Reviewed,
UniProtKB/Swiss-Prot Q06455 (MTG8_HUMAN)
Last modified
June 16, 2009.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Protein CBFA2T1 Alternative name(s): Protein MTG8 Protein ETO Eight twenty one protein Cyclin-D-related protein Zinc finger MYND domain-containing protein 2 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 604 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Transcription regulator that excerts its function by binding to histone deacetylases and transcription factors. Can repress transactivation mediated by TCF12. Ref.9 |
| Subunit structure | Homotetramer, and heterotetramer with CBFA2T2 and CBFA2T3. Interacts with TCF12, SIN3A, HDAC1, HDAC2, HDAC3, NCOR1 and NCOR2. Ref.9 Ref.7 Ref.8 Ref.10 Ref.11 |
| Subcellular location | Nucleus Potential. |
| Tissue specificity | Most abundantly expressed in brain. Lower levels in lung, heart, testis and ovary. |
| Domain | The TAFH domain mediates interaction with transcription regulators. Ref.11 |
| Involvement in disease | A chromosomal aberration involving RUNX1T1 is a cause of acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1/AML1. Ref.1 Ref.13 Ref.14 Ref.15 Defects in RUNX1T1 may be a cause of colorectal cancer (CRC) [MIM:114500]. |
| Sequence similarities | Belongs to the CBFA2T family. Contains 1 MYND-type zinc finger. Contains 1 TAFH (NHR1) domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Nucleus |
| Coding sequence diversity | Alternative splicing Chromosomal rearrangement Polymorphism |
| Disease | Proto-oncogene |
| Domain | Zinc-finger |
| Ligand | DNA-binding Metal-binding Zinc |
| Technical term | 3D-structure |
| Gene Ontology (GO) | |
| Biological process | generation of precursor metabolites and energy Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependentInferred from electronic annotation. Source: UniProtKB-KW transcriptionInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | transcription factor activity Traceable author statement. Source: ProtInc zinc ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| OTUD4 | Q01804 | 1 | EBI-743342,EBI-1054396 | |
| THRAP3 | Q9Y2W1 | 1 | EBI-743342,EBI-352039 | |
| ZNF652 | Q9Y2D9 | 1 | EBI-743342,EBI-1190229 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform MTG8B (identifier: Q06455-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform MTG8A (identifier: Q06455-2) The sequence of this isoform differs from the canonical sequence as follows: 1-29: MISVKRNTWRALSLVIGDCRKKGNFEYCQ → MP |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 604 | 604 | Protein CBFA2T1 | PRO_0000218299 | ||||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||||
| Domain | 120 – 215 | 96 | TAFH | |||||||||||||||||||||||||||
| Zinc finger | 515 – 551 | 37 | MYND-type | |||||||||||||||||||||||||||
| Region | 337 – 383 | 47 | Important for oligomerization | |||||||||||||||||||||||||||
| Compositional bias | 57 – 60 | 4 | Poly-Pro | |||||||||||||||||||||||||||
| Compositional bias | 102 – 108 | 7 | Poly-Ser | |||||||||||||||||||||||||||
| Compositional bias | 290 – 297 | 8 | Poly-Pro | |||||||||||||||||||||||||||
| Compositional bias | 408 – 413 | 6 | Poly-Ser | |||||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||||
| Site | 30 – 31 | 2 | Breakpoint for translocation to form AML1-MTG8 in AML-M2 | |||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 29 | 29 | MISVK…FEYCQ → MP in isoform MTG8A. | VSP_003327 | ||||||||||||||||||||||||||
| Natural variant | 386 | 1 | R → W in a colorectal cancer sample; somatic mutation. Ref.16 | VAR_036321 | ||||||||||||||||||||||||||
| Natural variant | 395 | 1 | R → W in a colorectal cancer sample; somatic mutation. Ref.16 | VAR_036322 | ||||||||||||||||||||||||||
| Natural variant | 471 | 1 | A → V in a colorectal cancer sample; somatic mutation. Ref.16 | VAR_036323 | ||||||||||||||||||||||||||
Experimental info | ||||||||||||||||||||||||||||||
| Mutagenesis | 125 | 1 | K → A or D: Loss of interaction with TCF12. Ref.9 | |||||||||||||||||||||||||||
| Mutagenesis | 126 | 1 | L → A: Loss of interaction with TCF12. Ref.9 | |||||||||||||||||||||||||||
| Mutagenesis | 128 | 1 | R → D: Loss of interaction with TCF12. Ref.9 | |||||||||||||||||||||||||||
| Mutagenesis | 129 | 1 | F → A: Loss of interaction with TCF12. Ref.9 Ref.11 | |||||||||||||||||||||||||||
| Mutagenesis | 129 | 1 | F → K: Abolishes interaction with corepressor. Ref.9 Ref.11 | |||||||||||||||||||||||||||
| Mutagenesis | 136 | 1 | F → A: Abolishes interaction with corepressor. Ref.11 | |||||||||||||||||||||||||||
| Mutagenesis | 170 | 1 | Q → A: Abolishes interaction with corepressor. Ref.11 | |||||||||||||||||||||||||||
| Mutagenesis | 173 | 1 | T → Q: Abolishes interaction with corepressor. Ref.11 | |||||||||||||||||||||||||||
| Mutagenesis | 175 | 1 | F → A: Abolishes interaction with corepressor. Ref.11 | |||||||||||||||||||||||||||
| Mutagenesis | 177 | 1 | L → A: Abolishes interaction with corepressor. Ref.11 | |||||||||||||||||||||||||||
| Mutagenesis | 178 | 1 | R → A or D: Loss of interaction with TCF12. Ref.9 | |||||||||||||||||||||||||||
| Mutagenesis | 184 | 1 | F → A: Loss of interaction with TCF12. Ref.9 | |||||||||||||||||||||||||||
| Mutagenesis | 547 | 1 | H → A: Causes unfolding of the MYND-type zinc finger domain. Ref.10 | |||||||||||||||||||||||||||
| Sequence conflict | 427 | 1 | D → G in AAC26143. Ref.2 | |||||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||||
| Helix | 121 – 123 | 3 | ||||||||||||||||||||||||||||
| Helix | 125 – 135 | 11 | ||||||||||||||||||||||||||||
| Helix | 137 – 140 | 4 | ||||||||||||||||||||||||||||
| Helix | 142 – 156 | 15 | ||||||||||||||||||||||||||||
| Helix | 162 – 172 | 11 | ||||||||||||||||||||||||||||
| Beta strand | 173 – 176 | 4 | ||||||||||||||||||||||||||||
| Beta strand | 179 – 181 | 3 | ||||||||||||||||||||||||||||
| Helix | 182 – 186 | 5 | ||||||||||||||||||||||||||||
| Helix | 189 – 199 | 11 | ||||||||||||||||||||||||||||
| Helix | 200 – 202 | 3 | ||||||||||||||||||||||||||||
| Helix | 209 – 212 | 4 | ||||||||||||||||||||||||||||
| Helix | 347 – 399 | 53 | ||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript." Miyoshi H., Kozu T., Shimizu K., Enomoto K., Maseki N., Kaneko Y., Kamada N., Ohki M. EMBO J. 12:2715-2721(1993) [PubMed: 8334990] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT AML1-MTG8/ETO FUSION IN AML-M2. Tissue: Fetal brain. |
| [2] | "Structure and expression of the human MTG8/ETO gene." Wolford J.K., Prochazka M. Gene 212:103-109(1998) [PubMed: 9661669] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. |
| [3] | "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MTG8A). |
| [4] | "The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved putative transcription factor." Erickson P.F., Robinson M., Owens G., Drabkin H.A. Cancer Res. 54:1782-1786(1994) [PubMed: 8137293] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 31-604. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-604. Tissue: Muscle. |
