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FLASH GENE

Symbol

WNK2

contributors: mct - updated : 15-06-2011

HGNC name	WNK lysine deficient protein kinase 2
HGNC id	14542

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	9q22.31      Physical location : 95.947.211 - 96.082.853
Genatlas name	[with-no-K(Lys)] kinases lysine deficient protein kinase 2
Synonym name	mitogen-activated protein kinase kinase kinase
	serogically defined colon cancer antigen 43
	antigen NY-CO-433
	protein kinase, lysine deficient 2
Synonym symbol(s)	PRKWNK2, NY-CO43, SDCAG43, RP11-165J3.2, KIAA1760, P/OKcl.13
EC.number	2.7.11.1

DNA

TYPE	functioning gene
STRUCTURE	135.64 kb     29 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006648 29 - 6834 NP_006639 - 2217 - 2001 11571656

EXPRESSION

Type	restricted

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       highly Homo sapiens Digestive intestine small intestine       Homo sapiens Adult   intestine large intestine colon     Homo sapiens Adult Nervous brain       predominantly Homo sapiens   brain forebrain cerebral cortex   highly Homo sapiens   brain limbic system hippocampus     Homo sapiens   brain diencephalon thalamus     Homo sapiens Olfactory (smell) olfactory bulb         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum       Homo sapiens Adult

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Nervous Purkinje cell Homo sapiens Nervous pyramidal cell Homo sapiens

cell lineage
cell lines	various cell lines
fluid/secretion

at STAGE

physiological period

fetal

Text	in neocortical pyramidal cells, thalamic relay cells, and cerebellar granule and Purkinje cells in the developing brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a small N-terminal domain followed by a kinase domain
	a cysteine in place of a lysine in catalytic subdomain II
	the WNK kinase sequence signature within the subdomains I and II
	regulatory C-terminal including a highly conserved acidic motif and two coil-coil domains

HOMOLOGY

Homologene

FAMILY	MEKK protein kinase family
	Ser/Thr protein kinase family
	WNK (with-no-lysine [K]) subfamily of protein kinases

CATEGORY

enzyme , antigen , receptor membrane serine/threonine

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm

basic FUNCTION	cytoplasmic serine-threonine kinase containing cysteine in place of the lysine found at the conserved ATP-binding location in subdomain II of protein kinases
	involved in the modulation of growth factor-induced cancer cell proliferation through the MAP2K1/ERK1/2 pathway
	candidate tumor suppressor gene, having potentially a coordinated activity of WNK kinases in the regulation of cell proliferation
	cell growth regulator that modulates activation of the ERK1/2 protein kinase and is epigenetically silenced in gliomas
	controls a RhoA-mediated cross-talk mechanism that regulates the efficiency with which MAP2K1 can activate ERK1/2 upon growth factor stimulation
	with WNK1, WNK3, WNK4, have vital roles in the control of salt homeostasis and blood pressure
	negatively regulate epidermal growth factor receptor signaling via inhibition of MAP2K1
	role for WNK2 in the regulation of SLC12A2, SLC12A5 in the mammalian brain, with implications for both cell volume regulation and/or GABAergic signaling
	might activate SLC12A2 indirectly via STK39
	control GTP-loading of RAC1, a signalling guanosine triphosphatase involved in cell migration and motility
	tumour-suppressing role of WNK2 that is related to RAC1 signalling and tumour cell invasion and proliferation
	important role for WNK2 in the control of glia-derived cell migration and tumorigenic growth

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

forms a protein complex in the mammalian brain with STK39, a known phosphoregulator of SLC12A2

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP binding

protein

promotes Cl- accumulation by reciprocally activating SLC12A2 and inhibiting SLC12A5 in a kinase-dependent manner

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   aberrantly methylated in 83p100 and 71p100 of grade II and III meningiomas, respectively tumoral     --low   by promoter methylation in 17.5 p100 of adult gliomas

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS