title: Novel transcripts reveal a complex structure of the human TRKA gene and imply the presence of multiple protein isoforms.
abstract: BACKGROUND
  Tropomyosin-related kinase A (TRKA) is a nerve growth factor (NGF) receptor that belongs to the tyrosine kinase receptor family. It is critical for the correct development of many types of neurons including pain-mediating sensory neurons and also controls proliferation, differentiation and survival of many neuronal and non-neuronal cells. TRKA (also known as NTRK1) gene is a target of alternative splicing which can result in several different protein isoforms. Presently, three human isoforms (TRKAI, TRKAII and TRKAIII) and two rat isoforms (TRKA L0 and TRKA L1) have been described.
  
  
  RESULTS
  We show here that human TRKA gene is overlapped by two genes and spans 67 kb--almost three times the size that has been previously described. Numerous transcription initiation sites from eight different 5' exons and a sophisticated splicing pattern among exons encoding the extracellular part of TRKA receptor indicate that there might be a large variety of alternative protein isoforms. TrkA genes in rat and mouse appear to be considerably shorter, are not overlapped by other genes and display more straightforward splicing patterns. We describe the expression profile of alternatively spliced TRKA transcripts in different tissues of human, rat and mouse, as well as analyze putative endogenous TRKA protein isoforms in human SH-SY5Y and rat PC12 cells. We also characterize a selection of novel putative protein isoforms by portraying their phosphorylation, glycosylation and intracellular localization patterns. Our findings show that an isoform comprising mainly of TRKA kinase domain is capable of entering the nucleus.
  
  
  CONCLUSIONS
  Results obtained in this study refer to the existence of a multitude of TRKA mRNA and protein isoforms, with some putative proteins possessing very distinct properties.
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia. kristi.luberg@ttu.ee.|Competence Center for Cancer Research, Tallinn, Estonia. kristi.luberg@ttu.ee.
authors.forename: Kristi
authors.initials: K
authors.lastname: Luberg
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia. rahelpark@gmail.com.|Competence Center for Cancer Research, Tallinn, Estonia. rahelpark@gmail.com.|VIB lab for Systems Biology & CMPG Lab for Genetics and Genomics, Leuven, Belgium. rahelpark@gmail.com.
authors.forename: Rahel
authors.initials: R
authors.lastname: Park
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia. eleksejeva@gmail.com.|Competence Center for Cancer Research, Tallinn, Estonia. eleksejeva@gmail.com.|French National Institute for Agricultural Research, Paris, France. eleksejeva@gmail.com.
authors.forename: Elina
authors.initials: E
authors.lastname: Aleksejeva
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia. tonis.timmusk@ttu.ee.|Competence Center for Cancer Research, Tallinn, Estonia. tonis.timmusk@ttu.ee.
authors.forename: Tõnis
authors.initials: T
authors.lastname: Timmusk
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D006801:Humans; D051379:Mice; D020033:Protein Isoforms; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000737:chemistry* / Q000235:genetics*; D014015:Tissue Banks; D059467:Transcriptome
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D020917:Receptor, trkA