General Information of the m6A Regulator (ID: REG00019)
Regulator Name NF-kappa-B-activating protein (NKAP)
Synonyms
FLJ22626, MRXSHD
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Gene Name NKAP
Sequence
MAPVSGSRSPDREASGSGGRRRSSSKSPKPSKSARSPRGRRSRSHSCSRSGDRNGLTHQL
GGLSQGSRNQSYRSRSRSRSRERPSAPRGIPFASASSSVYYGSYSRPYGSDKPWPSLLDK
EREESLRQKRLSERERIGELGAPEVWGLSPKNPEPDSDEHTPVEDEEPKKSTTSASTSEE
EKKKKSSRSKERSKKRRKKKSSKRKHKKYSEDSDSDSDSETDSSDEDNKRRAKKAKKKEK
KKKHRSKKYKKKRSKKSRKESSDSSSKESQEEFLENPWKDRTKAEEPSDLIGPEAPKTLT
SQDDKPLNYGHALLPGEGAAMAEYVKAGKRIPRRGEIGLTSEEIASFECSGYVMSGSRHR
RMEAVRLRKENQIYSADEKRALASFNQEERRKRENKILASFREMVYRKTKGKDDK
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Family NKAP family
Function
Acts as a transcriptional repressor. Plays a role as a transcriptional corepressor of the Notch-mediated signaling required for T-cell development. Also involved in the TNF and IL-1 induced NF-kappa-B activation. Associates with chromatin at the Notch-regulated SKP2 promoter.
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Gene ID 79576
Uniprot ID
NKAP_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
NKAP can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.
Browse Target Gene related Disease
Browse Target Gene related Drug
Cystine/glutamate transporter (SLC7A11)
Brain cancer [ICD-11: 2A00]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Glioblastoma [ICD-11: 2A00.00]
Target Regulation Up regulation
Pathway Response Ferroptosis hsa04216
Cell Process Ferroptosis
In-vitro Model
U87MG (Astroblastoma cells from human brain)
U251 (Fibroblasts or fibroblast like cells)
In-vivo Model The male BALB/c nude mice were randomized divide into two groups, each group including six 4 weeks old nude mice. Investigators were blinded to the treatment groups during data collection and subsequent data analysis. In the subcutaneous xenograft model, 5 × 105 cells were subcutaneously injected in the right flanks of nude mice. In the orthotopic intracranial mouse model, each mouse was intracranially injected with 1 × 105 luciferase transfected U87MG cells in 10 uL PBS solution.
Response Summary This study NKAP knockdown induced cell death in glioblastoma cells. NKAP acted as a new ferroptosis suppressor by binding to m6A and then promoting Cystine/glutamate transporter (SLC7A11) mRNA splicing and maturation.
microRNA let-7b (MIRLET7B)
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Lung cancer [ICD-11: 2C25]
Responsed Drug Metformin Approved
Pathway Response Notch signaling pathway hsa04330
In-vitro Model
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
H1975OR (Osimertinib resistant H1975 cells)
HCC827OR (Osimertinib resistant HCC827 cells)
Response Summary The participation of Metformin decreased the bindings of DNMT3a/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients.
microRNA let-7b (MIRLET7B)
Metformin [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene [2]
Responsed Disease Lung cancer ICD-11: 2C25
Pathway Response Notch signaling pathway hsa04330
In-vitro Model NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
H1975OR (Osimertinib resistant H1975 cells)
HCC827OR (Osimertinib resistant HCC827 cells)
Response Summary The participation of Metformin decreased the bindings of DNMT3a/b to the METTL3 promoter with the help of the readers of NKAP and HNRNPA2B1.the mediation of m6A formation on pri-Let-7b processing increased the mature microRNA let-7b (MIRLET7B), whose key role is to suppress the Notch signaling and to re-captivate the Osimertinib treatment.The findings open up future drug development, targeting this pathway for lung cancer patients.
