title: RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3.
abstract: We previously identified proteins that bind with high affinity to a peptide corresponding to the cytoplasmic regulatory domain (KVGFFKR) of the platelet-specific integrin subunit alpha(IIb). These included a hypothetical protein termed HSPC238, recently renamed as RING finger protein, RN181. Here, we establish the presence of RN181 in human platelets by RT-PCR, Western blotting and mass spectrometry and confirm its affinity for the platelet integrin. We demonstrate that RN181 has ubiquitin E3 ligase activity and that all other components of the ubiquitination pathway are abundant in platelets, suggesting a novel link of integrin signal transduction pathways with ubiquitin-conjugation events.
authors.affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Brophy
authors.forename: Markus
authors.initials: M
authors.lastname: Raab
authors.forename: Heide
authors.initials: H
authors.lastname: Daxecker
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Culligan
authors.forename: Ingo
authors.initials: I
authors.lastname: Lehmann
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Chubb
authors.forename: Achim
authors.initials: A
authors.lastname: Treumann
authors.forename: Niamh
authors.initials: N
authors.lastname: Moran
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D017124:Conserved Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; C547603:RNF181 protein, human; D044767:Ubiquitin-Protein Ligases; D002118:Calcium