title: C2360, a nuclear protein expressed in human proliferative cytotrophoblasts, is a representative member of a novel protein family with a conserved coiled coil-helix-coiled coil-helix domain.
abstract: In this study, we describe the identification of nine novel genes isolated from a unique human first-trimester cDNA library generated from the placental bed. One of these clones, called C2360 and located on chromosome 10q22, was selected as it showed restricted expression in placental bed tissue as well as in JEG3 choriocarcinoma cells with absent expression in adult tissues. We show that the expression is restricted to first-trimester proliferative trophoblasts of the proximal column and show that C2360 is a nuclear protein. No detectable transactivation potential was observed for different domains of the protein. Secondary structure prediction showed that C2360 is a representative member of a eukaryotic family of proteins with a low conservation at the amino acid level, but with strong conservation at the structural level, sharing the general domain (coiled coil 1)-(helix 1)-(coiled coil 2)-(helix 2), or CHCH domain. Each alpha-helix within this domain contains two cysteine amino acids, and these intrahelical cysteines are separated by nine amino acids (C-X(9)-C motif). The fixed position within each helix indicated that both helices could form a hairpin structure stabilized by two interhelical disulfide bonds. Other proteins belonging to the family include estrogen-induced gene 2 and the ethanol-induced 6 protein. The conserved motif was found in yeast, plant, Drosophila, Caenorhabditis elegans, mouse, and human proteins, indicating that the ancestor of this protein family is of eukaryotic origin. These results indicate that C2360 is a representative member of a multifamily of proteins, sharing a protein domain that is conserved in eukaryotes.
authors.affiliation: Molecular Biology Laboratory, Department of Clinical Chemistry, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Bart A
authors.initials: BA
authors.lastname: Westerman
authors.forename: Ankie
authors.initials: A
authors.lastname: Poutsma
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: Cees B M
authors.initials: CB
authors.lastname: Oudejans
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression / Q000235:genetics; D015723:Gene Library; D006801:Humans; D042541:Intracellular Space / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014327:Trophoblasts / Q000378:metabolism* / Q000648:ultrastructure; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: C495375:CHCHD1 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins