Protein:ADAM10 |
Protein Summary |
 Gene summary |
| Gene name: ADAM10 | ASpdb.0 ID: 102 | Gene | Gene symbol | ADAM10 | Gene ID | 102 |
| Gene name | ADAM metallopeptidase domain 10 |
| Synonyms | AD10|AD18|CD156c|CDw156|HsT18717|MADM|RAK|kuz |
| Cytomap | 15q21.3 |
| Type of gene | protein-coding |
| Description | disintegrin and metalloproteinase domain-containing protein 10a disintegrin and metalloprotease domain 10kuzbanian protein homologmammalian disintegrin-metalloprotease |
| Modification date | 20240411 |
| UniProtAcc | O14672 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | ADAM10 | GO:0004222 | metalloendopeptidase activity | 18676862 |
| Gene | ADAM10 | GO:0005794 | Golgi apparatus | 12475894 |
| Gene | ADAM10 | GO:0005798 | Golgi-associated vesicle | 12475894 |
| Gene | ADAM10 | GO:0005886 | plasma membrane | - |
| Gene | ADAM10 | GO:0006509 | membrane protein ectodomain proteolysis | 18355449 |
| Gene | ADAM10 | GO:0006509 | membrane protein ectodomain proteolysis | 12714508|17557115|18419754|18676862|19114711|31792032|34739841 |
| Gene | ADAM10 | GO:0007162 | negative regulation of cell adhesion | 12714508 |
| Gene | ADAM10 | GO:0008237 | metallopeptidase activity | 12475894 |
| Gene | ADAM10 | GO:0009986 | cell surface | 12475894|23035126|23091066 |
| Gene | ADAM10 | GO:0034612 | response to tumor necrosis factor | 11831872 |
| Gene | ADAM10 | GO:0043231 | intracellular membrane-bounded organelle | - |
| Gene | ADAM10 | GO:0051089 | constitutive protein ectodomain proteolysis | 12714508 |
| Gene | ADAM10 | GO:0097038 | perinuclear endoplasmic reticulum | 23091066 |
| Gene | ADAM10 | GO:0097060 | synaptic membrane | 23676497 |
| Gene | ADAM10 | GO:0097197 | tetraspanin-enriched microdomain | 23035126 |
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 |
| O14672-1 | O14672-1_6be6_C.pdb | 6BE6 | X-ray | 2.8 | C | 217 | 654 |
| 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 |
| O14672 | ADAM10 | O14672-1 | O14672-2 | 748 | 447 | 19 | 319 | Deletion | none | none | 18 | 18 |
| Multiple sequence alignment of our canonical and alternatively spliced ADAM10 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ADAM10 |
| UniProt-id | ENSG | ENST | ENSP |
| O14672-1 | ENSG00000137845.15 | ENST00000260408.8 | ENSP00000260408.3 |
| UniProt-id | NM ID | NP ID |
| O14672-1 | NM_001110.3 | NP_001101.1 |
| Amino acid sequences of our canonical and alternatively spliced ADAM10 |
| accession_id | Protein sequence |
| O14672-1 | MVLLRVLILLLSWAAGMGGQYGNPLNKYIRHYEGLSYNVDSLHQKHQRAKRAVSHEDQFLRLDFHAHGRHFNLRMKRDTSLFSDEFKVET SNKVLDYDTSHIYTGHIYGEEGSFSHGSVIDGRFEGFIQTRGGTFYVEPAERYIKDRTLPFHSVIYHEDDINYPHKYGPQGGCADHSVFE RMRKYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISF MVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNT GIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNN CFVESGQPICGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFT ALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGS PCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTL |
| O14672-2 | MVLLRVLILLLSWAAGMGDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGS PHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCKD ECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALCPASDPKPNFTDCNRHTQVCINGQCAGSI CEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAI |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| ADAM10 (go to UniProt):O14672 |
| 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 |
| O14672 | Topological domain | 20 | 672 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=19;End=319 |
| O14672 | Domain | 220 | 456 | Note=Peptidase M12B;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00276 | Type=Deletion;Start=19;End=319 |
| O14672 | Motif | 171 | 178 | Note=Cysteine switch;Ontology_term=ECO:0000250;evidence=ECO:0000250 | Type=Deletion;Start=19;End=319 |
Gene Isoform Structures and Expression Levels for ADAM10 |
| Gene structures of our canonical and alternative spliced genes of ADAM10 * 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 O14672-1 |
| 3D view using mol* of O14672-2 |
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 O14672-1 |
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| pLDDT distribution across the protein length of O14672-2 |
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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 O14672-1 |
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| Ramachandran plot of O14672-2 |
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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 |
| O14672-1 | 1.023 | 302 | 1.052 | 709.667 | 0.545 | 0.711 | 0.935 | 0.499 | 0.967 | 0.516 | 1.166 | 12,13,14,15,16,17,18,21,30,31,34,36,37,38,41,42,45 ,62,63,64,67,69,70,71,72,107,108,109,110,130,131,1 32,135,150,151,157,159,160,162,523,524,525,526,527 ,528,530,531,532,545,546,548,557,560,564,565,566,5 67,568,627,628,641 |
| O14672-2 | 1.028 | 177 | 1.003 | 403.368 | 0.511 | 0.74 | 0.971 | 0.416 | 1.169 | 0.356 | 1.034 | 25,26,27,28,29,30,75,78,79,82,83,86,91,92,93,94,95 ,99,102,115,117,118,119,120,121,332,335,337,346,34 7,348,349,350,351,354,358 |
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 O14672-1_O14672-1_6be6_C.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O14672-1_6be6_C_O14672-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O14672-1_O14672-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/O14672-1_vs_O14672-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/O14672-1_vs_O14672-2.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 ADAM10 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| O14672 | ADAM10 | DB04991 | XL784 | investigational |
Related Diseases to ADAM10 |
| Previous studies relating to the alternative splicing of ADAM10 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| ADAM10 | 18952609 | Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases. | The receptor for advanced glycation end products (RAGE) is a 55-kDa type I membrane glycoprotein of the immunoglobulin superfamily. Ligand-induced up-regulation of RAGE is involved in various pathophysiological processes, including late diabetic complications and Alzheimer disease. Application of recombinant soluble RAGE has been shown to block RAGE-mediated pathophysiological conditions. After expression of full-length RAGE in HEK cells we identified a 48-kDa soluble RAGE form (sRAGE) in the culture medium. This variant of RAGE is smaller than a 51-kDa soluble version derived from alternative splicing. The release of sRAGE can be induced by the phorbol ester PMA and the calcium ionophore calcimycin via calcium-dependent protein kinase C subtypes. Hydroxamic acid-based metalloproteinase inhibitors block the release of sRAGE, and by RNA interference experiments we identified ADAM10 and MMP9 to be involved in RAGE shedding. In protein biotinylation experiments we show that membrane-anchored full-length RAGE is the precursor of sRAGE and that sRAGE is efficiently released from the cell surface. We identified cleavage of RAGE to occur close to the cell membrane. Ectodomain shedding of RAGE simultaneously generates sRAGE and a membrane-anchored C-terminal RAGE fragment (RAGE-CTF). The amount of RAGE-CTF increases when RAGE-expressing cells are treated with a gamma-secretase inhibitor, suggesting that RAGE-CTF is normally further processed by gamma-secretase. Identification of these novel mechanisms involved in regulating the availability of cell surface-located RAGE and its soluble ectodomain may influence further research in RAGE-mediated processes in cell biology and pathophysiology. | D000544 | Alzheimer Disease |
| ADAM10 | 18952609 | Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases. | The receptor for advanced glycation end products (RAGE) is a 55-kDa type I membrane glycoprotein of the immunoglobulin superfamily. Ligand-induced up-regulation of RAGE is involved in various pathophysiological processes, including late diabetic complications and Alzheimer disease. Application of recombinant soluble RAGE has been shown to block RAGE-mediated pathophysiological conditions. After expression of full-length RAGE in HEK cells we identified a 48-kDa soluble RAGE form (sRAGE) in the culture medium. This variant of RAGE is smaller than a 51-kDa soluble version derived from alternative splicing. The release of sRAGE can be induced by the phorbol ester PMA and the calcium ionophore calcimycin via calcium-dependent protein kinase C subtypes. Hydroxamic acid-based metalloproteinase inhibitors block the release of sRAGE, and by RNA interference experiments we identified ADAM10 and MMP9 to be involved in RAGE shedding. In protein biotinylation experiments we show that membrane-anchored full-length RAGE is the precursor of sRAGE and that sRAGE is efficiently released from the cell surface. We identified cleavage of RAGE to occur close to the cell membrane. Ectodomain shedding of RAGE simultaneously generates sRAGE and a membrane-anchored C-terminal RAGE fragment (RAGE-CTF). The amount of RAGE-CTF increases when RAGE-expressing cells are treated with a gamma-secretase inhibitor, suggesting that RAGE-CTF is normally further processed by gamma-secretase. Identification of these novel mechanisms involved in regulating the availability of cell surface-located RAGE and its soluble ectodomain may influence further research in RAGE-mediated processes in cell biology and pathophysiology. | D048909 | Diabetes Complications |
Clinically important variants in ADAM10 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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