title: Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform.
abstract: Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC) protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions.
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. f.benthani@garvan.org.au.|St Vincent's Clinical School, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. f.benthani@garvan.org.au.
authors.forename: Fahad
authors.initials: F
authors.lastname: Benthani
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. p.tran@garvan.org.au.
authors.forename: Phuong N
authors.initials: PN
authors.lastname: Tran
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. n.currey@garvan.org.au.
authors.forename: Nicola
authors.initials: N
authors.lastname: Currey
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. i.ng@garvan.org.au.
authors.forename: Irvin
authors.initials: I
authors.lastname: Ng
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. m.giry-laterriere@garvan.org.au.
authors.forename: Marc
authors.initials: M
authors.lastname: Giry-Laterriere
authors.affiliation: Sydney Genome Diagnostics, the Children's Hospital at Westmead, Sydney, NSW 2145, Australia. louise.carey@health.nsw.gov.au.
authors.forename: Louise
authors.initials: L
authors.lastname: Carey
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. m.corish@garvan.org.au.|St Vincent's Clinical School, UNSW Medicine, UNSW Australia, Sydney, NSW 2052, Australia. m.corish@garvan.org.au.
authors.forename: Maija R J
authors.initials: MR
authors.lastname: Kohonen-Corish
authors.affiliation: The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. l.pangon@garvan.org.au.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pangon
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D040901:Proteomics / Q000379:methods; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C492357:SHANK3 protein, human; D025521:Tumor Suppressor Proteins; C067857:MCC protein, human
keywords: MCC; SHANK3; proteogenomic