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FLASH GENE

Symbol

MAP3K11

contributors: mct/ - updated : 20-05-2016

HGNC name	mitogen-activated protein kinase kinase kinase 11
HGNC id	6850

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 Digestive mouth tongue     highly   salivary gland       highly Lymphoid/Immune spleen       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES		basic
STRUCTURE

motifs/domains	glycine rich and N-terminal Src-homology 3 (SH3) domain (is autoinhibited through its SH3 domain)
	a kinase domain
	a leucine zipper
	a Cdc42/Rac interactive binding (CRIB) motif
	a catalytic domain (in MLK1 domain)
	C-terminal proline–serine–threonine rich domain, with signature sequences of both Ser/Thr and Tyr kinases in the catalytic domain

conjugated

PhosphoP

HOMOLOGY

interspecies

homolog to murine Map3k11

Homologene

FAMILY	protein kinase superfamily
	STE Ser/Thr protein kinase family
	MAP (mitogen activated protein) kinase family
	mixed-lineage kinase family

CATEGORY

enzyme , receptor membrane serine/threonine kinase

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome

basic FUNCTION	serine/threonine protein kinase that may contribute to promoting microtubule instability, a hallmark of M phase entry
	contributing to the TNF signaling pathway that activates JNK
	required for mitogen activation of BRAF and cell proliferation
	activates multiple mitogen-activated protein kinase (MAPK) pathways in response to growth factors, stresses and the pro-inflammatory cytokine, tumor necrosis factor (TNF)
	regulates the MAPKinase pathway activating ERK, MAPK14 and JNK, in response to extracellular signals
	scaffolding protein, involved in the formation of a multiprotein complex containing MAP3K11/BRAF/RAF1
	required for optimal activation of stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling by TNFA
	activates multiple MAPK pathways, including the JNK (c-Jun N-terminal kinase) pathway
	crucial requirement in the migration of invasive breast cancer cells
	induces luminal repopulation and suppresses the expression of the pro-apoptotic protein BCL2L11 in breast cancer
	having both a proliferative and antiapoptotic role in the acquisition of a malignant phenotype in mammary epithelial cells
	is an important regulator of MMP expression and invasion in ovarian cancer cells
	plays a crucial role in compromising mitochondrial integrity and functions as a proapoptotic competence factor in the early stages of cytokine-induced pancreatic beta cell death
	promotes saturated fatty acid-induced JNK activation and diet-induced metabolic dysfunction.
	mitogen-activated protein kinase kinase kinase that activates multiple mitogen-activated protein kinase pathways and has been implicated in regulating proliferation in several cell types
	is a critical factor controlling the activity of kinase networks that control the cellular responses to different concentrations of ROS

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

	JNK cascade
	MAP3K11-PIN1 signaling cascade plays a critical role in regulating the cell cycle, centrosome numbers, and oncogenesis

a component

MAP3K11-JNK-AP1 signaling is critical for breast cancer cell migration and invasion

INTERACTION

DNA

RNA

small molecule

protein	interacting specifically with the GTP bound form of RAC and CDC42, regulators of JNK pathway
	interacting with GSK3B (cell death induced by GSK3B was mediated by MAP3K11 in a manner dependent on its phosphorylation of the specific residues within the C-terminal domain by GSK3B)
	activation of MAP3K11 specifically by FGD1/CDC42 is important for skeletal mineralization
	associates with and uniquely phosphorylates S138 within the PPIase domain of PIN1
	promotes neointima formation through increased activation of the RHOA pathway in vascular smooth muscle cells
	direct interaction between PRKAA1 subunit and MAP3K11, and MAP3K11 serves as a common upstream kinase of AMPK and JNK and functions as a direct upstream kinase for AMPK independent of STK11
	serves as a common upstream kinase of PRKAA1 and JNK and functions as a direct upstream kinase for PRKAA1 independent of STK11
	ERBB2 activation inhibits the pro-apoptotic function of MAP3K11, which plays a mechanistic role in mediating anti-tumor activities of ERBB2-directed therapies

cell & other

REGULATION

activated by

phosphorylation

Other

activation of MAP3K11 specifically by FGD1/CDC42 is important for skeletal mineralization

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       in MSI gastrointestinal carcinomas tumoral     --over   in breast cancer cells

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     therapeutics that target MAP3K11 or PIN1 could prove beneficial for a subset of cancers where the MAP3K11-PIN1 pathway is dysregulated cancer reproductive breast may be an important therapeutic target for the treatment of invasive breast cancer

ANIMAL & CELL MODELS