WNK1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0140694Biological processnon-membrane-bounded organelle assembly
GO_0010793Biological processregulation of mRNA export from nucleus
GO_0018105Biological processpeptidyl-serine phosphorylation
GO_0034260Biological processnegative regulation of GTPase activity
GO_0002028Biological processregulation of sodium ion transport
GO_0090263Biological processpositive regulation of canonical Wnt signaling pathway
GO_0007507Biological processheart development
GO_0045766Biological processpositive regulation of angiogenesis
GO_0045050Biological processprotein insertion into ER membrane by stop-transfer membrane-anchor sequence
GO_0007165Biological processsignal transduction
GO_0038116Biological processchemokine (C-C motif) ligand 21 signaling pathway
GO_0006811Biological processmonoatomic ion transport
GO_0010820Biological processpositive regulation of T cell chemotaxis
GO_0018107Biological processpeptidyl-threonine phosphorylation
GO_0097022Biological processlymphocyte migration into lymph node
GO_0006884Biological processcell volume homeostasis
GO_0050852Biological processT cell receptor signaling pathway
GO_0055075Biological processpotassium ion homeostasis
GO_0034115Biological processnegative regulation of heterotypic cell-cell adhesion
GO_1904062Biological processregulation of monoatomic cation transmembrane transport
GO_0035556Biological processintracellular signal transduction
GO_0003084Biological processpositive regulation of systemic arterial blood pressure
GO_0031397Biological processnegative regulation of protein ubiquitination
GO_0048666Biological processneuron development
GO_0033633Biological processnegative regulation of cell-cell adhesion mediated by integrin
GO_0030644Biological processintracellular chloride ion homeostasis
GO_0010507Biological processnegative regulation of autophagy
GO_1990869Biological processcellular response to chemokine
GO_0071474Biological processcellular hyperosmotic response
GO_0090188Biological processnegative regulation of pancreatic juice secretion
GO_1903490Biological processpositive regulation of mitotic cytokinesis
GO_1903038Biological processnegative regulation of leukocyte cell-cell adhesion
GO_0006468Biological processprotein phosphorylation
GO_1904595Biological processpositive regulation of termination of RNA polymerase II transcription
GO_1902305Biological processregulation of sodium ion transmembrane transport
GO_0055080Biological processmonoatomic cation homeostasis
GO_0035725Biological processsodium ion transmembrane transport
GO_1903077Biological processnegative regulation of protein localization to plasma membrane
GO_0072686Cellular componentmitotic spindle
GO_0016020Cellular componentmembrane
GO_0032991Cellular componentprotein-containing complex
GO_0005829Cellular componentcytosol
GO_0043232Cellular componentintracellular non-membrane-bounded organelle
GO_0005737Cellular componentcytoplasm
GO_0005634Cellular componentnucleus
GO_0106310Molecular functionprotein serine kinase activity
GO_0019901Molecular functionprotein kinase binding
GO_0004674Molecular functionprotein serine/threonine kinase activity
GO_0004672Molecular functionprotein kinase activity
GO_0030295Molecular functionprotein kinase activator activity
GO_0019902Molecular functionphosphatase binding
GO_0140693Molecular functionmolecular condensate scaffold activity
GO_0005524Molecular functionATP binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameWNK1
Protein nameSerine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1)
non-specific serine/threonine protein kinase (EC 2.7.11.1)
Alternative protein WNK1
WNK lysine deficient protein kinase 1
WNK1 protein
SynonymsHSN2
KIAA0344
PRKWNK1
KDP
DescriptionFUNCTION: Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx . WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation . The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK . Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity . Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux . Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation . Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L . Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm . Acts as a negative regulator of autophagy . Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade . May also play a role in actin cytoskeletal reorganization . Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 . Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization . .; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 . Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). .

AccessionsENST00000545285.5
ENST00000535572.5
L8EA38
H0YF81
ENST00000340908.9 [Q9H4A3-5]
A5XEH6
ENST00000676347.1
ENST00000574679.1
ENST00000537687.5 [Q9H4A3-6]
ENST00000534872.1
F6UYG0
ENST00000315939.11 [Q9H4A3-1]
H0YH68
A5XEH8
F5GWT4
ENST00000530271.6 [Q9H4A3-7]
ENST00000535698.1
ENST00000675631.1 [Q9H4A3-4]
A5XEH9
H0YFP5
ENST00000544559.1
H0YH79
ENST00000447667.2
A5D8Z4
I3L251
A5XEH7
Q9H4A3
A0A6Q8PFM0