General Information of Target

Target ID LDTP06127
Target Name Endoplasmic reticulum membrane sensor NFE2L1 (NFE2L1)
Gene Name NFE2L1
Gene ID 4779
Synonyms
HBZ17; NRF1; TCF11; Endoplasmic reticulum membrane sensor NFE2L1; Locus control region-factor 1; LCR-F1; Nuclear factor erythroid 2-related factor 1; NF-E2-related factor 1; NFE2-related factor 1; Nuclear factor, erythroid derived 2, like 1; Protein NRF1, p120 form; Transcription factor 11; TCF-11) [Cleaved into: Transcription factor NRF1; Protein NRF1, p110 form)]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLSLKKYLTEGLLQFTILLSLIGVRVDVDTYLTSQLPPLREIILGPSSAYTQTQFHNLRN
TLDGYGIHPKSIDLDNYFTARRLLSQVRALDRFQVPTTEVNAWLVHRDPEGSVSGSQPNS
GLALESSSGLQDVTGPDNGVRESETEQGFGEDLEDLGAVAPPVSGDLTKEDIDLIDILWR
QDIDLGAGREVFDYSHRQKEQDVEKELRDGGEQDTWAGEGAEALARNLLVDGETGESFPA
QVPSGEDQTALSLEECLRLLEATCPFGENAEFPADISSITEAVPSESEPPALQNNLLSPL
LTGTESPFDLEQQWQDLMSIMEMQAMEVNTSASEILYSAPPGDPLSTNYSLAPNTPINQN
VSLHQASLGGCSQDFLLFSPEVESLPVASSSTLLPLAPSNSTSLNSTFGSTNLTGLFFPP
QLNGTANDTAGPELPDPLGGLLDEAMLDEISLMDLAIEEGFNPVQASQLEEEFDSDSGLS
LDSSHSPSSLSSSEGSSSSSSSSSSSSSSASSSASSSFSEEGAVGYSSDSETLDLEEAEG
AVGYQPEYSKFCRMSYQDPAQLSCLPYLEHVGHNHTYNMAPSALDSADLPPPSALKKGSK
EKQADFLDKQMSRDEHRARAMKIPFTNDKIINLPVEEFNELLSKYQLSEAQLSLIRDIRR
RGKNKMAAQNCRKRKLDTILNLERDVEDLQRDKARLLREKVEFLRSLRQMKQKVQSLYQE
VFGRLRDENGRPYSPSQYALQYAGDGSVLLIPRTMADQQARRQERKPKDRRK
Target Bioclass
Transcription factor
Family
BZIP family, CNC subfamily
Subcellular location
Nucleus; Endoplasmic reticulum membrane
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. Constitutes a precursor of the transcription factor NRF1. Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition. 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. 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. 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.; [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. 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. Activates or represses expression of target genes, depending on the context. 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. 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. 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. 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. 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. Also involved in regulating glucose flux. Together with CEBPB; represses expression of DSPP during odontoblast differentiation. In response to ascorbic acid induction, activates expression of SP7/Osterix in osteoblasts.
Uniprot ID
Q14494
Ensemble ID
ENST00000357480.9
HGNC ID
HGNC:7781

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CHL1 SNV: p.P463S .
FADU SNV: p.L413M .
HCT15 SNV: p.W314Ter .
IM95 SNV: p.A739V .
LS180 Deletion: p.P162QfsTer6 .
MINO SNV: p.D275Y .
MOLT4 SNV: p.D75E .
NALM6 SNV: p.V28M DBIA    Probe Info 
NCIH358 SNV: p.T263P .
NCIH716 SNV: p.S403R .
REC1 SNV: p.L413V .
