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Protein

Tumor necrosis factor receptor superfamily member 5

Gene

CD40

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for TNFSF5/CD40LG. Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion.

GO - Molecular functioni

  • antigen binding Source: Ensembl
  • enzyme binding Source: UniProtKB
  • receptor activity Source: ProtInc
  • signal transducer activity Source: ProtInc
  • tumor necrosis factor-activated receptor activity Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • apoptotic signaling pathway Source: GO_Central
  • B cell proliferation Source: UniProtKB
  • cellular calcium ion homeostasis Source: BHF-UCL
  • cellular response to lipopolysaccharide Source: Ensembl
  • cellular response to mechanical stimulus Source: UniProtKB
  • defense response to protozoan Source: Ensembl
  • defense response to virus Source: Ensembl
  • immune response Source: GO_Central
  • immune response-regulating cell surface receptor signaling pathway Source: Ensembl
  • inflammatory response Source: ProtInc
  • multicellular organism development Source: GO_Central
  • platelet activation Source: UniProtKB
  • positive regulation of B cell proliferation Source: Ensembl
  • positive regulation of endothelial cell apoptotic process Source: BHF-UCL
  • positive regulation of GTPase activity Source: BHF-UCL
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of interleukin-12 production Source: Ensembl
  • positive regulation of isotype switching to IgG isotypes Source: Ensembl
  • positive regulation of MAP kinase activity Source: BHF-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • positive regulation of protein kinase C signaling Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of Stat1 protein Source: BHF-UCL
  • protein complex assembly Source: ProtInc
  • protein kinase B signaling Source: Ensembl
  • regulation of cell proliferation Source: GO_Central
  • regulation of immune response Source: Reactome
  • regulation of immunoglobulin secretion Source: Ensembl
  • response to lipopolysaccharide Source: GO_Central
  • tumor necrosis factor-mediated signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101017-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
SIGNORiP25942.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor receptor superfamily member 5
Alternative name(s):
B-cell surface antigen CD40
Bp50
CD40L receptor
CDw40
CD_antigen: CD40
Gene namesi
Name:CD40
Synonyms:TNFRSF5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:11919. CD40.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 193ExtracellularSequence analysisAdd BLAST173
Transmembranei194 – 215HelicalSequence analysisAdd BLAST22
Topological domaini216 – 277CytoplasmicSequence analysisAdd BLAST62

GO - Cellular componenti

  • CD40 receptor complex Source: BHF-UCL
  • cell surface Source: UniProtKB
  • cytoplasm Source: Ensembl
  • external side of plasma membrane Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • intracellular membrane-bounded organelle Source: Ensembl
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency with hyper-IgM 3 (HIGM3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.
See also OMIM:606843
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01362883C → R in HIGM3. 1 PublicationCorresponds to variant rs28931586dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi958.
MalaCardsiCD40.
MIMi606843. phenotype.
OpenTargetsiENSG00000101017.
Orphaneti101090. Hyper-IgM syndrome type 3.
PharmGKBiPA36612.

Chemistry databases

ChEMBLiCHEMBL1250358.

Polymorphism and mutation databases

BioMutaiCD40.
DMDMi116000.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 203 PublicationsAdd BLAST20
ChainiPRO_000003455921 – 277Tumor necrosis factor receptor superfamily member 5Add BLAST257

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi26 ↔ 37
Disulfide bondi38 ↔ 51
Disulfide bondi41 ↔ 59
Disulfide bondi62 ↔ 77
Disulfide bondi83 ↔ 103
Disulfide bondi105 ↔ 119
Disulfide bondi111 ↔ 116
Disulfide bondi125 ↔ 143
Glycosylationi153N-linked (GlcNAc...)Sequence analysis1
Glycosylationi180N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP25942.
PaxDbiP25942.
PeptideAtlasiP25942.
PRIDEiP25942.

PTM databases

iPTMnetiP25942.
PhosphoSitePlusiP25942.

Miscellaneous databases

PMAP-CutDBP25942.

Expressioni

Tissue specificityi

B-cells and in primary carcinomas.

