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FLASH GENE
Symbol PLSCR1 contributors: mct - updated : 21-10-2019
HGNC name phospholipid scramblase 1
HGNC id 9092
Location 3q24      Physical location : 146.232.967 - 146.262.628
Synonym name
  • ca(2+)-dependent phospholipid scramblase 1
  • erythrocyte phospholipid scramblase
  • Synonym symbol(s) MMTRA1B, SCR
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text component of a cluster with PLSCR2 and PLSCR4
    STRUCTURE 29.63 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure a single IFN-stimulated response element in the first exon
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1976 - 318 - 2017 28372945
    8 - 1898 - 311 - 2017 28372945
    7 - 1720 - 237 - 2017 28372945
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
     thymus    
    Cardiovascularheart    
    Digestiveintestinelarge intestinecolon  
     liver    
    Endocrinepancreas    
    Reproductivefemale systemuterus   
     male systemtestis   
     male systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectiveadipose  highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticerthrocyte
    Blood/Hematopoieticplatelet
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal proline-rich domain is required for scrambling activity
  • three leucine repeats
  • a long N terminal cytoplasmic domain, proline rich N terminal domain with multiple PXXP motifs and a PPXY motif located near the N terminus, implying the potential for interaction with SH3 or WW domain-containing protein
  • a transmembrane region
  • two CTH peptides (288-306 and 288-318) show that they insert through phospholipid bilayers and that the presence of cholesterol improves their affinity for lipid vesicles
  • a Ca2+ binding motif that is a novel type of Ca2+ binding motif , and a single EF-hand-like Ca(2+)-binding motif
  • a short extracellular tail
  • contains an amino acid segment at the C-terminal region that shows a remarkable affinity for cholesterol, although it lacks the CRAC sequence , and also a C-terminal helix (CTH), required for membrane insertion and Ca(2+) coordination and also playing an important role in the functional conformation of PLSCR1
  • conjugated LipoP
    HOMOLOGY
    interspecies homolog to murine Plscr1
    homolog to Drosophila cg6590
    homolog to C.elegans zk1053.5
    Homologene
    FAMILY
  • phospholipid scramblase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text type II membrane protein
    basic FUNCTION
  • mediating maybe accelarated ATP-independent bidirectional transbilayer migration of phospholipids upon binding Ca2+
  • facilitate the translocation of aminophospholipids from the inner to the exterior leaf of the cell membrane
  • endofacial membrane protein, which is proposed to mediate the bidirectional movement of plasma membrane phospholipids during proliferation and apoptosis
  • physiologic regulator of PLAC8, with a functional interdependence between PLAC8 and PLSCR1
  • positive intracellular acute phase protein with a tissue-specific mechanism for up-regulation
  • may play a central role in the initiation of fibrin clot formation,in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system
  • possible role in nuclear transcription and may be contributing to post transcriptional effector pathway(s) mediating the cellular response to EGF
  • Ca(2+)-dependent endofacial plasma membrane protein, which is tyrosine-phosphorylated in activated cells
  • novel amplifier of MS4A2 signaling that acts selectively on the LYN-initiated LAT/PLCG1/calcium axis, resulting in potentiation of a selected set of mast cell responses
  • may, in part, contribute to the prothrombotic tendency in systemic lupus erythematosus
  • PLSCR1 prolongs the mitotic expansion of granulocyte precursors during CSF3-induced granulopoiesis
  • role of specific lipid reorganization and calcium-dependent PLSCR1 activity in neuroendocrine compensatory endocytosis
  • intrinsic membrane protein catalyzing transbilayer phospholipid transfer in the absence of ATP
  • mediate bidirectional scrambling of phospholipids in a Ca(2+)-dependent manner
  • role of PLSCR1 in negatively regulating trophoblast fusion
  • Ca2+-dependent protein known to scramble phospholipids in the plasma membrane resulting in loss of membrane asymmetry
  • PLSCR1 expression is regulated by low pH, providing insights into the role of PLSCR1 in cancer progression
  • protein that regulates bilayer asymmetry, and involved in altering the phospholipids of endothelial cells during hypoxia, a component of ischemia, leading to APOH and IgM binding and subsequent lipid-mediated, inflammatory responses
  • PLSCR1 positively regulates hepatic carcinoma cell proliferation and migration through interacting with MDK, thus deepening our understanding on the regulation of midkine during hepatic carcinoma growth and metastasis
  • type II endofacial membrane protein which mediates bi-directional transport of phospholipids across the plasma membrane
  • acts as a multifunctional signaling molecule rather than functioning as scramblase
  • shows a metal dependent nuclease activity which could play a role in key cellular processes
  • distributes lipids non-selectively between the cellular membrane leaflets
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • ABL
  • EGF receptor
  • adaptor protein SHC
  • interacts with the same cysteine-rich domain of PLAC8 as do AKT1 and MDM2, whereas the PLAC8-interacting domain of PLSCR1 centers around, but does not require, a previously identified palmitoylation signal
  • PLSCR1 physically interact with all known RELT family members
  • RELT family members physically interact with PLSCR1, and these interactions may regulate the phosphorylation of PLSCR1 by OXSR1
  • PLSCR1 positively regulates hepatic carcinoma cell proliferation and migration through interacting with MDK, thus deepening our understanding on the regulation of midkine during hepatic carcinoma growth and metastasis
  • MYC is a transcriptional regulator of PLSCR1
  • PLSCR1 aggravates anaphylactic reactions by increasing FCER1A-dependent mast cell degranulation
  • cell & other
    REGULATION
    induced by phosphorylation by PKC
    induced during the granulocytic differentiation of human myeloid leukemia cells
    Other regulation at the transcriptional level by IFN-alpha
    phosphorylated by EGF receptor kinase or another EGF-activated kinase
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in acute mylogenous leukemia (with poor prognosis)
    tumoral     --over  
    protein levels were significantly elevated in both the cancer tissue and plasma of colorectal carcinoma patients
    constitutional     --over  
    monocytes in antiphospholipid syndrome (APS) patients had increased PLSCR1 mRNA expression
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • might represent a noninvasive serological biomarker for the early diagnosis of Colorectal Cancer
  • Therapy target
    SystemTypeDisorderPubmed
    allergy  
    PLSCR1 could be a new therapeutic target in allergy
    ANIMAL & CELL MODELS