SNGM Deletion: p.G370AfsTer44 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info 
C671(1.53)  LDD1702  [1]
DBIA
 Probe Info 
C671(0.83)  LDD0531  [2]
NAIA_5
 Probe Info 
N.A.  LDD2224  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0214  AC1 HCT 116 C671(0.83)  LDD0531  [2]
 LDCM0215  AC10 HCT 116 C671(1.28)  LDD0532  [2]
 LDCM0226  AC11 HCT 116 C671(1.35)  LDD0543  [2]
 LDCM0237  AC12 HCT 116 C671(0.99)  LDD0554  [2]
 LDCM0246  AC128 HCT 116 C671(1.03)  LDD0563  [2]
 LDCM0247  AC129 HCT 116 C671(1.36)  LDD0564  [2]
 LDCM0249  AC130 HCT 116 C671(1.66)  LDD0566  [2]
 LDCM0250  AC131 HCT 116 C671(1.13)  LDD0567  [2]
 LDCM0251  AC132 HCT 116 C671(1.71)  LDD0568  [2]
 LDCM0252  AC133 HCT 116 C671(1.37)  LDD0569  [2]
 LDCM0253  AC134 HCT 116 C671(1.58)  LDD0570  [2]
 LDCM0254  AC135 HCT 116 C671(1.21)  LDD0571  [2]
 LDCM0255  AC136 HCT 116 C671(1.67)  LDD0572  [2]
 LDCM0256  AC137 HCT 116 C671(1.08)  LDD0573  [2]
 LDCM0257  AC138 HCT 116 C671(1.39)  LDD0574  [2]
 LDCM0258  AC139 HCT 116 C671(1.60)  LDD0575  [2]
 LDCM0259  AC14 HCT 116 C671(1.27)  LDD0576  [2]
 LDCM0260  AC140 HCT 116 C671(1.59)  LDD0577  [2]
 LDCM0261  AC141 HCT 116 C671(1.56)  LDD0578  [2]
 LDCM0262  AC142 HCT 116 C671(1.47)  LDD0579  [2]
 LDCM0270  AC15 HCT 116 C671(1.42)  LDD0587  [2]
 LDCM0279  AC2 HCT 116 C671(1.75)  LDD0596  [2]
 LDCM0290  AC3 HCT 116 C671(1.24)  LDD0607  [2]
 LDCM0296  AC35 HCT 116 C671(0.67)  LDD0613  [2]
 LDCM0297  AC36 HCT 116 C671(0.72)  LDD0614  [2]
 LDCM0298  AC37 HCT 116 C671(0.67)  LDD0615  [2]
 LDCM0299  AC38 HCT 116 C671(1.03)  LDD0616  [2]
 LDCM0300  AC39 HCT 116 C671(0.85)  LDD0617  [2]
 LDCM0301  AC4 HCT 116 C671(1.15)  LDD0618  [2]
 LDCM0302  AC40 HCT 116 C671(0.77)  LDD0619  [2]
 LDCM0303  AC41 HCT 116 C671(0.84)  LDD0620  [2]
 LDCM0304  AC42 HCT 116 C671(1.00)  LDD0621  [2]
 LDCM0305  AC43 HCT 116 C671(1.22)  LDD0622  [2]
 LDCM0306  AC44 HCT 116 C671(0.76)  LDD0623  [2]
 LDCM0307  AC45 HCT 116 C671(0.65)  LDD0624  [2]
 LDCM0308  AC46 HCT 116 C671(1.68)  LDD0625  [2]
 LDCM0309  AC47 HCT 116 C671(1.35)  LDD0626  [2]
 LDCM0310  AC48 HCT 116 C671(0.98)  LDD0627  [2]
 LDCM0311  AC49 HCT 116 C671(1.30)  LDD0628  [2]
 LDCM0312  AC5 HCT 116 C671(0.99)  LDD0629  [2]
 LDCM0313  AC50 HCT 116 C671(1.69)  LDD0630  [2]
 LDCM0314  AC51 HCT 116 C671(1.89)  LDD0631  [2]
 LDCM0315  AC52 HCT 116 C671(1.36)  LDD0632  [2]
 LDCM0316  AC53 HCT 116 C671(1.07)  LDD0633  [2]
 LDCM0317  AC54 HCT 116 C671(1.27)  LDD0634  [2]
 LDCM0318  AC55 HCT 116 C671(1.64)  LDD0635  [2]
 LDCM0319  AC56 HCT 116 C671(1.69)  LDD0636  [2]
 LDCM0323  AC6 HCT 116 C671(1.41)  LDD0640  [2]
 LDCM0332  AC68 HCT 116 C671(0.76)  LDD0649  [2]
 LDCM0333  AC69 HCT 116 C671(0.58)  LDD0650  [2]
 LDCM0334  AC7 HCT 116 C671(1.13)  LDD0651  [2]
 LDCM0335  AC70 HCT 116 C671(0.89)  LDD0652  [2]
 LDCM0336  AC71 HCT 116 C671(0.81)  LDD0653  [2]
 LDCM0337  AC72 HCT 116 C671(1.10)  LDD0654  [2]
