IRAS Splice Variants

Abstract

The human I(1)-imidazoline receptor candidate gene, iras, has previously been cloned and mapped to locus 3p21.1-9 (also known as Nischarin; accession No. AC006208). By comparison to a database of expressed sequence tags (ESTs), three alternatively spliced transcripts have been deduced. A map of 21 exons was constructed for the medium-length transcript (IRAS-M) containing 5,232 base pairs (bp) and encoding 1,504 amino acids (aas). Introns 13B and 13C are inserted into the two alternative transcripts, forming IRAS-S and IRAS-L mRNA (short and long isoforms). Northern blots confirmed the existence of these mRNA isoforms. In most brain regions the order of mRNA abundance was IRAS-M > IRAS-L > IRAS-S mRNA. Although aas 1 through 510 are theoretically identical, truncated proteins could be derived from IRAS-S (2,678 bp transcript yields 515 aas) and IRAS-L (9,457 bp transcript yields 583 aas). Because exon-16 of the iras gene has been proposed to encode the functional domains of imidazoline and a-5 integrin binding, only IRAS-M is expected to possess I(1) receptor properties. Subtype-selective cDNA expression constructs were therefore generated and used to transfect CHO cells. High-affinity I(1) binding was endowed by IRAS-M and IRAS-L, but not by IRAS-S transfection.

Distribution and cellular localization of imidazoleacetic acid-ribotide, an endogenous ligand at imidazol(in)e and adrenergic receptors, in rat brain

“…It is conceivable that this small imidazole molecule diffuses passively from the perikaryon to the nucleus and is stabilized in situ during the tissue fixation process. However, in light of the emerging literature concerning the complexity of the IAA-RP binding protein(s) (and putative receptor) IRAS/nischarin, and the apparent involvement of this protein in intracellular signaling (Piletz et al, 2003a;Piletz et al, 2003b), we cannot exclude the possibility that IAA-RP undergoes active nuclear transport, and that its presence in nuclei carries physiological significance.…”

Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin

“…Isoform 4, also known as IRAS-S, is also highly expressed in the brain, has amino acids 516-1504 spliced out, and has a change in amino acids between 512 and 515 (9). Isoform 1 is 166,629 Da, isoform 2 is 110,194 Da, isoform 3 is 63,997 Da, and isoform 4 is 56,867 Da (9).…”

“…The first function attributed to Nischarin was its role as an integrin a5b1 binding protein (9). In this way, Nischarin is able to regulate cell motility, specifically by anatomization of cell signaling proteins that contribute to tumor cell migration and invasion (10).…”

“…9). Isoform 2 has amino acids 1-511 spliced and is expressed in the brain (9). Isoform 3, also known as IRAS-L, is highly expressed in the brain, missing amino acids 584-1504, and has a modified sequence in amino acids 511-583 (9).…”

“…Human Nischarin has four isoforms that are achieved by alternative splicing (9). Isoform 1 encodes the full-length protein and is highly expressed in neural and endocrine tissue ( Fig.…”