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FLASH GENE

Symbol

STK25

contributors: mct - updated : 27-03-2018

HGNC name	serine/threonine kinase 25 (STE20 homolog, yeast)
HGNC id	11404

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DEL2Q37 chromosome 2q subtelomeric deletion syndrome
Location	2q37.3      Physical location : 242.434.432 - 242.448.034
Synonym name	sterile 20 (oxidant stress response kinase 1
	yeast Sps1/Ste20-related kinase 1)
Synonym symbol(s)	SOK1, YSK1
EC.number	2.7.1.37/ 2.7.11.1

DNA

TYPE	like-sequence
STRUCTURE	15.02 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence

MAPPING

cloned

Y

linked

status

provisional

Map	cen - D2S2158 - COL4A3 - D2S396 - D2S172 - D2S206 - D2S331 - D2S2202 - D2S345 - D2S2338 - STK25 - D2S2285 - D2S125 - qter
Authors	Gene Map (98)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006374 12 - 2527 NP_006365 - 426 - 2016 26553096 NM_001282305 11 - 2556 NP_001269234 - 332 - 2016 26553096 NM_001282308 11 - 2397 NP_001269237 - 332 - 2016 26553096 NM_001271980 11 - 2296 NP_001258909 - 349 - 2016 26553096 NM_001282307 11 - 2459 NP_001269236 - 332 - 2016 26553096 NM_001271979 11 - 2358 NP_001258908 - 349 - 2016 26553096 NM_001282306 12 - 2539 NP_001269235 - 352 - 2016 26553096 NM_001271977 12 - 2589 NP_001258906 - 426 - 2016 26553096 NM_001271978 11 - 2561 NP_001258907 - 426 - 2016 26553096

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive intestine large intestine     highly   stomach       highly Nervous brain       highly Reproductive male system testis     highly Respiratory lung       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

kinase domain in N terminus

HOMOLOGY

interspecies

homolog to C.elegans f14h12.4

Homologene

FAMILY	serine/threonine kinase family, GCK III subfamily
	Ste20 superfamily of kinases

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi

basic FUNCTION	functioning in a signaling pathway required for cell migration and polarization
	play distinctly different roles in stressed versus non-stressed cells, regulating cell death in the former
	can induce cell death entering the nucleus, but this is not necessarily the only way it can kill a cell
	RELN and STK25 have opposing roles in neuronal polarization and dendritic Golgi deployment
	STK25 regulates lipid partitioning in human liver cells by controlling triacylglycerol (TAG) synthesis as well as lipolytic activity
	is a critical regulator of ectopic lipid deposition, systemic glucose, and insulin homeostasis
	multiple roles of STK25 in nonalcoholic steatohepatitis (NASH) pathogenesis
	is a critical regulator of liver steatosis, hepatic lipid metabolism and whole body glucose and insulin homeostasis
	STK25 emerges as a new regulator of the complex interplay between lipid storage, mitochondrial energetics and insulin action in skeletal muscle
	is a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle
	is a critical regulator of energy homeostasis and Nonalcoholic fatty liver disease (NAFLD) progression

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

PDCD10 can heterodimerize with GCKIII kinases (STK24, MST4, and STK25) to regulate cardiovascular development

INTERACTION

DNA

RNA

small molecule

protein	activated by the Golgi matrix protein GOLGA2 and plays a role in cell migration through its substrate YWHAZ
	STK25 regulates neuronal polarization and Golgi morphology in an antagonistic manner to DAB1
	PDCD10 interacts with STK25, an oxidant stress response kinase related to sterile-20 (Ste20) that is activated by oxidative stress and induces apoptotic cell death
	CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling
	STK26 and STK25 belong to the Ste20-like kinases and interact with PDCD10 which is closely linked to cancer diseases
	STK25 as the kinase component of STRIPAK can inhibit the function of the STRIPAK inhibitor SAV1

cell & other

REGULATION

activated by	oxidant stress and by autophosphorylation
	not activated by growth factors,alkylating agents,cytokines or environmental stress
	chemical anoxia in a caspase-independent manner, something that has not been described for any other of the GCKIII family members

ASSOCIATED DISORDERS

corresponding disease(s)

DEL2Q37

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in conditions of excess dietary fuels associates with a shift in the metabolic balance in peripheral tissues from lipid oxidation to storage, leading to a systemic insulin resistance tumoral     --over   in prostate cancer

Susceptibility

Variant & Polymorphism

Candidate gene	pseudopseudohypoparathyroidism (PPHP)
	for brachymetaphalangism and/or obesity in the del2q37 syndrome
Marker
Therapy target
	System Type Disorder Pubmed diabete     reducing STK25 function may provide a new strategy for the treatment of patients with type 2 diabetes digestive liver   reducing STK25 function may provide a new strategy for the treatment of patients with Nonalcoholic fatty liver disease (NAFLD) metabolism     potential drug target for metabolic disease

ANIMAL & CELL MODELS

	Stk25-/- mice are protected against methionine and choline-deficient (MCD) diet-induced NASH, as evidenced by repressed liver steatosis, oxidative damage, inflammation, and fibrosis, whereas Stk25 transgenic mice developed a more severe nonalcoholic steatohepatitis (NASH) phenotype, compared with corresponding wild-type littermates
	transgenic mice overexpressing STK25, when challenged with a high-fat diet, develop reduced glucose tolerance and insulin sensitivity compared to wild-type siblings