| [6] | "Alternative, out-of-frame runt/MTG8 transcripts are encoded by the derivative (8) chromosome in the t(8;21) of acute myeloid leukemia M2." Tighe J.E., Calabi F. Blood 84:2115-2121(1994) [PubMed: 7919324] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 334-432, VARIANT AML1-MTG8/ETO FUSION. |
| [7] | "The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t(16; 21)-positive myeloid malignancies." Hoogeveen A.T., Rossetti S., Stoyanova V., Schonkeren J., Fenaroli A., Schiaffonati L., van Unen L., Sacchi N. Oncogene 21:6703-6712(2002) [PubMed: 12242670] [Abstract] Cited for: INTERACTION WITH CBFA2T3. |
| [8] | "The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity." Liu Y., Cheney M.D., Gaudet J.J., Chruszcz M., Lukasik S.M., Sugiyama D., Lary J., Cole J., Dauter Z., Minor W., Speck N.A., Bushweller J.H. Cancer Cell 9:249-260(2006) [PubMed: 16616331] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 335-403, INTERACTION WITH HDAC1; HDAC2; HDAC3; TCF12; NCOR1; NCOR2; SIN3A; CBFA2T2 AND CBFA2T3. |
| [9] | "The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain." Plevin M.J., Zhang J., Guo C., Roeder R.G., Ikura M. Proc. Natl. Acad. Sci. U.S.A. 103:10242-10247(2006) [PubMed: 16803958] [Abstract] Cited for: STRUCTURE BY NMR OF 120-222, INTERACTION WITH TCF12, FUNCTION, MUTAGENESIS OF LYS-125; LEU-126; ARG-128; PHE-129; ARG-178 AND PHE-184. |
| [10] | "Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO's activity." Liu Y., Chen W., Gaudet J., Cheney M.D., Roudaia L., Cierpicki T., Klet R.C., Hartman K., Laue T.M., Speck N.A., Bushweller J.H. Cancer Cell 11:483-497(2007) [PubMed: 17560331] [Abstract] Cited for: STRUCTURE BY NMR OF 510-559 IN COMPLEX WITH ZINC IONS AND NCOR2, MUTAGENESIS OF HIS-547, INTERACTION WITH NCOR 1 AND NCOR2. |
| [11] | "A TAF4-homology domain from the corepressor ETO is a docking platform for positive and negative regulators of transcription." Wei Y., Liu S., Lausen J., Woodrell C., Cho S., Biris N., Kobayashi N., Wei Y., Yokoyama S., Werner M.H. Nat. Struct. Mol. Biol. 14:653-661(2007) [PubMed: 17572682] [Abstract] Cited for: STRUCTURE BY NMR OF 119-225, INTERACTION WITH NCOR1 AND TCF12, MUTAGENESIS OF PHE-129; PHE-136; GLN-170; THR-173; PHE-175 AND LEU-177, DOMAIN. |
| [12] | "Solution structure of ZF-MYND domain of protein CBFA2TI (protein MTG8)." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2006) to the PDB data bank Cited for: STRUCTURE BY NMR OF 505-551. |
| [13] | "Identification of two transcripts of AML1/ETO-fused gene in t(8;21) leukemic cells and expression of wild-type ETO gene in hematopoietic cells." Era T., Asou N., Kunisada T., Yamasaki H., Asou H., Kamada N., Nishikawa S., Yamaguchi K., Takatsuki K. Genes Chromosomes Cancer 13:25-33(1995) [PubMed: 7541640] [Abstract] Cited for: VARIANT AML1-MTG8/ETO FUSION IN AML-M2. |
| [14] | "Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction." Kozu T., Miyoshi H., Shimizu K., Maseki N., Kaneko Y., Asou H., Kamada N., Ohki M. Blood 82:1270-1276(1993) [PubMed: 8353289] [Abstract] Cited for: VARIANT AML1-MTG8/ETO FUSION IN AML-M2. |
| [15] | "Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells." Nisson P.E., Watkins P.C., Sacchi N. Cancer Genet. Cytogenet. 63:81-88(1992) [PubMed: 1423235] [Abstract] Cited for: VARIANT AML1-MTG8/ETO FUSION IN AML-M2. |
