MAP2K6 (mitogen-activated protein kinase kinase 6)

Gene

• Entrez ID: 5608
• Gene name: Mitogen-activated protein kinase kinase 6
• Gene symbol: MAP2K6
• Synonyms (NCBI Gene): CRCMSL, MAPKK6, MEK6, MKK6, PRKMK6, SAPKK-3, SAPKK3
• Chromosome: 17
• Chromosome location: 17q24.3
• Summary: This gene encodes a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multipl

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT016670	hsa-miR-425-5p	Sequencing	20371350
MIRT021513	hsa-miR-145-5p	Reporter assay;Microarray	21351259
MIRT053745	hsa-miR-29b-3p	Microarray	22942087
MIRT720403	hsa-miR-6769a-3p	HITS-CLIP	19536157
MIRT720402	hsa-miR-5587-5p	HITS-CLIP	19536157
MIRT573371	hsa-miR-1178-5p	PAR-CLIP	20371350
MIRT573370	hsa-miR-1324	PAR-CLIP	20371350
MIRT573369	hsa-miR-922	PAR-CLIP	20371350
MIRT573368	hsa-miR-6804-5p	PAR-CLIP	20371350
MIRT573367	hsa-miR-3166	PAR-CLIP	20371350
MIRT573366	hsa-miR-6834-5p	PAR-CLIP	20371350
MIRT573365	hsa-miR-1226-5p	PAR-CLIP	20371350
MIRT573364	hsa-miR-6734-5p	PAR-CLIP	20371350
MIRT573363	hsa-miR-1304-5p	PAR-CLIP	20371350
MIRT573362	hsa-miR-8055	PAR-CLIP	20371350
MIRT473850	hsa-miR-590-3p	PAR-CLIP	23592263
MIRT473845	hsa-miR-411-5p	PAR-CLIP	23592263
MIRT473849	hsa-miR-6872-3p	PAR-CLIP	23592263
MIRT473847	hsa-miR-4735-5p	PAR-CLIP	23592263
MIRT473848	hsa-miR-6832-5p	PAR-CLIP	23592263
MIRT473846	hsa-miR-4775	PAR-CLIP	23592263
MIRT473845	hsa-miR-411-5p	PAR-CLIP	23592263
MIRT473844	hsa-miR-3149	PAR-CLIP	23592263
MIRT732300	hsa-miR-625-3p	Luciferase reporter assay, qRT-PCR, Western blot	27526785
MIRT732300	hsa-miR-625-3p	Luciferase reporter assay, qRT-PCR, Western blot	27526785
MIRT732300	hsa-miR-625-3p	Luciferase reporter assay, qRT-PCR, Western blot	27526785
MIRT735799	hsa-miR-10a-5p	Luciferase reporter assay, Western blotting, qRT-PCR	33128541
MIRT720403	hsa-miR-6769a-3p	HITS-CLIP	19536157
MIRT720402	hsa-miR-5587-5p	HITS-CLIP	19536157
MIRT573371	hsa-miR-1178-5p	PAR-CLIP	20371350
MIRT573370	hsa-miR-1324	PAR-CLIP	20371350
MIRT573369	hsa-miR-922	PAR-CLIP	20371350
MIRT573368	hsa-miR-6804-5p	PAR-CLIP	20371350
MIRT573367	hsa-miR-3166	PAR-CLIP	20371350
MIRT573366	hsa-miR-6834-5p	PAR-CLIP	20371350
MIRT573365	hsa-miR-1226-5p	PAR-CLIP	20371350
MIRT573364	hsa-miR-6734-5p	PAR-CLIP	20371350
MIRT573363	hsa-miR-1304-5p	PAR-CLIP	20371350
MIRT573362	hsa-miR-8055	PAR-CLIP	20371350
MIRT473850	hsa-miR-590-3p	PAR-CLIP	23592263
MIRT473845	hsa-miR-411-5p	PAR-CLIP	23592263
MIRT473849	hsa-miR-6872-3p	PAR-CLIP	23592263
MIRT473847	hsa-miR-4735-5p	PAR-CLIP	23592263
MIRT473848	hsa-miR-6832-5p	PAR-CLIP	23592263
MIRT473846	hsa-miR-4775	PAR-CLIP	23592263
MIRT473845	hsa-miR-411-5p	PAR-CLIP	23592263
MIRT473844	hsa-miR-3149	PAR-CLIP	23592263
MIRT755867	hsa-miR-643	Luciferase reporter assay, Western blotting, qRT-PCR, In situ hybridization, RNA pull down assay	34581623
MIRT1920611	hsa-miR-34c-3p	CLIP-seq
