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FLASH GENE
Symbol CD38 contributors: mct/pgu/shn - updated : 24-04-2013
HGNC name CD38 molecule
HGNC id 1667
Location 4p15.32      Physical location : 15.779.930 - 15.850.706
Synonym name
  • NAD(P)+ nucleosidase
  • cell differentiation antigen CD38 (T10), identified by monoclonal antibody OKT10, HB-7
  • CD38 antigen (p45)
  • ADP-ribosyl cyclase 1
  • NAD(+) nucleosidase
  • ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase
  • cADPr hydrolase 1
  • cyclic ADP-ribose hydrolase 1
  • Synonym symbol(s) MIC16, T10
    EC.number 3.2.2.5
    DNA
    TYPE functioning gene
    STRUCTURE 70.78 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure
  • presence of a GC-rich tract immediately upstream of the initiator codon, several transcription start sites, and potential binding sites for the immunologic transcription factors T cell-specific transcription factor alpha, nuclear factor-IL-6, and interferon responsive factor-1, and absence of canonical TATA and CAAT boxes
  • MAPPING cloned Y linked N status confirmed
    Map pter - D4S1602 - D4S2362 - CD38 - D4S3048 - D4S1601 - cen
    Physical map
    LOC391634 4 similar to heat-shock protein hsp84 RAB28 4p16.1 RAB28, member RAS oncogene family BAPX1 4p16.1 bagpipe homeobox homolog 1 (Drosophila) LOC285548 4p16.1 hypothetical protein LOC285548 FLJ33215 4p16.1 hypothetical protein FLJ33215 LOC391635 4 similar to 60S ribosomal protein L21 LOC391636 4 similar to hepatocellular carcinoma-associated antigen 59 CPEB2 4p15.33 cytoplasmic polyadenylation element binding protein 2 C1QTNF7 4p15.3 C1q and tumor necrosis factor related protein 7 KIAA1345 4p15.33 KIAA1345 protein FBXL5 4p15.3-p15.2 F-box and leucine-rich repeat protein 5 LOC285550 4p15.33 hypothetical protein LOC285550 BST1 14q32.3 bone marrow stromal cell antigen 1 CD38 4p15 CD38 antigen (p45) HBP17 4p16-p15 CD38 antigen (p45) KSP37 4p16 Ksp37 protein PROM1 4p16.1-p15.2 prominin 1 FLJ90013 4p15.33 hypothetical protein FLJ90013 FLJ39653 4p15.33 hypothetical protein FLJ39653 LOC391637 4 similar to Zinc finger homeobox protein 1b (Smad interacting protein 1) (SMADIP1) (HRIHFB2411) LDB2 4p15 LIM domain binding 2 LOC391638 4 similar to 40S ribosomal protein S7 (S8) QDPR 4p15.31 quinoid dihydropteridine reductase LOC391639 4 similar to alpha NAC/1.9.2. protein LAP3 4p15.33 leucine aminopeptidase 3 EG1 4p16 leucine aminopeptidase 3 KIAA1276 4p16 KIAA1276 protein FLJ20280 4p15.33 hypothetical protein FLJ20280 HCAP-G 4p16-p15 chromosome condensation protein G MLR1 4p15.33 transcription factor MLR1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1494 46 300 - - 2319135
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly Homo sapiensAdultNM_001775
     stomachmucous gland  moderately Homo sapiensAdultNM_001775
    Endocrinepancreas   highly Homo sapiensAdultNM_001775
    Nervousbrain   highly Homo sapiensAdultNM_001775
    Urinarykidney   highly Homo sapiensAdultNM_001775
    cell lineage
  • predominantly expressed on hematopoietic cells
  • preferentially expressed at both early and late stages of the B and T-cell maturation
  • also detected on erythroid and myeloid progenitors in bone marrow, where the level of surface expression was shown to decrease during differentiation of blast-forming unit E to colony-forming unit E
  • cell lines
  • B lymphoblastic cell line Daudi and the T lymphoblastic leukemia lines HPB-ALL and MOLT-4
  • insulinomas, malignant lymphoma, NB-1 and HeLa cells
  • fluid/secretion highly in lymph, moderately in blood
    at STAGE
    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