title: Systematic isolation and characterization of cDNAs encoding AAA proteins from human brain.
abstract: BACKGROUND
  The AAA (ATPases Associated with various cellular Activities) domain characterizes a diverse superfamily of proteins. Mutations in genes encoding AAA-domains cause a variety of human diseases including cystic fibrosis, Zellweger syndrome, adrenomyeloneuropathy, and dystonia. Recently, mutations in two AAA-containing proteins paraplegin and spastin have been shown to cause two types of hereditary spastic paraplegia (HSP). The HSPs are genetically heterogeneous degenerative spinal cord disorders characterized by lower extremity weakness and spasticity. Clinical similarity between various genetic types of HSP led us to propose that different genetic types of HSP were due to common biochemical abnormalities including disturbances in related proteins. For this reason, we sought to identify novel AAA-containing proteins as potential candidates for HSP and related neurodegnerative disorders. We used degenerative PCR, based on the conserved AAA peptide sequence to systematically clone and characterize AAA genes expressed in human brain.
  
  
  RESULTS
  We analyzed 646 clones and identified 19 known AAA-containing proteins including spastin and paraplegin, AAA-containing genes that cause HSP. In addition, we identified 14 unique DNA inserts representing novel putative AAA-containing proteins. Four of these novel genes are hypothetical AAA proteins and the rest of novel clones matched sequences of yet uncharacterized expressed sequence tags (ESTs).
  
  
  CONCLUSIONS
  Fourteen novel AAA-containing proteins are potential candidates for human diseases including degenerative neurologic disorders, and their further analysis is ongoing (Tab. 1, Fig. 1, Ref. 22).
authors.affiliation: Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Xinping
authors.initials: X
authors.lastname: Zhao
authors.forename: P
authors.initials: P
authors.lastname: Hedera
authors.forename: J K
authors.initials: JK
authors.lastname: Fink
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism*; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics*; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D000251:Adenosine Triphosphatases