{PDOC51112}
{PS51112; AMMECR1}
{BEGIN}
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* AMMECR1 domain profile *
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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
[1]. 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 alpha-helices and five beta-strands. These
five beta-strands   form  an  antiparallel  beta-sheet.  The  small  subdomain
consists of  four alpha-helices and three beta-strands, and these beta-strands
also form  an antiparallel beta-sheet. The conserved 'LRGCIG' motif is located
at beta  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 [3].

The profile we developed covers the entire AMMECR1 domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2005 / First entry.

[ 1] Vitelli F., Piccini M., Caroli F., Franco B., Malandrini A., Pober B.,
     Jonsson J., Sorrentino V., Renieri A.
     "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)."
     Genomics 55:335-340(1999).
     PubMed=10049589
[ 2] Vitelli F., Meloni I., Fineschi S., Favara F., Tiziana Storlazzi C.,
     Rocchi M., Renieri A.
     "Identification and characterization of mouse orthologs of the AMMECR1
     and FACL4 genes deleted in AMME syndrome: orthology of Xq22.3 and
     MmuXF1-F3."
     Cytogenet. Cell Genet. 88:259-263(2000).
     PubMed=10828604
[ 3] Tajika Y., Sakai N., Tamura T., Yao M., Watanabe N., Tanaka I.
     "Crystal structure of PH0010 from Pyrococcus horikoshii, which is
     highly homologous to human AMMECR 1C-terminal region."
     Proteins 58:501-503(2005).
     PubMed=15558565; DOI=10.1002/prot.20315

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