RUNX1T1

Runt-related transcription factor 1; translocated to, 1 (cyclin D-related)

PDB rendering based on 1wq6.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1WQ6, 2DJ8, 2H7B, 2KNH, 2KYG, 2OD1, 2ODD, 2PP4, 4JOL

Identifiers

Symbols

RUNX1T1 ; AML1-MTG8; AML1T1; CBFA2T1; CDR; ETO; MTG8; ZMYND2

External IDs

OMIM: 133435 MGI: 104793 HomoloGene: 3801 GeneCards: RUNX1T1 Gene

Gene ontology
Molecular function	• DNA binding • transcription factor activity, sequence-specific DNA binding • transcription corepressor activity • protein binding • identical protein binding • metal ion binding
Cellular component	• nucleus • nucleoplasm • cytoplasm • mitochondrion • nuclear matrix
Biological process	• generation of precursor metabolites and energy • transcription, DNA-templated • negative regulation of transcription, DNA-templated
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

862

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 8:
91.95 – 92.1 Mb

Chr 4:
13.74 – 13.89 Mb

PubMed search

Protein CBFA2T1 is a protein that in humans is encoded by the RUNX1T1 gene.^[1]^[2]^[3]

Function

The protein encoded by this gene is a putative zinc finger transcription factor and oncoprotein. In acute myeloid leukemia, especially in the M2 subtype, the t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities. The translocation produces a chimeric gene made up of the 5'-region of the RUNX1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Several transcript variants encoding multiple isoforms have been found for this gene.^[3]

Interactions

RUNX1T1 has been shown to interact with:

References

↑ Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H (October 1992). "Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt". Blood 80 (7): 1825–31. PMID 1391946.
↑ Calabi F, Cilli V (Dec 1998). "CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family". Genomics 52 (3): 332–341. doi:10.1006/geno.1998.5429. PMID 9790752.
1 2 "Entrez Gene: RUNX1T1 runt-related transcription factor 1; translocated to, 1 (cyclin D-related)".
↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
1 2 Lindberg SR, Olsson A, Persson AM, Olsson I (Dec 2003). "Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins". Eur. J. Haematol. 71 (6): 439–47. doi:10.1046/j.0902-4441.2003.00166.x. PMID 14703694.
1 2 Hoogeveen AT, Rossetti S, Stoyanova V, Schonkeren J, Fenaroli A, Schiaffonati L, van Unen L, Sacchi N (September 2002). "The transcriptional corepressor MTG16a contains a novel nucleolar targeting sequence deranged in t (16; 21)-positive myeloid malignancies". Oncogene 21 (43): 6703–12. doi:10.1038/sj.onc.1205882. PMID 12242670.
↑ Puccetti E, Obradovic D, Beissert T, Bianchini A, Washburn B, Chiaradonna F, Boehrer S, Hoelzer D, Ottmann OG, Pelicci PG, Nervi C, Ruthardt M (Dec 2002). "AML-associated translocation products block vitamin D(3)-induced differentiation by sequestering the vitamin D(3) receptor". Cancer Res. 62 (23): 7050–8. PMID 12460926.
↑ McGhee L, Bryan J, Elliott L, Grimes HL, Kazanjian A, Davis JN, Meyers S (August 2003). "Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism". J. Cell. Biochem. 89 (5): 1005–18. doi:10.1002/jcb.10548. PMID 12874834.
↑ Amann JM, Nip J, Strom DK, Lutterbach B, Harada H, Lenny N, Downing JR, Meyers S, Hiebert SW (October 2001). "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain". Mol. Cell. Biol. 21 (19): 6470–83. doi:10.1128/mcb.21.19.6470-6483.2001. PMC 99794. PMID 11533236.
1 2 Zhang J, Hug BA, Huang EY, Chen CW, Gelmetti V, Maccarana M, Minucci S, Pelicci PG, Lazar MA (January 2001). "Oligomerization of ETO is obligatory for corepressor interaction". Mol. Cell. Biol. 21 (1): 156–63. doi:10.1128/MCB.21.1.156-163.2001. PMC 88789. PMID 11113190.
↑ Takahashi S, McConnell MJ, Harigae H, Kaku M, Sasaki T, Melnick AM, Licht JD (June 2004). "The Flt3 internal tandem duplication mutant inhibits the function of transcriptional repressors by blocking interactions with SMRT". Blood 103 (12): 4650–8. doi:10.1182/blood-2003-08-2759. PMID 14982881.
↑ Fukuyama T, Sueoka E, Sugio Y, Otsuka T, Niho Y, Akagi K, Kozu T (September 2001). "MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". Oncogene 20 (43): 6225–32. doi:10.1038/sj.onc.1204794. PMID 11593431.
↑ Melnick AM, Westendorf JJ, Polinger A, Carlile GW, Arai S, Ball HJ, Lutterbach B, Hiebert SW, Licht JD (March 2000). "The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein". Mol. Cell. Biol. 20 (6): 2075–86. doi:10.1128/mcb.20.6.2075-2086.2000. PMC 110824. PMID 10688654.
↑ Melnick A, Carlile GW, McConnell MJ, Polinger A, Hiebert SW, Licht JD (Dec 2000). "AML-1/ETO fusion protein is a dominant negative inhibitor of transcriptional repression by the promyelocytic leukemia zinc finger protein". Blood 96 (12): 3939–47. PMID 11090081.