Gene expression databases

BgeeiENSG00000101017.
CleanExiHS_CD40.
ExpressionAtlasiP25942. baseline and differential.
GenevisibleiP25942. HS.

Organism-specific databases

HPAiCAB002495.
CAB072868.
HPA031567.
HPA031568.

Interactioni

Subunit structurei

Monomer and homodimer. The variant form found in the bladder carcinoma cell line Hu549 does not form homodimers. Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6. Interacts with TRAF6 and MAP3K8; the interaction is required for ERK activation.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TRAF2Q129336EBI-525714,EBI-355744
TRAF3Q131143EBI-525714,EBI-357631
TRAF6Q9Y4K32EBI-525714,EBI-359276

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107396. 47 interactors.
DIPiDIP-3014N.
IntActiP25942. 5 interactors.
MINTiMINT-1505936.
STRINGi9606.ENSP00000361359.

Chemistry databases

BindingDBiP25942.

Structurei

Secondary structure

1277
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni28 – 30Combined sources3
Beta strandi33 – 37Combined sources5
Beta strandi45 – 49Combined sources5
Beta strandi53 – 55Combined sources3
Beta strandi58 – 61Combined sources4
Beta strandi64 – 67Combined sources4
Beta strandi70 – 72Combined sources3
Helixi85 – 87Combined sources3
Beta strandi89 – 93Combined sources5
Beta strandi97 – 99Combined sources3
Beta strandi102 – 108Combined sources7
Beta strandi110 – 113Combined sources4
Beta strandi118 – 121Combined sources4
Beta strandi129 – 131Combined sources3
Beta strandi136 – 138Combined sources3
Beta strandi143 – 145Combined sources3
Beta strandi156 – 158Combined sources3
Beta strandi167 – 170Combined sources4
Beta strandi180 – 182Combined sources3
Beta strandi234 – 236Combined sources3
Beta strandi258 – 260Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CDFmodel-A24-144[»]
1CZZX-ray2.70D/E250-258[»]
1D00X-ray2.00I/J/K/L/M/N/O/P250-254[»]
1FLLX-ray3.50X/Y246-266[»]
1LB6X-ray1.80B230-236[»]
3QD6X-ray3.50R/S/T/U21-190[»]
5DMIX-ray3.69A23-193[»]
5DMJX-ray2.79A/D/F23-193[»]
5IHLX-ray3.30A/D/F/H23-193[»]
ProteinModelPortaliP25942.
SMRiP25942.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP25942.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati25 – 60TNFR-Cys 1Add BLAST36
Repeati61 – 103TNFR-Cys 2Add BLAST43
Repeati104 – 144TNFR-Cys 3Add BLAST41
Repeati145 – 187TNFR-Cys 4Add BLAST43

Sequence similaritiesi

Contains 4 TNFR-Cys repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IY0H. Eukaryota.
ENOG4112DB5. LUCA.
GeneTreeiENSGT00760000119204.
HOVERGENiHBG005117.
InParanoidiP25942.
KOiK03160.
OMAiEKCHPWT.
OrthoDBiEOG091G03XW.
PhylomeDBiP25942.
TreeFamiTF331157.

Family and domain databases

InterProiIPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020435. TNFR_5.
[Graphical view]
PfamiPF00020. TNFR_c6. 1 hit.
[Graphical view]
PRINTSiPR01922. TNFACTORR5.
SMARTiSM00208. TNFR. 4 hits.
[Graphical view]
PROSITEiPS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 4 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform I (identifier: P25942-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVRLPLQCVL WGCLLTAVHP EPPTACREKQ YLINSQCCSL CQPGQKLVSD
60 70 80 90 100
CTEFTETECL PCGESEFLDT WNRETHCHQH KYCDPNLGLR VQQKGTSETD
110 120 130 140 150
TICTCEEGWH CTSEACESCV LHRSCSPGFG VKQIATGVSD TICEPCPVGF
160 170 180 190 200
FSNVSSAFEK CHPWTSCETK DLVVQQAGTN KTDVVCGPQD RLRALVVIPI
210 220 230 240 250
IFGILFAILL VLVFIKKVAK KPTNKAPHPK QEPQEINFPD DLPGSNTAAP
260 270
VQETLHGCQP VTQEDGKESR ISVQERQ
Length:277
Mass (Da):30,619
Last modified:May 1, 1992 - v1
Checksum:iBC8776EC2C4A5680
GO
Isoform II (identifier: P25942-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     166-203: SCETKDLVVQ...ALVVIPIIFG → RSPGSAESPG...YQKGGQEANQ
     204-277: Missing.

