Reviewed,
UniProtKB/Swiss-Prot O75081 (MTG16_HUMAN)
Last modified
June 16, 2009.
Version 55.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
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Names and origin
| Protein names | Recommended name: Protein CBFA2T3 Alternative name(s): Myeloid translocation gene on chromosome 16 protein Short name=hMTG16 MTG8-related protein 2 Zinc finger MYND domain-containing protein 4 | ||||
| Gene names |
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| 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 | 653 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Functions as a transcriptional repressor. Regulates the proliferation and the differentiation of erythroid progenitors by repressing the expression of TAL1 target genes. Plays a role in granulocyte differentiation. Isoform 2 functions as an A-kinase-anchoring protein (Ref.8). Ref.7 Ref.8 Ref.10 Ref.14 |
| Subunit structure | Component of a TAL-1 complex composed at least of CBFA2T3, LDB1, TAL1 and TCF3 By similarity. Heterodimer with RUNX1T1 and CBFA2T2. Interacts with ERBB4, HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, NCOR1, NCOR2, and ZNF652. According to Hoogeveen et al (Ref.9) may not interact with HDAC6. Isoform 2 interacts with PRKAR2A, PDE7A and probably PDE4A. |
| Subcellular location | Isoform 1: Nucleus › nucleolus. Note: The RUNX1-CBFA2T3 fusion protein localizes to the nucleoplasm. Ref.8 Ref.9 Isoform 2: Nucleus › nucleoplasm. Golgi apparatus membrane. Ref.8 Ref.9 |
| Tissue specificity | Widely expressed with higher expression in heart, pancreas, skeletal muscle, spleen, thymus and peripheral blood leukocytes. Expressed in hematopoietic cells (at protein level). Ref.10 Ref.1 Ref.3 |
| Induction | Down-regulated by all-trans retinoic acid. Ref.12 |
| Involvement in disease | A chromosomal aberration involving CBFA2T3 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein. |
| Sequence similarities | Belongs to the CBFA2T family. Contains 1 MYND-type zinc finger. Contains 1 TAFH (NHR1) domain. |
| Sequence caution | The sequence BAA31276.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAA31277.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
Alternative products
| This entry describes 5 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O75081-1) Also known as: CBFA2T3A; MTG16a; 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. | ||||||
| Note: The RUNX1-CBFA2T3 fusion protein localizes to the nucleoplasm. Ref.8 Ref.9 | ||||||
| Isoform 2 (identifier: O75081-2) Also known as: CBFA2T3B; MTG16b; The sequence of this isoform differs from the canonical sequence as follows: 1-61: Missing. 102-126: Missing. | ||||||
| Isoform 3 (identifier: O75081-3) The sequence of this isoform differs from the canonical sequence as follows: 102-126: Missing. 312-324: Missing. | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 4 (identifier: O75081-4) Also known as: MTG16c; The sequence of this isoform differs from the canonical sequence as follows: 51-127: APVDRKAKAS...CLKWSMVCLL → V | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 5 (identifier: O75081-5) Also known as: MTG16HEL; The sequence of this isoform differs from the canonical sequence as follows: 51-51: A → GKPALAAAGAPALCTPGQADARPVLGPA 52-653: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 653 | 653 | Protein CBFA2T3 | PRO_0000307173 | |||||
Regions | |||||||||
| Domain | 171 – 266 | 96 | TAFH | ||||||
| Zinc finger | 556 – 592 | 37 | MYND-type | ||||||
| Region | 1 – 435 | 435 | Mediates localization to the nucleus By similarity | ||||||
| Region | 1 – 430 | 430 | Mediates interaction with PDE7A (in isoform 2) | ||||||
| Region | 1 – 127 | 127 | Required for nucleolar targeting (in isoform 1) | ||||||
| Region | 485 – 506 | 22 | Mediates interaction with PRKAR2A | ||||||
| Coiled coil | 488 – 543 | 56 | Potential | ||||||
| Compositional bias | 42 – 99 | 58 | Pro-rich | ||||||
Sites | |||||||||
| Site | 51 – 52 | 2 | Breakpoint for translocation to form type-1 RUNX1-CBFA2T3 fusion protein | ||||||
| Site | 127 – 128 | 2 | Breakpoint for translocation to form type-2 RUNX1-CBFA2T3 fusion protein | ||||||
Amino acid modifications | |||||||||
