ADAM (protein)

For the fictional biologically active substance called ADAM, see BioShock.
Diagram of an ectodomain shedding ADAM metalloprotease.
Disintegrin and metalloproteinase domain-containing proteins
Identifiers
SymbolADAM
PfamPF08516
InterProIPR027053
Membranome538
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

ADAMs (short for a disintegrin and metalloproteinase) are a family of single-pass transmembrane and secreted metalloendopeptidases.[1][2] All ADAMs are characterized by a particular domain organization featuring a pro-domain, a metalloprotease, a disintegrin, a cysteine-rich, an epidermal-growth factor like and a transmembrane domain, as well as a C-terminal cytoplasmic tail.[3] Nonetheless, not all human ADAMs have a functional protease domain, which indicates that their biological function mainly depends on protein–protein interactions.[4] Those ADAMs which are active proteases are classified as sheddases because they cut off or shed extracellular portions of transmembrane proteins.[4] For example, ADAM10 can cut off part of the HER2 receptor, thereby activating it.[5] ADAM genes are found in animals, choanoflagellates, fungi and some groups of green algae. Most green algae and all land plants likely lost ADAM proteins.[6]

ADAMs are categorized under the EC 3.4.24.46 enzyme group, and in the MEROPS peptidase family M12B.[3] The terms adamalysin and MDC family (metalloproteinase-like, disintegrin-like, cysteine rich) have been used to refer to this family historically.[7]

  1. ^ Brocker, C; Vasiliou, V; Nebert, DW (October 2009). "Evolutionary divergence and functions of the ADAM and ADAMTS gene families". Human Genomics. 4 (1): 43–55. doi:10.1186/1479-7364-4-1-43. PMC 3500187. PMID 19951893.
  2. ^ Wolfsberg TG, Straight PD, Gerena RL, et al. (1995). "ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain". Dev. Biol. 169 (1): 378–383. doi:10.1006/dbio.1995.1152. PMID 7750654.
  3. ^ a b "ADAM, cysteine-rich (IPR006586)". InterPro. Retrieved 18 February 2016.
  4. ^ a b Edwards DR, Handsley MM, Pennington CJ (October 2008). "The ADAM metalloproteinases". Mol. Aspects Med. 29 (5): 258–89. doi:10.1016/j.mam.2008.08.001. PMC 7112278. PMID 18762209.
  5. ^ Liu, P.C.; et al. (2006). "Identification of ADAM10 as a major source of HER2 ectodomain sheddase activity in HER2 overexpressing breast cancer cells". Cancer Biology and Therapy. 5 (6): 657–664. doi:10.4161/cbt.5.6.2708. PMID 16627989.
  6. ^ Souza J, Lisboa A, Santos T, Andrade M, Neves V, Teles-Souza J, Jesus H, Bezerra T, Falcão V, Oliveira R, Del-Bem L (2020). "The evolution of ADAM gene family in eukaryotes". Genomics. 112 (5): 3108–3116. doi:10.1016/j.ygeno.2020.05.010. PMID 32437852. S2CID 218832838.
  7. ^ Blobel, CP (22 August 1997). "Metalloprotease-disintegrins: links to cell adhesion and cleavage of TNF alpha and Notch". Cell. 90 (4): 589–92. doi:10.1016/s0092-8674(00)80519-x. PMID 9288739. S2CID 17710705.