CD38

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CD38
Protein CD38 PDB 1yh3.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCD38, ADPRC1, ADPRC 1, CD38 molecule
External IDsOMIM: 107270 MGI: 107474 HomoloGene: 1345 GeneCards: CD38
EC number2.4.99.20
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for CD38
Genomic location for CD38
Band4p15.32Start15,778,275 bp[1]
End15,853,230 bp[1]
RNA expression pattern
PBB GE CD38 205692 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001775

NM_007646

RefSeq (protein)

NP_001766

NP_031672

Location (UCSC)Chr 4: 15.78 – 15.85 MbChr 5: 43.87 – 43.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase is a glycoprotein[5] found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling.[6]

In humans, the CD38 protein is encoded by the CD38 gene which is located on chromosome 4.[7][8]

Function[edit]

CD38 is a multifunctional ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose (cADPR) from NAD+ to ADP-ribose in addition to synthesis of NAADP from NADP+.[9] These reaction products are essential for the regulation of intracellular Ca2+.[10]

Clinical significance[edit]

The loss of CD38 function is associated with impaired immune responses, metabolic disturbances, and behavioral modifications including social amnesia possibly related to autism.[10][11]

The CD38 protein is a marker of cell activation. It has been connected to HIV infection, leukemias, myelomas, solid tumors, type II diabetes mellitus and bone metabolism, as well as some genetically determined conditions.

CD38 produces an enzyme which regulates the release of oxytocin within the central nervous system.[11]

Daratumumab which targets CD38 has been used in treating multiple myeloma.[12][13]

Increased expression of CD 38 in chronic lymphocytic leukemia is an associated with shorter time to progression.[14]

Application[edit]

CD38 has been used as a prognostic marker in leukemia.[15] CD38 is also use as a target for daratumumab (Darzalex), a medicine that has been approved for the treatment of multiple myeloma.

The use of Daratumumab can interfere with pre transfusion tests, as CD38 is expressed on the surface of red cells. Thus, the screening for irregular antibodies can be possitive and also the direct immunoglobulin test. This can be sidelined by the treating cells with dithiothreitol (DTT)

Animal studies[edit]

A gradual increase in CD38 has been implicated in the decline of NAD+ with age.[16][17] Treatment of old mice with a specific CD38 inhibitor, 78c, prevents age-related NAD+ decline.[18]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000004468 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029084 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Orciani M, Trubiani O, Guarnieri S, Ferrero E, Di Primio R (October 2008). "CD38 is constitutively expressed in the nucleus of human hematopoietic cells". Journal of Cellular Biochemistry. 105 (3): 905–12. doi:10.1002/jcb.21887. PMID 18759251. 
  6. ^ "Entrez Gene: CD38 CD38 molecule". 
  7. ^ Jackson DG, Bell JI (April 1990). "Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation". Journal of Immunology. 144 (7): 2811–5. PMID 2319135. 
  8. ^ Nata K, Takamura T, Karasawa T, Kumagai T, Hashioka W, Tohgo A, Yonekura H, Takasawa S, Nakamura S, Okamoto H (February 1997). "Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): organization, nucleotide sequence and alternative splicing". Gene. 186 (2): 285–92. doi:10.1016/S0378-1119(96)00723-8. PMID 9074508. 
  9. ^ Chini EN, Chini CC, Kato I, Takasawa S, Okamoto H (February 2002). "CD38 is the major enzyme responsible for synthesis of nicotinic acid-adenine dinucleotide phosphate in mammalian tissues". The Biochemical Journal. 362 (Pt 1): 125–30. PMC 1222368Freely accessible. PMID 11829748. 
  10. ^ a b Malavasi F, Deaglio S, Funaro A, Ferrero E, Horenstein AL, Ortolan E, Vaisitti T, Aydin S (July 2008). "Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology". Physiological Reviews. 88 (3): 841–86. doi:10.1152/physrev.00035.2007. PMID 18626062. 
  11. ^ a b Higashida H, Yokoyama S, Huang JJ, Liu L, Ma WJ, Akther S, Higashida C, Kikuchi M, Minabe Y, Munesue T (November 2012). "Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38" (Submitted manuscript). Neurochemistry International. 61 (6): 828–38. doi:10.1016/j.neuint.2012.01.030. PMID 22366648. 
  12. ^ McKeage K (February 2016). "Daratumumab: First Global Approval". Drugs. 76 (2): 275–81. doi:10.1007/s40265-015-0536-1. PMID 26729183. 
  13. ^ Xia C, Ribeiro M, Scott S, Lonial S (October 2016). "Daratumumab: monoclonal antibody therapy to treat multiple myeloma". Drugs of Today. 52 (10): 551–560. doi:10.1358/dot.2016.52.10.2543308. PMID 27910963. 
  14. ^ Burgler S (2015). "Role of CD38 Expression in Diagnosis and Pathogenesis of Chronic Lymphocytic Leukemia and Its Potential as Therapeutic Target". Critical Reviews in Immunology. 35 (5): 417–32. doi:10.1615/CritRevImmunol.v35.i5.50. PMID 26853852. 
  15. ^ Deaglio S, Mehta K, Malavasi F (January 2001). "Human CD38: a (r)evolutionary story of enzymes and receptors". Leukemia Research. 25 (1): 1–12. doi:10.1016/S0145-2126(00)00093-X. PMID 11137554. 
  16. ^ Camacho-Pereira J, Tarragó MG, Chini CC, Nin V, Escande C, Warner GM, Puranik AS, Schoon RA, Reid JM, Galina A, Chini EN (June 2016). "CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism". Cell Metabolism. 23 (6): 1127–1139. doi:10.1016/j.cmet.2016.05.006. PMC 4911708Freely accessible. PMID 27304511. 
  17. ^ Schultz MB, Sinclair DA (June 2016). "Why NAD(+) Declines during Aging: It's Destroyed". Cell Metabolism. 23 (6): 965–966. doi:10.1016/j.cmet.2016.05.022. PMC 5088772Freely accessible. PMID 27304496. 
  18. ^ Tarragó MG, Chini CC, Kanamori KS, Warner GM, Caride A, de Oliveira GC, Rud M, Samani A, Hein KZ, Huang R, Jurk D, Cho DS, Boslett JJ, Miller JD, Zweier JL, Passos JF, Doles JD, Becherer DJ, Chini EN (May 2018). "+ Decline". Cell Metabolism. 27 (5): 1081–1095.e10. doi:10.1016/j.cmet.2018.03.016. PMC 5935140Freely accessible. PMID 29719225. 

