NFE2L1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

NFE2L1

UniProt ID: Q14494

Entrez ID: 4779

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for NFE2L1 in