| [16] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TRP-386; TRP-395 AND VAL-471. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D14821 mRNA. Translation: BAA03558.1. D13979 mRNA. Translation: BAA03089.1. Sequence problems. D14289 mRNA. Translation: BAA03247.1. Different initiation. AF018282 AF018281 Genomic DNA. Translation: AAC28932.1. AF018282 AF018281 Genomic DNA. Translation: AAC28931.1. AF018283 mRNA. Translation: AAC26143.1. CR456792 mRNA. Translation: CAG33073.1. D43638 mRNA. Translation: BAA07755.1. BC005850 mRNA. Translation: AAH05850.1. Different initiation. X79990 mRNA. Translation: CAA56311.1. S74096 Genomic DNA. Translation: AAB32126.1. S74092 Genomic DNA. No translation available. S78158 mRNA. Translation: AAB34819.2. Sequence problems. S78159 mRNA. Translation: AAB34820.2. Sequence problems. D14822 mRNA. Translation: BAA03559.1. Sequence problems. D14823 mRNA. Translation: BAA03560.1. Sequence problems. S50186 Genomic DNA. No translation available. | |||||||||||||||||||||||||||||||||||||||||||
| IPI | IPI00333194. IPI00465350. | ||||||||||||||||||||||||||||||||||||||||||
| PIR | A57784. C57784. | ||||||||||||||||||||||||||||||||||||||||||
| RefSeq | NP_004340.1. NP_783552.1. NP_783553.1. NP_783554.1. | ||||||||||||||||||||||||||||||||||||||||||
| UniGene | Hs.368431 | ||||||||||||||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||
| SMR | Q06455. Positions 505-551. | ||||||||||||||||||||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||||||||||||||
| IntAct | Q06455. 13 interactions. | ||||||||||||||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||||||||||||||
| PhosphoSite | Q06455. | ||||||||||||||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||||||||||||||
| PRIDE | Q06455. | ||||||||||||||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||||||||||||||
| Ensembl | ENSG00000079102. Homo sapiens. [Contig view] | ||||||||||||||||||||||||||||||||||||||||||
| GeneID | 862. | ||||||||||||||||||||||||||||||||||||||||||
| KEGG | hsa:862. | ||||||||||||||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||||||||||||||
| GeneCards | GC08M093041. | ||||||||||||||||||||||||||||||||||||||||||
| HGNC | HGNC:1535. RUNX1T1. | ||||||||||||||||||||||||||||||||||||||||||
| MIM | 114500. phenotype. 133435. gene. | ||||||||||||||||||||||||||||||||||||||||||
| PharmGKB | PA26111. | ||||||||||||||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||||||||||||||
| HOVERGEN | Q06455. | ||||||||||||||||||||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||||||||||||||||||||
| ArrayExpress | Q06455. | ||||||||||||||||||||||||||||||||||||||||||
| Bgee | Q06455. | ||||||||||||||||||||||||||||||||||||||||||
| GermOnline | ENSG00000079102. Homo sapiens. | ||||||||||||||||||||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||||||||||||||||||||
| InterPro | IPR013289. ETO. IPR013290. MTG8. IPR014896. NHR2. IPR003894. TAFH_NHR1. IPR002893. Znf_MYND. [Graphical view] | ||||||||||||||||||||||||||||||||||||||||||
| PANTHER | PTHR10379:SF5. MTG8. 1 hit. | ||||||||||||||||||||||||||||||||||||||||||
| Pfam | PF08788. NHR2. 1 hit. PF07531. TAFH. 1 hit. PF01753. zf-MYND. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||||||||
| PRINTS | PR01875. ETOFAMILY. PR01876. MTG8PROTEIN. | ||||||||||||||||||||||||||||||||||||||||||
| SMART | SM00549. TAFH. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||||||||
| PROSITE | PS51119. TAFH. 1 hit. PS01360. ZF_MYND_1. 1 hit. PS50865. ZF_MYND_2. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||||||||||||||||||||
| NextBio | 3586. | ||||||||||||||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||||||||||||||
Entry information
| Entry name | MTG8_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q06455 Secondary accession number(s): O14784 Q9BRZ0 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 8 Human chromosome 8: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