| Cross-link | 535 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15 | |||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 61 | 61 | Missing in isoform 2. | VSP_028620 | |||||
| Alternative sequence | 51 – 127 | 77 | APVDR…MVCLL → V in isoform 4. | VSP_028621 | |||||
| Alternative sequence | 51 | 1 | A → GKPALAAAGAPALCTPGQAD ARPVLGPA in isoform 5. | VSP_028622 | |||||
| Alternative sequence | 52 – 653 | 602 | Missing in isoform 5. | VSP_028623 | |||||
| Alternative sequence | 102 – 126 | 25 | Missing in isoform 2 and isoform 3. | VSP_028624 | |||||
| Alternative sequence | 312 – 324 | 13 | Missing in isoform 3. | VSP_028625 | |||||
| Natural variant | 306 | 1 | R → H in a colorectal cancer sample; somatic mutation. Ref.16 | VAR_035447 | |||||
| Natural variant | 429 | 1 | E → G: dbSNP rs1053526. Ref.1 | VAR_035374 | |||||
| Natural variant | 518 | 1 | E → K in a colorectal cancer sample; somatic mutation. Ref.16 | VAR_035448 | |||||
| Natural variant | 534 | 1 | A → V in a colorectal cancer sample; somatic mutation. Ref.16 | VAR_035449 | |||||
Experimental info | |||||||||
| Mutagenesis | 494 | 1 | V → P or A: Loss of interaction with PRKAR2A. Ref.8 | ||||||
| Sequence conflict | 231 | 1 | F → L in AAH47019. Ref.2 | ||||||
| Sequence conflict | 295 | 1 | T → S in AAC64702. Ref.3 | ||||||
| Sequence conflict | 305 | 1 | D → E in BAA29061. Ref.1 | ||||||
| Sequence conflict | 370 | 1 | R → P in AAC64698. Ref.3 | ||||||
| Sequence conflict | 420 | 1 | L → V in AAC64698. Ref.3 | ||||||
| Sequence conflict | 542 | 1 | A → D in AAC64701. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family." Gamou T., Kitamura E., Hosoda F., Shimuzu K., Hayashi Y., Nagase T., Yokoyama Y., Ohki M. Blood 91:4028-4037(1998) [PubMed: 9596646] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), CHROMOSOMAL TRANSLOCATION WITH RUNX1, TISSUE SPECIFICITY, VARIANT GLY-429. Tissue: Brain. |
| [2] | "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] (ISOFORMS 1 AND 3). Tissue: Lung and Pancreas. |
| [3] | "CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family." Calabi F., Cilli V. Genomics 52:332-341(1998) [PubMed: 9790752] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 128-297 AND 492-604, NUCLEOTIDE SEQUENCE [MRNA] OF 341-431, TISSUE SPECIFICITY. Tissue: Brain. |
| [4] | "AML1-MTG16 fusion gene in therapy-related acute leukemia with t(16;21)(q24;q22): two new cases." Salomon-Nguyen F., Busson-Le Coniat M., Lafage Pochitaloff M., Mozziconacci J., Berger R., Bernard O.A. Leukemia 14:1704-1705(2000) [PubMed: 10995019] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH RUNX1. |
| [5] | "AML1/MTG16 fusion gene from a t(16;21)(q24;q22) translocation in treatment-induced leukemia after breast cancer." La Starza R., Sambani C., Crescenzi B., Matteucci C., Martelli M.F., Mecucci C. Haematologica 86:212-213(2001) [PubMed: 11224496] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH RUNX1. |
| [6] | "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain." Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W. Mol. Cell. Biol. 21:6470-6483(2001) [PubMed: 11533236] [Abstract] Cited for: INTERACTION WITH HDAC1; HDAC2; HDAC3; HDAC6; HDAC8; NCOR1 AND NCOR2. |
| [7] | "CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast cancer loss of heterozygosity region at 16q24.3." Kochetkova M., McKenzie O.L.D., Bais A.J., Martin J.M., Secker G.A., Seshadri R., Powell J.A., Hinze S.J., Gardner A.E., Spendlove H.E., O'Callaghan N.J., Cleton-Jansen A.-M., Cornelisse C., Whitmore S.A., Crawford J., Kremmidiotis G., Sutherland G.R., Callen D.F. Cancer Res. 62:4599-4604(2002) [PubMed: 12183414] [Abstract] Cited for: FUNCTION. |
| [8] | "Identification and characterization of myeloid translocation gene 16b as a novel a kinase anchoring protein in T lymphocytes." Schillace R.V., Andrews S.F., Liberty G.A., Davey M.P., Carr D.W. J. Immunol. 168:1590-1599(2002) [PubMed: 11823486] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRKAR2A, MUTAGENESIS OF VAL-494, SUBCELLULAR LOCATION. |
| [9] | "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: ALTERNATIVE SPLICING (ISOFORMS 4 AND 5), SUBCELLULAR LOCATION, INTERACTION WITH CBFA2T2; HDAC1; HDAC3 AND RUNX1T1. |
