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NCBI Gene PubMed Count 62
PubMed Score 131.28
PubTator Score 88.03

Knowledge Summary

Patent (12,571)


  Differential Expression (15)

Gene RIF (55)

27082544 Single nucleotide polymorphisms STK39 and WNK1 were associated with hypertension and BP in our multicenter Belgian case-control study
26673921 SPAK and OSR1 are both stimulators of Kir2.1 activity.
26662444 STK39 mRNA and protein express abnormally in primary hypertension patients with genetic variation, which is related to the blood pressure.
26584301 SPAK protein has both the potential to up-regulate KCNQ1/E1 protein abundance in the cell membrane, an effect possibly participating in the regulation of cell volume, excitability, epithelial transport and metabolism.
26506223 SPAK and OSR1 are powerful stimulators of the intestinal Na+-coupled phosphate co-transporter NaPi-IIb
26469904 These findings suggested that the STK39 rs1955337 TT genotype is a risk factor for Han-Chinese patients with PD in Taiwan
26416847 Findings indicate that the serine threonine kinase 39 (STK39) mRNA expression is increased in rs3754777 knockin cell lines.
26233565 SPAK and OSR1 are powerful negative regulators of the excitatory glutamate transporters EAAT1 and EAAT2.
26112741 SPAK and OSR1 are negative regulators of EAAT3 activity
25994507 These observations establish that the CCT domain plays a crucial role in controlling SPAK activity and BP.
25531585 Both, SPAK and OSR1, are negative regulators of the creatine transporter SLC6A8
25515571 WNK 1, 3, 4, OSR1, and SPAK signaling system known to play a role in regulating the phosphorylation status, and hence activity of the CCCs in other tissues, is also present in the rat and human lenses.
25362046 study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells
25323061 SPAK and OSR1 are powerful negative regulators of the cell volume regulatory Cl- channel ClC-2
25164821 SPAK short forms in the kidney are created by aspartyl aminopeptidase (Dnpep)-mediated proteolytic cleavage
24873805 Taken together, our findings suggest the potential interactive role of STK39 gene multiple polymorphisms in the development of hypertension among northeastern Han Chinese.
24655550 SPAK may promote KCC3-mediated cervix tumor aggressiveness via the NF-kappaB/p38 MAPK/MMP2 axis.
24631562 the association of the loci rs11711441 near STK39 and sporadic Parkinson disease in the Chinese Han population is confirmed
24393035 the WNK-regulated SPAK/OSR1 kinases directly phosphorylate the N[K]CCs and KCCs, promoting their stimulation and inhibition respectively.
24312176 STK39 (rs2102808) and CCDC62/HIP1R (rs12817488) do not appear to influence PD risk.
24191005 OSR1 and SPAK integrate signals from osmosensing and survival pathways.
24133122 SPAK isoforms both inhibit NKCC1 and NKCC2 activity (cation cotransporter)that may be important in renal physiology.
23894895 Essential hypertension risk conferred by STK39 rs35929607 polymorphism *A/G) was different from that previously reported in a European population.
23759979 In Chinese children, no association of CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777 and FGF5 rs16998073 with BP/risk of hypertension.
23527223 The present meta-analysis confirms the significant association of STK39 polymorphism with susceptibility to hypertension in Europeans and East Asians.
23235358 A significant association between STK39 genetic variant rs6749447 and hypertension was found in a Finnish cohort.
23151749 study found no evidence that STK39 was associated with hypertension in the Chinese population
23034389 SPAK and OSR1, which are oftencoexpressed in cells can form functional heterodimers.
21705622 SPAK increases intestinal epithelial permeability; both SPAK-transfected Caco2-cells and SPAK transgenic mice exhibit loss of intestinal barrier function and homeostasis in inflammatory bowel disease.
21442361 our results suggest no significant assocation between any of the core autism symptom domains or the four additional previously identified familial features and the rs1807984 SNP on the STK39 gene.
21321328 Data demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms.
21317537 IRBIT opposes the effects of WNKs and SPAK by recruiting PP1 to the complex to dephosphorylate CFTR and NBCe1-B, restoring their cell surface expression, in addition to stimulating their activities
21178783 Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women.
20889219 STK39 is an independent risk factor for hypertension in men and its intragenic single nucleotide polymorphisms can interact and function in the control of blood pressure.
20889219 Observational study of gene-disease association. (HuGE Navigator)
20555294 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20442269 phosphorylation-induced activation of NKCC1 by osmotic shrinkage does not involve AMP-activated protein kinase and is likely to be due to STE20/SPS1-related proline/alanine-rich kinase activation
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20003416 STK39 expression is modified by polymorphisms acting in cis and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with blood pressure in a British Caucasian cohort
20003416 Observational study of gene-disease association. (HuGE Navigator)
19717643 SPAK loss in B-cell lymphomas promotes increased cell survival with DNA damage and provides a potential mechanism for increased resistance to genotoxic stress in cancer.
19470686 Brain WNK3 acts in tandem with SPAK, whereas renal WNK3 seems to upregulate NCCT through a SPAK-independent pathway.
19414679 Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
19343169 data suggest that SPAK, the transcription of which is regulated by hyperosmolarity, plays an important role in epithelial barrier function
19114657 variants in STK39 may influence blood pressure by increasing STK39 expression and consequently altering renal Na(+) excretion
19114657 Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
18787102 During inflammatory conditions, TNF-alpha is a key regulator of SPAK expression.
18550547 PKCdelta acts upstream of SPAK to increase activity of NKCC1 during hyperosmotic stress
18348195 evidence for linkage and association between autism and loci within the 2q24-q33 region, including at STK39
18348195 Observational study of gene-disease association. (HuGE Navigator)
18270262 The WNK1-SPAK/OSR1 signalling pathway plays a key role in controlling the phosphorylation and activity of NCC.
16950202 TNF-related apoptosis-inducing ligand down-regulation of SPAK is an important event that enhances its apoptotic effects
16669787 data establish that the CCT domain functions as a multipurpose docking site, enabling SPAK/OSR1 to interact with substrates (NKCC1) and activators (WNK1/WNK4)
16263722 WNK1 and SPAK/OSR1 mediate the hypotonic stress signaling pathway to cation-chloride-coupled cotransporters
12740379 roles in phosphorylation and activation of the Na-K-Cl cotransporter (NKCC1)

