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FLASH GENE
Symbol LPIN2 contributors: mct/npt - updated : 20-12-2016
HGNC name lipin 2
HGNC id 14450
Corresponding disease
RMODA Majeed syndrome
Location 18p11.32      Physical location : 2.916.992 - 3.011.945
Synonym name
  • phosphatidate phosphatase LPIN2
    • Synonym symbol(s) KIAA0249
    EC.number 3.1.3.4
    DNA
    TYPE functioning gene
    STRUCTURE 96.32 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 6245 99.3 896 - 2008 18023282
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
     liver   predominantly Homo sapiens
    Lymphoid/Immunespleen     Homo sapiens
     thymus     Homo sapiens
    Nervousbrain   highly Homo sapiens
    Respiratorylung   moderately Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
     bone marrow    Homo sapiens
    Connectiveadipose  highly
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerythrocyte Homo sapiens
    not specificadipocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • . N-LIP and C-LIP domains exhibit conservation between family members
  • P, serine residue 106, which is known to be phosphorylated in response to insulin
  • a NLS, nuclear localization signal
  • DXDXT, PAP1 enzyme active site
  • LXXIL, transcription factor interaction domain
    • mono polymer heteromer , oligo
    HOMOLOGY
    interspecies ortholog to murine Lpin2
    homolog to rattus Rn.47332
    homolog to Drosophila CG8709
    homolog to C.elegans H37A05.1
    intraspecies homolog to LPIN1
    homolog to LPIN3
    Homologene
    FAMILY
  • lipin family
  • Mg2+-dependent phosphatidate phoshatases (PAP1 enzymes)family
  • conserved haloacid dehalogenase superfamily
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    intracellular,nuclear envelope
    text lipid phosphatase enzyme at the endoplasmic reticular membrane, that can rapidly translocate within the cell
    basic FUNCTION
  • may play a role in triglyceride metabolism
  • having a distinct and non-redundant function in regulating lipid production during the cell cycle and adipocyte differentiation
  • having a role likely to carry out similar functions in glycerolipid biosynthesis and gene expression in a distinct tissue distribution
  • plays an important role as a hepatic PAP-1 enzyme
  • has transcriptional coactivator activity for peroxisome proliferator-activated receptor-response elements similar to LPIN1 and this activity is not affected by mutating the conserved serine
  • also play crucial roles in the nucleus as transcriptional regulatory proteins
  • lipin 1, 2, and 3 are bifunctional intracellular proteins that regulate metabolism by acting as coregulators of DNA-bound transcription factors and also dephosphorylate phosphatidate to form diacylglycerol
  • protective role for lipin-2 in proinflammatory signaling mediated by saturated fatty acids that occurs concomitant with an enhanced cellular capacity for triacylglycerol synthesis
  • plays potentially a key regulatory role in proinflammatory gene expression by macrophages exposed to saturated fatty acids
  • role for lipin-2 as a key participant in the regulation of proinflammatory gene expression by saturated fatty acids in macrophages
  • unique role for LPIN2 in central nervous system biology that may be particularly important with advancing age
  • phosphatidic acid phosphatase (PAP) responsible for the penultimate step of triglyceride synthesis and dephosphorylation of phosphatidic acid (PA) to generate diacylglycerol
  • LPIN2 functions likely as a constitutively active phosphatidic acid (PA) phosphatase in stark contrast to the high degree of phosphorylation-mediated regulation of LPIN1
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    triglyceride metabolism
    a component lipin proteins function as oligomeric complexes and that the three mammalian lipin isoforms can form combinatorial units
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CTDNEP1 (Lipin cellular location, protein partners, and biological function are directed by phosphorylation-dephosphorylation events catalyzed by the phosphoserine phosphatase CTDNEP1)
  • MAPK8 mediates the up-regulation of proinflammatory genes in lipin-2-deficient macrophages
  • LPIN2, a phosphatidic acid phosphatase and a co-factor of PPARGC1A is important for lipid metabolism and for suppressing autoinflammation
    • cell & other
    REGULATION
    Other dephosphorylated by CTDNEP1
    ASSOCIATED DISORDERS
    corresponding disease(s) RMODA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    result in the development of an inflammatory disorder
    constitutional       loss of function
    pathophysiology in LPIN2 deficiency is associated with dysregulation of lipid intermediates
    constitutional       loss of function
    of NF2, NIPSNAP1, UGT2B17, and LPIN2 genes during progression of a prostate epithelial cell line to a malignant metastatic state
    Susceptibility to type 2 diabetes
    Variant & Polymorphism SNP rs3745012 SNP of the LPIN2 gene is associated with type 2 diabetes and fat distribution (Aulchenko 2007)
    Candidate gene lipodystrophy
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Diet-induced obesity-triggered endoplasmic reticulum (ER) stress promotes hepatic insulin resistance in mouse models
  • similar to patients with Majeed syndrome, Lpin2-deficient mice developed anemia, but did not show evidence of osteomyelitis, suggesting that additional environmental or genetic components contribute to the bone abnormalities