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FLASH GENE
Symbol LAPTM5 contributors: mct - updated : 10-07-2013
HGNC name lysosomal associated multispanning membrane protein 5
HGNC id 29612
Location 1p35.2      Physical location : 31.205.314 - 31.230.683
Synonym name
  • CD40-ligand-activated specific transcripts
  • human retinoic acid-inducible E3 protein
  • Synonym symbol(s) LAMP5, E3, MGC125860, MGC125861, CLAST6
    DNA
    TYPE functioning gene
    STRUCTURE 25.37 kb     8 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2240 27 262 - 1996 8661146
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Lymphoid/Immunelymph node   highly
     spleen   highly
     thymus   highly
     tonsils   highly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage preferentially, in hematopoietic cell
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five transmembrane domains (5TM)
  • three PY motifs (L/PPxY), which bind NEDD4-WW domains
  • and a ubiquitin-interacting motif (UIM) motif
  • polyproline-tyrosine motifs and the ubiquitin-interacting motif are required for TCR downmodulation
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY unknown/unspecified
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • membrane protein on the intracellular vesicles
  • LAPTM5 and CD1E colocalize in trans-Golgi and late endosomal compartments
  • basic FUNCTION
  • may have a special functional role during embryogenesis and in adult hematopoietic cells
  • may be involved in cellular differentiation and apoptotic pathways in certain cell types
  • negatively regulated surface TCR expression by specifically interacting with the invariant signal-transducing CD247 chain and promoting its degradation without affecting other CD3 proteins, CD3epsilon, CD3delta, or CD3gamma
  • lysosomal protein important for CD247 degradation, illustrating a unique mechanism for the control of surface TCR expression and T cell activation
  • LAPTM5-induced cell death is lysosomal cell death with impaired autophagy, not cell death by autophagy, so-called autophagic cell death
  • role for LAPTM5 in the negative regulation of cell surface BCR levels and B cell activation
  • negatively regulates the level of LAPTM5 protein through ubiquitin-mediated degradation
  • negative regulator of T and B cell receptor levels at the plasma membrane
  • acts as a positive modulator of inflammatory signaling pathways and hence cytokine secretion in macrophages
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of membrane
  • NEDD4-LAPTM5 complex recruits ubiquitinated GGA3, which binds the LAPTM5-UIM
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to ubiquitin
  • binds the ubiquitin-ligase NEDD4 and GGA3 to promote LAPTM5 sorting from the Golgi to the lysosome, an event that is independent of LAPTM5 ubiquitination
  • substrate of the ITCH-mediated degradation and its protein level is negatively regulated by ITCH
  • interacts with the NEDD4 family of ubiquitin ligases
  • interaction of LAPTM5 with CD1E, suggesting that LAPTM5 might influence the role of CD1E in the presentation of lipid antigens
  • cell & other lysosomal associated
    REGULATION
    induced by by retinoic acid
    pre-BCR signal, inducing the expression LAPTM5, which leads to the prompt downmodulation of the pre-BCR (pre-B cell receptor)
    inhibited by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    t(1;14)(p34;q32), in the multiple myeloma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • macrophages from Laptm5(-/-) mice display up-regulated levels of Tnfaip3, a ubiquitin-editing enzyme responsible for deubiquitination of Ripk1 and subsequent termination of NFKB activation