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CD40 [CDw40], TNF receptor family member 5 (TNFRSF5), Bp50 or B-cell activation protein CD40

Function: - B lymphocyte activation molecule - CD40 is the receptor for CD40L or TRAP cytokine - CD40 transduces a signal inhibiting apoptosis of the cell bearing the CD40 receptor - stimulation of CD40 causes Tyr phosphorylation of multiple substrates including lyn - activates multiple serine/threonine kinases & induces phosphorylation of PLC-gamma2 & PI-3-kinase [4] - activation of CD40 by CD40L results in activation of bcl-x in B-cells inhibiting apoptosis [5] - interacts with TRAF1, TRAF2, TRAF3, TRAF5 & TRAF6 Structure: - monomer & homodimer - contains 4 TNFR-Cys repeats Compartment: - isoform 1: cell membrane - isoform 2: secreted Alternative splicing: named isoforms=2 Additional isoforms seem to exist Expression: - B cells - macrophages - dendritic cells - endothelial cells - fibroblasts - keratinocytes - plasma cells stain negatively with antibody Pathology: - expressed in: a) some carcinomas b) B cell lymphomas (most) c) B-ALL (some) - defects in CD40 are the cause of hyper-IgM immunodeficiency syndrome type 3

Related

B lymphocyte CD154; CD40 ligand; CD40-L; T-cell antigen Gp39; TNF-related activation protein; TRAP; tumor necrosis factor ligand superfamily member 5 (CD40LG, CD40L TNFSF5, TRAP) CD40 cells in blood dendritic cell epithelial cell macrophage

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein tumor necrosis factor [TNF] receptor family

Properties

SIZE: MW = 45-50 kD COMPARTMENT: plasma membrane CELL: B lymphocyte epithelial cell WITHIN: thymus dendritic cell macrophage epithelial cell MOTIF: cysteine-rich region {N-TERMINAL} MOTIF: cysteine residue {X+0} MODIFICATION: cysteine residue {X+14} cysteine residue {X+14} MODIFICATION: cysteine residue {X+0} cysteine residue {X+16} MODIFICATION: cysteine residue {X+29} cysteine residue {X+19} MODIFICATION: cysteine residue {X+34} cysteine residue {X+29} MODIFICATION: cysteine residue {X+16} cysteine residue {X+34} MODIFICATION: cysteine residue {X+19} cysteine-rich region {complement receptor type 2 COMPARTMENT: cellular membrane MOTIF: signal sequence {1-20} Sushi domain {21-659} (10) MOTIF: cysteine residue {C23} MODIFICATION: cysteine residue {C65} cysteine residue {C51} MODIFICATION: cysteine residue {C82} cysteine residue {C65} MODIFICATION: cysteine residue {C23} cysteine residue {C82} MODIFICATION: cysteine residue {C51} Sushi domain {660-716} MOTIF: cysteine residue {C662} MODIFICATION: cysteine residue {C699} N-glycosylation site {N682} cysteine residue {C685} MODIFICATION: cysteine residue {C714} cysteine residue {C699} MODIFICATION: cysteine residue {C662} cysteine residue {C714} MODIFICATION: cysteine residue {C685} Sushi domain {717-781} MOTIF: cysteine residue {C719} MODIFICATION: cysteine residue {C762} cysteine residue {C748} MODIFICATION: cysteine residue {C779} cysteine residue {C762} MODIFICATION: cysteine residue {C719} cysteine residue {C779} MODIFICATION: cysteine residue {C748} Sushi domain {786-845} MOTIF: cysteine residue {C788} MODIFICATION: cysteine residue {C830} N-glycosylation site {N800} cysteine residue {C816} MODIFICATION: cysteine residue {C843} N-glycosylation site {N823} cysteine residue {C830} MODIFICATION: cysteine residue {C788} cysteine residue {C843} MODIFICATION: cysteine residue {C816} Sushi domain {849-909} MOTIF: cysteine residue {C851} MODIFICATION: cysteine residue {C894} N-glycosylation site {N861} cysteine residue {C880} MODIFICATION: cysteine residue {C907} cysteine residue {C894} MODIFICATION: cysteine residue {C851} cysteine residue {C907} MODIFICATION: cysteine residue {C880} Sushi domain {910-970} MOTIF: N-glycosylation site {N911} cysteine residue {C912} MODIFICATION: cysteine residue {C955} cysteine residue {C941} MODIFICATION: cysteine residue {C968} cysteine residue {C955} MODIFICATION: cysteine residue {C912} cysteine residue {C968} MODIFICATION: cysteine residue {C941} transmembrane domain {972-999} Tyr phosphorylation site {Y1029}} MOTIF: cysteine residue {X+0} MODIFICATION: cysteine residue {X+14} cysteine residue {X+14} MODIFICATION: cysteine residue {X+0} cysteine residue {X+16} MODIFICATION: cysteine residue {X+29} cysteine residue {X+19} MODIFICATION: cysteine residue {X+34} cysteine residue {X+29} MODIFICATION: cysteine residue {X+16} cysteine residue {X+34} MODIFICATION: cysteine residue {X+19} cysteine-rich region {integrin alpha-M COMPARTMENT: cellular membrane MOTIF: signal sequence {1-16} FG-GAP {31-84} MOTIF: cysteine residue {C66} MODIFICATION: cysteine residue {C73} cysteine residue {C73} MODIFICATION: cysteine residue {C66} FG-GAP {85-163} MOTIF: N-glycosylation site {N86} cysteine residue {C105} MODIFICATION: cysteine residue {C123} cysteine residue {C123} MODIFICATION: cysteine residue {C105} VWFA domain {164-350} MOTIF: N-glycosylation site {N240} FG-GAP {337-400} MOTIF: N-glycosylation site {N391} FG-GAP {401-452} FG-GAP {454-515} MOTIF: Ca+2-binding site SITE: 465-473 N-glycosylation site {N469} FG-GAP {517-575} MOTIF: Ca+2-binding site SITE: 529-537 FG-GAP {580-632} MOTIF: Ca+2-binding site SITE: 592-600 cysteine residue {C654} MODIFICATION: cysteine residue {C711} N-glycosylation site {N692} N-glycosylation site {N696} cysteine residue {C711} MODIFICATION: cysteine residue {C654} N-glycosylation site {N734} cysteine residue {C770} MODIFICATION: cysteine residue {C776} cysteine residue {C776} MODIFICATION: cysteine residue {C770} N-glycosylation site {N801} cysteine residue {C847} MODIFICATION: cysteine residue {C864} cysteine residue {C864} MODIFICATION: cysteine residue {C847} N-glycosylation site {N880} N-glycosylation site {N900} N-glycosylation site {N911} N-glycosylation site {N940} N-glycosylation site {N946} N-glycosylation site {N978} N-glycosylation site {N993} cysteine residue {C998} MODIFICATION: cysteine residue {C1022} N-glycosylation site {N1021} cysteine residue {C1022} MODIFICATION: cysteine residue {C998} cysteine residue {C1027} MODIFICATION: cysteine residue {C1032} cysteine residue {C1032} MODIFICATION: cysteine residue {C1027} N-glycosylation site {N1044} N-glycosylation site {N1050} N-glycosylation site {N1075} transmembrane domain {1105-1128} GFFKR {1131-1135}} MOTIF: cysteine residue {X+0} MODIFICATION: cysteine residue {X+14} cysteine residue {X+14} MODIFICATION: cysteine residue {X+0} cysteine residue {X+16} MODIFICATION: cysteine residue {X+29} cysteine residue {X+19} MODIFICATION: cysteine residue {X+34} cysteine residue {X+29} MODIFICATION: cysteine residue {X+16} cysteine residue {X+34} MODIFICATION: cysteine residue {X+19} cysteine-rich region {integrin alpha-X COMPARTMENT: cellular membrane MOTIF: signal sequence {1-19} FG-GAP {34-87} MOTIF: N-glycosylation site {N61} cysteine residue {C69} MODIFICATION: cysteine residue {C76} cysteine residue {C76} MODIFICATION: cysteine residue {C69} consensus repeat {88} SEQUENCE-IS: FG-GAP N-glycosylation site {N89} cysteine residue {C108} MODIFICATION: cysteine residue {C126} cysteine residue {C126} MODIFICATION: cysteine residue {C108} VWFA domain {165-351} N-glycosylation site {N392} consensus repeat {401} SEQUENCE-IS: FG-GAP FG-GAP {402-453} FG-GAP {455-517} MOTIF: Ca+2-binding site SITE: 466-474 FG-GAP {518-576} MOTIF: Ca+2-binding site SITE: 530-538 FG-GAP {581-633} MOTIF: Ca+2-binding site SITE: 593-601 cysteine residue {C655} MODIFICATION: cysteine residue {C712} N-glycosylation site {N697} cysteine residue {C712} MODIFICATION: cysteine residue {C655} N-glycosylation site {N735} cysteine residue {C771} MODIFICATION: cysteine residue {C777} cysteine residue {C777} MODIFICATION: cysteine residue {C771} cysteine residue {C848} MODIFICATION: cysteine residue {C863} cysteine residue {C863} MODIFICATION: cysteine residue {C848} N-glycosylation site {N899} N-glycosylation site {N939} cysteine residue {C998} MODIFICATION: cysteine residue {C1022} cysteine residue {C1022} MODIFICATION: cysteine residue {C998} cysteine residue {C1027} MODIFICATION: cysteine residue {C1032} cysteine residue {C1032} MODIFICATION: cysteine residue {C1027} N-glycosylation site {N1050} transmembrane domain {1108-1128} GFFKR {1131-1135}} MOTIF: cysteine residue {X+0} MODIFICATION: cysteine residue {X+14} N-glycosylation site cysteine residue {X+14} MODIFICATION: cysteine residue {X+0} cysteine residue {X+16} MODIFICATION: cysteine residue {X+29} cysteine residue {X+19} MODIFICATION: cysteine residue {X+34} N-glycosylation site cysteine residue {X+29} MODIFICATION: cysteine residue {X+16} cysteine residue {X+34} MODIFICATION: cysteine residue {X+19} transmembrane domain binding site FOR-BINDING-OF: TNF receptor-associated factor 3

References

  1. Banchereau J et al Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science. 1991 Jan 4;251(4989):70-2. PMID: 1702555
  2. Taga T & Kishimoto T Cytokine receptors and signal transduction FASEB J 6:3387 1992 PMID: 1334470
  3. Nagata S, Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449-56. Review. PMID: 7533326
  4. Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science. 1995 Mar 10;267(5203):1494-8. PMID: 7533327
  5. Wang Z, Karras JG, Howard RG, Rothstein TL. Induction of bcl-x by CD40 engagement rescues sIg-induced apoptosis in murine B cells. J Immunol. 1995 Oct 15;155(8):3722-5. PMID: 7561075
  6. http://www.pathologyoutlines.com/cdmarkers.html 15 October 2002
  7. UniProt :accession P25942
  8. CD40base; Note: CD40 mutation db http://bioinf.uta.fi/CD40base/
  9. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD40
  10. Wikipedia; Note: CD40 entry http://en.wikipedia.org/wiki/CD40

Databases & Figures

OMIM 109535 MORBIDMAP 109535 UniProt P25942 Entrez Gene 958 Physiologic Inhibitors of Apoptosis