AA Sequence


Text Mined References (73)

PMID Year Title
27082544 2016 STK39 and WNK1 Are Potential Hypertension Susceptibility Genes in the BELHYPGEN Cohort.
26673921 2015 SPAK and OSR1 Sensitive Kir2.1 K+ Channels.
26662444 2015 Expression of STK39 in peripheral blood of hypertension patients and the relationship between its genetic polymorphism and blood pressure.
26584301 2015 SPAK and OSR1 Sensitive Cell Membrane Protein Abundance and Activity of KCNQ1/E1 K+ Channels.
26506223 2015 Up-Regulation of Intestinal Phosphate Transporter NaPi-IIb (SLC34A2) by the Kinases SPAK and OSR1.
26469904 2015 STK39, But Not BST1, HLA-DQB1, and SPPL2B Polymorphism, Is Associated With Han-Chinese Parkinson's Disease in Taiwan.
26416847 2015 Generation of Hypertension-Associated STK39 Polymorphism Knockin Cell Lines With the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 System.
26233565 2015 Down-Regulation of Excitatory Amino Acid Transporters EAAT1 and EAAT2 by the Kinases SPAK and OSR1.
26112741 2015 SPAK and OSR1 Sensitivity of Excitatory Amino Acid Transporter EAAT3.
25994507 2015 Critical role of the SPAK protein kinase CCT domain in controlling blood pressure.
25531585 2014 Negative regulation of the creatine transporter SLC6A8 by SPAK and OSR1.
25515571 2014 Identification of the WNK-SPAK/OSR1 signaling pathway in rodent and human lenses.
25362046 2014 Actions of the protein kinase WNK1 on endothelial cells are differentially mediated by its substrate kinases OSR1 and SPAK.
25323061 2014 Regulation of ClC-2 activity by SPAK and OSR1.
25164821 2014 Short forms of Ste20-related proline/alanine-rich kinase (SPAK) in the kidney are created by aspartyl aminopeptidase (Dnpep)-mediated proteolytic cleavage.
25064009 2014 Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
24873805 2014 Interactive contribution of serine/threonine kinase 39 gene multiple polymorphisms to hypertension among northeastern Han Chinese.
24722188 2014 Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism.
24655550 2014 SPAK mediates KCC3-enhanced cervical cancer tumorigenesis.
24631562 2014 Association analysis of STK39, MCCC1/LAMP3 and sporadic PD in the Chinese Han population.
24393035 2014 The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters.
24312176 2013 Genetic association study between STK39 and CCDC62/HIP1R and Parkinson's disease.
24191005 2013 Regulation of OSR1 and the sodium, potassium, two chloride cotransporter by convergent signals.
24133122 2013 Regulation of NKCC2 activity by inhibitory SPAK isoforms: KS-SPAK is a more potent inhibitor than SPAK2.
23894895 2013 Serene threonine kinase 39 gene single nucleotide A-G polymorphism rs35929607 is weakly associated with essential hypertension in population of Tharparkar, Pakistan.
23759979 2014 Association of common variants in/near six genes (ATP2B1, CSK, MTHFR, CYP17A1, STK39 and FGF5) with blood pressure/hypertension risk in Chinese children.
23527223 2013 STK39 polymorphism is associated with essential hypertension: a systematic review and meta-analysis.
23235358 2013 A functional variant in the serine-threonine kinase coding gene is associated with hypertension: a case-control study in a Finnish population, the Tampere adult population cardiovascular risk study.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23151749 2013 Lack of association between STK39 and hypertension in the Chinese population.
23034389 2012 Calcium-binding protein 39 facilitates molecular interaction between Ste20p proline alanine-rich kinase and oxidative stress response 1 monomers.
21705622 2011 Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice.
