UniProtKB - P27548 (CD40L_MOUSE)
CD40 ligand
Cd40lg
Functioni
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 (PubMed:1374165).
Involved in immunoglobulin class switching (PubMed:1374165).
By similarity1 PublicationActs 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.
By similarityGO - Molecular functioni
- CD40 receptor binding Source: UniProtKB
- cytokine activity Source: UniProtKB-KW
- integrin binding Source: MGI
- protein serine/threonine kinase activator activity Source: UniProtKB
- tumor necrosis factor receptor binding Source: InterPro
GO - Biological processi
- B cell differentiation Source: MGI
- B cell proliferation Source: UniProtKB
- CD40 signaling pathway Source: MGI
- dendritic cell differentiation Source: MGI
- inflammatory response Source: UniProtKB
- integrin-mediated signaling pathway Source: MGI
- isotype switching Source: UniProtKB
- negative regulation of apoptotic process Source: UniProtKB
- platelet activation Source: UniProtKB
- positive regulation of B cell proliferation Source: MGI
- positive regulation of dendritic cell differentiation Source: MGI
- positive regulation of endothelial cell apoptotic process Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of immune response to tumor cell Source: MGI
- positive regulation of interferon-gamma production Source: MGI
- positive regulation of interleukin-10 production Source: UniProtKB
- positive regulation of interleukin-12 production Source: MGI
- positive regulation of interleukin-4 production Source: UniProtKB
- positive regulation of MHC class II biosynthetic process Source: MGI
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of T cell proliferation Source: UniProtKB
- regulation of immunoglobulin production Source: MGI
- signal transduction Source: UniProtKB
Keywordsi
Molecular function | Cytokine |
Enzyme and pathway databases
Reactomei | R-MMU-198933, Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-MMU-5668541, TNFR2 non-canonical NF-kB pathway R-MMU-5676594, TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway |
Names & Taxonomyi
Protein namesi | Recommended name: CD40 ligandShort name: CD40-L Alternative name(s): T-cell antigen Gp39 TNF-related activation protein Short name: TRAP Tumor necrosis factor ligand superfamily member 5 CD_antigen: CD154 Cleaved into the following 2 chains: |
Gene namesi | Name:Cd40lg Synonyms:Cd40l, Tnfsf5 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:88337, Cd40lg |
VEuPathDBi | HostDB:ENSMUSG00000031132 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type II membrane protein By similarity
Other locations
- Cell surface By similarity
Extracellular region or secreted
- Secreted By similarity
Note: Release of soluble CD40L from platelets is partially regulated by GP IIb/IIIa, actin polymerization, and a matrix metalloproteinases (MMP) inhibitor-sensitive pathway.By similarity
Extracellular region or secreted
- extracellular space Source: MGI
Golgi apparatus
- Golgi apparatus Source: Ensembl
Plasma Membrane
- external side of plasma membrane Source: MGI
Other locations
- cell body Source: MGI
- cell projection Source: MGI
- cell surface Source: MGI
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 22 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 23 – 46 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 24 | |
Topological domaini | 47 – 260 | ExtracellularSequence analysisAdd BLAST | 214 |
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000034490 | 1 – 260 | CD40 ligand, membrane formAdd BLAST | 260 | |
ChainiPRO_0000034491 | 112 – 260 | CD40 ligand, soluble formBy similarityAdd BLAST | 149 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 177 ↔ 217 | 1 Publication | ||
Glycosylationi | 239 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 111 – 112 | CleavageBy similarity | 2 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PaxDbi | P27548 |
PRIDEi | P27548 |
ProteomicsDBi | 281269 |
PTM databases
GlyGeni | P27548, 1 site |
iPTMneti | P27548 |
PhosphoSitePlusi | P27548 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSMUSG00000031132, Expressed in thymus and 48 other tissues |
ExpressionAtlasi | P27548, baseline and differential |
Genevisiblei | P27548, MM |
Interactioni
Subunit structurei
Homotrimer (PubMed:8095800).
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).
