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Identification
HMDB Protein ID HMDBP02163
Secondary Accession Numbers
  • 7647
Name CD40 ligand
Synonyms
  1. CD154 antigen
  2. CD40 ligand, membrane form
  3. CD40 ligand, soluble form
  4. CD40-L
  5. T-cell antigen Gp39
  6. TNF-related activation protein
  7. TRAP
  8. Tumor necrosis factor ligand superfamily member 5
Gene Name CD40LG
Protein Type Enzyme
Biological Properties
General Function Involved in tumor necrosis factor receptor binding
Specific Function Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and an matrix metalloproteinases (MMP) inhibitor-sensitive pathway
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
binding
cytokine receptor binding
tumor necrosis factor receptor superfamily binding
tumor necrosis factor receptor binding
protein binding
receptor binding
Process
immune system process
immune response
Cellular Location
  1. soluble form:Secreted
  2. CD40 ligand
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs CD40LG
Gene Sequence
>786 bp
ATGATCGAAACATACAACCAAACTTCTCCCCGATCTGCGGCCACTGGACTGCCCATCAGC
ATGAAAATTTTTATGTATTTACTTACTGTTTTTCTTATCACCCAGATGATTGGGTCAGCA
CTTTTTGCTGTGTATCTTCATAGAAGGCTGGACAAGATAGAAGATGAAAGGAATCTTCAT
GAAGATTTTGTATTCATGAAAACGATACAGAGATGCAACACAGGAGAAAGATCCTTATCC
TTACTGAACTGTGAGGAGATTAAAAGCCAGTTTGAAGGCTTTGTGAAGGATATAATGTTA
AACAAAGAGGAGACGAAGAAAGAAAACAGCTTTGAAATGCAAAAAGGTGATCAGAATCCT
CAAATTGCGGCACATGTCATAAGTGAGGCCAGCAGTAAAACAACATCTGTGTTACAGTGG
GCTGAAAAAGGATACTACACCATGAGCAACAACTTGGTAACCCTGGAAAATGGGAAACAG
CTGACCGTTAAAAGACAAGGACTCTATTATATCTATGCCCAAGTCACCTTCTGTTCCAAT
CGGGAAGCTTCGAGTCAAGCTCCATTTATAGCCAGCCTCTGCCTAAAGTCCCCCGGTAGA
TTCGAGAGAATCTTACTCAGAGCTGCAAATACCCACAGTTCCGCCAAACCTTGCGGGCAA
CAATCCATTCACTTGGGAGGAGTATTTGAATTGCAACCAGGTGCTTCGGTGTTTGTCAAT
GTGACTGATCCAAGCCAAGTGAGCCATGGCACTGGCTTCACGTCCTTTGGCTTACTCAAA
CTCTGA
Protein Properties
Number of Residues 261
Molecular Weight 29273.3
Theoretical pI 8.46
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 23-46
Protein Sequence
>CD40 ligand
MIETYNQTSPRSAATGLPISMKIFMYLLTVFLITQMIGSALFAVYLHRRLDKIEDERNLH
EDFVFMKTIQRCNTGERSLSLLNCEEIKSQFEGFVKDIMLNKEETKKENSFEMQKGDQNP
QIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKRQGLYYIYAQVTFCSN
REASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGVFELQPGASVFVN
VTDPSQVSHGTGFTSFGLLKL
GenBank ID Protein 37270
UniProtKB/Swiss-Prot ID P29965
UniProtKB/Swiss-Prot Entry Name CD40L_HUMAN
PDB IDs
GenBank Gene ID X68550
GeneCard ID CD40LG
GenAtlas ID CD40LG
HGNC ID HGNC:11935
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Graf D, Korthauer U, Mages HW, Senger G, Kroczek RA: Cloning of TRAP, a ligand for CD40 on human T cells. Eur J Immunol. 1992 Dec;22(12):3191-4. [PubMed:1280226 ]
  3. Hollenbaugh D, Grosmaire LS, Kullas CD, Chalupny NJ, Braesch-Andersen S, Noelle RJ, Stamenkovic I, Ledbetter JA, Aruffo A: The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. EMBO J. 1992 Dec;11(12):4313-21. [PubMed:1385114 ]
  4. Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S, Bajorath J, Grosmaire LS, Stenkamp R, Neubauer M, et al.: The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell. 1993 Jan 29;72(2):291-300. [PubMed:7678782 ]
  5. Spriggs MK, Armitage RJ, Strockbine L, Clifford KN, Macduff BM, Sato TA, Maliszewski CR, Fanslow WC: Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. J Exp Med. 1992 Dec 1;176(6):1543-50. [PubMed:1281209 ]
  6. Gauchat JF, Aubry JP, Mazzei G, Life P, Jomotte T, Elson G, Bonnefoy JY: Human CD40-ligand: molecular cloning, cellular distribution and regulation of expression by factors controlling IgE production. FEBS Lett. 1993 Jan 11;315(3):259-66. [PubMed:7678552 ]
