MAP2K5 (mitogen-activated protein kinase kinase 5)

Gene

• Entrez ID: 5607
• Gene name: Mitogen-activated protein kinase kinase 5
• Gene symbol: MAP2K5
• Synonyms (NCBI Gene): HsT17454, MAPKK5, MEK5, PRKMK5
• Chromosome: 15
• Chromosome location: 15q23
• Summary: The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, a

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018716	hsa-miR-335-5p	Microarray	18185580
MIRT024959	hsa-miR-214-3p	Microarray;Other	19859982
MIRT438086	hsa-miR-330-3p	Genotyping	24436253
MIRT438086	hsa-miR-330-3p	Genotyping	24436253

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS
GO:0000165	Process	MAPK cascade	IBA
GO:0000165	Process	MAPK cascade	IEA
GO:0000165	Process	MAPK cascade	IEA
GO:0000165	Process	MAPK cascade	ISS	20551324
GO:0000166	Function	Nucleotide binding	IEA
GO:0004672	Function	Protein kinase activity	IEA
GO:0004672	Function	Protein kinase activity	TAS	7759517
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004708	Function	MAP kinase kinase activity	IBA
GO:0004708	Function	MAP kinase kinase activity	IEA
GO:0004713	Function	Protein tyrosine kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	7759517, 14743216, 17474147, 18588859, 21516116, 21988832, 22939624, 25241761, 28514442, 29892012, 31515488, 31980649, 32296183, 32707033, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005819	Component	Spindle	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0007165	Process	Signal transduction	TAS	7759517
GO:0007507	Process	Heart development	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0030307	Process	Positive regulation of cell growth	IEA
GO:0032717	Process	Negative regulation of interleukin-8 production	IEA
GO:0032717	Process	Negative regulation of interleukin-8 production	ISS	20551324
GO:0034115	Process	Negative regulation of heterotypic cell-cell adhesion	IEA
GO:0034115	Process	Negative regulation of heterotypic cell-cell adhesion	ISS	20551324
GO:0034392	Process	Negative regulation of smooth muscle cell apoptotic process	IEA
GO:0034392	Process	Negative regulation of smooth muscle cell apoptotic process	ISS
GO:0043124	Process	Negative regulation of canonical NF-kappaB signal transduction	IEA
GO:0043124	Process	Negative regulation of canonical NF-kappaB signal transduction	ISS	20551324
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046872	Function	Metal ion binding	IEA
GO:0048009	Process	Insulin-like growth factor receptor signaling pathway	IEA
GO:0050679	Process	Positive regulation of epithelial cell proliferation	IEA
GO:0051247	Process	Positive regulation of protein metabolic process	IEA
GO:0051247	Process	Positive regulation of protein metabolic process	ISS
GO:0060761	Process	Negative regulation of response to cytokine stimulus	IEA
GO:0060761	Process	Negative regulation of response to cytokine stimulus	ISS	20551324
GO:0070375	Process	ERK5 cascade	IEA
GO:0071363	Process	Cellular response to growth factor stimulus	IEA
GO:0071363	Process	Cellular response to growth factor stimulus	ISS	20551324
GO:0071499	Process	Cellular response to laminar fluid shear stress	TAS	20551324
GO:0090051	Process	Negative regulation of cell migration involved in sprouting angiogenesis	IEA
GO:0090051	Process	Negative regulation of cell migration involved in sprouting angiogenesis	ISS	20551324
GO:0106310	Function	Protein serine kinase activity	IEA
GO:2000342	Process	Negative regulation of chemokine (C-X-C motif) ligand 2 production	IEA
GO:2000342	Process	Negative regulation of chemokine (C-X-C motif) ligand 2 production	ISS	20551324
GO:2001240	Process	Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IEA
GO:2001240	Process	Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	ISS	20551324

Other IDs

• MIM: 602520
• HGNC: 6845
• e!Ensembl: ENSG00000137764

Protein

• UniProt ID: Q13163
• Protein name: Dual specificity mitogen-activated protein kinase kinase 5 (MAP kinase kinase 5) (MAPKK 5) (EC 2.7.12.2) (MAPK/ERK kinase 5) (MEK 5)
• Protein function: Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac developme
• PDB: 2NPT, 2O2V, 4IC7
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00564	PB1	18 → 100	PB1 domain	Domain
  PF00069	Pkinase	166 → 419	Protein kinase domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in many adult tissues. Abundant in heart and skeletal muscle.
• Sequence:

  MLWLALGPFPAMENQVLVIRIKIPNSGAVDWTVHSGPQLLFRDVLDVIGQVLPEATTTAF
  EYEDEDGDRITVRSDEEMKAMLSYYYSTVMEQQVNGQLIEPLQIFPRACKPPGERNIHGL
  KVNTRAGPSQHSSPAVSDSLPSNSLKKSSAELKKILANGQMNEQDIRYRDTLGHGNGGTV
  YKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYKCDSSYIIGFYGAFFVENRISIC
  TEFMDGGSLDVYRKMPEHVLGRIAVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLC
  DFGVSTQLVNSIAKTYVGTNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPYPQIQ
  KNQGSLMPLQLLQCIVDEDSPVLPVGEFSEPFVHFITQCMRKQPKERPAPEELMGHPFIV
  QFNDGNAAVVSMWVCRALEERRSQQGPP

