Reviewed, UniProtKB/Swiss-Prot Q06455 (MTG8_HUMAN)

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

Name:	RUNX1T1
Synonyms:	AML1T1, CBFA2T1, CDR, ETO, MTG8, ZMYND2

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	Putative transcription factor.
Subunit structure	Heterodimer with CBFA2T3.
Subcellular location	NucleusPotential.
Tissue specificity	Most abundantly expressed in brain. Lower levels in lung, heart, testis and ovary.
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. 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-dependent Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from electronic annotation. Source: InterPro
Molecular function	transcription factor activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
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

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.

VAR_036321

Natural variant

395

1

R → W in a colorectal cancer sample; somatic mutation.

VAR_036322

Natural variant

471

1

A → V in a colorectal cancer sample; somatic mutation.

VAR_036323

Experimental info

Sequence conflict

427

1

D → G in AAC26143. Ref.2

Secondary structure

1

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604

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Isoform MTG8B [UniParc]. Last modified November 1, 1997. Version 2. Checksum: C3D2452F96E65679	FASTA	604	67,566
	10 20 30 40 50 60 MISVKRNTWR ALSLVIGDCR KKGNFEYCQD RTEKHSTMPD SPVDVKTQSR LTPPTMPPPP 70 80 90 100 110 120 TTQGAPRTSS FTPTTLTNGT SHSPTALNGA PSPPNGFSNG PSSSSSSSLA NQQLPPACGA 130 140 150 160 170 180 RQLSKLKRFL TTLQQFGNDI SPEIGERVRT LVLGLVNSTL TIEEFHSKLQ EATNFPLRPF 190 200 210 220 230 240 VIPFLKANLP LLQRELLHCA RLAKQNPAQY LAQHEQLLLD ASTTSPVDSS ELLLDVNENG 250 260 270 280 290 300 KRRTPDRTKE NGFDREPLHS EHPSKRPCTI SPGQRYSPNN GLSYQPNGLP HPTPPPPQHY 310 320 330 340 350 360 RLDDMAIAHH YRDSYRHPSH RDLRDRNRPM GLHGTRQEEM IDHRLTDREW AEEWKHLDHL 370 380 390 400 410 420 LNCIMDMVEK TRRSLTVLRR CQEADREELN YWIRRYSDAE DLKKGGGSSS SHSRQQSPVN 430 440 450 460 470 480 PDPVALDAHR EFLHRPASGY VPEEIWKKAE EAVNEVKRQA MTELQKAVSE AERKAHDMIT 490 500 510 520 530 540 TERAKMERTV AEAKRQAAED ALAVINQQED SSESCWNCGR KASETCSGCN TARYCGSFCQ 550 560 570 580 590 600 HKDWEKHHHI CGQTLQAQQQ GDTPAVSSSV TPNSGAGSPM DTPPAATPRS TTPGTPSTIE TTPR
	Isoform MTG8A [UniParc]. Checksum: 70E84F0120C11C3B		577	64,396
	10 20 30 40 50 60 MPDRTEKHST MPDSPVDVKT QSRLTPPTMP PPPTTQGAPR TSSFTPTTLT NGTSHSPTAL 70 80 90 100 110 120 NGAPSPPNGF SNGPSSSSSS SLANQQLPPA CGARQLSKLK RFLTTLQQFG NDISPEIGER 130 140 150 160 170 180 VRTLVLGLVN STLTIEEFHS KLQEATNFPL RPFVIPFLKA NLPLLQRELL HCARLAKQNP 190 200 210 220 230 240 AQYLAQHEQL LLDASTTSPV DSSELLLDVN ENGKRRTPDR TKENGFDREP LHSEHPSKRP 250 260 270 280 290 300 CTISPGQRYS PNNGLSYQPN GLPHPTPPPP QHYRLDDMAI AHHYRDSYRH PSHRDLRDRN 310 320 330 340 350 360 RPMGLHGTRQ EEMIDHRLTD REWAEEWKHL DHLLNCIMDM VEKTRRSLTV LRRCQEADRE 370 380 390 400 410 420 ELNYWIRRYS DAEDLKKGGG SSSSHSRQQS PVNPDPVALD AHREFLHRPA SGYVPEEIWK 430 440 450 460 470 480 KAEEAVNEVK RQAMTELQKA VSEAERKAHD MITTERAKME RTVAEAKRQA AEDALAVINQ 490 500 510 520 530 540 QEDSSESCWN CGRKASETCS GCNTARYCGS FCQHKDWEKH HHICGQTLQA QQQGDTPAVS 550 560 570 SSVTPNSGAG SPMDTPPAAT PRSTTPGTPS TIETTPR

References

	« Hide 'large scale' referencesShow '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]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

D14821 mRNA. Translation: BAA03558.1.
D13979 mRNA. Translation: BAA03089.1. Sequence problems.
D14289 mRNA. Translation: BAA03247.1. Different initiation.
AF018282 , AF018271, AF018272, AF018273, AF018274, AF018275, AF018276, AF018277, AF018278, AF018279, AF018281 Genomic DNA. Translation: AAC28932.1.
AF018282 , AF018270, AF018272, AF018273, AF018274, AF018275, AF018276, AF018277, AF018278, AF018279, 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.

PIR

A57784.
C57784.

RefSeq

NP_004340.1.
NP_783552.1.
NP_783553.1.
NP_783554.1.

UniGene

Hs.368431

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WQ6	X-ray	2.00	A/B	335-403	[»]
2DJ8	NMR	-	A	505-551	[»]
2H7B	NMR	-	A	120-222	[»]
2OD1	NMR	-	A	510-559	[»]
2ODD	NMR	-	A	508-559	[»]
2PP4	NMR	-	A	119-225	[»]

SMR

Q06455. Positions 505-551.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q06455.

PTM databases

PhosphoSite

Q06455.

Genome annotation databases

Ensembl

ENSG00000079102. Homo sapiens. [Contig view]

GeneID

862.

KEGG

hsa:862.

Organism-specific databases

HGNC

HGNC:1535. RUNX1T1.

MIM

114500. phenotype.
133435. gene.

PharmGKB

PA26111.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

Q06455.

Gene expression databases

ArrayExpress

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 , Q06456, Q14873, Q16239, Q16346, Q16347, Q6IBL1, Q92479, Q9BRZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	November 25, 2008
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)