MIRT1920612	hsa-miR-374a	CLIP-seq
MIRT1920613	hsa-miR-374b	CLIP-seq
MIRT1920611	hsa-miR-34c-3p	CLIP-seq
MIRT1920612	hsa-miR-374a	CLIP-seq
MIRT1920613	hsa-miR-374b	CLIP-seq
MIRT2266661	hsa-miR-4305	CLIP-seq
MIRT2266662	hsa-miR-664	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IBA
GO:0000165	Process	MAPK cascade	IDA	8663074
GO:0000165	Process	MAPK cascade	IEA
GO:0000166	Function	Nucleotide binding	IEA
GO:0001649	Process	Osteoblast differentiation	IEA
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0004708	Function	MAP kinase kinase activity	IBA
GO:0004708	Function	MAP kinase kinase activity	IDA	8663074, 8663524, 9218798, 11460167
GO:0004708	Function	MAP kinase kinase activity	IEA
GO:0004708	Function	MAP kinase kinase activity	TAS	10848581
GO:0004713	Function	Protein tyrosine kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	11035004, 15229216, 17255949, 20067578, 32296183, 32707033, 32814053, 32911434
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	9768359
GO:0005829	Component	Cytosol	IDA	9768359
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0007165	Process	Signal transduction	TAS	8621675
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0019901	Function	Protein kinase binding	IEA
GO:0019901	Function	Protein kinase binding	IPI	11279118
GO:0031098	Process	Stress-activated protein kinase signaling cascade	IDA	35857590
GO:0031098	Process	Stress-activated protein kinase signaling cascade	IDA	35857590
GO:0031098	Process	Stress-activated protein kinase signaling cascade	IEA
GO:0035872	Process	Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	TAS
GO:0038066	Process	P38MAPK cascade	IDA	10330143
GO:0038066	Process	P38MAPK cascade	IDA	11460167
GO:0038066	Process	P38MAPK cascade	IEA
GO:0038066	Process	P38MAPK cascade	TAS
GO:0042770	Process	Signal transduction in response to DNA damage	TAS	10848581
GO:0042802	Function	Identical protein binding	IPI	19141286
GO:0043410	Process	Positive regulation of MAPK cascade	IEA
GO:0051403	Process	Stress-activated MAPK cascade	IDA	8663524, 9218798
GO:0051604	Process	Protein maturation	IDA	32109412
GO:0051726	Process	Regulation of cell cycle	TAS	10848581
GO:0060048	Process	Cardiac muscle contraction	IEA
GO:0060348	Process	Bone development	IEA
GO:0070269	Process	Pyroptotic inflammatory response	IDA	32109412
GO:0071493	Process	Cellular response to UV-B	IDA	35857590
GO:0090398	Process	Cellular senescence	IEA
GO:0090398	Process	Cellular senescence	TAS
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0120163	Process	Negative regulation of cold-induced thermogenesis	IEA
GO:0120163	Process	Negative regulation of cold-induced thermogenesis	ISS	29021624
GO:1901796	Process	Regulation of signal transduction by p53 class mediator	TAS
GO:1902531	Process	Regulation of intracellular signal transduction	IEA
GO:1904784	Process	NLRP1 inflammasome complex assembly	IDA	22665479

