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FLASH GENE

Symbol

MAPK4

contributors: mct - updated : 28-11-2012

HGNC name	mitogen-activated protein kinase 4
HGNC id	6878

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 heart         Endocrine parathyroid       highly Hearing/Equilibrium ear       highly Nervous brain

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a Thr-Xxx-Tyr motif in the activation loop, which is catalyzed by members of the MAP kinase kinase family
	canonical TXY motif within the activation loop of the classical MAPKs is replaced by SEG
	C-terminal extension responsible for its association with intact cyclin D3
	a novel MAPKAPK5 interaction motif (FRIEDE) within MAPK7, and MAPK4 essential for binding to the C-terminal region of MAPKAPK5, located within the L16 extension lying C-terminal to the CD (common docking) domain

HOMOLOGY

intraspecies

paralog to MAPK7

Homologene

FAMILY	protein kinase superfamily
	CMGC Ser/Thr protein kinase family
	mitogen-activated protein (MAP) kinase family

CATEGORY

receptor membrane tyrosine

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	shuttle between the cytoplasm and the nucleus, and selective inhibition of class I Pak kinase activity in cells promoted increased nuclear accumulation of MAPK4

basic FUNCTION	phosphorylating microtubule-associated protein 2 (MAP2)
	may promote entry in the cell cycle
	atypical mitogen-activated protein kinase having a role in in cell proliferation
	its function is essential for neonatal survival and critical for the establishment of fetal growth potential and pulmonary function
	MAPK4 and MAPK7 have acquired specialized functions through evolutionary diversification
	is a novel class I PAK substrate, further suggesting a role for PAK kinase activity in atypical MAPK signaling
	role in promoting lung cancer cell invasiveness by phosphorylating NCOA3 and regulating NCOA3 proinvasive activity by site-specific phosphorylation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

novel PAK-MAPK4/MAPK7-MAPKAPK5 signaling pathway

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

protein	interacting with CCND3
	MAPK4, an atypical mitogen-activated protein kinase (MAPK), ias a specific binding partner of CDC14A
	intimate functional relationship between the CDC14A phosphatase and the MAPK4 in signaling pathways that regulate key cell-fate decisions in human cells
	potential PAK2 substrate

cell & other

REGULATION

Phosphorylated by

PAK1, PAK2, PAK3 on Ser-189

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   highly upregulated in lung carcinomas

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer lung   may be an attractive target for therapeutic treatment of invasive lung cancer

ANIMAL & CELL MODELS

loss of Erk3 in mouse retards intrauterine growth, as reflected by a marked reduction in fetal lung, heart, and liver weights, and by low body weight at birth