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FLASH GENE
Symbol CD38 contributors: mct/pgu/shn - updated : 24-04-2013
HGNC name CD38 molecule
HGNC id 1667
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a short N terminal cytoplasmic domain
  • a signal-anchor for type II membrane
  • a long C terminal extracellular domain including 10 cysteines
  • two adjacent proline residues
  • four potential N-linked glycosylation sites asparagine residues, playing a crucial role in the structure stability by preventing the formation inter-molecular cross-links
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to Cd38, Rattus norvegicus
    ortholog to Cd38, Mus musculus
    ortholog to CD38, Pan troglodytes
    intraspecies paralog to BST1
    Homologene
    FAMILY
  • ADP-ribosyl cyclase family
  • CATEGORY adhesion , enzyme , immunity/defense , antigen , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic,microsome
    intracellular,nucleus
    text
  • plasma membrane and the microsome fractions of the COS-7 cells
  • constitutively present in the nucleus of cells belonging to distinct lineages and furthermore, nuclear CD38 appears to be independent of the plasma membrane pool
  • expressed in endosomes
  • basic FUNCTION
  • acting as an ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase
  • leukocyte activation antigen involved in numerous immune functions coreceptor
  • being a coreceptor with MHC class II molecules in superantigens of viral or bacterial origine (SAG) induced proliferation of T cells
  • involved in synthesis and hydrolysis of cADP-ribose in the process of insulin secretion in pancreatic beta-cells
  • involved in the induction of apoptosis by extracellular signals
  • catalyzing the synthesis of the calcium mobilizing molecule cyclic ADP-ribose from NAD
  • play important roles in the physical function and structural stability of the proteins on cell surfaces
  • may play an important role in vivo in regulating humoral immune responses
  • has a key role in neuropeptide release, and in regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders
  • catalyzes the synthesis of second messengers and has been implicated in the regulation of a wide variety of signaling pathways
  • have dual functions not only as a receptor but also as a multifunctional enzyme,catalyzing the synthesis of and hydrolysis of a general calcium messenger molecule, cyclic ADP-ribose(cADPR)
  • undergoes dramatic structural changes to an inhibited conformation in the presence of calcium and structural changes are highly localized and occur in only two regions
  • NAD-utilizing enzyme, is capable of catalyzing the cleavage reactions through both covalent and noncovalent intermediates, depending on the substrate used
  • nuclear CD38 during different stages of hematopoietic differentiation suggests that it may play a role in the control of nuclear Ca(2+) homeostasis and NAD level
  • with BST1, are NAD(+)-consuming ectoenzymes and surface receptors
  • required for endogenous NAADP (Nicotinic acid adenine dinucleotide phosphate) generation in response to CCK stimulation
  • NAADP synthase required for coupling receptor activation to NAADP-mediated Ca2+ release from lysosomal stores in pancreatic acinar cells
  • NAADP degrading rather than a NAADP forming enzyme, perhaps avoiding desensitizing NAADP levels in intact cells
  • an essential regulator of embryonic development
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    text ADP-ribosyl cyclase and a cyclic adenosine diphosphate ribose (cADPR) hydrolase that catalyzes the synthesis and hydrolysis of cyclic adenosine diphosphate ribose
    PATHWAY
    metabolism
    signaling signal transduction
    Ca2+ signaling
    a component
  • nearly obligatory component of the cellular cascade that led to diet-induced obesity
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • NAD
  • protein
  • CD4
  • CD31
  • Lck
  • CD16
  • antigen-DR (HLA-DR) and CD9
  • c-Cbl
  • appears to be a NAADP degrading rather than a NAADP forming enzyme, perhaps avoiding desensitizing NAADP levels in intact cells
  • cell & other
    REGULATION
    activated by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)
    induced by the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)
    retinoic acid in HL-60 human myeloblastic leukemia cells
    inhibited by ATP
    repressed by oestradiol
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in B cell chronic lymphocytic leukaemia (B-CLL) with poor outcome
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • CD38-/- mice showed a complete loss of tissue-associated NAD+ glycohydrolase activity, exhibit marked deficiencies in antibody responses to T-cell-dependent protein antigens and augmented antibody responses to at least one T-cell-independent type 2 polysaccharide antigen
  • adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity
  • The plasma level of oxytocin in CD38-/- mice is strongly decreased, and depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted
  • inhibition of CD38 in Xenopus laevis abolished ADP-ribosyl cyclase activity and disrupted elongation of the anterior-posterior axis and differentiation of skeletal muscle, culminating in embryonic death