ID CD40L_RAT Reviewed; 260 AA.
AC Q9Z2V2; Q9R254;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 06-JUN-2002, sequence version 2.
DT 08-NOV-2023, entry version 137.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Splenocyte;
RX PubMed=10826698; DOI=10.3109/10425170009015609;
RA Hallett K.M., Oaks M.K.;
RT "Nucleotide sequence of the rat CD40 ligand.";
RL DNA Seq. 10:405-406(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=PVG; TISSUE=Spleen;
RA Daniel K.C., Foss Y., Moussavi A., Macary P., Kemeny D.M., Farzaneh F.,
RA Gaken J.A.;
RT "Cloning and sequencing of rat CD40 ligand.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
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; AF116582; AAD22460.1; -; mRNA.
DR EMBL; AF013985; AAD09323.1; -; mRNA.
DR RefSeq; NP_445805.1; NM_053353.1.
DR AlphaFoldDB; Q9Z2V2; -.
DR SMR; Q9Z2V2; -.
DR STRING; 10116.ENSRNOP00000001162; -.
DR GlyCosmos; Q9Z2V2; 1 site, No reported glycans.
DR GlyGen; Q9Z2V2; 1 site.
DR iPTMnet; Q9Z2V2; -.
DR PhosphoSitePlus; Q9Z2V2; -.
DR PaxDb; 10116-ENSRNOP00000001162; -.
DR GeneID; 84349; -.
DR KEGG; rno:84349; -.
DR AGR; RGD:708418; -.
DR CTD; 959; -.
DR RGD; 708418; Cd40lg.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; Q9Z2V2; -.
DR OrthoDB; 4323672at2759; -.
DR PhylomeDB; Q9Z2V2; -.
DR Reactome; R-RNO-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-RNO-5668541; TNFR2 non-canonical NF-kB pathway.
DR Reactome; R-RNO-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR PRO; PR:Q9Z2V2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0042995; C:cell projection; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005174; F:CD40 receptor binding; IPI:RGD.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
DR GO; GO:0023035; P:CD40 signaling pathway; ISO:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0097028; P:dendritic cell differentiation; IMP:RGD.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0045190; P:isotype switching; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:RGD.
DR GO; GO:2001200; P:positive regulation of dendritic cell differentiation; IDA:RGD.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:RGD.
DR GO; GO:0002839; P:positive regulation of immune response to tumor cell; IDA:RGD.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:RGD.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:RGD.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IDA:RGD.
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:0032729; P:positive regulation of type II interferon production; IDA:RGD.
DR GO; GO:0002637; P:regulation of immunoglobulin production; ISO:RGD.
DR GO; GO:0033590; P:response to cobalamin; IEP:RGD.
DR GO; GO:1901652; P:response to peptide; IEP:RGD.
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; CD40 LIGAND; 1.
DR PANTHER; PTHR11471; TUMOR NECROSIS FACTOR FAMILY MEMBER; 1.
DR Pfam; PF00229; TNF; 1.
DR PIRSF; PIRSF016527; TNF_5; 1.
DR PRINTS; PR01702; CD40LIGAND.
DR SMART; SM00207; TNF; 1.
DR SUPFAM; SSF49842; TNF-like; 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..260
FT /note="CD40 ligand, membrane form"
FT /id="PRO_0000034494"
FT CHAIN 112..260
FT /note="CD40 ligand, soluble form"
FT /evidence="ECO:0000250|UniProtKB:P29965"
FT /id="PRO_0000034495"
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..260
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT SITE 111..112
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 177..217
FT /evidence="ECO:0000255"
FT CONFLICT 41
FT /note="P -> L (in Ref. 1; AAD09323)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="R -> K (in Ref. 1; AAD09323)"
FT /evidence="ECO:0000305"
FT CONFLICT 255
FT /note="I -> F (in Ref. 1; AAD09323)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 260 AA; 29260 MW; B3D3757DE60DB73A CRC64;
MIETYSQPSP RSVATGLPAS MKIFMYLLTV FLITQMIGSV PFAVYLHRRL DKVEEEASLH
EDFVFVKKLK RCNKGEGSLS LLNCEEMRRQ FEDLVKDISL NKEEKKEKSF EMQRGDEDPQ
IAAHVVSEAN SNAASVLQWA KKGYYTMKSN LVVLENGRQL TVKREGLYYV YTQVTFCSNR
EPLSQRPFIV SLWLKPSSGS ERILLRAANT HSSSKLCEQQ SIHLGGVFEL QAGASVFVNV
TEASQVIHGI GFSSIGLLKL
//