1 PublicationBy similarityGO - Molecular functioni
- CD40 receptor binding Source: UniProtKB
- cytokine activity Source: UniProtKB-KW
- integrin binding Source: MGI
- tumor necrosis factor receptor binding Source: InterPro
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000033466 |
Miscellaneous databases
RNActi | P27548, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT01040000240394 |
HOGENOMi | CLU_093203_0_0_1 |
InParanoidi | P27548 |
OMAi | YLHIPKE |
OrthoDBi | 1146113at2759 |
PhylomeDBi | P27548 |
TreeFami | TF332169 |
Family and domain databases
CDDi | cd00184, TNF, 1 hit |
Gene3Di | 2.60.120.40, 1 hit |
InterProi | View protein in InterPro IPR003263, CD40L IPR021184, TNF_CS IPR006052, TNF_dom IPR008983, Tumour_necrosis_fac-like_dom |
PANTHERi | PTHR11471:SF5, PTHR11471:SF5, 1 hit |
Pfami | View protein in Pfam PF00229, TNF, 1 hit |
PIRSFi | PIRSF016527, TNF_5, 1 hit |
PRINTSi | PR01702, CD40LIGAND |
SMARTi | View protein in SMART SM00207, TNF, 1 hit |
SUPFAMi | SSF49842, SSF49842, 1 hit |
PROSITEi | View protein in PROSITE PS00251, TNF_1, 1 hit PS50049, TNF_2, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MIETYSQPSP RSVATGLPAS MKIFMYLLTV FLITQMIGSV LFAVYLHRRL
60 70 80 90 100
DKVEEEVNLH EDFVFIKKLK RCNKGEGSLS LLNCEEMRRQ FEDLVKDITL
110 120 130 140 150
NKEEKKENSF EMQRGDEDPQ IAAHVVSEAN SNAASVLQWA KKGYYTMKSN
160 170 180 190 200
LVMLENGKQL TVKREGLYYV YTQVTFCSNR EPSSQRPFIV GLWLKPSSGS
210 220 230 240 250
ERILLKAANT HSSSQLCEQQ SVHLGGVFEL QAGASVFVNV TEASQVIHRV
260
GFSSFGLLKL
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 198 | S → I in AAC13640 (PubMed:7520529).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X65453 mRNA Translation: CAA46448.2 S71858 Genomic DNA Translation: AAC13639.1 S71861 Genomic DNA Translation: AAC13640.1 |
CCDSi | CCDS30152.1 |
PIRi | S21738 |
RefSeqi | NP_035746.2, NM_011616.2 |
Genome annotation databases
Ensembli | ENSMUST00000033466; ENSMUSP00000033466; ENSMUSG00000031132 |
GeneIDi | 21947 |
KEGGi | mmu:21947 |
UCSCi | uc009thb.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X65453 mRNA Translation: CAA46448.2 S71858 Genomic DNA Translation: AAC13639.1 S71861 Genomic DNA Translation: AAC13640.1 |
CCDSi | CCDS30152.1 |
PIRi | S21738 |
RefSeqi | NP_035746.2, NM_011616.2 |
3D structure databases
AlphaFoldDBi | P27548 |
SMRi | P27548 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000033466 |
PTM databases
GlyGeni | P27548, 1 site |
iPTMneti | P27548 |
PhosphoSitePlusi | P27548 |
Proteomic databases
PaxDbi | P27548 |
PRIDEi | P27548 |
ProteomicsDBi | 281269 |
Protocols and materials databases
ABCDi | P27548, 1 sequenced antibody |
Antibodypediai | 16693, 2083 antibodies from 48 providers |
DNASUi | 21947 |
Genome annotation databases
Ensembli | ENSMUST00000033466; ENSMUSP00000033466; ENSMUSG00000031132 |
GeneIDi | 21947 |
KEGGi | mmu:21947 |
UCSCi | uc009thb.1, mouse |
Organism-specific databases
CTDi | 959 |
MGIi | MGI:88337, Cd40lg |
VEuPathDBi | HostDB:ENSMUSG00000031132 |
Phylogenomic databases
eggNOGi | KOG3656, Eukaryota |
GeneTreei | ENSGT01040000240394 |
HOGENOMi | CLU_093203_0_0_1 |
InParanoidi | P27548 |
OMAi | YLHIPKE |
OrthoDBi | 1146113at2759 |
PhylomeDBi | P27548 |
TreeFami | TF332169 |
Enzyme and pathway databases
Reactomei | R-MMU-198933, Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-MMU-5668541, TNFR2 non-canonical NF-kB pathway R-MMU-5676594, TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway |
Miscellaneous databases
BioGRID-ORCSi | 21947, 0 hits in 109 CRISPR screens |
PROi | PR:P27548 |
RNActi | P27548, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000031132, Expressed in thymus and 48 other tissues |
ExpressionAtlasi | P27548, baseline and differential |
Genevisiblei | P27548, MM |
Family and domain databases
CDDi | cd00184, TNF, 1 hit |
Gene3Di | 2.60.120.40, 1 hit |
InterProi | View protein in InterPro IPR003263, CD40L IPR021184, TNF_CS IPR006052, TNF_dom IPR008983, Tumour_necrosis_fac-like_dom |
PANTHERi | PTHR11471:SF5, PTHR11471:SF5, 1 hit |
Pfami | View protein in Pfam PF00229, TNF, 1 hit |
PIRSFi | PIRSF016527, TNF_5, 1 hit |
PRINTSi | PR01702, CD40LIGAND |
SMARTi | View protein in SMART SM00207, TNF, 1 hit |
SUPFAMi | SSF49842, SSF49842, 1 hit |
PROSITEi | View protein in PROSITE PS00251, TNF_1, 1 hit PS50049, TNF_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CD40L_MOUSE | |
Accessioni | P27548Primary (citable) accession number: P27548 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1992 |
Last sequence update: | August 14, 2001 | |
Last modified: | May 25, 2022 | |
This is version 182 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families