KEAP1 (kelch like ECH associated protein 1)

Gene

• Entrez ID: 9817
• Gene name: Kelch like ECH associated protein 1
• Gene symbol: KEAP1
• Synonyms: INrf2, KLHL19
• Chromosome: 19
• Chromosome location: 19p13.2
• Summary: This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is follow

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006704	hsa-miR-200a-3p	Luciferase reporter assay, qRT-PCR, Western blot	21914820
MIRT006704	hsa-miR-200a-3p	Luciferase reporter assay, qRT-PCR, Western blot	21914820
MIRT025794	hsa-miR-7-5p	Sequencing	20371350
MIRT029595	hsa-miR-26b-5p	Microarray	19088304
MIRT040649	hsa-miR-92b-3p	CLASH	23622248
MIRT053761	hsa-miR-141-3p	Luciferase reporter assay, qRT-PCR, Western blot	24628843
MIRT053761	hsa-miR-141-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23045278
MIRT053761	hsa-miR-141-3p	Luciferase reporter assay, Microarray, qRT-PCR, Western blot	23045278
MIRT025794	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	26453926
MIRT025794	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	26453926
MIRT025794	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	26453926
MIRT025794	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	26453926
MIRT025794	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	26453926
MIRT025794	hsa-miR-7-5p	Luciferase reporter assay, qRT-PCR, Western blot	26453926
MIRT732785	hsa-miR-129-5p	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blotting	33569456
MIRT732785	hsa-miR-129-5p	Immunofluorescence, Luciferase reporter assay, qRT-PCR, Western blotting	33569456
MIRT736293	hsa-miR-941	Western blotting, qRT-PCR	32102665
MIRT737548	hsa-miR-26b-3p	Western blotting, qRT-PCR	32104267
MIRT1085126	hsa-miR-1273f	CLIP-seq
MIRT1085127	hsa-miR-141	CLIP-seq
MIRT1085128	hsa-miR-143	CLIP-seq
MIRT1085129	hsa-miR-1827	CLIP-seq
MIRT1085130	hsa-miR-200a	CLIP-seq
MIRT1085131	hsa-miR-2110	CLIP-seq
MIRT1085132	hsa-miR-3065-5p	CLIP-seq
MIRT1085133	hsa-miR-3176	CLIP-seq
MIRT1085134	hsa-miR-3922-3p	CLIP-seq
MIRT1085135	hsa-miR-4271	CLIP-seq
MIRT1085136	hsa-miR-4287	CLIP-seq
MIRT1085137	hsa-miR-4649-3p	CLIP-seq
MIRT1085138	hsa-miR-4685-3p	CLIP-seq
MIRT1085139	hsa-miR-4708-5p	CLIP-seq
MIRT1085140	hsa-miR-4725-3p	CLIP-seq
MIRT1085141	hsa-miR-4757-5p	CLIP-seq
MIRT1085142	hsa-miR-4770	CLIP-seq
MIRT1085143	hsa-miR-4793-5p	CLIP-seq
MIRT1085144	hsa-miR-491-5p	CLIP-seq
MIRT1085145	hsa-miR-5095	CLIP-seq
MIRT1085146	hsa-miR-616	CLIP-seq
MIRT1085131	hsa-miR-2110	CLIP-seq
MIRT1085132	hsa-miR-3065-5p	CLIP-seq
MIRT1085135	hsa-miR-4271	CLIP-seq
MIRT1085140	hsa-miR-4725-3p	CLIP-seq
MIRT1085144	hsa-miR-491-5p	CLIP-seq
MIRT2021691	hsa-miR-1269	CLIP-seq
MIRT2021692	hsa-miR-1269b	CLIP-seq
MIRT2021693	hsa-miR-2114	CLIP-seq
MIRT1085133	hsa-miR-3176	CLIP-seq
MIRT2021694	hsa-miR-3622b-5p	CLIP-seq
MIRT1085134	hsa-miR-3922-3p	CLIP-seq
MIRT2021695	hsa-miR-4283	CLIP-seq
MIRT1085136	hsa-miR-4287	CLIP-seq
MIRT2021696	hsa-miR-4304	CLIP-seq
MIRT2021697	hsa-miR-4426	CLIP-seq
MIRT2021698	hsa-miR-4449	CLIP-seq
MIRT2021699	hsa-miR-4508	CLIP-seq
MIRT2021700	hsa-miR-4520b-3p	CLIP-seq
MIRT2021701	hsa-miR-4529-3p	CLIP-seq
MIRT2021702	hsa-miR-4532	CLIP-seq
