Structural diversity and differential expression of novel human intersectin 1 isoforms.
Intersectin 1 (ITSN1) is an evolutionarily conserved adaptor protein that functions in clathrin-mediated endocytosis, cell signalling and cytoskeleton rearrangements. The ITSN1 gene encodes two main isoforms: a short form (ITSN1-s), which is ubiquitously expressed and consists of two Eps15 homology (EH) domains and five Src homology 3 (SH3) domains, and a long form (ITSN1-l), which is predominantly expressed in the brain and contains three additional domains, a Dbl homology (DH) domain, a Pleckstrin homology (PH) domain and a C2 domain. Using computational analysis of the EST database and 3' RACE we determined the length of the 3' untranslated region of ITSN1-l and demonstrated that the polyadenylation site is located 11,559 nt downstream of the stop codon of the ITSN1-l mRNA. Recently, additional splicing events affecting ITSN1 transcripts were reported, but full-length transcriptional isoforms with different combinations of alternatively spliced exons remained unknown. Here we report the identification of fifteen novel transcriptional isoforms of the human ITSN1 gene with full-length coding sequences that are the result of different combinations of the alternatively spliced exons 5, 6/6', 20, 23, 25, 26, 26a and 35. The isoforms identified differ in domain organization and expression level in different tissues and more likely contribute to the modulation of many complex protein interactions in which ITSN1 participates.
Kropyvko
Sergii
S
Institute of Molecular Biology and Genetics, 150 Zabolotnogo Street, 03680 Kyiv, Ukraine.
Gerasymchuk
Dmytro
D
Skrypkina
Inessa
I
Dergai
Mykola
M
Dergai
Oleksandr
O
Nikolaienko
Oleksii
O
Rynditch
Alla
A
Tsyba
Liudmyla
L
D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D033942:Adaptor Proteins, Vesicular Transport; C485568:ITSN1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger