Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

CD40

contributors: mct/npt - updated : 04-11-2015

HGNC name	CD40 molecule, TNF receptor superfamily member 5
HGNC id	11919

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HIGM3 immunodeficiency with hyper IgM, syndrome 3
Location	20q13.12      Physical location : 44.746.905 - 44.758.384
Synonym name	tumor necrosis factor receptor superfamily, member 5
	CD40 antigen
	CD40L receptor
	B-cell surface antigen CD40
	nerve growth factor receptor-related B-lymphocyte activation molecule
Synonym symbol(s)	p50, TNFRSF5, CDW40, Bp50, MGC9013

DNA

TYPE	functioning gene
STRUCTURE	11.49 kb     9 Exon(s)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - SRC - D20S106 - D20S187 - [D20S174 - PLCG1 - (D20S110 - D20S119 - D20S197 ) - ADA ADA - D20S17 - PPGB - D20S16 - D20S75 - D20S109 ] -D20S196 - qter
Authors	Asimakopoulos (95)
Text	[CD40 ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001250 9 - 1616 - 277 - 2008 18713981 NM_152854 8 - 1554 22.4 203 - 2008 18713981 frameshift distinct C terminus NM_001302753 9 - 1669 NP_001289682 - 237 - 2008 18713981

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel         Homo sapiens Endocrine pancreas         Lymphoid/Immune lymph node       highly   tonsils       highly Nervous brain         Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective adipose       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte Homo sapiens Blood/Hematopoietic monocyte Homo sapiens Cardiovascular endothelial cell Homo sapiens Lymphoid/Immune B cell Homo sapiens Lymphoid/Immune dendritic cell Homo sapiens Lymphoid/Immune macrophage Homo sapiens not specific adipocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	extracytoplasmic cysteine-rich pseudorepeats typical for the TNFR superfamily
	a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling, and cysteine-rich domain 1 (CRD1) participated to dimerization and was also required for efficient receptor expression
	a small cytoplasmic domain without catalytic activity and lacking the DEATH domain

conjugated

GlycoP

mono polymer

homomer , trimer

HOMOLOGY

interspecies	homolog to murine Tnfrsf5
	homolog to C.elegans Y57A10A.26

Homologene

FAMILY

tumor necrosis factor receptor superfamily

CATEGORY

immunity/defense , antigen , receptor membrane

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm
text	type 1 membrane protein

basic FUNCTION	pleiotropic modulator of immune response including germinal center formation
	Ig isotype switching and T cell activation in part by activation of NKFBs through binding to TRAF proteins and JAK3
	suppressor of apoptosis throught NFKB dependent upregulation of BCL2 family members
	CD40 signaling is critical for innate and adaptive immunity against pathogens
	regulator of retinal inflammation and neurovascular degeneration
	adipocyte CD40 may contribute to obesity-related inflammation and insulin resistance
	delivers signals regulating diverse cellular responses, including proliferation, differentiation, growth suppression, and cell death
	CD40 signaling is an active termination signal for germinal center reaction
	required for T cell-dependent humoral immunity, but it can also contribute to the pathogenesis of autoimmunity and B cell malignancy
	its activation can reverse immune suppression and drive antitumor T cell responses
	role for the CD40 pathway in regulating the immune reaction and fibrosis associated with pancreatic ductal adenocarcinoma by reeducation of tumor-associated macrophage
	sCD40LG/CD40 axis triggers NFKB1 activation in platelets
	activation of CD40 on B cells, macrophages, and dendritic cells by its ligand CD40LG is essential for the development of humoral and cellular immune responses
	CD40 self-assembly modulates signaling, possibly by maintaining the receptor in a quiescent state
	CD40-mediated maintenance of immune homeostasis in the adipose tissue microenvironment
	CD40-induced signalling through ligation with its natural ligand (CD40LG) is dependent on recruitment of TRAF molecules to the cytoplasmic domain of the receptor
	has a pivotal role in B-cell-mediated immunity through various effector pathways including AKT1 kinase
	CD4(+) T cells directly influence naive B cell development via CD40 signaling
	CD40 expression on the surface of B lymphocytes is essential for their biological function and fate decision
	co-stimulatory protein that is involved in T helper cell polarization and is found on the surface of antigen-presenting cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense , inflammation

PATHWAY

metabolism

signaling

signal transduction

host response against pathogens, NF-kappa B signaling pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with TRAF2 and TRAF6 adaptor proteins that are positive regulators of CD40 signaling required to activate downstream kinase cascades and transcription factors
	RIPK1 links the immunoregulatory CD40 receptor to apoptotic signaling in carcinomas
	TRAF3 can serve as a negative regulator of CD40 signaling
	CD40/CD40LG interaction induces SELE dependent adhesion of leukocytes to human endothelial cells and reduces endothelial cell migration by inhibiting the Akt/eNOS signaling pathway
	in platelets, soluble CD40LG induces association of CD40 with its adaptor protein the TNFR associated factor 2 and triggers phosphorylation of CHUK
	NFKB1 signaling pathway, which involves both NFKBIA and CHUK, plays an important role in platelet CD40 signaling, activation and aggregation in response to sCD40LG
	novel role of a scaffolding protein SPAG9 in the regulation of surface CD40 expression and fine-tuning of dendritic cells function
	TNFSF12 inhibits TRAF2-mediated CD40 signaling by destabilization of CD40 signaling complexes
	CD40LG is released from T-cells by ADAM10 and ADAM17 upon CD40 ligation
	FAF1 was able to interact with CD40, and CD40 ligation induced FAF1 expression in an NFKB1-dependent manner
	NEDD4 constitutively interacts with CD40 and mediates K63-linked ubiquitination of TRAF3
	ERK-1/2 inhibition or MAPK14 overexpression inhibited CD40-induced PTPN6 activation
	novel role of SPAG9 scaffold protein in the bridging of CD40LG-triggered CD40 internalization and CD40-dependent signaling in splenic B lymphocytes
	SQSTM1 is a critical regulator in CD40-mediated NFKB1 signaling via TRAF6

cell & other

REGULATION

activated by

CD40LG which plays a crucial role for the development and progression of a variety of inflammatory processes including atherosclerosis

ASSOCIATED DISORDERS

corresponding disease(s)

HIGM3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   during adipocyte differentiation constitutional     --other   aberrant CD40-induced NFKB1 activation in human lupus B lymphocytes

Susceptibility

to rheumatoid arthritis to Crohn disease and multiple sclerosis to variation of clinical disease manifestations in patients with systemic lupus erythematosus (SLE)

Variant & Polymorphism SNP , other	common variant increasing the risk of rheumatoid arthritis
	CD40 rs1883832 increasing the risk of Crohn disease and multiple sclerosis
	CD40 T variant might be negatively associated with some clinical disease manifestations in patients with SLE

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer endocrine pancreas CD40-dependent mechanism for targeting tumor stroma in the treatment of pancreatic cancer

ANIMAL & CELL MODELS

CD40-knocked-out mice