Further reading[edit]

  • States DJ, Walseth TF, Lee HC (December 1992). "Similarities in amino acid sequences of Aplysia ADP-ribosyl cyclase and human lymphocyte antigen CD38". Trends in Biochemical Sciences. 17 (12): 495. doi:10.1016/0968-0004(92)90337-9. PMID 1471258. 
  • Malavasi F, Funaro A, Roggero S, Horenstein A, Calosso L, Mehta K (March 1994). "Human CD38: a glycoprotein in search of a function". Immunology Today. 15 (3): 95–7. doi:10.1016/0167-5699(94)90148-1. PMID 8172650. 
  • Guse AH (May 1999). "Cyclic ADP-ribose: a novel Ca2+-mobilising second messenger". Cellular Signalling. 11 (5): 309–16. doi:10.1016/S0898-6568(99)00004-2. PMID 10376802. 
  • Funaro A, Malavasi F (1999). "Human CD38, a surface receptor, an enzyme, an adhesion molecule and not a simple marker". Journal of Biological Regulators and Homeostatic Agents. 13 (1): 54–61. PMID 10432444. 
  • Mallone R, Perin PC (2006). "Anti-CD38 autoantibodies in type? diabetes". Diabetes/Metabolism Research and Reviews. 22 (4): 284–94. doi:10.1002/dmrr.626. PMC 2763400Freely accessible. PMID 16544364. 
  • Partidá-Sánchez S, Rivero-Nava L, Shi G, Lund FE (2007). "CD38: an ecto-enzyme at the crossroads of innate and adaptive immune responses". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology. 590: 171–83. doi:10.1007/978-0-387-34814-8_12. ISBN 978-0-387-34813-1. PMID 17191385. 
  • Jackson DG, Bell JI (April 1990). "Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation". Journal of Immunology. 144 (7): 2811–5. PMID 2319135. 
  • Dianzani U, Bragardo M, Buonfiglio D, Redoglia V, Funaro A, Portoles P, Rojo J, Malavasi F, Pileri A (May 1995). "Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120". European Journal of Immunology. 25 (5): 1306–11. doi:10.1002/eji.1830250526. PMID 7539755. 
  • Nakagawara K, Mori M, Takasawa S, Nata K, Takamura T, Berlova A, Tohgo A, Karasawa T, Yonekura H, Takeuchi T (1995). "Assignment of CD38, the gene encoding human leukocyte antigen CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase), to chromosome 4p15". Cytogenetics and Cell Genetics. 69 (1–2): 38–9. doi:10.1159/000133933. PMID 7835083. 
  • Tohgo A, Takasawa S, Noguchi N, Koguma T, Nata K, Sugimoto T, Furuya Y, Yonekura H, Okamoto H (November 1994). "Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38". The Journal of Biological Chemistry. 269 (46): 28555–7. PMID 7961800. 
  • Takasawa S, Tohgo A, Noguchi N, Koguma T, Nata K, Sugimoto T, Yonekura H, Okamoto H (December 1993). "Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP". The Journal of Biological Chemistry. 268 (35): 26052–4. PMID 8253715. 
  • Nata K, Takamura T, Karasawa T, Kumagai T, Hashioka W, Tohgo A, Yonekura H, Takasawa S, Nakamura S, Okamoto H (February 1997). "Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): organization, nucleotide sequence and alternative splicing". Gene. 186 (2): 285–92. doi:10.1016/S0378-1119(96)00723-8. PMID 9074508. 
  • Feito MJ, Bragardo M, Buonfiglio D, Bonissoni S, Bottarel F, Malavasi F, Dianzani U (August 1997). "gp 120s derived from four syncytium-inducing HIV-1 strains induce different patterns of CD4 association with lymphocyte surface molecules". International Immunology. 9 (8): 1141–7. doi:10.1093/intimm/9.8.1141. PMID 9263011. 
  • Ferrero E, Malavasi F (October 1997). "Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide+-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosyl cyclase". Journal of Immunology. 159 (8): 3858–65. PMID 9378973. 
  • Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G, Dianzani U, Stockinger H, Malavasi F (January 1998). "Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member". Journal of Immunology. 160 (1): 395–402. PMID 9551996. 
  • Yagui K, Shimada F, Mimura M, Hashimoto N, Suzuki Y, Tokuyama Y, Nata K, Tohgo A, Ikehata F, Takasawa S, Okamoto H, Makino H, Saito Y, Kanatsuka A (September 1998). "A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro". Diabetologia. 41 (9): 1024–8. doi:10.1007/s001250051026. PMID 9754820. 

External links[edit]