ID   CD40L_MOUSE             Reviewed;         260 AA.
AC   P27548;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   14-AUG-2001, sequence version 2.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=CD40 ligand;
DE            Short=CD40-L;
DE   AltName: Full=T-cell antigen Gp39;
DE   AltName: Full=TNF-related activation protein;
DE            Short=TRAP;
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=1374165; DOI=10.1038/357080a0;
RA   Armitage R., Fanslow W., Sato T.A., Clifford K.N., Strockbine L.,
RA   Macduff B.M., Anderson D.M., Gimpel S.D., Davis-Smith T., Maliszewski C.R.,
RA   Clark E.A., Smith C.A., Grabstein K.H., Cosman D., Spriggs M.K.;
RT   "Molecular and biological characterization of a murine ligand for CD40.";
RL   Nature 357:80-82(1992).
RN   [2]
RP   SEQUENCE REVISION TO 198.
RA   Spriggs M.K.;
RL   Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52 AND 137-260.
RC   STRAIN=129/Sv; TISSUE=Liver;
RX   PubMed=7520529; DOI=10.1016/0161-5890(94)90009-4;
RA   Tsitsikov E.N., Ramesh N., Geha R.S.;
RT   "Structure of the murine CD40 ligand gene.";
RL   Mol. Immunol. 31:895-900(1994).
RN   [4]
RP   SIMILARITY TO THE TNF FAMILY.
RX   PubMed=1377364; DOI=10.1038/358026b0;
RA   Farrah T., Smith C.A.;
RT   "Emerging cytokine family.";
RL   Nature 358:26-26(1992).
RN   [5]
RP   3D-STRUCTURE MODELING OF 115-260, DISULFIDE BOND, AND SUBUNIT.
RX   PubMed=8095800; DOI=10.1093/intimm/5.2.233;
RA   Peitsch M.C., Jongeneel C.V.;
RT   "A 3-D model for the CD40 ligand predicts that it is a compact trimer
RT   similar to the tumor necrosis factors.";
RL   Int. Immunol. 5:233-238(1993).
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 (PubMed:1374165). Involved in
CC       immunoglobulin class switching (PubMed:1374165).
CC       {ECO:0000250|UniProtKB:P29965, ECO:0000269|PubMed:1374165}.
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 (PubMed:8095800). 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, ECO:0000303|PubMed:8095800}.
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   -!- TISSUE SPECIFICITY: Specifically expressed on activated CD4+ T-
CC       lymphocytes.
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; X65453; CAA46448.2; -; mRNA.
DR   EMBL; S71858; AAC13639.1; -; Genomic_DNA.
DR   EMBL; S71861; AAC13640.1; -; Genomic_DNA.
DR   CCDS; CCDS30152.1; -.
DR   PIR; S21738; S21738.
DR   RefSeq; NP_035746.2; NM_011616.2.
DR   AlphaFoldDB; P27548; -.
DR   SMR; P27548; -.
DR   STRING; 10090.ENSMUSP00000033466; -.
DR   GlyCosmos; P27548; 1 site, No reported glycans.
DR   GlyGen; P27548; 1 site.
DR   iPTMnet; P27548; -.
DR   PhosphoSitePlus; P27548; -.
DR   PaxDb; 10090-ENSMUSP00000033466; -.
DR   ProteomicsDB; 281269; -.
DR   ABCD; P27548; 1 sequenced antibody.
DR   Antibodypedia; 16693; 2231 antibodies from 49 providers.
DR   DNASU; 21947; -.
DR   Ensembl; ENSMUST00000033466.2; ENSMUSP00000033466.2; ENSMUSG00000031132.2.
DR   GeneID; 21947; -.
DR   KEGG; mmu:21947; -.
DR   UCSC; uc009thb.1; mouse.
DR   AGR; MGI:88337; -.
DR   CTD; 959; -.
DR   MGI; MGI:88337; Cd40lg.
DR   VEuPathDB; HostDB:ENSMUSG00000031132; -.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT01070000253816; -.
DR   HOGENOM; CLU_093203_0_0_1; -.
DR   InParanoid; P27548; -.
DR   OMA; VSFCTKA; -.
DR   OrthoDB; 4323672at2759; -.
DR   PhylomeDB; P27548; -.
DR   TreeFam; TF332169; -.
DR   Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR   Reactome; R-MMU-5668541; TNFR2 non-canonical NF-kB pathway.
DR   Reactome; R-MMU-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
DR   BioGRID-ORCS; 21947; 0 hits in 114 CRISPR screens.
DR   PRO; PR:P27548; -.
DR   Proteomes; UP000000589; Chromosome X.
DR   RNAct; P27548; Protein.
DR   Bgee; ENSMUSG00000031132; Expressed in thymus and 21 other cell types or tissues.
DR   ExpressionAtlas; P27548; baseline and differential.
DR   GO; GO:0044297; C:cell body; ISO:MGI.
DR   GO; GO:0042995; C:cell projection; ISO:MGI.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
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; ISO:MGI.
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; IGI:MGI.
DR   GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
DR   GO; GO:0023035; P:CD40 signaling pathway; ISO:MGI.
DR   GO; GO:0097028; P:dendritic cell differentiation; ISO:MGI.
DR   GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR   GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:MGI.
DR   GO; GO:0045190; P:isotype switching; IDA:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR   GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:MGI.
DR   GO; GO:2001200; P:positive regulation of dendritic cell differentiation; ISO:MGI.
DR   GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR   GO; GO:0002839; P:positive regulation of immune response to tumor cell; ISO:MGI.
DR   GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:MGI.
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; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0002637; P:regulation of immunoglobulin production; IDA:MGI.
DR   GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
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.
DR   Genevisible; P27548; MM.
PE   1: Evidence at protein 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_0000034490"
FT   CHAIN           112..260
FT                   /note="CD40 ligand, soluble form"
FT                   /evidence="ECO:0000250|UniProtKB:P29965"
FT                   /id="PRO_0000034491"
FT   TOPO_DOM        1..22
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        23..46
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        47..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:0000269|PubMed:8095800"
FT   CONFLICT        198
FT                   /note="S -> I (in Ref. 3; AAC13640)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   260 AA;  29370 MW;  7E1AC117473672AD CRC64;
     MIETYSQPSP RSVATGLPAS MKIFMYLLTV FLITQMIGSV LFAVYLHRRL DKVEEEVNLH
     EDFVFIKKLK RCNKGEGSLS LLNCEEMRRQ FEDLVKDITL NKEEKKENSF EMQRGDEDPQ
     IAAHVVSEAN SNAASVLQWA KKGYYTMKSN LVMLENGKQL TVKREGLYYV YTQVTFCSNR
     EPSSQRPFIV GLWLKPSSGS ERILLKAANT HSSSQLCEQQ SVHLGGVFEL QAGASVFVNV
     TEASQVIHRV GFSSFGLLKL
//