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CD40 ligand (CD40-L) (Tumor necrosis factor ligand superfamily member 5) (CD antigen CD154) [Cleaved into: CD40 ligand, membrane form; CD40 ligand, soluble form (sCD40L)]

 CD40L_MACMU             Reviewed;         261 AA.
P63304; Q9BDC7;
11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
11-OCT-2004, sequence version 1.
26-FEB-2020, entry version 97.
RecName: Full=CD40 ligand;
Short=CD40-L;
AltName: Full=Tumor necrosis factor ligand superfamily member 5;
AltName: CD_antigen=CD154;
Contains:
RecName: Full=CD40 ligand, membrane form;
Contains:
RecName: Full=CD40 ligand, soluble form {ECO:0000250|UniProtKB:P29965};
Short=sCD40L {ECO:0000250|UniProtKB:P29965};
Name=CD40LG; Synonyms=CD40L, TNFSF5;
Macaca mulatta (Rhesus macaque).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
Cercopithecidae; Cercopithecinae; Macaca.
NCBI_TaxID=9544;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLN-60; VAL-204; PRO-206 AND
THR-215.
TISSUE=Lymphocyte;
PubMed=11491535; DOI=10.1007/s002510100322;
Villinger F.J., Bostik P., Mayne A.E., King C.L., Genain C.P., Weiss W.R.,
Ansari A.A.;
"Cloning, sequencing, and homology analysis of nonhuman primate Fas/Fas-
ligand and co-stimulatory molecules.";
Immunogenetics 53:315-328(2001).
-!- FUNCTION: Cytokine that acts as a ligand to CD40/TNFRSF5 (By
similarity). Costimulates T-cell proliferation and cytokine production
(By similarity). Its cross-linking on T-cells generates a costimulatory
signal which enhances the production of IL4 and IL10 in conjunction
with the TCR/CD3 ligation and CD28 costimulation (By similarity).
Induces the activation of NF-kappa-B (By similarity). Induces the
activation of kinases MAPK8 and PAK2 in T-cells (By similarity).
Mediates B-cell proliferation in the absence of co-stimulus as well as
IgE production in the presence of IL4 (By similarity). Involved in
immunoglobulin class switching (By similarity).
{ECO:0000250|UniProtKB:P27548, ECO:0000250|UniProtKB:P29965}.
-!- FUNCTION: [CD40 ligand, soluble form]: Acts as a ligand for integrins,
specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40
receptor are required for activation of CD40-CD40LG signaling, which
have cell-type dependent effects, such as B-cell activation, NF-kappa-B
signaling and anti-apoptotic signaling. {ECO:0000250|UniProtKB:P29965}.
-!- SUBUNIT: Homotrimer (By similarity). Interacts with CD28 (By
similarity). CD40 ligand, soluble form: Exists as either a monomer or a
homotrimer (By similarity). Forms a ternary complex between CD40 and
integrins for CD40-CD40LG signaling (By similarity).
{ECO:0000250|UniProtKB:P29965}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P29965};
Single-pass type II membrane protein {ECO:0000250|UniProtKB:P29965}.
Cell surface {ECO:0000250|UniProtKB:P29965}.
-!- SUBCELLULAR LOCATION: [CD40 ligand, soluble form]: Secreted
{ECO:0000250|UniProtKB:P29965}. Note=Release of soluble CD40L from
platelets is partially regulated by GP IIb/IIIa, actin polymerization,
and a matrix metalloproteinases (MMP) inhibitor-sensitive pathway.
{ECO:0000250|UniProtKB:P29965}.
-!- PTM: The soluble form derives from the membrane form by proteolytic
processing. {ECO:0000250|UniProtKB:P29965}.
-!- SIMILARITY: Belongs to the tumor necrosis factor family. {ECO:0000305}.
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EMBL; AF344859; AAK37541.1; -; mRNA.
RefSeq; NP_001028011.1; NM_001032839.1.
STRING; 9544.ENSMMUP00000018111; -.
GeneID; 574160; -.
KEGG; mcc:574160; -.
CTD; 959; -.
eggNOG; ENOG410IVYF; Eukaryota.
eggNOG; ENOG4111TET; LUCA.
InParanoid; P63304; -.
KO; K03161; -.
OrthoDB; 1146113at2759; -.
Proteomes; UP000006718; Unplaced.
GO; GO:0009986; C:cell surface; ISS:UniProtKB.
GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0005174; F:CD40 receptor binding; ISS:UniProtKB.
GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro.
GO; GO:0007257; P:activation of JUN kinase activity; ISS:UniProtKB.
GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
GO; GO:0006955; P:immune response; IEA:InterPro.
GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:UniProtKB.
CDD; cd00184; TNF; 1.
Gene3D; 2.60.120.40; -; 1.
InterPro; IPR003263; CD40L.
InterPro; IPR021184; TNF_CS.
InterPro; IPR006052; TNF_dom.
InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
PANTHER; PTHR11471:SF5; PTHR11471:SF5; 1.
Pfam; PF00229; TNF; 1.
PIRSF; PIRSF016527; TNF_5; 1.
PRINTS; PR01702; CD40LIGAND.
SMART; SM00207; TNF; 1.
SUPFAM; SSF49842; SSF49842; 1.
PROSITE; PS00251; TNF_1; 1.
PROSITE; PS50049; TNF_2; 1.
2: Evidence at transcript level;
Cell membrane; Cytokine; Disulfide bond; Glycoprotein; Membrane;
Polymorphism; Reference proteome; Secreted; Signal-anchor; Transmembrane;
Transmembrane helix.
CHAIN 1..261
/note="CD40 ligand, membrane form"
/id="PRO_0000034486"
CHAIN 113..261
/note="CD40 ligand, soluble form"
/evidence="ECO:0000250|UniProtKB:P29965"
/id="PRO_0000034487"
TOPO_DOM 1..22
/note="Cytoplasmic"
/evidence="ECO:0000255"
TRANSMEM 23..43
/note="Helical; Signal-anchor for type II membrane protein"
/evidence="ECO:0000255"
TOPO_DOM 44..261
/note="Extracellular"
/evidence="ECO:0000255"
SITE 112..113
/note="Cleavage"
/evidence="ECO:0000250"
CARBOHYD 240
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
DISULFID 178..218
/evidence="ECO:0000255"
VARIANT 60
/note="H -> Q"
/evidence="ECO:0000269|PubMed:11491535"
VARIANT 204
/note="I -> V"
/evidence="ECO:0000269|PubMed:11491535"
VARIANT 206
/note="L -> P"
/evidence="ECO:0000269|PubMed:11491535"
VARIANT 215
/note="A -> T"
/evidence="ECO:0000269|PubMed:11491535"
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


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