CD40L_CERAT
ID CD40L_CERAT Reviewed; 261 AA.
AC P63305; Q9BDC7;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=CD40 ligand;
DE Short=CD40-L;
DE AltName: Full=Tumor necrosis factor ligand superfamily member 5;
DE AltName: CD_antigen=CD154;
DE Contains:
DE RecName: Full=CD40 ligand, membrane form;
DE Contains:
DE RecName: Full=CD40 ligand, soluble form {ECO:0000250|UniProtKB:P29965};
DE Short=sCD40L {ECO:0000250|UniProtKB:P29965};
GN Name=CD40LG; Synonyms=CD40L, TNFSF5;
OS Cercocebus atys (Sooty mangabey) (Cercocebus torquatus atys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Cercocebus.
OX NCBI_TaxID=9531;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphocyte;
RX PubMed=11491535; DOI=10.1007/s002510100322;
RA Villinger F.J., Bostik P., Mayne A.E., King C.L., Genain C.P., Weiss W.R.,
RA Ansari A.A.;
RT "Cloning, sequencing, and homology analysis of nonhuman primate Fas/Fas-
RT ligand and co-stimulatory molecules.";
RL Immunogenetics 53:315-328(2001).
CC -!- FUNCTION: Cytokine that acts as a ligand to CD40/TNFRSF5 (By
CC similarity). Costimulates T-cell proliferation and cytokine production
CC (By similarity). Its cross-linking on T-cells generates a costimulatory
CC signal which enhances the production of IL4 and IL10 in conjunction
CC with the TCR/CD3 ligation and CD28 costimulation (By similarity).
CC Induces the activation of NF-kappa-B (By similarity). Induces the
CC activation of kinases MAPK8 and PAK2 in T-cells (By similarity).
CC Mediates B-cell proliferation in the absence of co-stimulus as well as
CC IgE production in the presence of IL4 (By similarity). Involved in
CC immunoglobulin class switching (By similarity).
CC {ECO:0000250|UniProtKB:P27548, ECO:0000250|UniProtKB:P29965}.
CC -!- FUNCTION: [CD40 ligand, soluble form]: Acts as a ligand for integrins,
CC specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40
CC receptor are required for activation of CD40-CD40LG signaling, which
CC have cell-type dependent effects, such as B-cell activation, NF-kappa-B
CC signaling and anti-apoptotic signaling. {ECO:0000250|UniProtKB:P29965}.
CC -!- SUBUNIT: Homotrimer (By similarity). Interacts with CD28 (By
CC similarity). CD40 ligand, soluble form: Exists as either a monomer or a
CC homotrimer (By similarity). Forms a ternary complex between CD40 and
CC integrins for CD40-CD40LG signaling (By similarity).
CC {ECO:0000250|UniProtKB:P29965}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P29965};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:P29965}.
CC Cell surface {ECO:0000250|UniProtKB:P29965}.
CC -!- SUBCELLULAR LOCATION: [CD40 ligand, soluble form]: Secreted
CC {ECO:0000250|UniProtKB:P29965}. Note=Release of soluble CD40L from
CC platelets is partially regulated by GP IIb/IIIa, actin polymerization,
CC and a matrix metalloproteinases (MMP) inhibitor-sensitive pathway.
CC {ECO:0000250|UniProtKB:P29965}.
CC -!- PTM: The soluble form derives from the membrane form by proteolytic
CC processing. {ECO:0000250|UniProtKB:P29965}.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
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DR EMBL; AF344841; AAK37600.1; -; mRNA.
DR RefSeq; NP_001292887.1; NM_001305958.1.
DR AlphaFoldDB; P63305; -.
DR SMR; P63305; -.
DR STRING; 9531.ENSCATP00000025206; -.
DR Ensembl; ENSCATT00000049436; ENSCATP00000025206; ENSCATG00000036087.
DR GeneID; 105592681; -.
DR CTD; 959; -.
DR GeneTree; ENSGT01050000244878; -.
DR OMA; YLHIPKE; -.
DR OrthoDB; 1146113at2759; -.
DR Proteomes; UP000233060; Unplaced.
DR Bgee; ENSCATG00000036087; Expressed in bone marrow and 3 other tissues.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005174; F:CD40 receptor binding; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; IEA:Ensembl.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:UniProtKB.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
DR GO; GO:0023035; P:CD40 signaling pathway; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0002637; P:regulation of immunoglobulin production; IEA:Ensembl.
DR CDD; cd00184; TNF; 1.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR003263; CD40L.
DR InterPro; IPR021184; TNF_CS.
DR InterPro; IPR006052; TNF_dom.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR PANTHER; PTHR11471:SF5; PTHR11471:SF5; 1.
DR Pfam; PF00229; TNF; 1.
DR PIRSF; PIRSF016527; TNF_5; 1.
DR PRINTS; PR01702; CD40LIGAND.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS00251; TNF_1; 1.
DR PROSITE; PS50049; TNF_2; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytokine; Disulfide bond; Glycoprotein; Membrane;
KW Reference proteome; Secreted; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..261
FT /note="CD40 ligand, membrane form"
FT /id="PRO_0000034480"
FT CHAIN 113..261
FT /note="CD40 ligand, soluble form"
FT /evidence="ECO:0000250|UniProtKB:P29965"
FT /id="PRO_0000034481"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..43
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..261
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT SITE 112..113
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 178..218
FT /evidence="ECO:0000255"
SQ SEQUENCE 261 AA; 29366 MW; AA2E0F11C0F28ABB CRC64;
MIETYNQPSP RSAATGLPVR MKIFMYLLTI FLITQMIGSA LFAVYLHRRL DKIEDERNLH
EDFVFMKTIQ RCNTGERSLS LLNCEEIKSQ FEGFVKDIML NKEEKKKENS FEMQKGDQNP
QIAAHVISEA SSKTTSVLQW AEKGYYTMSN NLVTLENGKQ LTVKRQGLYY IYAQVTFCSN
REASSQAPFI ASLCLKSPGR FERILLRAAN THSSAKPCGQ QSIHLGGVFE LQPGASVFVN
VTDPSQVSHG TGFTSFGLLK L
