Alternative splicing and alternative initiation of translation explain the four forms of the Ia antigen-associated invariant chain.

Abstract

The Ia antigen-associated invariant chain (In) exists in humans as four related polypeptides, p33, p35, p41 and p43, all associated with HLA-class H antigens. As described previously, two of these forms of In chain, p33 and p35, result from the use of two in-phase initiation AUG codons on the unique In p33 mRNA. In addition to cDNA clones derived from In p33 mRNA, we have isolated a new cDNA clone, called p41-1, which differs from p33-1 by an additional segment in the coding region. The DNA sequence encoding the segment unique to p41-1 was identified in the genomic sequence in the intron between exon 6 and 7, and we refer to it as exon 6b. Cells transfected with a full length p41 cDNA clone in an expression vector synthesize the two larger forms of the In chain, p41 and p43. We propose that the larger mRNA, encoding p41, results from alternative splicing of exon 6b, and that p41 and p43 result from the use of the two functional initiation AUG codons identified in p33 mRNA. Alternative splicing, together with alternative initiation of translation, allows therefore the synthesis of four related In chain polypeptides from a single gene.

Thyroglobulin Type-1 Domains in Equistatin Inhibit Both Papain-like Cysteine Proteinases and Cathepsin D

“…This domain is exclusively present on the N-terminal section and is repeated 11 times (4). Similar type-1 domains, recognizable by the sequence motif of Cys-Trp-Cys-Val, have been found in many other proteins including saxiphilin (5,6), nidogen (7), insulin-like growth factor-binding proteins (8), pancreatic carcinoma marker proteins (GA-733) (9), testican (10), major histocompatibility complex class II-associated p41 invariant chain (11), chum salmon egg cysteine proteinase inhibitor (ECI) 1 (12), and equistatin (13,14). In these proteins (except ECI and equistatin) the type-1 domain represents only part of the molecule.…”

“…In these proteins (except ECI and equistatin) the type-1 domain represents only part of the molecule. The function of these repetitive sequences is unknown, although there is evidence that the type-1 domain itself can act as an inhibitor of cysteine proteinases, as shown in equistatin, ECI, and p41 fragment (11)(12)(13)(14)(15).Equistatin is a protein isolated from sea anemone Actinia equina. It is a reversible and tightly binding competitive inhibitor of papain-like cysteine proteinases.…”

Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.

“…The GA733 genes are related to the HLA-DR-associated invariant chain gene (25,26), in that exon 6b of this gene (27) is homologous to the second type I repeat of thyroglobulin, and the second and fourth type I repeats derive from an ancestral 60-amino acid unit (24). The relationships among these three genes are depicted in Fig.…”

Molecular characterization and tissue-specific expression of invariant chain isoform in Muscovy Duck (Cairina moschata)

“…There are 4 isoforms of the human invariant chain, including p33, p35, p41, and p43, which are generated through a combination of alternative translation initiation and splicing events for a single gene (Strubin et al, 1986). p33 is the predominant isoform (Warmerdam et al, 1996;Bergmann, 2012) and forms a complex with MHC II to drive antigen presentation.…”