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PR01877

Identifier
MTGR1PROTEIN  [View Relations]  [View Alignment]  
Accession
PR01877
No. of Motifs
4
Creation Date
06-JUN-2003
Title
Myeloid transforming gene related protein-1 (MTGR1) family signature
Database References
PRINTS; PR01875 ETOFAMILY
Literature References
1. HILDEBRAND, D., TIEFENBACH, J., HEINZEL, T., GREZ, M. AND MAURER, A.B.
Multiple regions of ETO cooperate in transcriptional repression.
J.BIOL.CHEM. 276 9889-9895 (2001).
 
2. DAVIS, J.N., MCGHEE, L. AND MYERS, S.
The ETO (MTG8) gene family.
GENE 303 1-10 (2003).
 
3. FRACCHIOLA, N.S., COLOMBO, G., FINELLI, P., MAIOLO, A.T. AND NERI, A.
EHT, a new member of the MTG8/ETO gene family, maps on 20q11 region and is
deleted in acute myeloid leukemias.
BLOOD 92 3481-3484 (1998).

Documentation
Transcriptional activation and repression is required for control of
cell proliferation and differentiation during embryonic development and
homeostasis in the adult organism. Perturbations of these processes can
lead to the development of cancer [1]. The Eight-Twenty-One (ETO) gene
product is able to form complexes with corepressors and deacetylases,
such as nuclear receptor corepressor (N-CoR), which repress transcription
when recruited by transcription factors [2].
 
The ETO gene derives its name from its association with many cases of
acute myelogenous leukaemia (AML), in which a reciprocal translocation,
t(8;21), brings together a large portion of the ETO gene from chromosome
eight and part of the AML1 gene from chromosome 21. The human ETO gene
family currently comprises three major subfamilies: ETO/myeloid
transforming gene on chromosome 8 (MTG8); myeloid transforming gene related
protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16).
 
ETO proteins are composed of four evolutionarily conserved domains termed
nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation
of high molecular weight complexes, but is not directly responsible for
repressor activity. NHR2 and its flanking sequence comprise the core
repressor domain, which mediates 50% of the wild type repressor activity.
Furthermore, there is evidence that the amphipathic helical structure of
NHR2 promotes the formation of ETO/AML1 homodimers [1]. NHR3 and NHR4 have
been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger
motifs, which are thought to play a role in protein interactions rather
than DNA binding [2].
 
Screening of dbEST with the entire ETO cDNA sequence revealed a number
of ESTs showing significant similarity to the query sequence. Of those
identified, two overlapping clones were sequenced, revealing an ORF coding
for a putative 575 amino acid protein. This was subsequently mapped to
chromosome 20 and named EHT (ETO Homologous on chromosome Twenty), and later
as MTGR1 [3].
 
MTGR1PROTEIN is a 4-element fingerprint that provides a signature for the
myeloid transforming gene related protein-1 (MTGR1) family. The fingerprint
was derived from an initial alignment of 3 sequences: the motifs were drawn
from conserved regions spanning the full alignment length, focusing on those
sections that characterise MTGR1 proteins but distinguish them from closely
related ETO family members: motif 1 lies between NHR1 and NHR2; motif 2 
resides between NHR2 and NHR3; motif 3 lies within NHR4; and motif 4 resides 
at the C-terminus. A single iteration on SPTR40_22f was required to reach 
convergence, no further sequences being identified beyond the starting set.
Summary Information
3 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
43333
30000
20000
1234
True Positives
O43439        Q9IAB2        Q9UP24        
Sequence Titles
O43439      MTG8-like protein (MTG8 related protein) (EHT) (EHT protein) (MTG8- like protein MTGR1A) - Homo sapiens (Human). 
Q9IAB2 MTGR1-like protein - Xenopus laevis (African clawed frog).
Q9UP24 MTG8-like protein - Homo sapiens (Human).
Scan History
SPTR40_22f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
NKMLEHREVRDRH Q9UP24 280 280 -
NKIGEHRDVRDRH Q9IAB2 296 296 -
NKMLEHREVRDRH O43439 309 309 -

Motif 2 width=11
Element Seqn Id St Int Rpt
GSADSLSNDSQ O43439 411 89 -
GSADSLSNDSQ Q9UP24 382 89 -
SSTDSGASDSV Q9IAB2 401 92 -

Motif 3 width=21
Element Seqn Id St Int Rpt
GRGSSARSADCSVPSPALDKT Q9UP24 534 141 -
GRGSSARSADCSVPSPALDKT O43439 563 141 -
SRSLIPKASDPVLLSPTLERS Q9IAB2 547 135 -

Motif 4 width=10
Element Seqn Id St Int Rpt
STPASVTAVD Q9IAB2 575 7 -
STPASVTAID O43439 591 7 -
STPASVTAID Q9UP24 562 7 -
Final Motifs
Motif 1  width=13
Element Seqn Id St Int Rpt
NKMLEHREVRDRH Q9UP24 280 280 -
NKIGEHRDVRDRH Q9IAB2 296 296 -
NKMLEHREVRDRH O43439 309 309 -

Motif 2 width=11
Element Seqn Id St Int Rpt
GSADSLSNDSQ O43439 411 89 -
GSADSLSNDSQ Q9UP24 382 89 -
SSTDSGASDSV Q9IAB2 401 92 -

Motif 3 width=21
Element Seqn Id St Int Rpt
GRGSSARSADCSVPSPALDKT Q9UP24 534 141 -
GRGSSARSADCSVPSPALDKT O43439 563 141 -
SRSLIPKASDPVLLSPTLERS Q9IAB2 547 135 -

Motif 4 width=10
Element Seqn Id St Int Rpt
STPASVTAVD Q9IAB2 575 7 -
STPASVTAID O43439 591 7 -
STPASVTAID Q9UP24 562 7 -