 LDCM0338  AC73 HCT 116 C671(0.87)  LDD0655  [2]
 LDCM0339  AC74 HCT 116 C671(0.88)  LDD0656  [2]
 LDCM0340  AC75 HCT 116 C671(0.79)  LDD0657  [2]
 LDCM0341  AC76 HCT 116 C671(1.07)  LDD0658  [2]
 LDCM0342  AC77 HCT 116 C671(0.58)  LDD0659  [2]
 LDCM0343  AC78 HCT 116 C671(1.06)  LDD0660  [2]
 LDCM0344  AC79 HCT 116 C671(0.80)  LDD0661  [2]
 LDCM0345  AC8 HCT 116 C671(1.06)  LDD0662  [2]
 LDCM0346  AC80 HCT 116 C671(1.10)  LDD0663  [2]
 LDCM0347  AC81 HCT 116 C671(0.63)  LDD0664  [2]
 LDCM0348  AC82 HCT 116 C671(0.68)  LDD0665  [2]
 LDCM0248  AKOS034007472 HCT 116 C671(1.12)  LDD0565  [2]
 LDCM0356  AKOS034007680 HCT 116 C671(1.23)  LDD0673  [2]
 LDCM0275  AKOS034007705 HCT 116 C671(1.72)  LDD0592  [2]
 LDCM0367  CL1 HCT 116 C671(0.63)  LDD0684  [2]
 LDCM0368  CL10 HCT 116 C671(0.81)  LDD0685  [2]
 LDCM0369  CL100 HCT 116 C671(1.01)  LDD0686  [2]
 LDCM0370  CL101 HCT 116 C671(1.03)  LDD0687  [2]
 LDCM0371  CL102 HCT 116 C671(1.12)  LDD0688  [2]
 LDCM0372  CL103 HCT 116 C671(1.06)  LDD0689  [2]
 LDCM0373  CL104 HCT 116 C671(1.01)  LDD0690  [2]
 LDCM0379  CL11 HCT 116 C671(0.81)  LDD0696  [2]
 LDCM0387  CL117 HCT 116 C671(0.94)  LDD0704  [2]
 LDCM0388  CL118 HCT 116 C671(1.19)  LDD0705  [2]
 LDCM0389  CL119 HCT 116 C671(1.01)  LDD0706  [2]
 LDCM0390  CL12 HCT 116 C671(0.78)  LDD0707  [2]
 LDCM0391  CL120 HCT 116 C671(0.81)  LDD0708  [2]
 LDCM0392  CL121 HCT 116 C671(0.86)  LDD0709  [2]
 LDCM0393  CL122 HCT 116 C671(1.07)  LDD0710  [2]
 LDCM0394  CL123 HCT 116 C671(1.81)  LDD0711  [2]
 LDCM0395  CL124 HCT 116 C671(0.92)  LDD0712  [2]
 LDCM0400  CL13 HCT 116 C671(1.02)  LDD0717  [2]
 LDCM0401  CL14 HCT 116 C671(0.88)  LDD0718  [2]
 LDCM0402  CL15 HCT 116 C671(0.76)  LDD0719  [2]
 LDCM0407  CL2 HCT 116 C671(1.15)  LDD0724  [2]
 LDCM0418  CL3 HCT 116 C671(0.68)  LDD0735  [2]
 LDCM0420  CL31 HCT 116 C671(1.18)  LDD0737  [2]
 LDCM0421  CL32 HCT 116 C671(1.04)  LDD0738  [2]
 LDCM0422  CL33 HCT 116 C671(1.08)  LDD0739  [2]
 LDCM0423  CL34 HCT 116 C671(1.00)  LDD0740  [2]
 LDCM0424  CL35 HCT 116 C671(0.93)  LDD0741  [2]
 LDCM0425  CL36 HCT 116 C671(1.00)  LDD0742  [2]
 LDCM0426  CL37 HCT 116 C671(1.05)  LDD0743  [2]
 LDCM0428  CL39 HCT 116 C671(0.97)  LDD0745  [2]
 LDCM0429  CL4 HCT 116 C671(1.16)  LDD0746  [2]
 LDCM0430  CL40 HCT 116 C671(0.98)  LDD0747  [2]
 LDCM0431  CL41 HCT 116 C671(0.86)  LDD0748  [2]
 LDCM0432  CL42 HCT 116 C671(0.98)  LDD0749  [2]
 LDCM0433  CL43 HCT 116 C671(0.89)  LDD0750  [2]
 LDCM0434  CL44 HCT 116 C671(1.16)  LDD0751  [2]
 LDCM0435  CL45 HCT 116 C671(0.98)  LDD0752  [2]
 LDCM0436  CL46 HCT 116 C671(1.01)  LDD0753  [2]
 LDCM0437  CL47 HCT 116 C671(1.05)  LDD0754  [2]
 LDCM0438  CL48 HCT 116 C671(1.18)  LDD0755  [2]
 LDCM0439  CL49 HCT 116 C671(1.06)  LDD0756  [2]
 LDCM0440  CL5 HCT 116 C671(0.65)  LDD0757  [2]
 LDCM0441  CL50 HCT 116 C671(0.97)  LDD0758  [2]
 LDCM0442  CL51 HCT 116 C671(1.47)  LDD0759  [2]
