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FLASH GENE

Symbol

MAPK7

contributors: mct - updated : 31-08-2018

HGNC name	mitogen-activated protein kinase 7
HGNC id	6880

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	17p11.2      Physical location : 19.281.033 - 19.286.856
Synonym name	BMK1 kinase
	big MAP kinase 1
	big mitogen-activated protein (MAP) kinase
	extracellular signal regulated kinase 5
Synonym symbol(s)	ERK5, BMK1, PRKM7, ERK4
EC.number	2.7.11.24

DNA

TYPE	functioning gene
STRUCTURE	5.08 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

regionally located

between SMS-REPM and SMS-REPP

RNA

TRANSCRIPTS	type	messenger

text	possible differential mRNA splicing (PMID: 7646528)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002749 7 - 2972 NP_002740 - 816 - 2009 19089993 also called BMK1 gamma or variant 3/isoform 1 NM_139032 5 - 2780 NP_620601 - 677 - 2009 19089993 NM_139033 7 - 3183 NP_620602 - 816 - 2009 19089993 also called BMK1 alpha or variant 1/isoform 1 NM_139034 7 - 2884 NP_620603 - 816 - 2009 19089993 also called BMK1 beta or variant 4/isoform 1

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 Digestive gallbladder         Homo sapiens Nervous brain       highly Homo sapiens Fetal   brain limbic system hippocampus dentate gyrus   Mus musculus Adult

cells

System Cell Pubmed Species Stage Rna symbol Digestive hepatocyte

cell lineage	in proliferating cortical progenitor cells
cell lines
fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	placenta highly
	highly expressed in the developing nervous system

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	conserved thr-glu-tyr activation motif
	a unique long C-tail, suggesting specific mechanisms of regulation
	canonical TXY motif within the activation loop of the classical MAPKs is replaced by SEG
	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

interspecies	ortholog to murine Mapk7
	homolog to C.elegans f39h11.3

intraspecies

paralog to MAPK4

Homologene

FAMILY	protein kinase superfamily
	MAP kinase subfamily
	CMGC Ser/Thr protein kinase family

CATEGORY

enzyme , transcription factor , signaling , receptor membrane serine/threonine

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,peroxisome
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	translocates to the nucleus upon prolactin stimulation

basic FUNCTION	serine-threonine kinase, involved in the transcriptional activation of factors modulating expression of genes required for cell proliferation
	promotes the growth of hepatocellular carcinomas cells by regulating mitotic entry
	playing a role during brain development and raise the interesting possibility that extrinsic factors may instruct cortical progenitors to become neurons by activating the ERK5 pathway
	may be promting neuronal fate specification and contributing to cortical development
	negative regulator of HIF1A and angiogenesis by increasing HIF1A ubiquitination and inhibiting HIF1A activity in endothelial cells
	having a critical role for the regulation of FOS
	activated during the G2/M phases and may be involved in G2/M progression
	playing a role in integrin-mediated cell adhesion and motility in cancer cells via PTK2 signaling
	potential importance in aggressive prostate cancer
	required for AKT phosphorylation and cell survival and is crucial for endothelial cell differentiation in response to VEGFA
	MAPK4 and MAPK7 have acquired specialized functions through evolutionary diversification
	regulates muscle cell fusion through KLF transcription factors
	MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis
	novel signaling pathway regulating developmental olfactory bulb neurogenesis and olfactory behavior
	MAPK7 signaling is potentially a critical regulator of adult hippocampal neurogenesis
	MAPK7 activation exerts NFE2L2 transcriptional activation and nuclear translocation via potential protein-protein interaction in a kinase activity-dependent manner
	is an important mediator in prolactin-stimulated adult neurogenesis
	essential role in prolactin-induced adult neurogenesis in the subventricular zone (SVZ)and olfactory bulb (OB)
	is required in prolactin-induced olfactory bulb neurogenesis
	MAPK7/MAP2K5 pathway mediates fluid shear stress induced RUNX2 expression in osteoblast differentiation
	integration of MAPK7 with NFATC4 nucleo-cytoplasmic shuttling and PKA activation in adipocyte signaling
	is a mediator of cancer-associated inflammation in the setting of epidermal carcinogenesis
	proinflammatory role for MAPK7 in primary human endothelial cells and monocytes
	multiple critical functions for MAPK7 in controlling embryonic stem cells (ESCs) identity
	plays an essential role in the gestational augmentation of pancreatic beta-cell proliferation

