|PROSITE documentation PDOC51112 [for PROSITE entry PS51112]|
The contiguous gene deletion syndrome is characterized by Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E), as well as generalized hypoplasia and cardiac abnormalities. It is caused by a deletion in Xq22.3, comprising several genes including AMME chromosomal region gene 1 (AMMECR1), which encodes a protein with a nuclear location and presently unknown function. The C-terminal region of AMMECR1 (from residue 122 to 333) is well conserved, and homologues appear in species ranging from bacteria and archaea to eukaryotes. The high level of conservation of the AMMECR1 domain points to a basic cellular function, potentially in either the transcription, replication, repair or translation machinery [1,2,3].
The AMMECR1 domain contains a 6-amino-acid motif (LRGCIG) that might be functionally important since it is strikingly conserved throughout evolution . The AMMECR1 domain consists of two distinct subdomains of different sizes (see <PDB:1VAJ>). The large subdomain, which contains both the N- and C-terminal regions, consists of five α-helices and five β-strands. These five β-strands form an antiparallel β-sheet. The small subdomain consists of four α-helices and three β-strands, and these β-strands also form an antiparallel β-sheet. The conserved 'LRGCIG' motif is located at β 2 and its N-terminal loop, and most of the side chains of these residues point toward the interface of the two subdomains. The two subdomains are connected by only two loops, and the interaction between the two subdomains is not strong. Thus, these subdomains may move dynamically when the substrate enters the cleft. The size of the cleft suggests that the substrate is large, e.g., the substrate may be a nucleic acid or protein. However, the inner side of the cleft is not filled with positively charged residues, and therefore it is unlikely that negatively charged nucleic acids such as DNA or RNA interact at this site .
The profile we developed covers the entire AMMECR1 domain.Last update:
April 2005 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Vitelli F. Piccini M. Caroli F. Franco B. Malandrini A. Pober B. Jonsson J. Sorrentino V. Renieri A.|
|Title||Identification and characterization of a highly conserved protein absent in the Alport syndrome (A), mental retardation (M), midface hypoplasia (M), and elliptocytosis (E) contiguous gene deletion syndrome (AMME).|
|2||Authors||Vitelli F. Meloni I. Fineschi S. Favara F. Tiziana Storlazzi C. Rocchi M. Renieri A.|
|Title||Identification and characterization of mouse orthologs of the AMMECR1 and FACL4 genes deleted in AMME syndrome: orthology of Xq22.3 and MmuXF1-F3.|
|Source||Cytogenet. Cell Genet. 88:259-263(2000).|
|3||Authors||Tajika Y. Sakai N. Tamura T. Yao M. Watanabe N. Tanaka I.|
|Title||Crystal structure of PH0010 from Pyrococcus horikoshii, which is highly homologous to human AMMECR 1C-terminal region.|