Stk39 serine/threonine kinase 39 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Stk39provided by MGI
Official Full Name: serine/threonine kinase 39provided by MGI
Primary source: MGI:MGI:1858416
See related: Ensembl:ENSMUSG00000027030 AllianceGenome:MGI:1858416
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: DCHT; Rnl5; SPAK; RF005; Gm50618
Summary: Enables protein serine/threonine kinase activity. Involved in several processes, including intracellular chloride ion homeostasis; negative regulation of transport; and protein phosphorylation. Acts upstream of or within monoatomic ion homeostasis; regulation of blood pressure; and regulation of inflammatory response. Located in basolateral plasma membrane. Is active in apical plasma membrane and cell body. Is expressed in brain and metanephros. Used to study Gitelman syndrome and pseudohypoaldosteronism. Orthologous to human STK39 (serine/threonine kinase 39). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Broad expression in testis adult (RPKM 29.2), cerebellum adult (RPKM 12.7) and 19 other tissues See more
Orthologs: human all
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Genomic context

Location:: 2; 2 C1.3

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	2	NC_000068.8 (68040789..68302381, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	2	NC_000068.7 (68210445..68472108, complement)

Chromosome 2 - NC_000068.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Suppression of STK39 weakens the MASLD/MASH process by protecting the intestinal barrier.
Title: Suppression of STK39 weakens the MASLD/MASH process by protecting the intestinal barrier.
Gut microbiota-induced microRNA-206-3p increases anxiety-like behaviors by inhibiting expression of Cited2 and STK39.
Title: Gut microbiota-induced microRNA-206-3p increases anxiety-like behaviors by inhibiting expression of Cited2 and STK39.
Roles of WNK4 and SPAK in K(+)-mediated dephosphorylation of the NaCl cotransporter.
Title: Roles of WNK4 and SPAK in K(+)-mediated dephosphorylation of the NaCl cotransporter.
SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure.
Title: SPAK-p38 MAPK signal pathway modulates claudin-18 and barrier function of alveolar epithelium after hyperoxic exposure.
Results show that the serine/threonine-protein kinase WNK4 (WNK4)-serine/threonine-protein kinase 39 (SPAK)-NKCC1 transport protein (NKCC1) cascade plays an important role in modulating macrophage activation to regulate lipopolysaccharides (LPS)-induced lung inflammation and lung injury.
Title: WNK4-SPAK modulates lipopolysaccharide-induced macrophage activation.
SPAK KI mice are hypotensive without any differences being observed in the physical activity and heart rate.
Title: Area under the curve analysis of blood pressure reveals increased spontaneous locomotor activity in SPAK knock-in mice: relevance for hypotension induced by SPAK inhibition?
Although these results confirm that familial hyperkalemic hypertension caused by WNK1 mutations is dependent on the activation of SPAK, they suggest that WNK1 and WNK4 play different roles in the distal nephron.
Title: Consequences of SPAK inactivation on Hyperkalemic Hypertension caused by WNK1 mutations: evidence for differential roles of WNK1 and WNK4.
A previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.
Title: Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity.
Study shows that in the absence of aspartyl aminopeptidase (DNPEP), the kidney lysates retain their ability to cleave STE20/SPS1-related proline/alanine-rich kinase(SPAK), indicating that DNPEP might have been misidentified as the protease behind the kidney lysate activity, or that the aspartyl aminopeptidase might not be the only protease cleaving SPAK in kidney.
Title: DNPEP is not the only peptidase that produces SPAK fragments in kidney.
SPAK could be involved in the NO overproduction and vascular hyporesponsiveness to vasoconstrictors in endotoxic shock
Title: Effects of SPAK on vascular reactivity and nitric oxide production in endotoxemic mice.

Submit: New GeneRIF Correction See all GeneRIFs (57)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (2)
Targeted (10) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

BE107798 (e-PCR)
- UniSTS:247058

AW556857 (e-PCR)
- UniSTS:185477

NoName (e-PCR)
- UniSTS:225172

Stk39 (e-PCR), detects polymorphism
- UniSTS:547994

AW227544 (e-PCR)
- UniSTS:178632

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables kinase activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IEA Inferred from Electronic Annotation more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell volume homeostasis	IEA Inferred from Electronic Annotation more info
involved_in cell volume homeostasis	ISO Inferred from Sequence Orthology more info
involved_in cellular hyperosmotic response	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular hyperosmotic response	IEA Inferred from Electronic Annotation more info
involved_in cellular hyperosmotic response	ISO Inferred from Sequence Orthology more info
involved_in cellular hypotonic response	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular hypotonic response	ISO Inferred from Sequence Orthology more info
involved_in cellular response to chemokine	ISO Inferred from Sequence Orthology more info
involved_in cellular response to potassium ion	IDA Inferred from Direct Assay more info	PubMed
involved_in chemokine (C-X-C motif) ligand 12 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in chemokine (C-X-C motif) ligand 12 signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular chloride ion homeostasis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in intracellular signal transduction	ISO Inferred from Sequence Orthology more info
involved_in macrophage activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in maintenance of lens transparency	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within monoatomic ion homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of creatine transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of pancreatic juice secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of potassium ion transmembrane transport	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of potassium ion transmembrane transporter activity	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of potassium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of sodium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
involved_in peptidyl-serine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in peptidyl-threonine phosphorylation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in peptidyl-threonine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-threonine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in peptidyl-threonine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of T cell chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of T cell chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of T cell chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of p38MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of p38MAPK cascade	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of potassium ion transport	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein autophosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in renal sodium ion absorption	IEA Inferred from Electronic Annotation more info
involved_in renal sodium ion absorption	ISO Inferred from Sequence Orthology more info
involved_in response to aldosterone	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to dietary excess	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in cell body	IDA Inferred from Direct Assay more info	PubMed
located_in cell cortex	IEA Inferred from Electronic Annotation more info
located_in cell cortex	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: STE20/SPS1-related proline-alanine-rich protein kinase

Names: Ste-20 related kinase; kidney-specific SPAK; serine/threonine kinase 39, STE20/SPS1 homolog; serine/threonine-protein kinase 39; ste-20-related kinase

NP_001399473.1

EC 2.7.11.1

NP_001399474.1

EC 2.7.11.1

NP_001399475.1

EC 2.7.11.1

NP_001399476.1

EC 2.7.11.1

NP_001408409.1

EC 2.7.11.1

NP_001408410.1

EC 2.7.11.1

NP_058562.1

EC 2.7.11.1

XP_017174617.1

EC 2.7.11.1

XP_017174618.1

EC 2.7.11.1

XP_017174619.1

EC 2.7.11.1

XP_030107738.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001412544.1 → NP_001399473.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform 2

Status: VALIDATED

Source sequence(s)

AL844841, AL845486
NM_001412545.1 → NP_001399474.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform 3

Status: VALIDATED

Source sequence(s)

AL844841, AL845486, BX936296
NM_001412546.1 → NP_001399475.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform 4

Status: VALIDATED

Source sequence(s)

AL844841, AL845486, BX936296
NM_001412547.1 → NP_001399476.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform 5

Status: VALIDATED

Source sequence(s)

AL844841, AL845486, BX936296
NM_001421480.1 → NP_001408409.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform 6

Status: VALIDATED

Source sequence(s)

AL844841, AL845486

Related

ENSMUST00000123781.8
NM_001421481.1 → NP_001408410.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform 7

Status: VALIDATED

Source sequence(s)

AL845486, BX936296
NM_016866.3 → NP_058562.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform 1

See identical proteins and their annotated locations for NP_058562.1

Status: VALIDATED

Source sequence(s)

AL844841, AL845486, BX936296

Consensus CDS

CCDS16084.1

UniProtKB/Swiss-Prot

Q80W13, Q9Z1W9

UniProtKB/TrEMBL

A2AQL0

Related

ENSMUSP00000099776.4, ENSMUST00000102715.4

Conserved Domains (2) summary

smart00220
Location:75 → 349

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd06610
Location:73 → 349

STKc_OSR1_SPAK; Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase

RNA

NR_178213.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AL844841, AL845486, BX936296

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000068.8 Reference GRCm39 C57BL/6J

Range

68040789..68302381 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017319130.2 → XP_017174619.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform X4

Conserved Domains (2) summary

cd06610
Location:11 → 277

STKc_OSR1_SPAK; Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase

pfam12202
Location:391 → 448

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_017319129.1 → XP_017174618.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform X2

Conserved Domains (2) summary

cd06610
Location:5 → 271

STKc_OSR1_SPAK; Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase

pfam12202
Location:364 → 421

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_017319128.1 → XP_017174617.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform X1

Conserved Domains (2) summary

cd06610
Location:5 → 271

STKc_OSR1_SPAK; Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase

pfam12202
Location:385 → 442

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain
XM_030251878.2 → XP_030107738.1 STE20/SPS1-related proline-alanine-rich protein kinase isoform X5

UniProtKB/TrEMBL

G1JLS7, Q3V256

Conserved Domains (2) summary

pfam12202
Location:213 → 270

OSR1_C; Oxidative-stress-responsive kinase 1 C-terminal domain

cl21453
Location:1 → 99

PKc_like; Protein Kinases, catalytic domain