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FLASH GENE
Symbol STEAP4 contributors: mct - updated : 04-06-2014
HGNC name STEAP family member 4
HGNC id 21923
Location 7q21.12      Physical location : 87.905.749 - 87.936.209
Synonym name
  • tumor necrosis factor, alpha-induced protein 9
  • tumor necrosis-alpha-induced adipose-related protein
  • six transmembrane prostate protein 2
  • six-transmembrane epithelial antigen of prostate 4
    • Synonym symbol(s) FLJ23153, TIARP, TNFAIP9, STAMP2, DKFZp666D049
    EC.number 1.16.1.-
    DNA
    TYPE functioning gene
    STRUCTURE 30.48 kb     5 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 4488 - 459 - -
    4 - 3960 - 283 - -
    6 - 4587 - 459 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Reproductivefemale systemplacenta  highly
     female systemuterus  highly
     male systemprostate  highly Homo sapiens
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic Homo sapiens
    not specificadipocyte Homo sapiens
    Reproductiveepithelial cell Homo sapiens
    Skeletonosteoclast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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