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FLASH GENE

Symbol

MAPK6

contributors: mct - updated : 16-03-2018

HGNC name	mitogen-activated protein kinase 6
HGNC id	6879

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002748 6 - 4225 NP_002739 - 721 - 2003 12915405

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel       moderately Digestive esophagus       moderately   mouth tongue     moderately   salivary gland       predominantly   stomach       moderately Hearing/Equilibrium ear       highly Nervous brain hindbrain       Reproductive female system uterus     moderately Respiratory respiratory tract trachea     highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Connective         Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol   digestive

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies

ortholog to murine Mapk6 (94.9pc)

intraspecies

homolog to MAPK4

Homologene

FAMILY	SER/THR family of protein kinases
	MAP kinase subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	translocated to the nucleus after activation

basic FUNCTION	acting as a serine/threonine kinase
	playing a pivotal role in converting tyrosine phosphorylation
	involved in TNFA and tyrosine phosphorylated in response to insulin NGF and other signals
	atypical mitogen-activated protein kinase (MAPK), which is regulated by protein stability
	phosphorylating microtubule-associated protein 2 (MAP2)
	may promote entry in the cell cycle
	contrary to most protein kinases, MAPK6 is a highly unstable protein that is subject to dynamic regulation by the ubiquitin-proteasome system

CELLULAR PROCESS	cell cycle

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

activation loop phosphorylation of MAPK4 and MAPK6 stimulates their intrinsic catalytic activity and is required for the formation of stable active complexes with MAPKAPK5 and, consequently, for efficient cytoplasmic redistribution of MAPK4/MAPK6/MAPKAPK5 complexes

INTERACTION

DNA

RNA

small molecule	metal binding, nucleotide,
	Mg2+
	ATP

protein	specific interaction between MAPK6 and MAPKAPK5 (binding results in nuclear exclusion of both MAPK6 and MAPKAPK5 and is accompanied by MAPK6-dependent phosphorylation and activation of MAPKAPK5)
	is a potential PAK2 substrate
	interacted with and phosphorylated steroid receptor NCOA3, an oncogenic protein overexpressed in multiple human cancers at serine 857 (S857)
	several new UBE3A-interacting proteins, including HIF1AN, NEURL4, and mitogen-activated protein kinase 6 (MAPK6)
	MAPK6, an atypical MAPK, phosphorylates TDP2 at S60 and regulates TDP2 phosphodiesterase activity, thereby cooperatively protecting lung cancer cells against TOP2A inhibitors-induced DNA damage and growth inhibition
	USP20 is a novel MAPK6 regulator (USP20 interacts with and deubiquitinates MAPK6 both in vitro and in intact cells)

cell & other

REGULATION

activated by	TNFA
	treatment with serum or phorbol esters in fibroblasts
	in response to BRAF signaling

Other

its phosphorylation can be modulated indirectly by interaction with the substrate MAP kinase-activated protein kinase 5 (MAPKAPK5)

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	biomarker for thyroid cancer exhibiting differences in the correlation coefficients between benign and malignant samples that indicate its discriminatory power
Therapy target
	System Type Disorder Pubmed cancer skin   potential pharmacodynamic marker for targeting BRAF signaling in melanoma

ANIMAL & CELL MODELS