Identification and Characterization of a Novel Family of Mammalian Ependymin-Related Proteins (MERPs) in Hematopoietic, Nonhematopoietic, and Malignant Tissues

Abstract

Evidence is presented for a family of mammalian homologs of ependymin, which we have termed the mammalian ependymin-related proteins (MERPs). Ependymins are secreted glycoproteins that form the major component of the cerebrospinal fluid in many teleost fish. We have cloned the entire coding region of human MERP-1 and mapped the gene to chromosome 7p14.1 by fluorescence in situ hybridization. In addition, three human MERP pseudogenes were identified on chromosomes 8, 16, and X. We have also cloned the mouse MERP-1 homolog and an additional family member, mouse MERP-2. Then, using bioinformatics, the mouse MERP-2 gene was localized to chromosome 13, and we identified the monkey MERP-1 homolog and frog ependymin-related protein (ERP). Despite relatively low amino acid sequence conservation between piscine ependymins, toad ERP, and MERPs, several amino acids (including four key cysteine residues) are strictly conserved, and the hydropathy profiles are remarkably alike, suggesting the possibilities of similar protein conformation and function. As with fish ependymins, frog ERP and MERPs contain a signal peptide typical of secreted proteins. The MERPs were found to be expressed at high levels in several hematopoietic cell lines and in nonhematopoietic tissues such as brain, heart, and skeletal muscle, as well as several malignant tissues and malignant cell lines. These findings suggest that MERPs have several potential roles in a range of cells and tissues.

Demonstration of Lysosomal Localization for the Mammalian Ependymin-related Protein Using Classical Approaches Combined with a Novel Density Shift Method

“…2). This tissue distribution is consistent with that observed by Northern blot analysis (30). An additional band of ϳ32 kDa was also observed in two of the three skeletal muscles examined (see Fig.…”

Ependymin, a gene involved in regeneration and neuroplasticity in vertebrates, is overexpressed during regeneration in the echinoderm Holothuria glaberrima

“…The sequence analysis of the conceptual translation of the ependymin clone reveals 63% similarity (47% identity) with mammalian ependymin-related proteins MERP-1/upregulated in colon cancer 1 (UCC1) (accession no. AY027862 and AJ250475, respectively) (Apostolopoulos et al, 2001;Nimmrich et al, 2001), close relationship (30% similarity, 40% identity) with the frog X. laevis (accession no. BG553216.1) and 40 -46% similarity, 24 -32% identity with the piscine ependymins (Orti and Meyer, 1996).…”

“…Examples of that similarity are the sequences perfectly conserved Q 36 WEGR 40 , and V 137 QEWSDR 143 , and the highly conserved R 66 VIEEKKSFMPGRRFYEYIMEYK 88 , and E 150 SWIGIYT 157 (numbers with reference to the EpenHg sequence). Previously, two consensus patterns that include all the ependymin proteins known from vertebrates (Apostolopoulos et al, 2001) were identified. By including the echinoderm sequences, we have updated the ependymin consensus pattern including all the vertebrate and the invertebrate sequences known so far:…”

“…Subsequently, the ependymins of several other fishes have been localized (Rother et al, 1995) and their proteins and gene sequences characterized (Orti and Meyer, 1996). More recently, genes belonging to a family of ependymin-related proteins have been identified in the frog Xenopus laevis and in mammals (i.e., human, monkey and mouse) (Apostolopoulos et al, 2001;Nimmrich et al, 2001). Since, until now, ependymins had only been found in vertebrate species, they were proposed to be vertebrate-specific molecules that define the evolution of the chordate nervous system (Landers et al, 2001;Venter et al, 2001;Ponting and Russell, 2002).…”

Over-Expression, Secondary Structure Characterization, and Preliminary X-ray Crystallographic Analysis of Xenopus tropicalis Ependymin

“…Interestingly, orthologues of fish EPN, also exist in other animals such as sea urchin, frog, and even in mammals, and have been also named as EPDR (ependymin-related) protein or MERP (mammalian ependymin-related protein). Humans, in particular, have one isoform of EPN and its expression has been reported in various human normal tissues [8,9]. More interestingly, the transcription level of human EPN was elevated in colorectal tumor cells, and hence is also called UCC1 (upregulated in colorectal cancer gene 1) [10].…”