Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

WNK3

contributors: mct - updated : 15-06-2014

HGNC name	WNK lysine deficient protein kinase 3
HGNC id	14543

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001002838 23 - 7573 NP_001002838 191.8 1743 brain isoform 2004 15194194 contains a short version of exon 18 (18a), and exon 22 acts in tandem with STK39 NM_020922 24 - 7744 NP_065973 198.4 1800 brain isoform 2004 15194194 contains a long version of exon 18 (18b) that has an additional 47 amino acids, and exon 22 acts in tandem with STK39 isoform 3 22 - - - - renal 2009 19470686 contains only the shorter exon 18 (18a) and lacks exon 22 C-terminal fragment of renal WNK3 is able to stimulate SLC12A3 expression points to key motifs within it being responsible for the stimulatory actions of WNK3 seems to upregulate SLC12A3 through a STK39-independent pathway

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       predominantly Digestive liver         Nervous brain       predominantly Homo sapiens Reproductive male system testis       Urinary kidney nephron     predominantly Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a short N terminus
	a catalytic domain containing a cysteine in place of a lysine in catalytic subdomain II
	the WNK kinase sequence signature within the subdomain I and II, kinase domain of WNK3 alone sufficient to increase TRPV5-mediated Ca2+ transport
	regulatory C-terminal including a highly conserved acidic motif and two coil-coil domains
	C-terminal motifs contributed by exons 18 and 22 play an important role in the actions of WNK3 isoforms on SLC12A3 , and coiled-coil domain in the C terminus of WNK3 was important to its interaction with RBFOX1

HOMOLOGY

Homologene

FAMILY	With No Lysine (K) family of protein serine/threonine kinases
	Ser/Thr family of protein kinase
	WNK kinase family

CATEGORY

enzyme , receptor membrane serine/threonine

SUBCELLULAR LOCALIZATION	plasma membrane,junction,adherens
	intracellular
	intracellular,cytoplasm,cytosolic
text	colocalizes with SLC12A2 and SLC12A4, SLC12A5 in diverse chlore-transporting epithelia and in neurons expressing ionotropic GABA(A) receptors in the hippocampus, cerebellum, cerebral cortex, and reticular activating system

basic FUNCTION	regulating the activity of SLC12A1 and SLC12A3 transporters by altering their expression at the plasma membrane
	implicated in NaCl, water, and blood pressure homeostasis, perhaps via signaling downstream of vasopressin
	being part of the Cl(-)/volume-sensing mechanism necessary for the maintenance of cell volume during osmotic stress and the dynamic modulation of GABA neurotransmission
	enhanced Ca2+ influx and Na+ current mediated by TRPV6, which is the closest homolog of TRPV5 that mediates active intestinal Ca2+ absorption
	positive regulator of the transcellular Ca2+ transport pathway
	with WNK2, WNK1, WNK4, have vital roles in the control of salt homeostasis and blood pressure
	when activated, subsequently phosphorylate and activate the related protein kinases STK39 and OXSR1
	might have a pivotal role in regulating neuronal excitability by stimulating Cl&
	8722; entry through SLC12A2 and inhibit Cl&
	8722; exit through the K/Cl co-transporter SLC12A5
	increase membrane expression of SLC12A3, SLC12A2, SLC12A1 in oocytes and also to inhibit the basolateral K-Cl transporters SLC12A4, SLC12A5, SLC12A6, SLC12A7
	an important regulator of SLC12A3 activity
	role of WNK3 in RNA processing
	modulates RBFOX1-mediated mRNA splicing by causing its subcellular relocalization
	modulates the subcellular localization of RBFOX1 in a kinase activity-dependent manner

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

WNK3/STK39 pathway involved in the regulation of SLC12A1

a component

INTERACTION

DNA

RNA

small molecule	cofactor, nucleotide,
	ATP binding
	magnesium

protein	interacting with SLC12A1, SLC12A3 (regulating the phosphorylation)
	interacting with SLC12A4, SLC12A5, SLC12A2
	interacts with WNK4 and WNK1 to regulate SLC12A3 in both human kidney cells and Xenopus oocytes
	WNK3, implicated in the control of neuronal excitability through actions on ion transport, binds RBFOX1 and inhibits its splicing activity in a kinase activity-dependent manner
	RBFOX1 differentially binds neuronal relative to nonneuronal forms of WNK3
	LINGO1 potentiates neuronal apoptosis, likely by inhibiting WNK3 kinase activity
	potential role for WNK3 on SLC12A3 expression at the plasma membrane, an effect apparently independent of the STK39 and the aldosterone-SGK1 pathway
	WNK3 is an activator of SLC12A3, and NEDD4L is an inhibitor

cell & other

REGULATION

ASSOCIATED DISORDERS

ANIMAL & CELL MODELS