21442361 2012 The effect of an autism-associated polymorphism in the STK39 gene on the autism symptom domains.
21423148 2011 MO25 is a master regulator of SPAK/OSR1 and MST3/MST4/YSK1 protein kinases.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21321328 2011 Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways.
21317537 2011 IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway.
21292315 2011 Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.
21269460 2011 Initial characterization of the human central proteome.
21178783 2011 Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.
20889219 2012 STK39 is an independent risk factor for male hypertension in Han Chinese.
20555294 2010 Lack of association between polymorphisms in STK39, a putative thiazide response gene, and blood pressure response to hydrochlorothiazide.
20442269 2010 Stimulation of human and mouse erythrocyte Na(+)-K(+)-2Cl(-) cotransport by osmotic shrinkage does not involve AMP-activated protein kinase, but is associated with STE20/SPS1-related proline/alanine-rich kinase activation.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20003416 2009 STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression.
19717643 2009 Epigenetic silencing of Stk39 in B-cell lymphoma inhibits apoptosis from genotoxic stress.
19690332 2009 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19608861 2009 Lysine acetylation targets protein complexes and co-regulates major cellular functions.
19470686 2009 Renal and brain isoforms of WNK3 have opposite effects on NCCT expression.
19414679 2009 Genome-wide analysis of survival in early-stage non-small-cell lung cancer.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19343169 2009 Ste20-related proline/alanine-rich kinase (SPAK) regulated transcriptionally by hyperosmolarity is involved in intestinal barrier function.
19114657 2009 From the Cover: Whole-genome association study identifies STK39 as a hypertension susceptibility gene.
18787102 2008 Nuclear factor-kappaB is a critical mediator of Ste20-like proline-/alanine-rich kinase regulation in intestinal inflammation.
18550547 2008 PKCdelta acts upstream of SPAK in the activation of NKCC1 by hyperosmotic stress in human airway epithelial cells.
18348195 2008 An analysis of candidate autism loci on chromosome 2q24-q33: evidence for association to the STK39 gene.
18270262 2008 Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1.
18088087 2008 Phosphoproteome of resting human platelets.
17487921 2007 Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line.
17321610 2007 Cloning and characterization of a new intestinal inflammation-associated colonic epithelial Ste20-related protein kinase isoform.
17081983 2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
16964243 2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization.
16950202 2006 TRAIL-induced cleavage and inactivation of SPAK sensitizes cells to apoptosis.
16669787 2006 Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1.
16263722 2005 WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
14988727 2004 SPAK kinase is a substrate and target of PKCtheta in T-cell receptor-induced AP-1 activation pathway.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14563843 2003 Characterization of the interaction of the stress kinase SPAK with the Na+-K+-2Cl- cotransporter in the nervous system: evidence for a scaffolding role of the kinase.
12740379 2003 PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1).
11514053 2001 Androgens induce expression of SPAK, a STE20/SPS1-related kinase, in LNCaP human prostate cancer cells.
10980603 2000 SPAK, a STE20/SPS1-related kinase that activates the p38 pathway.