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FLASH GENE

Symbol

STEAP4

contributors: mct - updated : 04-06-2014

HGNC name	STEAP family member 4
HGNC id	21923

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a long N-terminal tail predicted to have NADP+/NADPH oxidoreductase activity
	utilizes potentially an interdomain flavin-binding site to shuttle electrons between the oxidoreductase and transmembrane domains

HOMOLOGY

intraspecies

homolog to STAMP1

Homologene

FAMILY

six-transmembrane epithelial antigen of prostate (Steap) family proteins

CATEGORY

antigen , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
text	primarily localized to the Golgi complex, trans-Golgi network, and the plasma membrane
	also localizes to vesicular-tubular structures in the cytosol and colocalizes with the Early Endosome Antigen1 (EEA1)
	resides predominantly in endosomes and may functions as a ferrireductase in osteoclast lineage cells as it does in other cells

basic FUNCTION	may be participating in adipocyte development and metabolism and mediating some TNF alpha effects on the fat cell as a channel or a transporter
	may contribute to the normal biology of the prostate cell, as well as prostate cancer progression
	critical modulator of this integrated response system of inflammation and metabolism in adipocytes
	participating in integrating inflammatory and metabolic responses and thus playing a key role in systemic metabolic homeostasis
	acting in a similar regulatory capacity in response to acute nutritional challenges or chronic hyperglycemia
	might modulate proinflammatory and insulin resistance-inducing effects of IL1B (Kralisch 2009)
	plasma membrane metalloreductase involved in the transport of iron and copper
	transcriptional regulation of hepatic STEAP4 may play a critical role in the response to nutritional and inflammatory stress and contributes to the protective effect of STEAP4
	STEAP1, STEAP2, STEAP3, STEAP4 share an innate activity as metalloreductases, indicating their importance in metal metabolism
	STEAP4 and LCN2 mRNA and protein levels in visceral adipose tissue are related to iron status
	is a critical enzyme for cellular iron uptake and utilization in osteoclasts and, thus, indispensable for osteoclast development and function
	is a novel anti-obesity gene that is significantly down-regulated in adipose tissue of obese patients

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

may be involved in the secretory/endocytic pathways

a component

INTERACTION

DNA

RNA

small molecule

protein

TNF, IL6, and leptin, which have been implicated in insulin sensitivity regulation, regulate the expression of STEAP4

cell & other

REGULATION

activated by

IL1B in a dose- and time-dependent fashion in 3T3-L1 adipocytes (Kralisch 2009)

induced by

interleukin 6 (IL6)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in prostate cancer cells compared with normal prostate epithelial cells constitutional     --other   deficiency is sufficient to spontaneously recapitulate many cardinal features of the metabolic syndrome, including inflammation, insulin resistance, glucose intolerance, mild hyperglycemia, dyslipidemia, and fatty infiltration of liver constitutional     --over   can improve glucose uptake and mitochondrial function, and increase insulin sensitivity constitutional     --over   during osteoclast differentiation constitutional     --low   might reflect visceral adipose dysfunction in subjects with obesity and type 2 diabetes constitutional     --low   in metabolic syndrome, especially women patients, down-regulated in peripheral blood mononuclear cell, which was correlated with carotid atherosclerosis and cardiac adaptation

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	STEAP4-deficiency in mice leads to overt inflammation and development of spontaneous metabolic disease on a regular diet characterized by insulin resistance, glucose intolerance, mild hyperglycemia, dyslipidemia, and fatty liver disease (Kralisch 2009)
	loss of Steap4 expression in mice leads to increased production of inflammatory cytokines in visceral white adipose tissue and systemic insulin resistance