Ferrara F, Del Vecchio L (2002). "Acute myeloid leukemia with t(8;21)/AML1/ETO: a distinct biological and clinical entity". Haematologica 87 (3): 306–19. PMID 11869944.
Nisson PE, Watkins PC, Sacchi N (1992). "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". Cancer Genet. Cytogenet. 63 (2): 81–88. doi:10.1016/0165-4608(92)90384-K. PMID 1423235.
Era T, Asou N, Kunisada T, Yamasaki H, Asou H, Kamada N, Nishikawa S, Yamaguchi K, Takatsuki K (1995). "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". Genes Chromosomes Cancer 13 (1): 25–33. doi:10.1002/gcc.2870130105. PMID 7541640.
Tighe JE, Calabi F (1994). "Alternative, out-of-frame runt/MTG8 transcripts are encoded by the derivative (8) chromosome in the t(8;21) of acute myeloid leukemia M2". Blood 84 (7): 2115–21. PMID 7919324.
Erickson PF, Robinson M, Owens G, Drabkin HA (1994). "The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor". Cancer Res. 54 (7): 1782–6. PMID 8137293.
Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M (1993). "The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript". EMBO J. 12 (7): 2715–21. PMC 413521. PMID 8334990.
Kozu T, Miyoshi H, Shimizu K, Maseki N, Kaneko Y, Asou H, Kamada N, Ohki M (1993). "Junctions of the AML1/MTG8(ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction". Blood 82 (4): 1270–6. PMID 8353289.
Niwa-Kawakita M, Miyoshi H, Gotoh O, Matsushima Y, Nishimura M, Shisa H, Ohki M (1996). "Cloning and gene mapping of the mouse homologue of the CBFA2T1 gene associated with human acute myeloid leukemia". Genomics 29 (3): 755–759. doi:10.1006/geno.1995.9941. PMID 8575770.
Erickson PF, Dessev G, Lasher RS, Philips G, Robinson M, Drabkin HA (1996). "ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease". Blood 88 (5): 1813–23. PMID 8781439.
Wolford JK, Bogardus C, Prochazka M (1998). "Polymorphism in the 3' untranslated region of MTG8 is associated with obesity in Pima Indian males". Biochem. Biophys. Res. Commun. 246 (3): 624–626. doi:10.1006/bbrc.1998.8683. PMID 9618262.
Sacchi N, Tamanini F, Willemsen R, Denis-Donini S, Campiglio S, Hoogeveen AT (1998). "Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells". Oncogene 16 (20): 2609–2615. doi:10.1038/sj.onc.1201824. PMID 9632137.
Wolford JK, Prochazka M (1998). "Structure and expression of the human MTG8/ETO gene". Gene 212 (1): 103–109. doi:10.1016/S0378-1119(98)00141-3. PMID 9661669.
Komori A, Sueoka E, Fujiki H, Ishii M, Kozu T (1999). "Association of MTG8 (ETO/CDR), a leukemia-related protein, with serine/threonine protein kinases and heat shock protein HSP90 in human hematopoietic cell lines". Jpn. J. Cancer Res. 90 (1): 60–8. doi:10.1111/j.1349-7006.1999.tb00666.x. PMID 10076566.
Morohoshi F, Mitani S, Mitsuhashi N, Kitabayashi I, Takahashi E, Suzuki M, Munakata N, Ohki M (2000). "Structure and expression pattern of a human MTG8/ETO family gene, MTGR1". Gene 241 (2): 287–295. doi:10.1016/S0378-1119(99)00481-3. PMID 10675041.
Melnick AM, Westendorf JJ, Polinger A, Carlile GW, Arai S, Ball HJ, Lutterbach B, Hiebert SW, Licht JD (2000). "The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein". Mol. Cell. Biol. 20 (6): 2075–2086. doi:10.1128/MCB.20.6.2075-2086.2000. PMC 110824. PMID 10688654.
Miyamoto T, Weissman IL, Akashi K (2000). "AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation". Proc. Natl. Acad. Sci. U.S.A. 97 (13): 7521–7526. doi:10.1073/pnas.97.13.7521. PMC 16578. PMID 10861016.
Odaka Y, Mally A, Elliott LT, Meyers S (2000). "Nuclear import and subnuclear localization of the proto-oncoprotein ETO (MTG8)". Oncogene 19 (32): 3584–3597. doi:10.1038/sj.onc.1203689. PMID 10951564.
Wood JD, Nucifora FC, Duan K, Zhang C, Wang J, Kim Y, Schilling G, Sacchi N, Liu JM, Ross CA (2000). "Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription". J. Cell Biol. 150 (5): 939–948. doi:10.1083/jcb.150.5.939. PMC 2175251. PMID 10973986.

PDB gallery

1wq6: The tetramer structure of the nervy homolgy two (NHR2) domain of AML1-ETO is critical for AML1-ETO'S activity

2dj8: Solution Structure of zf-MYND Domain of Protein CBFA2TI (Protein MTG8)

2h7b: Solution structure of the eTAFH domain from the human leukemia-associated fusion protein AML1-ETO

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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RUNX1T1

Function

Interactions

References

Further reading