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O75081 (MTG16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein CBFA2T3
Alternative name(s):
MTG8-related protein 2
Myeloid translocation gene on chromosome 16 protein
Short name=hMTG16
Zinc finger MYND domain-containing protein 4
Gene names
Name:CBFA2T3
Synonyms:MTG16, MTGR2, ZMYND4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length653 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.8 Ref.9 Ref.11 Ref.15

Isoform 2 functions as an A-kinase-anchoring protein. Ref.8 Ref.9 Ref.11 Ref.15

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 Ref.10, may not interact with HDAC6. Interacts with PLXNA1, PLXNA3 and PRKAR1A. Isoform 2 interacts with PRKAR2A, PDE7A and probably PDE4A. Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.18

Subcellular location

Isoform 1: Nucleusnucleolus. Note: The RUNX1-CBFA2T3 fusion protein localizes to the nucleoplasm. Ref.9 Ref.10

Isoform 2: Nucleusnucleoplasm. Golgi apparatus membrane Ref.9 Ref.10.

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.1 Ref.4 Ref.11

Induction

Down-regulated by all-trans retinoic acid (ATRA). Ref.13

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 AAH62624.1 differs from that shown. Reason: Aberrant splicing.

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.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PLXNA3P518052EBI-1190217,EBI-7135904
ZNF652Q9Y2D92EBI-1190217,EBI-1190229

Alternative products

This entry describes 4 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.
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: O75081-4)

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 4 (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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 653653Protein CBFA2T3
PRO_0000307173

Regions

Domain171 – 26696TAFH
Zinc finger556 – 59237MYND-type
Region1 – 435435Mediates localization to the nucleus By similarity
Region1 – 430430Mediates interaction with PDE7A (in isoform 2)
Region1 – 127127Required for nucleolar targeting (in isoform 1)
Region485 – 50622Mediates interaction with PRKAR2A
Coiled coil488 – 54356 Potential
Compositional bias42 – 9958Pro-rich

Sites

Site51 – 522Breakpoint for translocation to form type-1 RUNX1-CBFA2T3 fusion protein
Site127 – 1282Breakpoint for translocation to form type-2 RUNX1-CBFA2T3 fusion protein

Amino acid modifications

Cross-link535Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.16

Natural variations

Alternative sequence1 – 6161Missing in isoform 2.
VSP_028620
Alternative sequence51 – 12777APVDR…MVCLL → V in isoform 3.
VSP_028621
Alternative sequence511A → GKPALAAAGAPALCTPGQAD ARPVLGPA in isoform 4.
VSP_028622
Alternative sequence52 – 653602Missing in isoform 4.
VSP_028623
Alternative sequence102 – 12625Missing in isoform 2.
VSP_028624
Natural variant3061R → H in a colorectal cancer sample; somatic mutation. Ref.19
VAR_035447
Natural variant4291E → G. Ref.1
Corresponds to variant rs1053526 [ dbSNP | Ensembl ].
VAR_035374
Natural variant5181E → K in a colorectal cancer sample; somatic mutation. Ref.19
VAR_035448
Natural variant5341A → V in a colorectal cancer sample; somatic mutation. Ref.19
VAR_035449

Experimental info

Mutagenesis4941V → P or A: Loss of interaction with PRKAR2A. Ref.9
Sequence conflict2311F → L in AAH47019. Ref.3
Sequence conflict2951T → S in AAC64702. Ref.4
Sequence conflict3051D → E in BAA29061. Ref.1
Sequence conflict3701R → P in AAC64698. Ref.4
Sequence conflict4201L → V in AAC64698. Ref.4
Sequence conflict5421A → D in AAC64701. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CBFA2T3A) (MTG16a) [UniParc].

Last modified October 23, 2007. Version 2.
Checksum: 0B72B602120FA5DE

FASTA65371,192
        10         20         30         40         50         60 
MPASRLRDRA ASSASGSTCG SMSQTHPVLE SGLLASAGCS APRGPRKGGP APVDRKAKAS 

        70         80         90        100        110        120 
AMPDSPAEVK TQPRSTPPSM PPPPPAASQG ATRPPSFTPH THREDGPATL PHGRFHGCLK 

       130        140        150        160        170        180 
WSMVCLLMNG SSHSPTAING APCTPNGFSN GPATSSTASL STQHLPPACG ARQLSKLKRF 

       190        200        210        220        230        240 
LTTLQQFGSD ISPEIGERVR TLVLGLVNST LTIEEFHSKL QEATNFPLRP FVIPFLKANL 

       250        260        270        280        290        300 
PLLQRELLHC ARLAKQTPAQ YLAQHEQLLL DASASSPIDS SELLLEVNEN GKRRTPDRTK 

       310        320        330        340        350        360 
ENGSDRDPLH PEHLSKRPCT LNPAQRYSPS NGPPQPTPPP HYRLEDIAMA HHFRDAYRHP 

       370        380        390        400        410        420 
DPRELRERHR PLVVPGSRQE EVIDHKLTER EWAEEWKHLN NLLNCIMDMV EKTRRSLTVL 

       430        440        450        460        470        480 
RRCQEADREE LNHWARRYSD AEDTKKGPAP AAARPRSSSA GPEGPQLDVP REFLPRTLTG 

       490        500        510        520        530        540 
YVPEDIWRKA EEAVNEVKRQ AMSELQKAVS DAERKAHELI TTERAKMERA LAEAKRQASE 

       550        560        570        580        590        600 
DALTVINQQE DSSESCWNCG RKASETCSGC NAARYCGSFC QHRDWEKHHH VCGQSLQGPT 

       610        620        630        640        650 
AVVADPVPGP PEAAHSLGPS LPVGAASPSE AGSAGPSRPG SPSPPGPLDT VPR 

« Hide

Isoform 2 (CBFA2T3B) (MTG16b) [UniParc].