MIRT2021703	hsa-miR-4540	CLIP-seq
MIRT2021704	hsa-miR-4647	CLIP-seq
MIRT2021705	hsa-miR-4662b	CLIP-seq
MIRT1085138	hsa-miR-4685-3p	CLIP-seq
MIRT1085141	hsa-miR-4757-5p	CLIP-seq
MIRT2021706	hsa-miR-4783-3p	CLIP-seq
MIRT1085143	hsa-miR-4793-5p	CLIP-seq
MIRT1085145	hsa-miR-5095	CLIP-seq
MIRT2021707	hsa-miR-512-3p	CLIP-seq
MIRT1085131	hsa-miR-2110	CLIP-seq
MIRT1085132	hsa-miR-3065-5p	CLIP-seq
MIRT1085135	hsa-miR-4271	CLIP-seq
MIRT1085140	hsa-miR-4725-3p	CLIP-seq
MIRT1085144	hsa-miR-491-5p	CLIP-seq
MIRT1085145	hsa-miR-5095	CLIP-seq
MIRT1085145	hsa-miR-5095	CLIP-seq
MIRT2389716	hsa-miR-3148	CLIP-seq
MIRT2389717	hsa-miR-3189-3p	CLIP-seq
MIRT2389718	hsa-miR-3647-3p	CLIP-seq
MIRT2389719	hsa-miR-3978	CLIP-seq
MIRT2389720	hsa-miR-502-5p	CLIP-seq
MIRT1085145	hsa-miR-5095	CLIP-seq
MIRT2556014	hsa-miR-2116	CLIP-seq
MIRT1085132	hsa-miR-3065-5p	CLIP-seq
MIRT2556015	hsa-miR-3117-5p	CLIP-seq
MIRT2389716	hsa-miR-3148	CLIP-seq
MIRT2389717	hsa-miR-3189-3p	CLIP-seq
MIRT2389718	hsa-miR-3647-3p	CLIP-seq
MIRT2389719	hsa-miR-3978	CLIP-seq
MIRT2556016	hsa-miR-4474-5p	CLIP-seq
MIRT2556017	hsa-miR-4677-5p	CLIP-seq
MIRT2556018	hsa-miR-4704-5p	CLIP-seq
MIRT2389720	hsa-miR-502-5p	CLIP-seq
MIRT1085145	hsa-miR-5095	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001701	Process	In utero embryonic development	IEA
GO:0005515	Function	Protein binding	IPI	15601839, 16189514, 16888629, 17015834, 17510365, 18757741, 19424503, 19615732, 19706542, 20173742, 20452972, 20562859, 20600852, 21044950, 21145461, 21516116, 21903422, 21988832, 23274085, 24089205, 25416956, 25910212, 26517842, 26649820, 29792731, 31169361, 31262713, 31515488, 322
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	15601839, 19424503
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS	17015834
GO:0005884	Component	Actin filament	IEA
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IDA	15601839
GO:0008134	Function	Transcription factor binding	IBA	21873635
GO:0008134	Function	Transcription factor binding	IPI	17015834
GO:0010506	Process	Regulation of autophagy	IDA	20452972
GO:0016032	Process	Viral process	IEA
GO:0016234	Component	Inclusion body	IDA	20452972
GO:0016567	Process	Protein ubiquitination	IDA	15601839, 15983046
GO:0016567	Process	Protein ubiquitination	IEA
GO:0016579	Process	Protein deubiquitination	TAS
GO:0030496	Component	Midbody	IDA	15166316
GO:0031463	Component	Cul3-RING ubiquitin ligase complex	IDA	15601839, 15983046
GO:0032436	Process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	TAS	17015834
GO:0034451	Component	Centriolar satellite	IDA
GO:0034599	Process	Cellular response to oxidative stress	IDA	15601839
GO:0042802	Function	Identical protein binding	IEA
GO:0042994	Process	Cytoplasmic sequestering of transcription factor	IBA	21873635
GO:0043433	Process	Negative regulation of DNA-binding transcription factor activity	TAS	17015834
GO:0043687	Process	Post-translational protein modification	TAS
GO:0045604	Process	Regulation of epidermal cell differentiation	IEA
GO:0071353	Process	Cellular response to interleukin-4	IEA
GO:0097718	Function	Disordered domain specific binding	IEA