  7. Shimadzu M, Nunoi H, Terasaki H, Ninomiya R, Iwata M, Kanegasaka S, Matsuda I: Structural organization of the gene for CD40 ligand: molecular analysis for diagnosis of X-linked hyper-IgM syndrome. Biochim Biophys Acta. 1995 Jan 2;1260(1):67-72. [PubMed:7999797 ]
  8. Pietravalle F, Lecoanet-Henchoz S, Blasey H, Aubry JP, Elson G, Edgerton MD, Bonnefoy JY, Gauchat JF: Human native soluble CD40L is a biologically active trimer, processed inside microsomes. J Biol Chem. 1996 Mar 15;271(11):5965-7. [PubMed:8626375 ]
  9. Khandekar SS, Silverman C, Wells-Marani J, Bacon AM, Birrell H, Brigham-Burke M, DeMarini DJ, Jonak ZL, Camilleri P, Fishman-Lobell J: Determination of carbohydrate structures N-linked to soluble CD154 and characterization of the interactions of CD40 with CD154 expressed in Pichia pastoris and Chinese hamster ovary cells. Protein Expr Purif. 2001 Nov;23(2):301-10. [PubMed:11676606 ]
  10. Furman MI, Krueger LA, Linden MD, Barnard MR, Frelinger AL 3rd, Michelson AD: Release of soluble CD40L from platelets is regulated by glycoprotein IIb/IIIa and actin polymerization. J Am Coll Cardiol. 2004 Jun 16;43(12):2319-25. [PubMed:15193700 ]
  11. Karpusas M, Hsu YM, Wang JH, Thompson J, Lederman S, Chess L, Thomas D: 2 A crystal structure of an extracellular fragment of human CD40 ligand. Structure. 1995 Oct 15;3(10):1031-9. [PubMed:8589998 ]
  12. Singh J, Garber E, Van Vlijmen H, Karpusas M, Hsu YM, Zheng Z, Naismith JH, Thomas D: The role of polar interactions in the molecular recognition of CD40L with its receptor CD40. Protein Sci. 1998 May;7(5):1124-35. [PubMed:9605317 ]
  13. Korthauer U, Graf D, Mages HW, Briere F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA: Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):539-41. [PubMed:7679206 ]
  14. DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G: CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993 Feb 11;361(6412):541-3. [PubMed:8094231 ]
  15. Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG, Bedell MA, Edelhoff S, Disteche CM, Simoneaux DK, et al.: CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science. 1993 Feb 12;259(5097):990-3. [PubMed:7679801 ]
  16. Macchi P, Villa A, Strina D, Sacco MG, Morali F, Brugnoni D, Giliani S, Mantuano E, Fasth A, Andersson B, et al.: Characterization of nine novel mutations in the CD40 ligand gene in patients with X-linked hyper IgM syndrome of various ancestry. Am J Hum Genet. 1995 Apr;56(4):898-906. [PubMed:7717401 ]
  17. Saiki O, Tanaka T, Wada Y, Uda H, Inoue A, Katada Y, Izeki M, Iwata M, Nunoi H, Matsuda I, et al.: Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM. J Clin Invest. 1995 Feb;95(2):510-4. [PubMed:7532185 ]
  18. Katz F, Hinshelwood S, Rutland P, Jones A, Kinnon C, Morgan G: Mutation analysis in CD40 ligand deficiency leading to X-linked hypogammaglobulinemia with hyper IgM syndrome. Hum Mutat. 1996;8(3):223-8. [PubMed:8889581 ]
  19. Lin Q, Rohrer J, Allen RC, Larche M, Greene JM, Shigeoka AO, Gatti RA, Derauf DC, Belmont JW, Conley ME: A single strand conformation polymorphism study of CD40 ligand. Efficient mutation analysis and carrier detection for X-linked hyper IgM syndrome. J Clin Invest. 1996 Jan 1;97(1):196-201. [PubMed:8550833 ]
  20. Nonoyama S, Shimadzu M, Toru H, Seyama K, Nunoi H, Neubauer M, Yata J, Och HD: Mutations of the CD40 ligand gene in 13 Japanese patients with X-linked hyper-IgM syndrome. Hum Genet. 1997 May;99(5):624-7. [PubMed:9150729 ]
  21. Seyama K, Nonoyama S, Gangsaas I, Hollenbaugh D, Pabst HF, Aruffo A, Ochs HD: Mutations of the CD40 ligand gene and its effect on CD40 ligand expression in patients with X-linked hyper IgM syndrome. Blood. 1998 Oct 1;92(7):2421-34. [PubMed:9746782 ]