PMID- 19440452 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20110714 LR - 20211020 IS - 1389-2029 (Print) IS - 1875-5488 (Electronic) IS - 1389-2029 (Linking) VI - 9 IP - 2 DP - 2008 Apr TI - Analysis of NCL Proteins from an Evolutionary Standpoint. PG - 115-36 LID - 10.2174/138920208784139573 [doi] AB - The Neuronal Ceroid Lipofuscinoses (NCLs) are the most common group of neurodegenerative disorders of childhood. While mutations in eight different genes have been shown to be responsible for these clinically distinct types of NCL, the NCLs share many clinical and pathological similarities. We have conducted an exhaustive Basic Local Alignment Search Tool (BLAST) analysis of the human protein sequences for each of the eight known NCL proteins- CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8 and CLN10. The number of homologous species per CLN-protein identified by BLAST searches varies depending on the parameters set for the BLAST search. For example, a lower threshold is able to pull up more homologous sequences whereas a higher threshold decreases this number. Nevertheless, the clade confines are consistent despite this variation in BLAST searching parameters. Further phylogenetic analyses on the appearance of NCL proteins through evolution reveals a different time line for the appearance of the CLN-proteins. Moreover, divergence of each protein shows a different pattern, providing important clues on the evolving role of these proteins. We present and review in-depth bioinformatic analysis of the NCL proteins and classify the CLN-proteins into families based on their structures and evolutionary relationships, respectively. Based on these analyses, we have grouped the CLN-proteins into common clades indicating a common evolving pathway within the evolutionary tree of life. CLN2 is grouped in Eubacteria, CLN1 and CLN10 in Viridiplantae, CLN3 in Fungi/ Metazoa, CLN7 in Bilateria and CLN5, CLN6 and CLN8 in Euteleostomi. FAU - Muzaffar, Neda E AU - Muzaffar NE AD - Center for Neural Development and Disease, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. FAU - Pearce, David A AU - Pearce DA LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Genomics JT - Current genomics JID - 100960527 PMC - PMC2674804 EDAT- 2009/05/15 09:00 MHDA- 2009/05/15 09:01 PMCR- 2008/10/01 CRDT- 2009/05/15 09:00 PHST- 2008/02/06 00:00 [received] PHST- 2008/02/18 00:00 [revised] PHST- 2008/02/27 00:00 [accepted] PHST- 2009/05/15 09:00 [entrez] PHST- 2009/05/15 09:00 [pubmed] PHST- 2009/05/15 09:01 [medline] PHST- 2008/10/01 00:00 [pmc-release] AID - CG-9-115 [pii] AID - 10.2174/138920208784139573 [doi] PST - ppublish SO - Curr Genomics. 2008 Apr;9(2):115-36. doi: 10.2174/138920208784139573.