Other IDs

• MIM: 606016
• HGNC: 23177
• e!Ensembl: ENSG00000079999

Protein

• UniProt ID: Q14145
• Protein name: Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) (Kelch-like protein 19)
• Protein function: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:14585973, PubMed:15379550, PubMed:15572695, PubMed:15601839, PubM
• PDB: 1U6D, 1ZGK, 2FLU, 3VNG, 3VNH, 3ZGC, 3ZGD, 4CXI, 4CXJ, 4CXT, 4IFJ, 4IFL, 4IFN, 4IN4, 4IQK, 4L7B, 4L7C, 4L7D, 4N1B, 4XMB, 5DAD, 5DAF, 5F72, 5GIT, 5NLB, 5WFL, 5WFV, 5WG1, 5WHL, 5WHO, 5WIY, 5X54, 6FFM, 6FMP, 6FMQ, 6HWS, 6LRZ, 6ROG, 6SP1, 6SP4, 6T7V, 6T7Z, 6TG8, 6TYM, 6TYP, 6UF0, 6V6Z, 6W66, 6W67, 6W68, 6W69
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00651	BTB	67 → 179	BTB/POZ domain	Domain
  PF07707	BACK	184 → 286	BTB And C-terminal Kelch	Domain
  PF01344	Kelch_1	318 → 359	Kelch motif	Repeat
  PF01344	Kelch_1	361 → 410	Kelch motif	Repeat
  PF01344	Kelch_1	412 → 457	Kelch motif	Repeat
  PF01344	Kelch_1	459 → 504	Kelch motif	Repeat
  PF01344	Kelch_1	506 → 551	Kelch motif	Repeat
  PF01344	Kelch_1	553 → 598	Kelch motif	Repeat

• Sequence:

  MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHT
  KQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGM
  EVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLD
  PSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVR
  CESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDY
  LVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQV
  PRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGV
  IDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDG
  TNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVE
  TETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSG
  RSGVGVAVTMEPCRKQIDQQNCTC

• Sequence length: 624

Pathways

KEGG:

Ubiquitin mediated proteolysis
Parkinson disease
Pathways in cancer
Chemical carcinogenesis - reactive oxygen species
Hepatocellular carcinoma
Fluid shear stress and atherosclerosis

Reactome:

Ub-specific processing proteases
Neddylation
Antigen processing: Ubiquitination & Proteasome degradation