• Sequence length: 448

Pathways

KEGG:

MAPK signaling pathway
Gap junction
Neurotrophin signaling pathway
Oxytocin signaling pathway
Fluid shear stress and atherosclerosis

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
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMPHETAMINE OR RELATED ACTING SYMPATHOMIMETIC ABUSE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMPHETAMINE-RELATED DISORDERS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BODY WEIGHT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL ADENOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART FAILURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MORBID OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOVEMENT DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERIODIC LIMB MOVEMENT DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POSTERIOR CORTICAL ATROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESTLESS LEGS SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	25855966		★☆☆☆☆ Found in Text Mining only
Adult Medulloblastoma	Medulloblastoma	BEFREE	15994942		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	28596290, 28683849, 31005259		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	24436253		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety disorder	Pubtator	24436253	Associate	★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	24436253		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety disorder	Pubtator	24436253	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	12219026, 15378007, 23950888, 27878304, 29713055		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	19087274, 35609325	Associate	★☆☆☆☆ Found in Text Mining only
Cap Myopathy	Cap myopathy	Pubtator	23321517	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	21861603, 22458985, 27160304, 39972514	Associate	★☆☆☆☆ Found in Text Mining only
Cervical Intraepithelial Neoplasia	Cervical Intraepithelial Neoplasia	BEFREE	17143621		★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	15994942		★☆☆☆☆ Found in Text Mining only
Cholelithiasis	Cholelithiasis	BEFREE	28799434		★☆☆☆☆ Found in Text Mining only
Chronic kidney disease stage 5	Kidney Disease	BEFREE	21572129		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	25855966, 27144434		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	21861603, 27160304		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	21861603, 22458985	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	27160304	Stimulate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	24436253		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive disorder	Mental Depression	PSYGENET_DG	24436253		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder	Major depressive disorder	Pubtator	24436253	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive Disorder Major	Major depressive disorder	Pubtator	24436253	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	28812028	Associate	★☆☆☆☆ Found in Text Mining only
Gilles de la Tourette syndrome	Tourette Syndrome	BEFREE	19822783		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	36968222	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	36968222	Associate	★☆☆☆☆ Found in Text Mining only
Hypertension Pulmonary	Pulmonary hypertension	Pubtator	11282888	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure, Chronic	Kidney Failure	BEFREE	21572129		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	21820407		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	27160304	Stimulate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	15378007, 23950888, 27878304, 29713055		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	12618764, 15805119, 17406359, 18071319		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	15378007, 28153789, 29713055		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	25855966, 27144434		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	15994942		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	24436253		★☆☆☆☆ Found in Text Mining only
Mesothelioma	Mesothelioma	BEFREE	17872495		★☆☆☆☆ Found in Text Mining only
Metastatic Prostate Carcinoma	Metastatic Prostate Carcinoma	BEFREE	12618764		★☆☆☆☆ Found in Text Mining only
Motion Sickness	Motion Sickness	GWASCAT_DG	25628336		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17143621, 25855966, 27160304		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	31005259		★☆☆☆☆ Found in Text Mining only
Nonmedullary Thyroid Carcinoma	Nonmedullary thyroid carcinoma	BEFREE	30132833		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	22041983, 22594783, 25637721, 26800887		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	Pubtator	22513296, 22594783, 23539184, 24626232, 26449484, 26800887, 27421018, 29220676, 29666371	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	GWASDB_DG	23563607		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	GWASCAT_DG	23563607		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoporosis	Osteoporosis	Pubtator	34142171	Associate	★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	39972514	Associate	★☆☆☆☆ Found in Text Mining only
Pediatric Obesity	Childhood obesity	BEFREE	25637721		★☆☆☆☆ Found in Text Mining only
Polycystic Kidney Diseases	Polycystic kidney disease	BEFREE	23097114		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	12618764, 15805119, 17406359, 18071319		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	LHGDN	12618764		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	15805119, 17406359, 23321517	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Restless Legs Syndrome	Restless Legs Syndrome	BEFREE	17637780, 18081164, 19279021, 21572129, 21925394, 24436253, 28329290, 29422930, 30111810		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Restless Legs Syndrome	Restless Legs Syndrome	GWASCAT_DG	17637780, 21779176, 29029846		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Restless Legs Syndrome	Restless Legs Syndrome	GWASDB_DG	17637780, 21779176		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Restless Legs Syndrome	Willis-ekbom disease	Pubtator	19279021, 21572129, 21925394, 24436253, 25817513, 30111810	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tremor	Tremor	Pubtator	25817513	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	31464004		★☆☆☆☆ Found in Text Mining only
Vascular Diseases	Vascular Diseases	BEFREE	20551324		★☆☆☆☆ Found in Text Mining only