Show »
Length:203
Mass (Da):22,259
Checksum:i07399D5F79D59A4F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti112T → A in BAD96616 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03930126C → Q in bladder carcinoma cell line Hu549; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_03930235S → G in bladder carcinoma cell line Hu549. 1 PublicationCorresponds to variant rs750234130dbSNPEnsembl.1
Natural variantiVAR_03930339S → T in bladder carcinoma cell line Hu549. 1 Publication1
Natural variantiVAR_01362883C → R in HIGM3. 1 PublicationCorresponds to variant rs28931586dbSNPEnsembl.1
Natural variantiVAR_018751124S → L.1 PublicationCorresponds to variant rs11569321dbSNPEnsembl.1
Natural variantiVAR_018752227P → A.1 PublicationCorresponds to variant rs11086998dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006472166 – 203SCETK…PIIFG → RSPGSAESPGGDPHHLRDPV CHPLGAGLYQKGGQEANQ in isoform II. 1 PublicationAdd BLAST38
Alternative sequenceiVSP_006473204 – 277Missing in isoform II. 1 PublicationAdd BLAST74

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60592 mRNA. Translation: CAA43045.1.
AJ300189 mRNA. Translation: CAC29424.1.
BT019901 mRNA. Translation: AAV38704.1.
AK222896 mRNA. Translation: BAD96616.1.
AY504960 Genomic DNA. Translation: AAR84238.1.
EF064754 Genomic DNA. Translation: ABK41937.1.
AL035662 Genomic DNA. Translation: CAC17670.1.
AL035662 Genomic DNA. Translation: CAI42973.1.
CH471077 Genomic DNA. Translation: EAW75758.1.
CH471077 Genomic DNA. Translation: EAW75760.1.
CH471077 Genomic DNA. Translation: EAW75762.1.
BC012419 mRNA. Translation: AAH12419.1.
AY225405 mRNA. Translation: AAO43990.1.
CCDSiCCDS13393.1. [P25942-1]
CCDS13394.1. [P25942-2]
PIRiB60771.
S04460. A60771.
RefSeqiNP_001241.1. NM_001250.5. [P25942-1]
NP_001289682.1. NM_001302753.1.
NP_001309351.1. NM_001322422.1.
NP_690593.1. NM_152854.3. [P25942-2]
UniGeneiHs.472860.

Genome annotation databases

EnsembliENST00000372276; ENSP00000361350; ENSG00000101017. [P25942-2]
ENST00000372285; ENSP00000361359; ENSG00000101017. [P25942-1]
GeneIDi958.
KEGGihsa:958.
UCSCiuc002xrg.2. human. [P25942-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