 LDCM0443  CL52 HCT 116 C671(1.63)  LDD0760  [2]
 LDCM0444  CL53 HCT 116 C671(1.08)  LDD0761  [2]
 LDCM0445  CL54 HCT 116 C671(1.38)  LDD0762  [2]
 LDCM0446  CL55 HCT 116 C671(1.07)  LDD0763  [2]
 LDCM0447  CL56 HCT 116 C671(1.34)  LDD0764  [2]
 LDCM0448  CL57 HCT 116 C671(0.95)  LDD0765  [2]
 LDCM0449  CL58 HCT 116 C671(0.99)  LDD0766  [2]
 LDCM0450  CL59 HCT 116 C671(1.17)  LDD0767  [2]
 LDCM0451  CL6 HCT 116 C671(0.71)  LDD0768  [2]
 LDCM0452  CL60 HCT 116 C671(1.29)  LDD0769  [2]
 LDCM0462  CL7 HCT 116 C671(0.64)  LDD0779  [2]
 LDCM0469  CL76 HCT 116 C671(0.97)  LDD0786  [2]
 LDCM0470  CL77 HCT 116 C671(1.13)  LDD0787  [2]
 LDCM0471  CL78 HCT 116 C671(0.98)  LDD0788  [2]
 LDCM0472  CL79 HCT 116 C671(1.06)  LDD0789  [2]
 LDCM0473  CL8 HCT 116 C671(0.79)  LDD0790  [2]
 LDCM0474  CL80 HCT 116 C671(1.56)  LDD0791  [2]
 LDCM0475  CL81 HCT 116 C671(1.12)  LDD0792  [2]
 LDCM0476  CL82 HCT 116 C671(1.12)  LDD0793  [2]
 LDCM0477  CL83 HCT 116 C671(1.03)  LDD0794  [2]
 LDCM0478  CL84 HCT 116 C671(0.90)  LDD0795  [2]
 LDCM0479  CL85 HCT 116 C671(1.54)  LDD0796  [2]
 LDCM0480  CL86 HCT 116 C671(0.89)  LDD0797  [2]
 LDCM0481  CL87 HCT 116 C671(1.31)  LDD0798  [2]
 LDCM0482  CL88 HCT 116 C671(1.08)  LDD0799  [2]
 LDCM0483  CL89 HCT 116 C671(1.05)  LDD0800  [2]
 LDCM0484  CL9 HCT 116 C671(0.90)  LDD0801  [2]
 LDCM0485  CL90 HCT 116 C671(1.19)  LDD0802  [2]
 LDCM0486  CL91 HCT 116 C671(1.16)  LDD0803  [2]
 LDCM0487  CL92 HCT 116 C671(1.43)  LDD0804  [2]
 LDCM0488  CL93 HCT 116 C671(0.91)  LDD0805  [2]
 LDCM0489  CL94 HCT 116 C671(0.90)  LDD0806  [2]
 LDCM0490  CL95 HCT 116 C671(1.16)  LDD0807  [2]
 LDCM0491  CL96 HCT 116 C671(1.08)  LDD0808  [2]
 LDCM0492  CL97 HCT 116 C671(1.20)  LDD0809  [2]
 LDCM0493  CL98 HCT 116 C671(1.71)  LDD0810  [2]
 LDCM0494  CL99 HCT 116 C671(1.33)  LDD0811  [2]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C671(1.53)  LDD1702  [1]
 LDCM0427  Fragment51 HCT 116 C671(1.62)  LDD0744  [2]
 LDCM0022  KB02 786-O C134(2.20)  LDD2247  [4]
 LDCM0023  KB03 786-O C134(5.69)  LDD2664  [4]
 LDCM0024  KB05 NALM-6 C134(5.43)  LDD3339  [4]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transcription factor
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
CREB/ATF bZIP transcription factor (CREBZF) BZIP family Q9NS37
Endoplasmic reticulum membrane sensor NFE2L1 (NFE2L1) BZIP family Q14494
Transcription factor MafF (MAFF) BZIP family Q9ULX9
Transcription factor MafG (MAFG) BZIP family O15525
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Kelch-like ECH-associated protein 1 (KEAP1) KEAP1 family Q14145

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Dodecyldimethylamine N-oxide Small molecular drug DB04147

References

1 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
2 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
3 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
4 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840