Other IDs

• MIM: 601254
• HGNC: 6846
• e!Ensembl: ENSG00000108984

Protein

• UniProt ID: P52564
• Protein name: Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3)
• Protein function: Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11,
• PDB: 2Y8O, 3ENM, 3FME, 3VN9, 5ETF, 8A8M, 8P7J, 8PM3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	53 → 314	Protein kinase domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Isoform 2 is only expressed in skeletal muscle. Isoform 1 is expressed in skeletal muscle, heart, and in lesser extent in liver or pancreas. {ECO:0000269|PubMed:8621675}.
• Sequence:

  MSQSKGKKRNPGLKIPKEAFEQPQTSSTPPRDLDSKACISIGNQNFEVKADDLEPIMELG
  RGAYGVVEKMRHVPSGQIMAVKRIRATVNSQEQKRLLMDLDISMRTVDCPFTVTFYGALF
  REGDVWICMELMDTSLDKFYKQVIDKGQTIPEDILGKIAVSIVKALEHLHSKLSVIHRDV
  KPSNVLINALGQVKMCDFGISGYLVDSVAKTIDAGCKPYMAPERINPELNQKGYSVKSDI
  WSLGITMIELAILRFPYDSWGTPFQQLKQVVEEPSPQLPADKFSAEFVDFTSQCLKKNSK
  ERPTYPELMQHPFFTLHESKGTDVASFVKLILGD

• Sequence length: 334

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
COLONIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EDEMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERSENSITIVITY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, HIP	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIPHERAL NEUROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROGRESSIVE SUPRANUCLEAR PALSY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESTRICTIVE CARDIOMYOPATHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of colon	Adenocarcinoma Of Colon	BEFREE	29402903		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma Of Esophagus	Esophageal Cancer	BEFREE	30102978		★☆☆☆☆ Found in Text Mining only
Adrenocortical carcinoma	Adrenocortical carcinoma	BEFREE	31634687		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	24085465		★☆☆☆☆ Found in Text Mining only
Arthritis	Arthritis	BEFREE	22488549		★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	14695331, 33483588	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	16000313, 19245689, 32977823, 35441810, 35919504	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	23228696		★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	11531284, 28604448		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	LHGDN	15722372		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	15037631		★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	CTD_human_DG	15037631		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colonic Neoplasms	Colonic neoplasm	Pubtator	27526785, 29402903	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	15037631	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	29021624		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	29021624		★☆☆☆☆ Found in Text Mining only
Esophageal carcinoma	Esophageal Carcinoma	BEFREE	30391783		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophagus Neoplasm	BEFREE	30391783		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	21132268, 29669288		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	21132268, 29669288		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	17012236	Associate	★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington Disease	BEFREE	18327563		★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	31689375		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	23661466		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	23661466	Associate	★☆☆☆☆ Found in Text Mining only
Liposarcoma	Liposarcoma	Pubtator	31801397	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	31213506		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	30391783		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	23228696		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	11531284, 28604448		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	29751559		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	15037631, 25019214		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	CTD_human_DG	15037631		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	19245689	Associate	★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy	Muscular dystrophy	BEFREE	24876160		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	15492008		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	30245131, 30588096		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	15611662, 30102978		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	19265796	Associate	★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29021624		★☆☆☆☆ Found in Text Mining only
Osteoarthritis of hip	Osteoarthritis Of Hip	GWASCAT_DG	29559693, 30374069		★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	GWASCAT_DG	29559693		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteopenia	Osteopenia	BEFREE	26059046		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	11531284, 28604448		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	28604448	Associate	★☆☆☆☆ Found in Text Mining only
Paralysis	Paralysis	Pubtator	24737428	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	20067578		★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	Pubtator	36214094	Associate	★☆☆☆☆ Found in Text Mining only
Pierre Robin Syndrome	Pierre-Robin Syndrome	BEFREE	26059046		★☆☆☆☆ Found in Text Mining only
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	33372369	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	20168333	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Rhabdomyosarcoma Embryonal	Rhabdomyosarcoma	Pubtator	35801577	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	16780590	Associate	★☆☆☆☆ Found in Text Mining only