Molecular cloning, structural analysis, and expression of a human IRLB, MYC promoter-binding protein: new DENN domain-containing protein family emerges.
IRLB was originally identified as a partial cDNA clone, encoding a 191-aa protein binding the interferon-stimulated response element (ISRE) in the P2 promoter of human MYC. Here, we cloned the full-size IRLB using different bioinformatics tools and an RT-PCR approach. The full-size gene encompasses 131 kb within chromosome 15q22 and consists of 32 exons. IRLB is transcribed as a 6.6-kb mRNA encoding a protein of 1865 aa. IRLB is ubiquitously expressed and its expression is regulated in a growth- and cell cycle-dependent manner. In addition to the ISRE-binding domain IRLB contains a tripartite DENN domain, a nuclear localization signal, two PPRs, and a calmodulin-binding domain. The presence of DENN domains predicts possible interactions of IRLB with GTPases from the Rab family or regulation of growth-induced MAPKs. Strongly homologous proteins were identified in all available vertebrate genomes as well as in Caenorhabditis elegans and Drosophila melanogaster. In human and mouse a family of IRLB proteins exists, consisting of at least three members.
Semova
Natalia
N
Genome Analysis Laboratory, Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
Kapanadze
Bagrat
B
Corcoran
Martin
M
Kutsenko
Alexei
A
Baranova
Ancha
A
Semov
Alexandre
A
D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D053418:Death Domain Receptor Signaling Adaptor Proteins; D005347:Fibroblasts; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein
C088830:DENND4A protein, human; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; C105852:MADD protein, human; C491371:Madd protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger