Protein:CD40 |
Protein Summary |
 Gene summary |
| Gene name: CD40 | ASpdb.0 ID: 958 | Gene | Gene symbol | CD40 | Gene ID | 958 |
| Gene name | CD40 molecule |
| Synonyms | Bp50|CDW40|TNFRSF5|p50 |
| Cytomap | 20q13.12 |
| Type of gene | protein-coding |
| Description | tumor necrosis factor receptor superfamily member 5B cell surface antigen CD40B cell-associated moleculeCD40 molecule, TNF receptor superfamily member 5CD40L receptor |
| Modification date | 20240411 |
| UniProtAcc | P25942 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CD40 | GO:0023035 | CD40 signaling pathway | 31331973 |
| Gene | CD40 | GO:2000353 | positive regulation of endothelial cell apoptotic process | 12885753 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P25942-1 | P25942-1_5ihl_A.pdb | 5IHL | X-ray | 3.3 | A | 23 | 190 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P25942 | CD40 | P25942-1 | P25942-2 | 277 | 203 | 166 | 203 | Substitution | SCETKDLVVQQAGTNKTDVVCGPQDRLRALVVIPIIFG | RSPGSAESPGGDPHHLRDPVCHPLGAGLYQKGGQEANQ | 166 | 203 |
| P25942 | CD40 | P25942-1 | P25942-2 | 277 | 203 | 204 | 277 | Deletion | none | none | 203 | 203 |
| Multiple sequence alignment of our canonical and alternatively spliced CD40 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CD40 |
| UniProt-id | ENSG | ENST | ENSP |
| P25942-1 | ENSG00000101017.15 | ENST00000372285.8 | ENSP00000361359.3 |
| P25942-2 | ENSG00000101017.15 | ENST00000372276.7 | ENSP00000361350.3 |
| UniProt-id | NM ID | NP ID |
| P25942-1 | NM_001250.5 | NP_001241.1 |
| P25942-2 | NM_152854.3 | NP_690593.1 |
| Amino acid sequences of our canonical and alternatively spliced CD40 |
| accession_id | Protein sequence |
| P25942-1 | MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLR VQQKGTSETDTICTCEEGWHCTSEACESCVLHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCETKDLVVQQAGTN KTDVVCGPQDRLRALVVIPIIFGILFAILLVLVFIKKVAKKPTNKAPHPKQEPQEINFPDDLPGSNTAAPVQETLHGCQPVTQEDGKESR |
| P25942-2 | MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTETECLPCGESEFLDTWNRETHCHQHKYCDPNLGLR VQQKGTSETDTICTCEEGWHCTSEACESCVLHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTRSPGSAESPGGDPHH |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CD40 (go to UniProt):P25942 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P25942 | Topological domain | 21 | 193 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=166;End=203 |
| P25942 | Transmembrane | 194 | 215 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=166;End=203 |
| P25942 | Transmembrane | 194 | 215 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=204;End=277 |
| P25942 | Topological domain | 216 | 277 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=204;End=277 |
| P25942 | Repeat | 145 | 187 | Note=TNFR-Cys 4 | Type=Substitution;Start=166;End=203 |
| P25942 | Region | 223 | 277 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=204;End=277 |
Gene Isoform Structures and Expression Levels for CD40 |
| Gene structures of our canonical and alternative spliced genes of CD40 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P25942-1 |
| 3D view using mol* of P25942-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P25942-1 |
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| pLDDT distribution across the protein length of P25942-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P25942-1 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P25942-1 | 0.396 | 11 | 0.312 | 28.126 | 0.853 | 0.485 | 0.591 | 0.086 | 0.893 | 0.096 | 0.873 | 90,105,106,107,108,109,122,135,136,137
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| P25942-2 | 0.711 | 30 | 0.697 | 105.644 | 0.756 | 0.641 | 0.794 | 0.962 | 0.622 | 1.547 | 1.231 | 127,128,151,152,153,164,188,191,192,194
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Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P25942-1_P25942-1_5ihl_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P25942-1_5ihl_A_P25942-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P25942-1_P25942-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P25942-1_vs_P25942-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P25942-1_vs_P25942-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CD40 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P25942 | CD40 | DB06360 | Lucatumumab | investigational | |
| P25942 | CD40 | DB12589 | Dacetuzumab | investigational |
Related Diseases to CD40 |
| Previous studies relating to the alternative splicing of CD40 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CD40 | 19751723 | Identification, characterisation and regulation by CD40 activation of novel CD95 splice variants in CD95-apoptosis-resistant, human, B-cell non-Hodgkin's lymphoma. | CD95 gene and splicing aberrations have been detected in B-cell non-Hodgkin lymphoma (B-NHL) where they are thought to contribute to CD95 apoptosis resistance. To further investigate this, we have performed extensive CD95 transcript sequencing and functional analysis in B-NHL with demonstrated resistance to CD95-induced apoptosis (B-NHLr). Strikingly, instead of showing CD95 mutations per se, B cells from B-NHLr co-expressed wild-type and multiple, normal (CD95nv) and novel alternatively spliced variant CD95 transcripts (CD95av). CD95av were predicted, by sequencing, to encode soluble, potentially apoptosis inhibitory proteins. However, their overexpression, by transfection, in Jurkat cells did not interfere with endogenous CD95 death signalling. Furthermore, CD95av-expressing B-NHLr did not show mutations in CD95 splice-regulatory elements and CD95av expression was 'reversible' by CD40 activation. This, in conjunction with treatment by the protein synthesis inhibitor, cycloheximide, could sensitise a subset of B-NHLr to CD95 apoptosis. In normal and lymphoma B cells, this correlated to increased CD95 membrane expression, enhanced DISC activity and engagement of the mitochondrial death pathway via Bid cleavage, although the latter occurred less efficiently in B-NHLr. Thus, immune modulation of CD95 transcription and alternative splicing combined with enhanced engagement of mitochondrial death signalling offer potential for restoration of CD95 apoptosis sensitivity in B-NHLr. | D016393 | Lymphoma, B-Cell |
Clinically important variants in CD40 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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