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FLASH GENE
Symbol SLC11A2 contributors: SGE/npt - updated : 25-09-2018
HGNC name solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2
HGNC id 10908
DNA
TYPE functioning gene
STRUCTURE 76.07 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
16 - 4164 61.3 561 - 2017 28367088
16 - 4156 - 590 - 2017 28367088
17 - 3790 - 568 - 2017 28367088
17 - 3795 - 568 - 2017 28367088
16 - 4159 - 561 - 2017 28367088
16 - 4424 - 561 - 2017 28367088
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   highly
Digestiveesophagus   highly
 mouth   highly
Endocrinepancreas   predominantly Rattus norvegicus
Lymphoid/Immunethymus   highly
Nervousbrain   highly
Reproductivefemale systemuterus  highly
 female systemplacenta  highly
 male systemtestis  highly
Respiratoryrespiratory tracttrachea  predominantly
Urinarybladder   highly
 kidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal moderately
Nervouscentral   
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunemacrophage
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 12 membrane spanning domains (TM12)
  • a N terminal cytoplasmic domain
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Slc11a2 (91.1 pc)
    homolog to murine Slc11a2 (91.9 pc)
    Homologene
    FAMILY
  • solute carrier family 11
  • proton-coupled divalent metal ion transporter family
  • NRAMP family
  • CATEGORY signaling cytokine , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • SLC11A2 not only exports iron from endosomes, but also serves to import the metal into the mitochondria
  • basic FUNCTION
  • mediating apical iron uptake into duodenal enterocyte and also transfering iron from the endosome into the cytosol via the transferrin receptor
  • playing important roles in intestinal iron absorption, erythroid iron utilization, hepatic iron accumulation, placental iron transfer, but not needed for materno-fetal iron transfer
  • involved in macrophage-specific membrane transport
  • plays a central role in the regulation of Fe as well as other metals (Howitt 2009)
  • SLC11A1, SLC11A2, are iron transporters that localize, respectively, to the early and late endosomal compartments
  • is critical for nonheme iron import
  • is the major transporter for iron entrance into mammalian cells and iron exit from endosomes during the transferrin cycle
  • SLC39A14 plays more of a role than SLC11A2 in iron overload
  • may likely play an important role in iron uptake into beta-cells of the pancreatic islets, which can be destroyed during iron overload
  • influence of cytokines on SLC11A2 iron transporter and ferritin expression in insulin-secreting cells
  • its deficiency negatively affects metabolism and life span of mature erythrocytes
  • role of SLC11A2 in mediating the neuroregenerative action of iron
  • is a major iron transporter required for iron absorption and erythropoiesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS endocytosis transport
    text
  • iron transport
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with 2 WW domain-interacting proteins, NDFIP1 and NDFIP2)
  • NDFIP1 is a critical mediator of SLC11A2 regulation particularly under iron restricted conditions
  • iron uptake induces the production of ROS, which modify SLC11A2 endocytic cycling, thus changing the iron transport activity at the apical membrane
  • NDFIP2 is a potential regulator of the iron transporter SLC11A2 in the liver
  • cell & other
    REGULATION
    induced by HIF-signaling (Hypoxia-inducible factor (HIF) signaling was induced in the intestine following acute iron deficiency in the duodenum, resulting in activation of CYBRD1 and SLC11A2 expression and an increase in iron uptake) (Shah 2009)
    inhibited by Ca2+, which is a non competitive inhibitor (not a transported substrate), explaining in part the effect of high dietary calcium on iron bioavailability (Shawki 2010)
    Other regulated by NDFIP1 (Nedd4 family-interacting protein 1), an adaptor protein that recruits E3 ligases to ubiquitinate target proteins
    SLC11A2 regulation in an isoform specific fashion can occur by ubiquitination and the events involved have implications for SLC11A2 function and disease processes
    ASSOCIATED DISORDERS
    corresponding disease(s) PIDA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     loss of function
    results in multiple biosynthetic and functional defects combined to produce the impaired iron deficiency that results in microcytic anemia
    constitutional     --low  
    simultaneous loss of both SLC11A1 and SLC11A2 iron transport activity is detrimental to the iron recycling capacity of the macrophage
    constitutional     --over  
    induces iron overload and iron overload induces osteoblast autophagy and apoptosis, thus affecting the pathological processes of osteoporosis
    constitutional       loss of function
    copper loading in SLC11A2 deficiency could induce oxidative stress and impair GABA metabolism, which promote impulsivity-like behavior
    constitutional       loss of function
    impairs erythroid differentiation and induces apoptosis of erythroid cells
    Susceptibility to Parkinson disease (PD)
    Variant & Polymorphism other C alleles of 1254T and IVS4+44C/A polymorphisms) occurred at greater frequencies in PD subjects compared with that of control
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • loss of Ndfip1 from mouse dopaminergic neurons resulted in misregulation of Dmt1 levels and increased susceptibility to iron induced death
  • Ndfip2(-/-) female mice showed an increase in Slc11a2 expression in the liver, with no change in male mice