| [10] | "AML1-ETO decreases ETO-2 (MTG16) interactions with nuclear receptor corepressor, an effect that impairs granulocyte differentiation." Ibanez V., Sharma A., Buonamici S., Verma A., Kalakonda S., Wang J., Kadkol S., Saunthararajah Y. Cancer Res. 64:4547-4554(2004) [PubMed: 15231665] [Abstract] Cited for: FUNCTION, INTERACTION WITH NCOR1, TISSUE SPECIFICITY. |
| [11] | "A-kinase anchoring proteins interact with phosphodiesterases in T lymphocyte cell lines." Asirvatham A.L., Galligan S.G., Schillace R.V., Davey M.P., Vasta V., Beavo J.A., Carr D.W. J. Immunol. 173:4806-4814(2004) [PubMed: 15470020] [Abstract] Cited for: INTERACTION WITH PDE4A AND PDE7A. |
| [12] | "The leukemia-associated ETO homologues are differently expressed during hematopoietic differentiation." Lindberg S.R., Olsson A., Persson A.-M., Olsson I. Exp. Hematol. 33:189-198(2005) [PubMed: 15676213] [Abstract] Cited for: INDUCTION. |
| [13] | "ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional repression." Linggi B., Carpenter G. J. Biol. Chem. 281:25373-25380(2006) [PubMed: 16815842] [Abstract] Cited for: INTERACTION WITH ERBB4. |
| [14] | "ZNF652, a novel zinc finger protein, interacts with the putative breast tumor suppressor CBFA2T3 to repress transcription." Kumar R., Manning J., Spendlove H.E., Kremmidiotis G., McKirdy R., Lee J., Millband D.N., Cheney K.M., Stampfer M.R., Dwivedi P.P., Morris H.A., Callen D.F. Mol. Cancer Res. 4:655-665(2006) [PubMed: 16966434] [Abstract] Cited for: FUNCTION, INTERACTION WITH ZNF652. |
| [15] | "The proteomic reactor facilitates the analysis of affinity-purified proteins by mass spectrometry: application for identifying ubiquitinated proteins in human cells." Vasilescu J., Zweitzig D.R., Denis N.J., Smith J.C., Ethier M., Haines D.S., Figeys D. J. Proteome Res. 6:298-305(2007) [PubMed: 17203973] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-535, MASS SPECTROMETRY. Tissue: Lung adenocarcinoma. |
| [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] HIS-306; LYS-518 AND VAL-534. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AB010419 mRNA. Translation: BAA29061.1. AB010420 mRNA. Translation: BAA29062.1. AB013286 Genomic DNA. Translation: BAA31276.1. Sequence problems. AB013286 Genomic DNA. Translation: BAA31277.1. Sequence problems. BC047019 mRNA. Translation: AAH47019.1. BC062624 mRNA. Translation: AAH62624.1. AF052217, AF052216 Genomic DNA. Translation: AAC64701.1. AF052215, AF052213, AF052214 Genomic DNA. Translation: AAC64702.1. AF052220 mRNA. Translation: AAC64698.1. | |
| IPI | IPI00218436. IPI00306845. IPI00640985. IPI00868925. IPI00869145. |
| RefSeq | NP_005178.4. NP_787127.1. |
| UniGene | Hs.513811 |
3D structure databases | |
| SMR | O75081. Positions 171-273, 384-442, 546-598. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | O75081. 2 interactions. |
PTM databases | |
| PhosphoSite | O75081. |
Proteomic databases | |
| PRIDE | O75081. |
Genome annotation databases | |
| Ensembl | ENSG00000129993. Homo sapiens. [Contig view] |
| GeneID | 863. |
| KEGG | hsa:863. |
Organism-specific databases | |
| GeneCards | GC16M087468. |
| HGNC | HGNC:1537. CBFA2T3. |
| MIM | 603870. gene. |
| PharmGKB | PA26113. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | O75081. |
| HOVERGEN | O75081. |
| OMA | O75081. DRDPLHP. |
Gene expression databases | |
| ArrayExpress | O75081. |
| Bgee | O75081. |
Family and domain databases | |
| InterPro | IPR013289. ETO. IPR013292. MTG16. IPR014896. NHR2. IPR003894. TAFH_NHR1. IPR002893. Znf_MYND. [Graphical view] |
| Pfam | PF08788. NHR2. 1 hit. PF07531. TAFH. 1 hit. PF01753. zf-MYND. 1 hit. [Graphical view] |
| PRINTS | PR01875. ETOFAMILY. PR01878. MTG16PROTEIN. |
| 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 | 3596. |
| SOURCE | Search... |
Entry information
| Entry name | MTG16_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O75081 Secondary accession number(s): O60615 Q6P5W6 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 16 Human chromosome 16: 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 |
| SIMILARITY comments Index of protein domains and families |

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