CD40L_MOUSE
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 03-AUG-2022, entry version 183.
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 GlyGen; P27548; 1 site.
DR iPTMnet; P27548; -.
DR PhosphoSitePlus; P27548; -.
DR PaxDb; P27548; -.
DR PRIDE; P27548; -.
DR ProteomicsDB; 281269; -.
DR ABCD; P27548; 1 sequenced antibody.
DR Antibodypedia; 16693; 1981 antibodies from 48 providers.
DR DNASU; 21947; -.
DR Ensembl; ENSMUST00000033466; ENSMUSP00000033466; ENSMUSG00000031132.
DR GeneID; 21947; -.
DR KEGG; mmu:21947; -.
DR UCSC; uc009thb.1; mouse.
DR CTD; 959; -.
DR MGI; MGI:88337; Cd40lg.
DR VEuPathDB; HostDB:ENSMUSG00000031132; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_093203_0_0_1; -.
DR InParanoid; P27548; -.
DR OMA; YLHIPKE; -.
DR OrthoDB; 1146113at2759; -.
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 109 CRISPR screens.
DR PRO; PR:P27548; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P27548; protein.
DR Bgee; ENSMUSG00000031132; Expressed in thymus and 21 other tissues.
DR ExpressionAtlas; P27548; baseline and differential.
DR Genevisible; P27548; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0032729; P:positive regulation of interferon-gamma production; 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: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; 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 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