CELLULAR PROCESS	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

	activation of MAP2K5/MAPK7 signaling strongly inhibits endothelial cells migration and results in massive morphological changes
	novel PAK-MAPK4/MAPK7-MAPKAPK5 signaling pathway
	PTK6-BCAR1-MAPK7 signaling cascade plays an important role in cancer cell migration and invasion
	YAP1 promotes myogenic differentiation via the MAP2K5-MAPK7 pathway

a component

MAPK7 pathway mediates DLGs cell cycle dependent phosphorylation, which likely to have important implications in the correct timely mitotic entry and mitosis progression

INTERACTION

DNA

RNA

small molecule

protein	MEK5, actin
	binding YWHAB(demonstrate an inhibitory function and regulatory mechanism for BMK1)
	critical target of PTK2 in cell adhesion signaling
	PRKCZ binds and phosphorylates MAPK7, thereby decreasing NOS3 protein stability and contributing to early events of atherosclerosis
	MAP5K5 activates MAPK7 and induces KLF4 to modulate TNF responses in dermal microvascular endothelial cells
	CCL19 stimulation of na
	ve T cells regulates expression of MAPK7, KLF2, and S1PR1
	is a newly identified mediator of TLR2 signaling, and TLR2 signaling pathways differ in ECs and monocytes
	MAPK7 interacts with NFE2L2 to induce its nuclear translocation and transcriptional activity
	activation of the MAPK7/MAP2K5 pathway with CSF1R is required for osteoclast differentiation, which may induce differentiation through the induction of FOS
	TNFSF13B activation of the MAPK7 MAP kinase pathway regulates B cell survival
	MAPK7 mediates proinflammatory responses in primary human cells in response to stimulation of TLR2
	ANKRD1 is a MAPK7-dependent and ERK1/2-independent gene
	specific interactions between YAP1 and proteins in the ERK5 pathway, such as MEK kinase 3 (MAP3K3) and MAPK7
	MAPK7 regulation of PPARGC1A is critical for cardiac mitochondrial function

cell & other

REGULATION

activated by

tyrosine and threonine phosphorylation

Phosphorylated by

PAK1, PAK2, PAK3 on Ser-186

Other

activity regulated by insulin and angiotensin II

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     in Smith-Magenis syndrome tumoral   amplification     in hepatocellular carcinoma tumoral     --over   might contribute to ovarian cancer metastasis through up-regulating type II collagen expression ( might contribute to ovarian cancer metastasis through up-regulating type II collagen expression

Susceptibility

Variant & Polymorphism other

Candidate gene
Marker	MAPK7 and MAP2K4 could be good markers in assessing response to treatment and development of osteosarcoma
	may be a new prognostic marker in clear cell renal cell carcinoma owing to its relationship with metastasis and more advanced stages
Therapy target
	System Type Disorder Pubmed cancer digestive liver cancer bone   may be a new therapeutic target in invasive osteosarcoma expressing MMP9 diabete type 1   may be a promising target for increasing beta-cell mass in diabetes patients cardiovascular cardiomyopathy   maintenance of cardiac MAPK7 is a therapeutic approach for cardiomyopathy prevention and/or treatment cancer reproductive ovary may be a potential therapeutic target in the clinical treatment for ovarian cancer immunology inflammatory   is a potential therapeutic target in diverse disorders that cause inflammatory critical illness cardiovascular atheroma   Molecules that upregulate ERK5 and its signaling in macrophages may be good drug targets for suppressing cardiovascular diseases

ANIMAL & CELL MODELS

	Erk4-deficient mice are viable and fertile and exhibit no gross morphological or physiological anomalies
	conditional deletion of the erk5 gene in mouse neural stem cells during development reduces the number of GABAergic interneurons in the main olfactory bulb (OB)