CD40base

CD40 mutation db

NIEHS-SNPs
Wikipedia

CD40 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60592 mRNA. Translation: CAA43045.1.
AJ300189 mRNA. Translation: CAC29424.1.
BT019901 mRNA. Translation: AAV38704.1.
AK222896 mRNA. Translation: BAD96616.1.
AY504960 Genomic DNA. Translation: AAR84238.1.
EF064754 Genomic DNA. Translation: ABK41937.1.
AL035662 Genomic DNA. Translation: CAC17670.1.
AL035662 Genomic DNA. Translation: CAI42973.1.
CH471077 Genomic DNA. Translation: EAW75758.1.
CH471077 Genomic DNA. Translation: EAW75760.1.
CH471077 Genomic DNA. Translation: EAW75762.1.
BC012419 mRNA. Translation: AAH12419.1.
AY225405 mRNA. Translation: AAO43990.1.
CCDSiCCDS13393.1. [P25942-1]
CCDS13394.1. [P25942-2]
PIRiB60771.
S04460. A60771.
RefSeqiNP_001241.1. NM_001250.5. [P25942-1]
NP_001289682.1. NM_001302753.1.
NP_001309351.1. NM_001322422.1.
NP_690593.1. NM_152854.3. [P25942-2]
UniGeneiHs.472860.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CDFmodel-A24-144[»]
1CZZX-ray2.70D/E250-258[»]
1D00X-ray2.00I/J/K/L/M/N/O/P250-254[»]
1FLLX-ray3.50X/Y246-266[»]
1LB6X-ray1.80B230-236[»]
3QD6X-ray3.50R/S/T/U21-190[»]
5DMIX-ray3.69A23-193[»]
5DMJX-ray2.79A/D/F23-193[»]
5IHLX-ray3.30A/D/F/H23-193[»]
ProteinModelPortaliP25942.
SMRiP25942.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107396. 47 interactors.
DIPiDIP-3014N.
IntActiP25942. 5 interactors.
MINTiMINT-1505936.
STRINGi9606.ENSP00000361359.

Chemistry databases

BindingDBiP25942.
ChEMBLiCHEMBL1250358.

PTM databases

iPTMnetiP25942.
PhosphoSitePlusiP25942.

Polymorphism and mutation databases

BioMutaiCD40.
DMDMi116000.

Proteomic databases

MaxQBiP25942.
PaxDbiP25942.
PeptideAtlasiP25942.
PRIDEiP25942.

Protocols and materials databases

DNASUi958.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372276; ENSP00000361350; ENSG00000101017. [P25942-2]
ENST00000372285; ENSP00000361359; ENSG00000101017. [P25942-1]
GeneIDi958.
KEGGihsa:958.
UCSCiuc002xrg.2. human. [P25942-1]

Organism-specific databases

CTDi958.
DisGeNETi958.
GeneCardsiCD40.
HGNCiHGNC:11919. CD40.
HPAiCAB002495.
CAB072868.
HPA031567.
HPA031568.
MalaCardsiCD40.
MIMi109535. gene.
606843. phenotype.
neXtProtiNX_P25942.
OpenTargetsiENSG00000101017.
Orphaneti101090. Hyper-IgM syndrome type 3.
PharmGKBiPA36612.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IY0H. Eukaryota.
ENOG4112DB5. LUCA.
GeneTreeiENSGT00760000119204.
HOVERGENiHBG005117.
InParanoidiP25942.
KOiK03160.
OMAiEKCHPWT.
OrthoDBiEOG091G03XW.
PhylomeDBiP25942.
TreeFamiTF331157.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101017-MONOMER.
ReactomeiR-HSA-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
R-HSA-5668541. TNFR2 non-canonical NF-kB pathway.
R-HSA-5676594. TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway.
SIGNORiP25942.

Miscellaneous databases

EvolutionaryTraceiP25942.
GeneWikiiCD40_(protein).
GenomeRNAii958.
PMAP-CutDBP25942.
PROiP25942.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101017.
CleanExiHS_CD40.
ExpressionAtlasiP25942. baseline and differential.
GenevisibleiP25942. HS.

Family and domain databases

InterProiIPR001368. TNFR/NGFR_Cys_rich_reg.
IPR020435. TNFR_5.
[Graphical view]
PfamiPF00020. TNFR_c6. 1 hit.
[Graphical view]
PRINTSiPR01922. TNFACTORR5.
SMARTiSM00208. TNFR. 4 hits.
[Graphical view]
PROSITEiPS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNR5_HUMAN
AccessioniPrimary (citable) accession number: P25942
Secondary accession number(s): E1P5S9
, Q53GN5, Q5JY15, Q5U007, Q7M4Q8, Q86YK5, Q9BYU0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: November 30, 2016
This is version 197 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.