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PR01875

Identifier
ETOFAMILY  [View Relations]  [View Alignment]  
Accession
PR01875
No. of Motifs
4
Creation Date
10-JUN-2003
Title
Eight-Twenty-One (ETO) family signature
Database References
PRINTS; PR01878 MTG16PROTEIN; PR01876 MTG8PROTEIN; PR01877 MTGR1PROTEIN
PRINTS; PR01879 NERVYPROTEIN
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).

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].
 
ETOFAMILY is a 4-element fingerprint that provides a signature for the 
Eight-Twenty-One (ETO) family. The fingerprint was derived from an initial 
alignment of 7 sequences: the motifs were drawn from conserved regions
spanning the full alignment length - motifs 1 and 2 lie within NHR1; motif 3
resides between NHR3 and NHR4; and motif 4 is located within NHR4. Two
iterations on SPTR40_22f were required to reach convergence, at which point
a true set comprising 14 sequences was identified. A single partial match
was also found, Q96L00, a human MTGR1 protein matching motifs 1 and 2.
Summary Information
  14 codes involving  4 elements
0 codes involving 3 elements
1 codes involving 2 elements
Composite Feature Index
414141414
30000
21100
1234
True Positives
MTG8_HUMAN    MTG8_MOUSE    O43439        O54972        
O75081 O75082 O75107 O75108
Q24037 Q9I9D7 Q9I9D8 Q9IAB2
Q9UP24 Q9W186
True Positive Partials
Codes involving 2 elements
Q96L00
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).
O43439 MTG8-like protein (MTG8 related protein) (EHT) (EHT protein) (MTG8- like protein MTGR1A) - Homo sapiens (Human).
O54972 ETO/MTG8-related protein ETO-2 - Mus musculus (Mouse).
O75081 MTG8-related protein MTG16a - Homo sapiens (Human).
O75082 MTG8-related protein MTG16b - Homo sapiens (Human).
O75107 MTG16 - Homo sapiens (Human).
O75108 MTG16 - Homo sapiens (Human).
Q24037 NERVY - Drosophila melanogaster (Fruit fly).
Q9I9D7 MTG8/ETOb - Gallus gallus (Chicken).
Q9I9D8 MTG8/ETOa - Gallus gallus (Chicken).
Q9IAB2 MTGR1-like protein - Xenopus laevis (African clawed frog).
Q9UP24 MTG8-like protein - Homo sapiens (Human).
Q9W186 NVY protein - Drosophila melanogaster (Fruit fly).

Q96L00 Core-binding factor, runt domain, alpha subunit 2, translocated to, 2 - Homo sapiens (Human).
Scan History
SPTR40_22f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=29
Element Seqn Id St Int Rpt
TLTIEEFHSKLQEATNFPLRPFVIPFLKA O75081 210 210 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA O75108 124 124 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA O75082 124 124 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA MTG8_HUMAN 159 159 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA MTG8_MOUSE 132 132 -
TVTIEEFHCKLQEATNFPLRPFVIPFLKA Q9IAB2 141 141 -
TVTIEEFHCKLQEATNFPLRPFVIPFLKA Q9UP24 123 123 -

Motif 2 width=21
Element Seqn Id St Int Rpt
QRELLHCARLAKQTPAQYLAQ O75081 244 5 -
QRELLHCARLAKQTPAQYLAQ O75108 158 5 -
QRELLHCARLAKQTPAQYLAQ O75082 158 5 -
QRELLHCARLAKQNPAQYLAQ MTG8_HUMAN 193 5 -
QRELLHCARLAKQNPAQYLAQ MTG8_MOUSE 166 5 -
QRELLHCARAGKQTPSQYLAQ Q9IAB2 175 5 -
QRELLHCARAAKQTPSQYLAQ Q9UP24 157 5 -

Motif 3 width=29
Element Seqn Id St Int Rpt
EVKRQAMSELQKAVSDAERKAHELITTER O75081 496 231 -
EVKRQAMSELQKAVSDAERKAHELITTER O75108 302 123 -
EVKRQAMSELQKAVSDAERKAHELITTER O75082 410 231 -
EVKRQAMTELQKAVSEAERKAHDMITTER MTG8_HUMAN 455 241 -
EVKRQAMTELQKAVSEAERKAHDMITTER MTG8_MOUSE 428 241 -
EVKRQAMSEVQKAVSEAEQKAFEMIASER Q9IAB2 437 241 -
KVKIQAMSEVQKAVAEAEQKAFEVIATER Q9UP24 418 240 -

Motif 4 width=29
Element Seqn Id St Int Rpt
CSGCNAARYCGSFCQHRDWEKHHHVCGQS O75081 567 42 -
CSGCNAARYCGSFCQHRDWEKHHHVCGQS O75108 373 42 -
CSGCNAARYCGSFCQHRDWEKHHHVCGQS O75082 481 42 -
CSGCNTARYCGSFCQHKDWEKHHHICGQT MTG8_HUMAN 526 42 -
CSGCNTARYCGSFCQHKDWEKHHHICGQT MTG8_MOUSE 499 42 -
CSGCNIARYCGSFCQHKDWEKHHRICGQS Q9IAB2 508 42 -
CSGCNIARYCGSFCQHKDWERHHRLCGQN Q9UP24 489 42 -
Final Motifs
Motif 1  width=29
Element Seqn Id St Int Rpt
TLTIEEFHSKLQEATNFPLRPFVIPFLKA O75081 210 210 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA O75108 124 124 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA O75107 210 210 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA O75082 124 124 -
TLTIEEFHAKLQEATNFPLRPFVIPFLKA O54972 185 185 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA MTG8_HUMAN 159 159 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA MTG8_MOUSE 132 132 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA Q9I9D7 159 159 -
TLTIEEFHSKLQEATNFPLRPFVIPFLKA Q9I9D8 132 132 -
TVTIEEFHCKLQEATNFPLRPFVIPFLKA Q9IAB2 141 141 -
TVTIEEFHCKLQEATNFPLRPFVIPFLKA O43439 152 152 -
TVTIEEFHCKLQEATNFPLRPFVIPFLKA Q9UP24 123 123 -
SISVEEFRLALQEAINLPLRPYVVPLLKN Q24037 251 251 -
SISVEEFRLALQEAINLPLRPYVVPLLKN Q9W186 250 250 -

Motif 2 width=21
Element Seqn Id St Int Rpt
QRELLHCARLAKQTPAQYLAQ O75081 244 5 -
QRELLHCARLAKQTPAQYLAQ O75108 158 5 -
QRELLHCARLAKQTPAQYLAQ O75107 244 5 -
QRELLHCARLAKQTPAQYLAQ O75082 158 5 -
QRELLHCARLAKQTPAQYLAQ O54972 219 5 -
QRELLHCARLAKQNPAQYLAQ MTG8_HUMAN 193 5 -
QRELLHCARLAKQNPAQYLAQ MTG8_MOUSE 166 5 -
QRELVHCARLAKQNPAQYLAQ Q9I9D7 193 5 -
QRELVHCARLAKQNPAQYLAQ Q9I9D8 166 5 -
QRELLHCARAGKQTPSQYLAQ Q9IAB2 175 5 -
QRELLHCARAAKQTPSQYLAQ O43439 186 5 -
QRELLHCARAAKQTPSQYLAQ Q9UP24 157 5 -
QREILALARATNQSALQYVTN Q24037 285 5 -
QREILALARATNQSALQYVTN Q9W186 284 5 -

Motif 3 width=29
Element Seqn Id St Int Rpt
EVKRQAMSELQKAVSDAERKAHELITTER O75081 496 231 -
EVKRQAMSELQKAVSDAERKAHELITTER O75108 302 123 -
EVKRQAMSELQKAVSDAERKAHELITTER O75107 388 123 -
EVKRQAMSELQKAVSDAERKAHELITTER O75082 410 231 -
EVKRQAMSELQKAVSDAERKAHELITTER O54972 473 233 -
EVKRQAMTELQKAVSEAERKAHDMITTER MTG8_HUMAN 455 241 -
EVKRQAMTELQKAVSEAERKAHDMITTER MTG8_MOUSE 428 241 -
EVKRQAMAELQKAVSEAERQAHDMITSER Q9I9D7 455 241 -
EVKRQAMAELQKAVSEAERQAHDMITSER Q9I9D8 428 241 -
EVKRQAMSEVQKAVSEAEQKAFEMIASER Q9IAB2 437 241 -
KVKIQAMSEVQKAVAEAEQKAFEVIATER O43439 447 240 -
KVKIQAMSEVQKAVAEAEQKAFEVIATER Q9UP24 418 240 -
QVKRQAVIEIQRAVVAAETRAAEIMTQER Q24037 525 219 -
QVKRQAVIEIQRAVVAAETRAAEIMTQER Q9W186 524 219 -

Motif 4 width=29
Element Seqn Id St Int Rpt
CSGCNAARYCGSFCQHRDWEKHHHVCGQS O75081 567 42 -
CSGCNAARYCGSFCQHRDWEKHHHVCGQS O75108 373 42 -
CSGCNAARYCGSFCQHRDWEKHHHVCGQS O75107 459 42 -
CSGCNAARYCGSFCQHRDWEKHHHVCGQS O75082 481 42 -
CSGCNAARYCGSFCQHKDWEKHHHVCGQS O54972 544 42 -
CSGCNTARYCGSFCQHKDWEKHHHICGQT MTG8_HUMAN 526 42 -
CSGCNTARYCGSFCQHKDWEKHHHICGQT MTG8_MOUSE 499 42 -
CSGCNTARYCGSFCQHKDWEKHHHICGQT Q9I9D7 526 42 -
CSGCNTARYCGSFCQHKDWEKHHHICGQT Q9I9D8 499 42 -
CSGCNIARYCGSFCQHKDWEKHHRICGQS Q9IAB2 508 42 -
CSGCNIARYCGSFCQHKDWERHHRLCGQN O43439 518 42 -
CSGCNIARYCGSFCQHKDWERHHRLCGQN Q9UP24 489 42 -
CSGCNMARYCSASCQYRDWDSHHQVCGNT Q24037 604 50 -
CSGCNMARYCSASCQYRDWDSHHQVCGNT Q9W186 603 50 -