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Breast cancer	Malignant neoplasm of breast	rs587776547, rs1137887, rs137853007, rs587776650, rs80359351, rs80359714, rs121917783, rs104886456, rs121964878, rs80359874, rs80357868, rs80357508, rs387906843, rs80357569, rs80358158, rs80357524, rs80357115, rs80357945, rs80357729, rs80357609, rs80357259, rs80357981, rs80358063, rs80357389, rs80356862, rs80359876, rs80357580, rs80358053, rs80358089, rs80187739, rs397507241, rs80358069, rs80357590, rs80357284, rs80357941, rs80359261, rs80359272, rs80359276, rs276174813, rs80358474, rs80359316, rs1555282969, rs80359388, rs80359499, rs80359505, rs80359520, rs80359526, rs80359533, rs56253082, rs80358824, rs80359554, rs80359636, rs80359651, rs80359659, rs80359011, rs80359012, rs80359013, rs80359718, rs397507410, rs81002812, rs80359730, rs80359152, rs80359159, rs397507419, rs28897759, rs80359211, rs80359775, rs397514577, rs397507584, rs80358435, rs80358456, rs80359340, rs80359343, rs80359365, rs80358579, rs397507670, rs80358593, rs80359406, rs80359444, rs80359454, rs276174853, rs276174854, rs80359483, rs80359537, rs80358815, rs80358843, rs80359558, rs80359560, rs80359594, rs80358893, rs28897743, rs397507900, rs397507906, rs397507918, rs80358971, rs80358981, rs397507941, rs80359030, rs80359035, rs41293511, rs397507396, rs81002806, rs80359112, rs397508006, rs81002893, rs45580035, rs80359760, rs397508051, rs80359772, rs4987049, rs80359777, rs80357770, rs397508867, rs62625303, rs397508874, rs80357506, rs80357287, rs273898674, rs80358042, rs80358083, rs80357058, rs41286296, rs80357960, rs80356945, rs80357223, rs386134270, rs80358116, rs80357856, rs80357424, rs397509050, rs80357485, rs80357966, rs397509067, rs80357310, rs80356866, rs80357260, rs80357437, rs80358023, rs80358086, rs80357133, rs80356993, rs80357997, rs80357239, rs80357227, rs397509243, rs80356969, rs80356959, rs63750617, rs63751319, rs587779315, rs200640585, rs398122546, rs80357543, rs398122687, rs80359328, rs398122779, rs398122783, rs62517194, rs80358029, rs515726060, rs180177103, rs180177111, rs180177133, rs587776527, rs180177135, rs180177136, rs515726117, rs587779813, rs587779909, rs587780024, rs587780100, rs28909982, rs121908698, rs180177100, rs587780210, rs587780240, rs587780639, rs587781269, rs587781353, rs587781471, rs587781658, rs587781697, rs587781730, rs587781894, rs587781948, rs587782005, rs587782011, rs200928781, rs587781558, rs370228071, rs587782245, rs587782401, rs180177110, rs587782504, rs72552322, rs587782531, rs587782620, rs587782680, rs587782774, rs587782818, rs730881411, rs730881389, rs564652222, rs397507768, rs587776419, rs730881868, rs730881940, rs56383036, rs758972589, rs201089102, rs730881348, rs786202608, rs786201886, rs786203318, rs786203775, rs786203714, rs786202033, rs750621215, rs786203884, rs786203650, rs772821016, rs863224521, rs864622223, rs864622655, rs375699023, rs876659572, rs768362387, rs876659535, rs876658957, rs483353072, rs876659435, rs267608041, rs876661113, rs730881369, rs878853535, rs772228129, rs878855122, rs760551339, rs80359596, rs397509222, rs886039630, rs886039683, rs886040828, rs587781799, rs886040374, rs886040649, rs397507967, rs878854957, rs886040043, rs1057517589, rs1060502769, rs866380588, rs863224765, rs1064793243, rs747563556, rs1555074976, rs1064795885, rs753961188, rs1064794708, rs869312772, rs1064793887, rs1131690820, rs1135401928, rs1135401868, rs1135401859, rs1553370324, rs397507630, rs1555283160, rs1555283251, rs1555283262, rs1555283361, rs1555286298, rs1555288462, rs886040950, rs1555289566, rs776323117, rs80357123, rs1555579627, rs1555580697, rs80358054, rs1555593302, rs1328985852, rs763470424, rs1555139694, rs878854697, rs1555461217, rs1555461765, rs774684620, rs766416564, rs1554558613, rs1305740166, rs1555461460, rs1555461407, rs1555461586, rs1555567202, rs1555607022, rs1555069815, rs1442299125, rs1474786480, rs1555084947, rs1555457867, rs141087784, rs1482641121, rs1564830522, rs1565469955, rs1565503137, rs864622613, rs755263466, rs757679199, rs1593903166, rs1597801649, rs1603293306, rs879253880, rs80358754, rs1597062038, rs45494092, rs1603275367, rs887358871, rs1597091518, rs1966967065, rs1064793049, rs2082872908, rs2085078278, rs2072475243
Carcinoma	Carcinoma, Basal Cell	rs121912654, rs555607708, rs786202962, rs1564055259
Cholestasis	Cholestasis, Extrahepatic	rs121909103, rs751511532, rs376368459, rs762702807, rs1578490102, rs1578499691, rs1578504946, rs1317656688, rs199791850, rs1452792080, rs1578491039	30026087
Euthyroid goiter	Euthyroid Goiter	rs1595314576, rs1595447577, rs1595374375, rs1595380836, rs387906934, rs754818927, rs1595363945	23724128
Gallbladder cancer	Malignant neoplasm of gallbladder	rs121913530, rs377767360, rs121913529, rs730882029, rs730882005, rs786202799, rs876659802, rs1057519718, rs764146326	18692501
Hypothyroidism	Hypothyroidism	rs869320723, rs121908862, rs121908863, rs121908865, rs121908866, rs121908867, rs121908870, rs121908871, rs121908872, rs2140110277, rs121908881, rs121908884, rs121908885, rs786205080, rs1586182912, rs121917847, rs104893655, rs104893657, rs104893658, rs104893659, rs104893660, rs104893656, rs121917719, rs786204790, rs189261858, rs879255608, rs868197660, rs879255609, rs1586744173, rs1586182837, rs771222349, rs1587618417, rs1601844140, rs760832986, rs780982673, rs1603336347, rs1691155605	30595370
Lung carcinoma	Non-Small Cell Lung Carcinoma	rs1805076, rs121909071, rs121913530, rs112445441, rs121913529, rs121913535, rs121913297, rs121913279, rs104886003, rs397516975, rs11554290, rs121913364, rs121913351, rs121913369, rs121913355, rs121912470, rs121913273, rs121913281, rs121913348, rs727503093, rs121913353, rs397516890, rs397516896, rs121913378, rs397516897, rs397516977, rs397516978, rs397516979, rs397516980, rs397516981, rs397516982, rs121913240, rs17851045, rs397517086, rs121913428, rs397517094, rs397517098, rs397517106, rs121913465, rs397517108, rs397517111, rs397517112, rs397517114, rs397517116, rs1554350366, rs397517127, rs397517200, rs397517202, rs121913283, rs121913370, rs121913357, rs727503106, rs121913238, rs727503108, rs397517040, rs397516976, rs1555618025, rs1057519729, rs1584238193	22684020
Lung adenocarcinoma	Adenocarcinoma of lung (disorder)	rs28934576, rs121913530, rs397516975, rs587776805, rs121913469, rs121913364, rs121913351, rs121913366, rs397516896, rs397516977, rs397516981, rs397517127, rs121913344, rs727504233, rs121913370, rs760043106, rs1057519788, rs1131692238, rs1131692237, rs1554350382
Papillary renal carcinoma	Papillary Renal Cell Carcinoma	rs5030823, rs2137087134, rs121913668, rs121913669, rs121913670, rs121913671, rs121913673, rs121913243, rs786202724	23797736
Pleuropulmonary blastoma	Pleuropulmonary blastoma	rs137852976, rs137852977, rs137852978, rs137852979, rs1595314576, rs878855246, rs886037690, rs754081635, rs1060503605, rs1131691197, rs1595313951
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	29610475, 24763052
Psoriasis	Psoriasis	rs281875215, rs587777763, rs281875213, rs281875212	26974007
Renal carcinoma	Renal Cell Carcinoma, Conventional (Clear Cell) Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Collecting Duct Carcinoma of the Kidney	rs121913668, rs121913670, rs121913243, rs786202724	23797736

