title: Deranged hypothetical proteins Rik protein, Nit protein 2 and mitochondrial inner membrane protein, Mitofilin, in fetal Down syndrome brain.
abstract: Down syndrome (DS) is the most common genetic disorder with mental retardation and a host of deranged proteins has already been described. Protein hunting leads to rapid accumulation of aberrant proteins and proteomics methods not only allow unambiguous identification of proteins, they are also a powerful tools to identify new or predicted proteins. We applied two-dimensional gel electrophoresis with in-gel digestion of proteins and subsequent MALDI-TOF mass-spectrometrical identification and quantification of spots using specific software on cortical brain samples from 7 controls and 7 samples from fetal DS at the early second trimester. Nine hypothetical proteins were identified: three of them (4833418L03Rik protein Q9D614, mitochondrial inner membrane protein Q16891 and Nit protein 2 Q8WUF0) were significantly and about doublefold reduced in fetal DS brain. Hypothetical proteins CGI 99, FLJ10463, 70 kDa WD-repeat tumor rejection antigen homolog, KSRP, Hypothetical protein 49.6 kDa and Elongin A were comparable between groups. Domain analysis of deranged structures revealed a t_SNARE domain for the Rik protein, indicating involvement of this protein in the exocytotic-synaptic machinery impaired in DS, a CN hydrolase domain for Nit protein 2, possibly reflecting aberrant nitrilase-related metabolism and handling and an inner mitochondrial protein, extending knowledge on the mitochondrial deficit in in fetal DS early in life.
authors.affiliation: Department of Pediatrics, Division of Neonatology, University of Vienna, Währinger Gürtel 18, A-1090 Vienna, Austria.
authors.forename: J  K
authors.initials: J
authors.lastname: Myung
authors.forename: T
authors.initials: T
authors.lastname: Gulesserian
authors.forename: M
authors.initials: M
authors.lastname: Fountoulakis
authors.forename: G
authors.initials: G
authors.lastname: Lubec
authors.forename: M
authors.initials: M
authors.lastname: Jae-Kyung
mesh_terms: D037881:Aborted Fetus / Q000737:chemistry*; D002540:Cerebral Cortex / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000032:analysis*; D030562:Databases, Protein; D004314:Down Syndrome / Q000196:embryology / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D000075065:Elongin; D005260:Female; D005656:Fungal Proteins / Q000032:analysis*; D006801:Humans; D006868:Hydrolysis; D007091:Image Processing, Computer-Assisted; D007525:Isoelectric Focusing; D007526:Isoelectric Point; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D024101:Mitochondrial Proteins; D008970:Molecular Weight; D009124:Muscle Proteins / Q000032:analysis*; D010449:Peptide Mapping; D011247:Pregnancy; D011506:Proteins / Q000032:analysis / Q000302:isolation & purification; D016601:RNA-Binding Proteins / Q000032:analysis; D050600:SNARE Proteins; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis*; D014357:Trypsin / Q000378:metabolism; D033921:Vesicular Transport Proteins
chemical_list: D004268:DNA-Binding Proteins; C000616397:ELOA protein, human; D000075065:Elongin; D005656:Fungal Proteins; C088548:IMMT protein, human; C105789:KHSRP protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; C068100:NIT2 protein, Neurospora crassa; D011506:Proteins; D016601:RNA-Binding Proteins; D050600:SNARE Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; C433889:WRAP73 protein, human; D014357:Trypsin