Protein:TNFRSF8 |
Protein Summary |
 Gene summary |
| Gene name: TNFRSF8 | ASpdb.0 ID: 943 | Gene | Gene symbol | TNFRSF8 | Gene ID | 943 |
| Gene name | TNF receptor superfamily member 8 |
| Synonyms | CD30|D1S166E|Ki-1 |
| Cytomap | 1p36.22 |
| Type of gene | protein-coding |
| Description | tumor necrosis factor receptor superfamily member 8CD30L receptorKi-1 antigencytokine receptor CD30lymphocyte activation antigen CD30 |
| Modification date | 20240407 |
| UniProtAcc | P28908 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TNFRSF8 | GO:0005654 | nucleoplasm | - |
| Gene | TNFRSF8 | GO:0005886 | plasma membrane | - |
| Gene | TNFRSF8 | GO:0032759 | positive regulation of TRAIL production | 16108830 |
| Gene | TNFRSF8 | GO:0032760 | positive regulation of tumor necrosis factor production | 16108830 |
| Gene | TNFRSF8 | GO:0043065 | positive regulation of apoptotic process | 16108830 |
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 |
| P28908-1 | P28908-1_1d01_G.pdb | 1D01 | X-ray | 2.0 | G | 576 | 583 |
| 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 |
| P28908 | TNFRSF8 | P28908-1 | P28908-2 | 595 | 132 | 1 | 463 | Deletion | none | none | 0 | 0 |
| P28908 | TNFRSF8 | P28908-1 | P28908-3 | 595 | 483 | 1 | 111 | Deletion | none | none | 0 | 0 |
| P28908 | TNFRSF8 | P28908-1 | P28908-3 | 595 | 483 | 446 | 446 | Deletion | none | none | 334 | 334 |
| Multiple sequence alignment of our canonical and alternatively spliced TNFRSF8 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TNFRSF8 |
| UniProt-id | ENSG | ENST | ENSP |
| P28908-1 | ENSG00000120949.15 | ENST00000263932.7 | ENSP00000263932.2 |
| P28908-2 | ENSG00000120949.15 | ENST00000413146.6 | ENSP00000398337.2 |
| P28908-3 | ENSG00000120949.15 | ENST00000417814.3 | ENSP00000390650.2 |
| UniProt-id | NM ID | NP ID |
| P28908-1 | NM_001243.4 | NP_001234.3 |
| P28908-3 | NM_001281430.2 | NP_001268359.2 |
| Amino acid sequences of our canonical and alternatively spliced TNFRSF8 |
| accession_id | Protein sequence |
| P28908-1 | MRVLLAALGLLFLGALRAFPQDRPFEDTCHGNPSHYYDKAVRRCCYRCPMGLFPTQQCPQRPTDCRKQCEPDYYLDEADRCTACVTCSRD DLVEKTPCAWNSSRVCECRPGMFCSTSAVNSCARCFFHSVCPAGMIVKFPGTAQKNTVCEPASPGVSPACASPENCKEPSSGTIPQAKPT PVSPATSSASTMPVRGGTRLAQEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDCRKQCEPDYYLDEAGRCTACVSCSRDDLVEK TPCAWNSSRTCECRPGMICATSATNSCARCVPYPICAAETVTKPQDMAEKDTTFEAPPLGTQPDCNPTPENGEAPASTSPTQSLLVDSQA SKTLPIPTSAPVALSSTGKPVLDAGPVLFWVILVLVVVVGSSAFLLCHRRACRKRIRQKLHLCYPVQTSQPKLELVDSRPRRSSTQLRSG ASVTEPVAEERGLMSQPLMETCHSVGAAYLESLPLQDASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVGTVKAELPEGRGL |
| P28908-2 | MSQPLMETCHSVGAAYLESLPLQDASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVGTVKAELPEGRGLAGPAEPELEEELE |
| P28908-3 | MFCSTSAVNSCARCFFHSVCPAGMIVKFPGTAQKNTVCEPASPGVSPACASPENCKEPSSGTIPQAKPTPVSPATSSASTMPVRGGTRLA QEAASKLTRAPDSPSSVGRPSSDPGLSPTQPCPEGSGDCRKQCEPDYYLDEAGRCTACVSCSRDDLVEKTPCAWNSSRTCECRPGMICAT SATNSCARCVPYPICAAETVTKPQDMAEKDTTFEAPPLGTQPDCNPTPENGEAPASTSPTQSLLVDSQASKTLPIPTSAPVALSSTGKPV LDAGPVLFWVILVLVVVVGSSAFLLCHRRACRKRIRQKLHLCYPVQTSQPKLELVDSRPRRSSTLRSGASVTEPVAEERGLMSQPLMETC HSVGAAYLESLPLQDASPAGGPSSPRDLPEPRVSTEHTNNKIEKIYIMKADTVIVGTVKAELPEGRGLAGPAEPELEEELEADHTPHYPE |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TNFRSF8 (go to UniProt):P28908 |
| 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 |
| P28908 | Topological domain | 19 | 385 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=1;End=463 |
| P28908 | Topological domain | 19 | 385 | Note=Extracellular;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=1;End=111 |
| P28908 | Transmembrane | 386 | 406 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=1;End=463 |
| P28908 | Topological domain | 407 | 595 | Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=1;End=463 |
| P28908 | Topological domain | 407 | 595 | Note=Cytoplasmic;Ontology_term=ECO:0000305;evidence=ECO:0000305 | Type=Deletion;Start=446;End=446 |
| P28908 | Repeat | 28 | 66 | Note=TNFR-Cys 1 | Type=Deletion;Start=1;End=463 |
| P28908 | Repeat | 28 | 66 | Note=TNFR-Cys 1 | Type=Deletion;Start=1;End=111 |
| P28908 | Repeat | 68 | 106 | Note=TNFR-Cys 2 | Type=Deletion;Start=1;End=463 |
| P28908 | Repeat | 68 | 106 | Note=TNFR-Cys 2 | Type=Deletion;Start=1;End=111 |
| P28908 | Repeat | 107 | 150 | Note=TNFR-Cys 3 | Type=Deletion;Start=1;End=463 |
| P28908 | Repeat | 107 | 150 | Note=TNFR-Cys 3 | Type=Deletion;Start=1;End=111 |
| P28908 | Repeat | 205 | 241 | Note=TNFR-Cys 4 | Type=Deletion;Start=1;End=463 |
| P28908 | Repeat | 243 | 281 | Note=TNFR-Cys 5 | Type=Deletion;Start=1;End=463 |
| P28908 | Repeat | 282 | 325 | Note=TNFR-Cys 6 | Type=Deletion;Start=1;End=463 |
| P28908 | Region | 167 | 238 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=463 |
| P28908 | Region | 323 | 355 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=463 |
| P28908 | Region | 438 | 457 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=463 |
| P28908 | Region | 438 | 457 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=446;End=446 |
| P28908 | Compositional bias | 167 | 195 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=463 |
| P28908 | Compositional bias | 209 | 230 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=463 |
| P28908 | Compositional bias | 335 | 355 | Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=1;End=463 |
Gene Isoform Structures and Expression Levels for TNFRSF8 |
| Gene structures of our canonical and alternative spliced genes of TNFRSF8 * 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 P28908-1 |
| 3D view using mol* of P28908-2 |
| 3D view using mol* of P28908-3 |
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 P28908-1 |
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| pLDDT distribution across the protein length of P28908-2 |
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| pLDDT distribution across the protein length of P28908-3 |
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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 P28908-1 |
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| Ramachandran plot of P28908-2 |
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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 |
| P28908-1 | 0.842 | 63 | 0.847 | 198.597 | 0.741 | 0.635 | 0.826 | 0.445 | 0.858 | 0.519 | 0.776 | 229,230,231,232,233,237,238,240,241,242,243,244,25 0,254,255,256,275 |
| P28908-2 | 0.403 | 16 | 0.245 | 5.145 | 0.765 | 0.463 | 0.623 | 0 | 1.254 | 0 | 2.38 | 45,47,50,70,71,72,73
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| P28908-3 | 0.455 | 18 | 0.38 | 39.788 | 0.772 | 0.492 | 0.623 | 0 | 0.963 | 0 | 0.86 | 138,160,166,167,169,183,184
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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 P28908-1_P28908-1_1d01_G.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P28908-1_1d01_G_P28908-2.pdb |
| 3D view using mol* of P28908-1_1d01_G_P28908-3.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P28908-1_P28908-2.pdb |
| 3D view using mol* of P28908-1_P28908-3.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P28908-1_vs_P28908-2.png |
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| ./stats/secondary_structure/figure/P28908-1_vs_P28908-3.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P28908-1_vs_P28908-2.png |
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| ./stats/relative_asa/P28908-1_vs_P28908-3.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 TNFRSF8 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P28908 | TNFRSF8 | DB06324 | XmAb 2513 | investigational | |
| P28908 | TNFRSF8 | DB08870 | Brentuximab vedotin | approved, investigational | binder, antibody, regulator |
| P28908 | TNFRSF8 | DB05550 | Iratumumab | investigational | antibody, regulator |
Related Diseases to TNFRSF8 |
| Previous studies relating to the alternative splicing of TNFRSF8 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| TNFRSF8 | 8839832 | A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages. | We identified and cloned cDNAs for two novel CD30 mRNAs of 2.3 kb that are induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in the human myeloid leukemia cell line HL-60. These transcripts were transcribed from the intronic region just upstream of the exon coding for the transmembrane domain of the CD30 protein. The shorter cDNA had a deletion of 54 nucleotides corresponding to the 3' region of the transmembrane domain of the CD30 and which was probably caused by alternative splicing. Translation of these transcripts appeared to start from the internal methionine codon at nucleotide position 289 that corresponds to that of 1612 in the CD30 cDNA, and encode a protein of 132 amino acid residues which corresponds exactly to the C-terminal cytoplasmic domain of CD30 protein. The calculated molecular mass of this variant CD30 (CD30v) protein was 14,087. Thus, the predicted CD30v protein retains most of the cytoplasmic region, but lacks the extracellular and transmembrane domains. Northern blots detected the expression of CD30v transcripts only in the lung and the TPA-stimulated HL-60 cell line. Translation of this mRNA in vitro produced a protein of 25 kD. Immunoblotting analysis with HCD30C1, a rabbit polyclonal antibody raised against the cytoplasmic domain of CD30 protein, detected proteins with an apparent Mr 25 kD expressed in TPA-stimulated HL-60 and COS-7 cells that were transfected with both types of CD30v cDNAs. Constitutive phosphorylation of the CD30v protein was demonstrated by in vitro labeling with [32P]. Immunohistochemical studies demonstrated CD30v protein was in alveolar macrophages. Cotransfection experiments using a kappa B-site-dependent reporter construct showed that CD30v can transactivate gene expression through activation of NF kappa B, as was noted on the authentic CD30 protein. Overexpression of the CD30v induced differentiation of HL-60 cells as evidenced by an increased NBT reduction activity. These observations provided new insights into the molecular heterogeneity and biological function of CD30 in myeloid cells. | D007951 | Leukemia, Myeloid |
| TNFRSF8 | 8839832 | A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages. | We identified and cloned cDNAs for two novel CD30 mRNAs of 2.3 kb that are induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in the human myeloid leukemia cell line HL-60. These transcripts were transcribed from the intronic region just upstream of the exon coding for the transmembrane domain of the CD30 protein. The shorter cDNA had a deletion of 54 nucleotides corresponding to the 3' region of the transmembrane domain of the CD30 and which was probably caused by alternative splicing. Translation of these transcripts appeared to start from the internal methionine codon at nucleotide position 289 that corresponds to that of 1612 in the CD30 cDNA, and encode a protein of 132 amino acid residues which corresponds exactly to the C-terminal cytoplasmic domain of CD30 protein. The calculated molecular mass of this variant CD30 (CD30v) protein was 14,087. Thus, the predicted CD30v protein retains most of the cytoplasmic region, but lacks the extracellular and transmembrane domains. Northern blots detected the expression of CD30v transcripts only in the lung and the TPA-stimulated HL-60 cell line. Translation of this mRNA in vitro produced a protein of 25 kD. Immunoblotting analysis with HCD30C1, a rabbit polyclonal antibody raised against the cytoplasmic domain of CD30 protein, detected proteins with an apparent Mr 25 kD expressed in TPA-stimulated HL-60 and COS-7 cells that were transfected with both types of CD30v cDNAs. Constitutive phosphorylation of the CD30v protein was demonstrated by in vitro labeling with [32P]. Immunohistochemical studies demonstrated CD30v protein was in alveolar macrophages. Cotransfection experiments using a kappa B-site-dependent reporter construct showed that CD30v can transactivate gene expression through activation of NF kappa B, as was noted on the authentic CD30 protein. Overexpression of the CD30v induced differentiation of HL-60 cells as evidenced by an increased NBT reduction activity. These observations provided new insights into the molecular heterogeneity and biological function of CD30 in myeloid cells. | D012859 | Sjogren's Syndrome |
Clinically important variants in TNFRSF8 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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