InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: WNK1

Summary

InnateDB Protein

IDBP-11527.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

WNK1

Protein Name

WNK lysine deficient protein kinase 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000341292

InnateDB Gene

IDBG-11521 (WNK1)

Protein Structure

UniProt Annotation

Function

Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide- sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L. {ECO:0000269PubMed:10660600, ECO:0000269PubMed:15060842}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:10660600}.

Disease Associations

Pseudohypoaldosteronism 2C (PHA2C) [MIM:614492]: An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, mild hyperchloremic metabolic acidosis in some cases, and correction of physiologic abnormalities by thiazide diuretics. {ECO:0000269PubMed:11498583}. Note=The disease is caused by mutations affecting the gene represented in this entry.Neuropathy, hereditary sensory and autonomic, 2A (HSAN2A) [MIM:201300]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2A is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves. {ECO:0000269PubMed:15060842, ECO:0000269PubMed:15911806, ECO:0000269PubMed:18521183}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed, with highest levels observed in the testis, heart, kidney and skeletal muscle. Isoform 3 is kidney-specific and specifically expressed in the distal convoluted tubule (DCT) and connecting tubule (CNT) of the nephron. {ECO:0000269PubMed:10660600, ECO:0000269PubMed:11571656, ECO:0000269PubMed:14645531, ECO:0000269PubMed:22701532}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 53 experimentally validated interaction(s) in this database.

Experimentally validated
Total	53 [view]
Protein-Protein	51 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004860	protein kinase inhibitor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019869	chloride channel inhibitor activity
GO:0019902	phosphatase binding

Biological Process

GO:0003084	positive regulation of systemic arterial blood pressure
GO:0006468	protein phosphorylation
GO:0006469	negative regulation of protein kinase activity
GO:0006811	ion transport
GO:0010923	negative regulation of phosphatase activity
GO:0018107	peptidyl-threonine phosphorylation
GO:0035556	intracellular signal transduction
GO:0048666	neuron development
GO:0050794	regulation of cellular process
GO:0090188	negative regulation of pancreatic juice secretion

Cellular Component

GO:0005737

cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR024678 Serine/threonine-protein kinase OSR1/WNK, CCT domain

PFAM

PF00069
PF07714
PF12202

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt