STK39 serine threonine kinase 39 [Homo sapiens] - Gene

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Summary

Official Symbol: STK39provided by HGNC
Official Full Name: serine threonine kinase 39provided by HGNC
Primary source: HGNC:17717
See related: Ensembl:ENSG00000198648; HPRD:09627; MIM:607648; Vega:OTTHUMG00000133745
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DCHT; PASK; SPAK; DKFZp686K05124
Summary: This gene encodes a serine/threonine kinase that is thought to function in the cellular stress response pathway. The kinase is activated in response to hypotonic stress, leading to phosphorylation of several cation-chloride-coupled cotransporters. The catalytically active kinase specifically activates the p38 MAP kinase pathway, and its interaction with p38 decreases upon cellular stress, suggesting that this kinase may serve as an intermediate in the response to cellular stress. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 2q24.3

Sequence :: Chromosome: 2; NC_000002.11 (168810530..169104105, complement)

See STK39 in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

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.
Title: Overexpression of Ste20-related proline/alanine-rich kinase exacerbates experimental colitis in mice.
Data demonstrate that hypotonic low-chloride conditions that activate the WNK1-SPAK and OSR1 pathway promote phosphorylation of NKCC2 isoforms.
Title: Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways.
Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women.
Title: Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.
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
Title: IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway.
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
Title: 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.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Lack of association between polymorphisms in STK39, a putative thiazide response gene, and blood pressure response to hydrochlorothiazide.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
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
Title: STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression.
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.
Title: Epigenetic silencing of Stk39 in B-cell lymphoma inhibits apoptosis from genotoxic stress.
Brain WNK3 acts in tandem with SPAK, whereas renal WNK3 seems to upregulate NCCT through a SPAK-independent pathway.
Title: Renal and brain isoforms of WNK3 have opposite effects on NCCT expression.

Submit: New GeneRIF Correction See all (23)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

From the Cover: Whole-genome association study identifies STK39 as a hypertension susceptibility gene.

Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.

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Products	Interactant	Other Gene	Source	Pubs	Description
Q9UEW8	Q16539	MAPK14	HPRD	PubMed
Q9UEW8	P02686	MBP	HPRD	PubMed
Q9UEW8	Q04759	PRKCQ	HPRD	PubMed
Q9UEW8	Q969Z4	RELT	HPRD	PubMed
Q9UEW8	Q13621	SLC12A1	HPRD	PubMed
Q9UEW8	P55011	SLC12A2	HPRD	PubMed
Q9UEW8	Q9UHW9	SLC12A6	HPRD	PubMed
Q9UEW8	Q96J92	WNK4	HPRD	PubMed
BioGRID:118159	BioGRID:114984	AATK	BioGRID	PubMed	Two-hybrid
BioGRID:118159	BioGRID:109189	GSN	BioGRID	PubMed	Two-hybrid
BioGRID:118159	BioGRID:116022	HSPH1	BioGRID	PubMed	Two-hybrid
BioGRID:118159	BioGRID:107819	MAPK14	BioGRID	PubMed	Affinity Capture-Western
BioGRID:118159	BioGRID:110325	MBP	BioGRID	PubMed	Biochemical Activity
BioGRID:118159	BioGRID:114782	OTOF	BioGRID	PubMed	Two-hybrid
BioGRID:118159	BioGRID:112447	SLC12A2	BioGRID	PubMed	Two-hybrid
BioGRID:118159	BioGRID:118159	STK39	BioGRID	PubMed	Biochemical Activity
BioGRID:118159	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:118159	BioGRID:122421	WNK4	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
ATP binding	NAS Non-traceable Author Statement more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein kinase binding	IEA Inferred from Electronic Annotation more info
receptor signaling protein serine/threonine kinase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
positive regulation of potassium ion transport	IEA Inferred from Electronic Annotation more info
protein phosphorylation	NAS Non-traceable Author Statement more info	PubMed
response to stress	NAS Non-traceable Author Statement more info	PubMed
signal transduction by phosphorylation	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
apical plasma membrane	IEA Inferred from Electronic Annotation more info
basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
cytoplasm	NAS Non-traceable Author Statement more info	PubMed
cytoskeleton	IEA Inferred from Electronic Annotation more info
membrane fraction	IEA Inferred from Electronic Annotation more info
nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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

Names: STE20/SPS1-related proline-alanine-rich protein kinase; STE20/SPS1 homolog; ste-20-related kinase; Ste20-like protein kinase; small intestine SPAK-like kinase; serine/threonine-protein kinase 39; proline-alanine-rich STE20-related kinase; serine threonine kinase 39 (STE20/SPS1 homolog, yeast)

NP_037365.2

EC 2.7.11.1

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NCBI Reference Sequences (RefSeq)

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_013233.2 → NP_037365.2 STE20/SPS1-related proline-alanine-rich protein kinase

Status: REVIEWED

Source sequence(s)

AC016723, AF099989, BF516344

Consensus CDS

CCDS42770.1

UniProtKB/Swiss-Prot

Q9UEW8

Related

ENSP00000348278, OTTHUMP00000165175, ENST00000355999, OTTHUMT00000258112

Conserved Domains (3) summary

cd06610
Location:61 – 337
Blast Score: 1370

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

smart00220
Location:63 – 337
Blast Score: 699

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam12202
Location:452 – 483
Blast Score: 112

OSR1_C; Oxidative-stress-responsive kinase 1 C terminal

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p5 Primary Assembly

Range

168810530..169104105, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

160690590..160918691, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC016723.11	AAY15003.1
genomic	AC017069.12	AAY14897.1
genomic	AC067940.5	AAY24032.1
genomic	BX648046.1	None
genomic	CH471058.2	EAX11304.1
genomic	DQ537524.1	ABG34553.1
mRNA	AF017635.1	AAB70552.1
mRNA	AF030403.1	AAD01901.1
mRNA	AF099989.1	AAC72238.1
mRNA	AK126343.1	None
mRNA	BC146813.1	None
mRNA	BF516344.1	None
mRNA	BX647113.1	None
other-genetic	BC166614.1	AAI66614.1