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FLASH GENE
Symbol MAPK7 contributors: mct - updated : 31-08-2018
HGNC name mitogen-activated protein kinase 7
HGNC id 6880
RNA
TRANSCRIPTS type messenger
text possible differential mRNA splicing (PMID: 7646528)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
7 - 2972 - 816 - 2009 19089993
also called BMK1 gamma or variant 3/isoform 1
5 - 2780 - 677 - 2009 19089993
7 - 3183 - 816 - 2009 19089993
also called BMK1 alpha or variant 1/isoform 1
7 - 2884 - 816 - 2009 19089993
also called BMK1 beta or variant 4/isoform 1
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivegallbladder     Homo sapiens
Nervousbrain   highly Homo sapiensFetal
 brainlimbic systemhippocampusdentate gyrus  Mus musculusAdult
cells
SystemCellPubmedSpeciesStageRna symbol
Digestivehepatocyte
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
  • 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    cancerbone 
    may be a new therapeutic target in invasive osteosarcoma expressing MMP9
    diabetetype 1 
    may be a promising target for increasing beta-cell mass in diabetes patients
    cardiovascularcardiomyopathy 
    maintenance of cardiac MAPK7 is a therapeutic approach for cardiomyopathy prevention and/or treatment
    cancerreproductiveovary
    may be a potential therapeutic target in the clinical treatment for ovarian cancer
    immunologyinflammatory 
    is a potential therapeutic target in diverse disorders that cause inflammatory critical illness
    cardiovascularatheroma 
    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)