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FLASH GENE

Symbol

MAP3K14

contributors: mct - updated : 02-01-2017

HGNC name	mitogen-activated protein kinase kinase kinase 14
HGNC id	6853

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	17q21.31      Physical location : 43.340.487 - 43.394.414
Synonym name	serine/threonine protein kinase
	NF-kappa beta-inducing kinase
Synonym symbol(s)	NIKPK, MS, NIK, MSNIK, FTDCR1B, HS, HSNIK
EC.number	2.7.11.25

DNA

TYPE	functioning gene
STRUCTURE	53.93 kb     17 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map

see MAPT

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003954 16 - 4468 NP_003945 - 947 - 2003 12853971

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 intestine small intestine     highly Lymphoid/Immune spleen       highly   thymus       highly Reproductive female system uterus cervix   highly   male system prostate     moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Lymphoid         Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to murine Map3k14 (85.0pc)
	homolog to rattus Map3k14 (85.7pc)

Homologene

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

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleolus
text	nuclear MAP3K14 is capable of activating NF-kappaB

basic FUNCTION	participating in NF-kappa-B-inducing signalling cascade common to TNF/NGF receptors family and IL1R
	involved in the constitutive activation of the alternative pathways and controlling cell proliferation in pancreatic cancer cells
	selective role in signaling by the LTBR
	component of the EGF/heregulin receptor signaling complexes
	SMG1 and MAP3K14 function as critical repressors of Smac mimetic compounds-mediated apoptosis by potentially converging on the regulation of CFLAR metabolism
	role of TRAF3 and MAP3K14 in T cell malignancies, indicating that TRAF3 differentially governs the growth of B and T cell cancers
	non-redundant role for MAP3K14 in human immune responses, demonstrating that loss-of-function mutations in MAP3K14 can cause multiple aberrations of lymphoid immunity

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

TRAF2/MAP3K14/NFKB2 pathway regulates pancreatic ductal adenocarcinoma (PDAC) cell tumorigenicity

INTERACTION

DNA

RNA

small molecule

protein	binding TRAF2, TRAF5, TRAF6, IKKA (IKBKA) and stimulating NF-kappa-B activity
	interacting with PEBP1
	interacting with RCAN1 in brain and phosphorylating it, increasing its stability and blocking its proteasomal degradation
	cooperates with MAP3K8 to trigger NF-Kappa B p65 phosphorylation
	its expression is negatively regulated by the full-length isoform of TRAF3 as formation of a MAP3K14-TRAF3-TRAF2 complex targets MAP3K14 for degradation

cell & other

REGULATION

activated by

phosphorylation and IL1

repressed by

TNAP

Other	HIV Tat can substantially enhance the capacity of MAP3K14 to accelerate degradation of IKappaB
	redox regulation of MAP3K14 by H2O2 is mechanistically important in IL-1 beta induction of NF-Kappa activation
	critical target of reactive oxygen species in NF-kappaB pathways in oral squamous carcinoma cells

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         significantly expressed in pancreatic cancer cells

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer endocrine pancreas TRAF2/MAP3K14/NFKB2 pathway could be a valuable target for therapy of this cancer

ANIMAL & CELL MODELS