Unknown
Disease name	Disease term	dbSNP ID	References
Alveolar rhabdomyosarcoma	Alveolar rhabdomyosarcoma
Ankylosing spondylitis	Ankylosing spondylitis		26974007
Biliary cirrhosis	Biliary cirrhosis, Biliary Cirrhosis, Primary, 1, Primary biliary cirrhosis		30026087
Cerebellar medulloblastoma	Cerebellar medulloblastoma
Cholangitis	Cholangitis, Sclerosing		26974007
Chromophobe carcinoma	Chromophobe Renal Cell Carcinoma	rs137853247	23797736
Crohn disease	Crohn Disease	rs2066847, rs2066844, rs886052047, rs5743265, rs111608429, rs104895438	26974007
Functional gastrointestinal disorders	Functional Gastrointestinal Disorders		20404090
Neoplasm of gallbladder	gallbladder neoplasm		18692501
Gastrointestinal diseases	Gastrointestinal Diseases		20404090
Keratoma	Keratoma		20404090
Keratosis	Keratosis		20404090
Keratosis blennorrhagica	Keratosis Blennorrhagica		20404090
Medulloepithelioma	Medulloepithelioma
Multinodular goiter	Multinodular goiter, Familial multinodular goiter
Ovarian neoplasm	ovarian neoplasm
Pilomatrixoma	Pilomatrixoma
Polyp of large intestine	Polyp of large intestine
Prostatic neoplasms	Prostatic Neoplasms		29610475, 24763052
Biliary cholangitis	Secondary Biliary Cholangitis		30026087
Seminoma	Seminoma
Sertoli cell neoplasm	Sertoli cell neoplasm
Thyroid carcinoma	Thyroid carcinoma
Ulcerative colitis	Ulcerative Colitis		26974007