Checksum: 6BF84FE5AA33B71B
Show »

FASTA56762,372
Isoform 3 (MTG16c) [UniParc].

Checksum: D8F4F45B7DE9C0B7
Show »

FASTA57763,121
Isoform 4 (MTG16HEL) [UniParc].

Checksum: 03A1369FCDF569CA
Show »

FASTA787,436

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), CHROMOSOMAL TRANSLOCATION WITH RUNX1, TISSUE SPECIFICITY, VARIANT GLY-429.
Tissue: Brain.
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung and Pancreas.
[4]"CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family."
Calabi F., Cilli V.
Genomics 52:332-341(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 128-297 AND 492-604, NUCLEOTIDE SEQUENCE [MRNA] OF 341-431, TISSUE SPECIFICITY.
Tissue: Brain.
[5]"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] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH RUNX1.
[6]"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] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH RUNX1.
[7]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC1; HDAC2; HDAC3; HDAC6; HDAC8; NCOR1 AND NCOR2.
[8]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION (ISOFORM 2), INTERACTION WITH PRKAR2A, MUTAGENESIS OF VAL-494, SUBCELLULAR LOCATION (ISOFORM 2).
[10]"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] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING (ISOFORMS 3 AND 4), SUBCELLULAR LOCATION, INTERACTION WITH CBFA2T2; HDAC1; HDAC3 AND RUNX1T1.
[11]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NCOR1, TISSUE SPECIFICITY.
[12]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PDE4A AND PDE7A.
[13]"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] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[14]"ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional repression."
Linggi B., Carpenter G.
J. Biol. Chem. 281:25373-25380(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ERBB4.
[15]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ZNF652.
[16]"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] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-535.
Tissue: Lung adenocarcinoma.
[17]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[18]"Myeloid translocation gene 16b is a dual A-kinase anchoring protein that interacts selectively with plexins in a phospho-regulated manner."
Fiedler S.E., Schillace R.V., Daniels C.J., Andrews S.F., Carr D.W.
FEBS Lett. 584:873-877(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLXNA1; PLXNA3 AND PRKAR1A.
[19]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-306; LYS-518 AND VAL-534.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CH471184 Genomic DNA. Translation: EAW66748.1.
CH471184 Genomic DNA. Translation: EAW66752.1.
BC047019 mRNA. Translation: AAH47019.1.
BC062624 mRNA. Translation: AAH62624.1. Sequence problems.
AF052217, AF052216 Genomic DNA. Translation: AAC64701.1.
AF052215, AF052213, AF052214 Genomic DNA. Translation: AAC64702.1.
AF052220 mRNA. Translation: AAC64698.1.
RefSeqNP_005178.4. NM_005187.5.
NP_787127.1. NM_175931.2.
UniGeneHs.513811.

3D structure databases

ProteinModelPortalO75081.
SMRO75081. Positions 170-267, 383-442, 479-508, 551-598.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107311. 20 interactions.
DIPDIP-48898N.
IntActO75081. 11 interactions.
MINTMINT-3000909.

PTM databases

PhosphoSiteO75081.

Proteomic databases

PaxDbO75081.
PRIDEO75081.

Protocols and materials databases

DNASU863.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268679; ENSP00000268679; ENSG00000129993. [O75081-1]
ENST00000327483; ENSP00000332122; ENSG00000129993. [O75081-2]
ENST00000360302; ENSP00000353449; ENSG00000129993. [O75081-2]
ENST00000448839; ENSP00000401254; ENSG00000129993. [O75081-4]
GeneID863.
KEGGhsa:863.
UCSCuc002fml.2. human. [O75081-2]
uc002fmm.2. human. [O75081-1]

Organism-specific databases

CTD863.
GeneCardsGC16M088941.
H-InvDBHIX0013342.
HGNCHGNC:1537. CBFA2T3.
MIM603870. gene.
neXtProtNX_O75081.
Orphanet329469. Acute megakaryoblastic leukemia without Down syndrome.
PharmGKBPA26113.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG79810.
HOVERGENHBG000169.
InParanoidO75081.
OMADMAMAHH.
OrthoDBEOG70W3D2.
PhylomeDBO75081.
TreeFamTF106303.

Gene expression databases

ArrayExpressO75081.
BgeeO75081.
GenevestigatorO75081.

Family and domain databases

InterProIPR013289. ETO.
IPR013292. MTG16.
IPR014896. NHR2.
IPR003894. TAFH_NHR1.
IPR002893. Znf_MYND.
[Graphical view]
PfamPF08788. NHR2. 1 hit.
PF07531. TAFH. 1 hit.
PF01753. zf-MYND. 1 hit.
[Graphical view]
PRINTSPR01875. ETOFAMILY.
PR01878. MTG16PROTEIN.
SMARTSM00549. TAFH. 1 hit.
[Graphical view]
PROSITEPS51119. TAFH. 1 hit.
PS01360. ZF_MYND_1. 1 hit.
PS50865. ZF_MYND_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCBFA2T3. human.
GeneWikiCBFA2T3.
GenomeRNAi863.
NextBio3596.
PROO75081.
SOURCESearch...

Entry information

Entry nameMTG16_HUMAN
AccessionPrimary (citable) accession number: O75081
Secondary accession number(s): D3DX78 expand/collapse secondary AC list , O60615, O60616, O60617, O75082, O75107, O75108, Q0P5Z6, Q6P5W6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 23, 2007
Last sequence update: October 23, 2007
Last modified: March 19, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM