|
|
|
Primary Information | |
|---|---|
| BoMiProt ID | Bomi210 |
| Protein Name | Disintegrin and metalloproteinase domain-containing protein 10 |
| Organism | Bos taurus |
| Uniprot ID | Q10741 |
| Milk Fraction | Whey, Exosome |
| Ref Sequence ID | NP_776921.1 |
| Aminoacid Length | 748 |
| Molecular Weight | 84188 |
| FASTA Sequence | Download |
| Gene Name | ADAM10 |
| Gene ID | 282132 |
| Protein Existence Status | Reviewed: Experimental evidence at protein level |
Secondary Information | |
| Presence in other biological fluids/tissue/cells | detected in secreted vesicles identified as exosomes; |
| Protein Function | metalloproteinases; regulate the bioavailability of adhesion molecules and ligands to various cellularsignaling receptors; functions include: (i) collagen processing as procollagen N-proteinase; (ii) cleavage of the matrix proteoglycans aggrecan, versican and brevican; (iii) inhibition of angiogenesis; and (iv) blood coagulation homoeostasis as the von Willebrand factor cleaving protease; involved in the intramembrane proteolysis process, whereby it mediates ectodomain shedding of various membrane-bound receptors, adhesion molecules, growth factors, and cytokines; involved in the regulation of the shedding of Notch, HER-2, CD44, IL-6 receptor,amyloid precursor protein, and cadherins; modulates the activation status of various cellularsignaling pathways that have an impact on cellular responses such as proliferation and migration; Disintegrin And Metalloproteinase 10 (ADAM10), a zinc-dependent protease, was heavily invested in by the pharmaceutical industry |
| Biochemical Properties | extracellular, multidomain enzymes; paired basic amino acid converting enzyme; secreted as a precursor protein and consists of multiple functional domains, including a prodomain, catalytic domain, cysteine-rich domain, transmembranous domain, and cytoplasmic domain |
| PTMs | As found in bovine ADAM 10, four potential N-glycosylation sites (N267, N278, N439 and N551); contain high-mannose and complex-type glycans; three located in the metalloprotease domain (N267, N278 and N439) and one in the disintegrin domain (N551) |
| Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation | >sp|Q10741|ADA10_BOVIN Disintegrin and metalloproteinase domain-containing protein 10 OS=Bos taurus OX=9913 GN=ADAM10 PE=1 SV=1 MVLLRVLILLLSWVAGLGGQYGNPLNKYIRHYEGLSYDVDSLHQKHQRAKRAVSHEDQFL RLDFHAHGRHFNLRMKRDTSLFSEEFRVETSNAVLDYDTSHIYTGHIYGEEGSFSHGSVI DGRFEGFIQTHGGTFYVEPAERYIKDRTLPFHSVIYHEDDIKYPHKYGPQGGCADHSVFE RMRKYQMTGVEEVTQTPQEKHAINGPELLRKKRTTVAEKNTCQLYIQTDHLFFKYYGTRE AVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKF LELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNT GIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYAR ATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCK DECCYDANQPEGKKCKLKPGKQCSPSQGPCCTAHCAFKSKTEKCRDDSDCAKEGICNGIT ALCPASDPKPN*551FTDCNRHTQVCINGQCAGSICEKHGLEECTCASSDGKDDKELCHVCCMK KMEPSTCASTGSVQWNKYFLGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKA IFSPELYENIAEWIVAYWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTL KRRRPPQPIQQPQRQRPRESYQMGHMRR |
| CATH | Matched CATH superfamily 2.60.40.10 |
| Predicted Disorder Regions | (704-748) |
| DisProt Annotation | |
| TM Helix Prediction | 1TMH; (674-696) |
| Significance of PTMs | role in processing, stability, activity and intracellular localization of ADAM 10; N278 are important for the folding of the protein probably mediating the interaction with calnexin; N439 glycosylation site resulted in increased susceptibility of bADAM10 to proteases |
| PDB ID | 5L0Q,2AO7, |
| Bibliography | 1. Armanious, H., Gelebart, P., Anand, M., Belch, A., & Lai, R. (2011). Constitutive activation of metalloproteinase ADAM10 in mantle cell lymphoma promotes cell growth and activates the TNFα/NFκB pathway. Blood, 117(23), 6237–6246. https://doi.org/10.1182/blood-2010-10-313940. 2. Kuno, K., Kanada, N., Nakashima, E., Fujiki, F., Ichimura, F., & Matsushima, K. (1997). Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombospondin motifs as an inflammation associated gene. The Journal of Biological Chemistry, 272(1), 556–562. https://doi.org/10.1074/jbc.272.1.556. 3. Escrevente, C., Morais, V. A., Keller, S., Soares, C. M., Altevogt, P., & Costa, J. (2008). Functional role of N-glycosylation from ADAM10 in processing, localization and activity of the enzyme. Biochimica et Biophysica Acta, 1780(6), 905–913. https://doi.org/10.1016/j.bbagen.2008.03.004. 4.Atapattu L, Saha N, Chheang C, Eissman MF, Xu K, Vail ME, Hii L, Llerena C, Liu Z, Horvay K, Abud HE, Kusebauch U, Moritz RL, Ding BS, Cao Z, Rafii S, Ernst M, Scott AM, Nikolov DB, Lackmann M, Janes PW. An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth. J Exp Med. 2016 Aug 22;213(9):1741-57. doi: 10.1084/jem.20151095. Epub 2016 Aug 8. PMID: 27503072; PMCID: PMC4995075. 5.Smith TM Jr, Tharakan A, Martin RK. Targeting ADAM10 in Cancer and Autoimmunity. Front Immunol. 2020 Mar 24;11:499. doi: 10.3389/fimmu.2020.00499. PMID: 32265938; PMCID: PMC7105615. |