CD40L_CANLF
ID CD40L_CANLF Reviewed; 260 AA.
AC O97626;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 140.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hosie M.H., Willett B.J.;
RT "Adjuvant properties of canine CD40L.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Yang S., Sim G.-K.;
RT "Canine CD40 and CD40 ligand cDNA sequences.";
RL Submitted (JUL-2003) 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; AF086711; AAD04375.1; -; mRNA.
DR EMBL; AY333790; AAP86654.1; -; mRNA.
DR RefSeq; NP_001002981.1; NM_001002981.1.
DR AlphaFoldDB; O97626; -.
DR SMR; O97626; -.
DR STRING; 9612.ENSCAFP00000027967; -.
DR PaxDb; O97626; -.
DR Ensembl; ENSCAFT00030032974; ENSCAFP00030028766; ENSCAFG00030017860.
DR Ensembl; ENSCAFT00040016529; ENSCAFP00040014323; ENSCAFG00040008883.
DR Ensembl; ENSCAFT00845051855; ENSCAFP00845040687; ENSCAFG00845029290.
DR GeneID; 403468; -.
DR KEGG; cfa:403468; -.
DR CTD; 959; -.
DR VEuPathDB; HostDB:ENSCAFG00845029290; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244878; -.
DR HOGENOM; CLU_093203_0_0_1; -.
DR InParanoid; O97626; -.
DR OMA; YLHIPKE; -.
DR OrthoDB; 1146113at2759; -.
DR TreeFam; TF332169; -.
DR Reactome; R-CFA-5668541; TNFR2 non-canonical NF-kB pathway.
DR Proteomes; UP000002254; Chromosome X.
DR Bgee; ENSCAFG00000018945; Expressed in blood and 33 other tissues.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
DR GO; GO:0023035; P:CD40 signaling pathway; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
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; IEA:Ensembl.
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 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_0000034478"
FT CHAIN 112..260
FT /note="CD40 ligand, soluble form"
FT /evidence="ECO:0000250|UniProtKB:P29965"
FT /id="PRO_0000034479"
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:0000255"
SQ SEQUENCE 260 AA; 28688 MW; 604F69A19E98EB70 CRC64;
MIETYSQTAP RSVATGPPVS MKIFMYLLTV FLITQMIGSA LFAVYLHRRL DKIEDERNLY
EDFVFMKTLQ KCNKGEGSLS LLNCEEIKSQ FEAFLKEIML NNEMKKEENI AMQKGDQDPR
IAAHVISEAS SNPASVLRWA PKGYYTISSN LVSLENGKQL AVKRQGLYYV YAQVTFCSNR
AASSQAPFVA SLCLHSPSGT ERVLLRAASS RGSSKPCGQQ SIHLGGVFEL HPGASVFVNV
TDPSQVSHGT GFTSFGLLKL
