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PR01876

Identifier
MTG8PROTEIN  [View Relations]  [View Alignment]  
Accession
PR01876
No. of Motifs
6
Creation Date
06-JUN-2003
Title
Myeloid transforming gene on chromosome 8 (MTG8) protein 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. MIYOSHI, H., KOZO, T., SHIMIZU, K., KEIICHIRO, E., MASEKI, N.,
KANEKO, Y., KAMADA, N. AND OHKI, M.
The t(8;21) translocation in acute myeloid leukemia results in production
of an AML1 - MTG8 fusion transcript
EMBO J. 12 2715-2721 (1993).

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].
 
MTG8 was the first family member to be characterised after being observed as
the chromosome 8 component of the t(8;21) fusion transcript. Northern blot 
analysis revealed high levels of MTG8 expression in the brain, with lower 
levels present in the lung, heart, testis and ovary. Interestingly, no 
detectable levels of MTG8 were observed in haematopoetic tissues, such as 
the spleen and thymus [3].
 
MTG8PROTEIN is a 6-element fingerprint that provides a signature for the
myeloid transforming gene on chromosome 8 (MTG8) protein. The fingerprint
was derived from an initial alignment of 4 sequences: the motifs were drawn
from conserved regions spanning the full alignment length, focusing on
those sections that characterise MTG8 proteins but distinguish them from
closely related ETO family members - motif 1 lies between NHR1 and NHR2; 
motif 2 is located within NHR4; motif 3 resides between NHR4 and the
zinc-finger domain; and motifs 4-6 span the C-terminal region. A single
iteration on SPTR40_22f was required to reach convergence, no further
sequences being identified beyond the starting set.
Summary Information
4 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6444444
5000000
4000000
3000000
2000000
123456
True Positives
MTG8_HUMAN    MTG8_MOUSE    Q9I9D7        Q9I9D8        
Sequence Titles
MTG8_HUMAN  MTG8 protein (ETO protein) (Eigth twenty one protein) (Cyclin D related protein) - Homo sapiens (Human). 
MTG8_MOUSE MTG8 protein - Mus musculus (Mouse).
Q9I9D7 MTG8/ETOb - Gallus gallus (Chicken).
Q9I9D8 MTG8/ETOa - Gallus gallus (Chicken).
Scan History
SPTR40_22f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
CQDRTEKHST Q9I9D7 28 28 -
MPDRTEKHST Q9I9D8 1 1 -
CQDRTEKHST MTG8_HUMAN 28 28 -
MPDRTEKHST MTG8_MOUSE 1 1 -

Motif 2 width=12
Element Seqn Id St Int Rpt
GLSYQPNGLPHP Q9I9D7 281 243 -
GLSYQPNGLPHP Q9I9D8 254 243 -
GLSYQPNGLPHP MTG8_HUMAN 281 243 -
GLSYQPNGLPHP MTG8_MOUSE 254 243 -

Motif 3 width=11
Element Seqn Id St Int Rpt
PVNPDPVTLES Q9I9D7 418 125 -
PVNPDPVTLES Q9I9D8 391 125 -
PVNPDPVALDA MTG8_HUMAN 418 125 -
PVNPDPVALDA MTG8_MOUSE 391 125 -

Motif 4 width=10
Element Seqn Id St Int Rpt
QAQQQGETPA Q9I9D7 556 127 -
QAQQQGETPA Q9I9D8 529 127 -
QAQQQGDTPA MTG8_HUMAN 556 127 -
QAPQQGDTPA MTG8_MOUSE 529 127 -

Motif 5 width=13
Element Seqn Id St Int Rpt
SSGAGSPSTTPPA Q9I9D7 573 7 -
SSGAGSPSTTPPA Q9I9D8 546 7 -
NSGAGSPMDTPPA MTG8_HUMAN 573 7 -
SSGAGSPMDTPPA MTG8_MOUSE 546 7 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ATPRSTTPGTPSTIE Q9I9D7 586 0 -
ATPRSTTPGTPSTIE Q9I9D8 559 0 -
ATPRSTTPGTPSTIE MTG8_HUMAN 586 0 -
ATPRSTTPGTPSTIE MTG8_MOUSE 559 0 -
Final Motifs
Motif 1  width=10
Element Seqn Id St Int Rpt
CQDRTEKHST Q9I9D7 28 28 -
MPDRTEKHST Q9I9D8 1 1 -
CQDRTEKHST MTG8_HUMAN 28 28 -
MPDRTEKHST MTG8_MOUSE 1 1 -

Motif 2 width=12
Element Seqn Id St Int Rpt
GLSYQPNGLPHP Q9I9D7 281 243 -
GLSYQPNGLPHP Q9I9D8 254 243 -
GLSYQPNGLPHP MTG8_HUMAN 281 243 -
GLSYQPNGLPHP MTG8_MOUSE 254 243 -

Motif 3 width=11
Element Seqn Id St Int Rpt
PVNPDPVTLES Q9I9D7 418 125 -
PVNPDPVTLES Q9I9D8 391 125 -
PVNPDPVALDA MTG8_HUMAN 418 125 -
PVNPDPVALDA MTG8_MOUSE 391 125 -

Motif 4 width=10
Element Seqn Id St Int Rpt
QAQQQGETPA Q9I9D7 556 127 -
QAQQQGETPA Q9I9D8 529 127 -
QAQQQGDTPA MTG8_HUMAN 556 127 -
QAPQQGDTPA MTG8_MOUSE 529 127 -

Motif 5 width=13
Element Seqn Id St Int Rpt
SSGAGSPSTTPPA Q9I9D7 573 7 -
SSGAGSPSTTPPA Q9I9D8 546 7 -
NSGAGSPMDTPPA MTG8_HUMAN 573 7 -
SSGAGSPMDTPPA MTG8_MOUSE 546 7 -

Motif 6 width=15
Element Seqn Id St Int Rpt
ATPRSTTPGTPSTIE Q9I9D7 586 0 -
ATPRSTTPGTPSTIE Q9I9D8 559 0 -
ATPRSTTPGTPSTIE MTG8_HUMAN 586 0 -
ATPRSTTPGTPSTIE MTG8_MOUSE 559 0 -