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Protein

Tumor necrosis factor receptor superfamily member 5

Gene

CD40

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • protein domain specific binding Source: Ensembl
  • signaling receptor activity Source: ProtInc
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processImmunity

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000101017.13
HGNCiHGNC:11919 CD40
MIMi109535 gene
neXtProtiNX_P25942

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency with hyper-IgM 3 (HIGM3)2 Publications
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_07756937C → G in HIGM3. 1 Publication1
Natural variantiVAR_01362883C → R in HIGM3. 1 PublicationCorresponds to variant dbSNP:rs28931586EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry databases

ChEMBLiCHEMBL1250358
GuidetoPHARMACOLOGYi1874

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...) asparagineSequence analysis1
Glycosylationi180N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP25942
MaxQBiP25942
PaxDbiP25942
PeptideAtlasiP25942
PRIDEiP25942
ProteomicsDBi54302
54303 [P25942-2]

PTM databases

GlyConnecti1866
iPTMnetiP25942
PhosphoSitePlusiP25942

Miscellaneous databases

PMAP-CutDBiP25942

Expressioni

Tissue specificityi

B-cells and in primary carcinomas.

Gene expression databases

BgeeiENSG00000101017 Expressed in 203 organ(s), highest expression level in left coronary artery
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107396, 48 interactors
DIPiDIP-3014N
ELMiP25942
IntActiP25942, 24 interactors
STRINGi9606.ENSP00000361359

Chemistry databases

BindingDBiP25942

Structurei

Secondary structure

1277
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IY0H Eukaryota
ENOG4112DB5 LUCA
GeneTreeiENSGT00760000119204
HOVERGENiHBG005117
InParanoidiP25942
KOiK03160
OMAiPGLGVKQ
OrthoDBiEOG091G03XW
PhylomeDBiP25942
TreeFamiTF331157

Family and domain databases

CDDicd13407 TNFRSF5, 1 hit
InterProiView protein in InterPro
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR020435 TNFR_5
IPR034021 TNFRSF5_N
PfamiView protein in Pfam
PF00020 TNFR_c6, 1 hit
PRINTSiPR01922 TNFACTORR5
SMARTiView protein in SMART
SM00208 TNFR, 4 hits
PROSITEiView protein in PROSITE
PS00652 TNFR_NGFR_1, 1 hit
PS50050 TNFR_NGFR_2, 4 hits

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.

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YE23H0YE23_HUMAN
Tumor necrosis factor receptor supe...
CD40
159Annotation score:
A0A087X1D0A0A087X1D0_HUMAN
CD40 antigen (TNF receptor superfam...
CD40 hCG_40016
151Annotation score:

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 dbSNP:rs750234130Ensembl.1
Natural variantiVAR_07756937C → G in HIGM3. 1 Publication1
Natural variantiVAR_03930339S → T in bladder carcinoma cell line Hu549. 1 Publication1
Natural variantiVAR_01362883C → R in HIGM3. 1 PublicationCorresponds to variant dbSNP:rs28931586EnsemblClinVar.1
Natural variantiVAR_018751124S → L1 PublicationCorresponds to variant dbSNP:rs11569321EnsemblClinVar.1
Natural variantiVAR_018752227P → A1 PublicationCorresponds to variant dbSNP:rs11086998EnsemblClinVar.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 No translation available.
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

Similar proteinsi

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 No translation available.
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[»]
6FAXX-ray2.99R21-193[»]
ProteinModelPortaliP25942
SMRiP25942
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107396, 48 interactors
DIPiDIP-3014N
ELMiP25942
IntActiP25942, 24 interactors
STRINGi9606.ENSP00000361359

Chemistry databases

BindingDBiP25942
ChEMBLiCHEMBL1250358
GuidetoPHARMACOLOGYi1874

PTM databases

GlyConnecti1866
iPTMnetiP25942
PhosphoSitePlusiP25942

Polymorphism and mutation databases

BioMutaiCD40
DMDMi116000

Proteomic databases

EPDiP25942
MaxQBiP25942
PaxDbiP25942
PeptideAtlasiP25942
PRIDEiP25942
ProteomicsDBi54302
54303 [P25942-2]

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
EuPathDBiHostDB:ENSG00000101017.13
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
OMAiPGLGVKQ
OrthoDBiEOG091G03XW
PhylomeDBiP25942
TreeFamiTF331157

Enzyme and pathway databases

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

ChiTaRSiCD40 human
EvolutionaryTraceiP25942
GeneWikiiCD40_(protein)
GenomeRNAii958
PMAP-CutDBiP25942
PROiPR:P25942
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101017 Expressed in 203 organ(s), highest expression level in left coronary artery
CleanExiHS_CD40
ExpressionAtlasiP25942 baseline and differential
GenevisibleiP25942 HS

Family and domain databases

CDDicd13407 TNFRSF5, 1 hit
InterProiView protein in InterPro
IPR001368 TNFR/NGFR_Cys_rich_reg
IPR020435 TNFR_5
IPR034021 TNFRSF5_N
PfamiView protein in Pfam
PF00020 TNFR_c6, 1 hit
PRINTSiPR01922 TNFACTORR5
SMARTiView protein in SMART
SM00208 TNFR, 4 hits
PROSITEiView protein in PROSITE
PS00652 TNFR_NGFR_1, 1 hit
PS50050 TNFR_NGFR_2, 4 hits
ProtoNetiSearch...

Entry informationi

Entry nameiTNR5_HUMAN
AccessioniPrimary (citable) accession number: P25942
Secondary accession number(s): E1P5S9
, Q53GN5, Q5JY15, Q5U007, Q7M4Q8, Q86YK5, Q9BYU0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: November 7, 2018
This is version 218 of the entry and version 1 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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Main funding by: National Institutes of Health

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