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Regulator
DNA modification
m6A Target: microRNA 25 (MIR25)
In total 2 item(s) under this m6A target
Crosstalk ID: M6ACROT02032
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 1 (DNMT1)
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship DNA modification → m6A
Disease Pancreatic cancer
Crosstalk ID: M6ACROT02033
Epigenetic Regulator Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship DNA modification → m6A
Disease Pancreatic cancer
m6A Target: microRNA let-7b (MIRLET7B)
In total 4 item(s) under this m6A target
Crosstalk ID: M6ACROT02059
Epigenetic Regulator Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship DNA modification → m6A
Disease Lung cancer
Drug Metformin
Crosstalk ID: M6ACROT02062
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship DNA modification → m6A
Disease Lung cancer
Drug Metformin
Crosstalk ID: M6ACROT02065
Epigenetic Regulator Cysteine methyltransferase DNMT3A (DNMT3A)
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship DNA modification → m6A
Disease Lung cancer
Drug Osimertinib
Crosstalk ID: M6ACROT02068
Epigenetic Regulator DNA (cytosine-5)-methyltransferase 3B (DNMT3B)
Regulated Target Methyltransferase-like protein 3 (METTL3)
Crosstalk relationship DNA modification → m6A
Disease Lung cancer
Drug Osimertinib
Non-coding RNA
m6A Target: microRNA let-7b (MIRLET7B)
In total 1 item(s) under this m6A target
Crosstalk ID: M6ACROT05550
Epigenetic Regulator MicroRNA let-7b (MIRLET7B)
Crosstalk relationship m6A → ncRNA
Disease Lung cancer
Drug Metformin
Xenobiotics Compound(s) Regulating the m6A Methylation Regulator
Compound Name Geniposide Investigative
Synonyms
Geniposide; 24512-63-8; Jasminoidin; UNII-145295QLXY; CHEBI:5299; 145295QLXY; 169799-41-1; methyl (1S,4aS,7aS)-7-(hydroxymethyl)-1-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate; Cyclopenta[c]pyran-4-carboxylic acid, 1-(beta-D-glucopyranosyloxy)-1,4a,5,7a-tetrahydro-7-(hydroxymethyl)-, methyl ester, (1S,4aS,7aS)-; methyl (1S,4aS,7aR)-7-(hydroxymethyl)-1-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate; methyl (1S,4aS,7aS)-7-(hydroxymethyl)-1-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate; (1S,4aS,7aS)-Methyl 7-(hydroxymethyl)-1-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate; Cyclopenta(c)pyran-4-carboxylic acid, 1-(beta-D-glucopyranosyloxy)-1,4a,5,7a-tetrahydro-7-(hydroxymethyl)-, methyl ester, (1S,4aS,7aS)-; Genipin 1-glucoside; CHEMBL462894; Geniposide, >=98% (HPLC); AOB5625; HMS3884F17; ZINC3882101; BDBM50478840; MFCD16036219; s2411; AKOS025311228; CCG-268498; MCULE-3871054229; NCGC00346662-04; NCGC00346662-06; 27745-20-6; N1360; C09781; AB01558902_03; BRD-K57275767-001-03-2; Q27106709; Cyclopenta(c)pyran-4-carboxylic acid, 1-(beta-D-glucopyranosyloxy)-1,4a,5,7a-tetrahydro-7-(hydroxymethyl)-, methyl ester, (1S-(1alpha,4aalpha,7aalpha))-
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Description
Gardenia jasminoides extracts (GJE) attenuated expression of cytokines (IL-1Beta, IL-6 and TNF-Alpha), NFKB activating protein (NKAP) and TLR4 in ARPE-19 cells.
[3]
Compound Name Crocin Investigative
Synonyms
Crocin; Gardenia Yellow; alpha-Crocin; 42553-65-1; Crocin I; Crocine; 94238-00-3; Crocin 1; Saffron; crocin-1; UNII-877GWI46C2; crocetin di-gentiobiose ester; CHEMBL446785; bis[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl] (2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate; CHEBI:79068; Crocetin digentiobiose ester; 877GWI46C2; 11012-59-2; Crocetin bis(gentiobiosyl) ester; NCGC00160471-01; all-trans-Crocetin di-beta-D-gentiobiosyl ester; Crocin A; CCRIS 678; CCRIS 7705; crocetin digentiobiosyl ester; EINECS 255-881-6; BRN 6473367; .alpha.-crocin; Crocin-I; HSDB 8211; Natural red 1; EINECS 254-465-1; Natural yellow 19; crocetin digentiobioside; trans-Crocetin di(beta-D-gentiobiosyl) ester; DSSTox_CID_1457; DSSTox_RID_81403; DSSTox_GSID_46172; SCHEMBL1463936; DTXSID7046172; bis(beta-D-gentiobiosyl) crocetin; HMS3887O07; Crocetin Di(Beta-Gentiobiosyl)Ester; HY-N0697; crocetin di-beta-D-gentiobiose ester; Tox21_111837; BDBM50260195; s9511; AKOS015896765; ZINC245224178; DB11874; Bis(6-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl) 8,8'-diapo-psi,psi-carotenedioate; NCGC00160471-02; 8,8'-Diapo-psi,psi-carotenedioic acid, bis(6-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl) ester; beta-D-Glucopyranose, 6-O-beta-D-glucopyranosyl-, 1,1'-((2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethyl-2,4,6,8,10,12,14-hexadecaheptaenedioate); CAS-42553-65-1; C.I. 75100; CS-0009714; N1653; N1661; N1889; trans-crocetin bis(beta-D-gentiobiosyl) ester; C08589; A872860; Q424767; UNII-F32BA2H92Z component SEBIKDIMAPSUBY-RTJKDTQDSA-N; (2E,4E,6E,8E,10E,12E,14E)-Bis((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-((((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)methyl)tetrahydro-2H-pyran-2-yl) 2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate; bis(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl (2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate; bis[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}methyl)tetrahydro-2H-pyran-2-yl] (2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate
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External link
Description
Gardenia jasminoides extracts (GJE) attenuated expression of cytokines (IL-1Beta, IL-6 and TNF-Alpha), NFKB activating protein (NKAP) and TLR4 in ARPE-19 cells.
[3]
References
Ref 1 RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m(6)A-dependent manner. Cell Death Dis. 2022 Jan 21;13(1):73. doi: 10.1038/s41419-022-04524-2.
Ref 2 Stimulation of Let-7 Maturation by Metformin Improved the Response to Tyrosine Kinase Inhibitor Therapy in an m6A Dependent Manner. Front Oncol. 2022 Jan 6;11:731561. doi: 10.3389/fonc.2021.731561. eCollection 2021.
Ref 3 Anti-inflammatory activities of Gardenia jasminoides extracts in retinal pigment epithelial cells and zebrafish embryos. Exp Ther Med. 2021 Jul;22(1):700. doi: 10.3892/etm.2021.10132. Epub 2021 May 2.