Cloning and characterization of human PREB; a gene that maps to a genomic region associated with trisomy 2p syndrome

Abstract

We have isolated the human homolog of a novel rodent gene that may be involved in the regulation of pituitary gene transcription. The human PREB gene encodes a predicted protein of 417 amino acids, exhibiting several sequences characteristic of the WD-motif protein family. PREB transcripts were detected in every human fetal and adult tissue examined, although a great variation in levels of expression was observed. PREB was mapped to human Chromosome 2p23, a region of the genome associated with partial trisomy 2p syndrome. Although variable, the common duplication phenotype includes facial abnormalities, skeletal defects, growth and mental retardation, congenital heart and neural tube defects, and abnormalities of the genitalia. We propose that PREB has a role during human development and that abnormal dosage of this transcription factor may be involved in some of the developmental abnormalities observed in patients with partial trisomy 2p.

The Mammalian Guanine Nucleotide Exchange Factor mSec12 is Essential for Activation of the Sar1 GTPase Directing Endoplasmic Reticulum Export

“…While we have shown that mSec12 is a Sar1‐specific exchange factor, other functions for mSec12 may exist. During our cloning and characterization of mouse mSec12, nearly identical (> 99%) rat and human homologs of mSec12 were identified as a putative prolactin regulatory element binding (PREB) transcription factor (19,27). PREB has been characterized as a ubiquitously expressed protein that is highly abundant in tissues that are active in secretion (liver, pancreas, pituitary).…”

The gene structure and expression of human ABHD1: overlapping polyadenylation signal sequence with Sec12

“…The cDNA sequence of the human Sec12/PREB gene has previously been reported [34]. However, nucleotide cytidine-186 is thymidine in their sequence and this alters the deduced amino acid sequence from a leucine to a phenylalanine at residue 19.…”

“…However, the ORF reported here differs by the inclusion of an inserted glycine-136 residue. Glycine-136 is conserved in the human and rat homologues [29,34]. …”

“…Previously, the human PREB gene was mapped to chromosome 2p23 [34]. A BLAST search of the human genome identified the location of the ABHD1 and Sec12 genes as 2p23.3, being encoded on opposite strands.…”

“…A recombinant part of rat Sec12, encompassing residues 175–417, has been reported as the prolactin regulatory element binding protein (PREB) transcription factor which regulates the activity of the prolactin promoter [29]. The murine PREB gene has been localised to the proximal end of chromosome 5 [26] and a partial human cDNA encoding PREB was cloned from brain and mapped to 2p23 [34]. Overall, Sec12/PREB transcripts are highly abundant in tissues that are active in secretion [29].…”