MTG16_HUMAN
ID MTG16_HUMAN Reviewed; 653 AA.
AC O75081; D3DX78; O60615; O60616; O60617; O75082; O75107; O75108; Q0P5Z6;
AC Q6P5W6;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Protein CBFA2T3;
DE AltName: Full=MTG8-related protein 2;
DE AltName: Full=Myeloid translocation gene on chromosome 16 protein;
DE Short=hMTG16;
DE AltName: Full=Zinc finger MYND domain-containing protein 4;
GN Name=CBFA2T3; Synonyms=MTG16, MTGR2, ZMYND4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), CHROMOSOMAL
RP TRANSLOCATION WITH RUNX1, TISSUE SPECIFICITY, AND VARIANT GLY-429.
RC TISSUE=Brain;
RX PubMed=9596646;
RA Gamou T., Kitamura E., Hosoda F., Shimuzu K., Hayashi Y., Nagase T.,
RA Yokoyama Y., Ohki M.;
RT "The partner gene of AML1 in t(16;21) myeloid malignancies is a novel
RT member of the MTG8(ETO) family.";
RL Blood 91:4028-4037(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 128-297 AND 492-604, NUCLEOTIDE
RP SEQUENCE [MRNA] OF 341-431, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9790752; DOI=10.1006/geno.1998.5429;
RA Calabi F., Cilli V.;
RT "CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene
RT family.";
RL Genomics 52:332-341(1998).
RN [5]
RP CHROMOSOMAL TRANSLOCATION WITH RUNX1.
RX PubMed=10995019; DOI=10.1038/sj.leu.2401885;
RA Salomon-Nguyen F., Busson-Le Coniat M., Lafage Pochitaloff M.,
RA Mozziconacci J., Berger R., Bernard O.A.;
RT "AML1-MTG16 fusion gene in therapy-related acute leukemia with
RT t(16;21)(q24;q22): two new cases.";
RL Leukemia 14:1704-1705(2000).
RN [6]
RP CHROMOSOMAL TRANSLOCATION WITH RUNX1.
RX PubMed=11224496;
RA La Starza R., Sambani C., Crescenzi B., Matteucci C., Martelli M.F.,
RA Mecucci C.;
RT "AML1/MTG16 fusion gene from a t(16;21)(q24;q22) translocation in
RT treatment-induced leukemia after breast cancer.";
RL Haematologica 86:212-213(2001).
RN [7]
RP INTERACTION WITH HDAC1; HDAC2; HDAC3; HDAC6; HDAC8; NCOR1 AND NCOR2.
RX PubMed=11533236; DOI=10.1128/mcb.21.19.6470-6483.2001;
RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N.,
RA Downing J.R., Meyers S., Hiebert S.W.;
RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with
RT multiple histone deacetylases and binds mSin3A through its oligomerization
RT domain.";
RL Mol. Cell. Biol. 21:6470-6483(2001).
RN [8]
RP FUNCTION.
RX PubMed=12183414;
RA Kochetkova M., McKenzie O.L.D., Bais A.J., Martin J.M., Secker G.A.,
RA Seshadri R., Powell J.A., Hinze S.J., Gardner A.E., Spendlove H.E.,
RA O'Callaghan N.J., Cleton-Jansen A.-M., Cornelisse C., Whitmore S.A.,
RA Crawford J., Kremmidiotis G., Sutherland G.R., Callen D.F.;
RT "CBFA2T3 (MTG16) is a putative breast tumor suppressor gene from the breast
RT cancer loss of heterozygosity region at 16q24.3.";
RL Cancer Res. 62:4599-4604(2002).
RN [9]
RP FUNCTION (ISOFORM 2), INTERACTION WITH PRKAR2A, MUTAGENESIS OF VAL-494, AND
RP SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=11823486; DOI=10.4049/jimmunol.168.4.1590;
RA Schillace R.V., Andrews S.F., Liberty G.A., Davey M.P., Carr D.W.;
RT "Identification and characterization of myeloid translocation gene 16b as a
RT novel a kinase anchoring protein in T lymphocytes.";
RL J. Immunol. 168:1590-1599(2002).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORMS 3 AND 4), SUBCELLULAR LOCATION, AND
RP INTERACTION WITH CBFA2T2; HDAC1; HDAC3 AND RUNX1T1.
RX PubMed=12242670; DOI=10.1038/sj.onc.1205882;
RA Hoogeveen A.T., Rossetti S., Stoyanova V., Schonkeren J., Fenaroli A.,
RA Schiaffonati L., van Unen L., Sacchi N.;
RT "The transcriptional corepressor MTG16a contains a novel nucleolar
RT targeting sequence deranged in t(16; 21)-positive myeloid malignancies.";
RL Oncogene 21:6703-6712(2002).
RN [11]
RP REVIEW.
RX PubMed=12559562; DOI=10.1016/s0378-1119(02)01172-1;
RA Davis J.N., McGhee L., Meyers S.;
RT "The ETO (MTG8) gene family.";
RL Gene 303:1-10(2003).
RN [12]
RP FUNCTION, INTERACTION WITH NCOR1, AND TISSUE SPECIFICITY.
RX PubMed=15231665; DOI=10.1158/0008-5472.can-03-3689;
RA Ibanez V., Sharma A., Buonamici S., Verma A., Kalakonda S., Wang J.,
RA Kadkol S., Saunthararajah Y.;
RT "AML1-ETO decreases ETO-2 (MTG16) interactions with nuclear receptor
RT corepressor, an effect that impairs granulocyte differentiation.";
RL Cancer Res. 64:4547-4554(2004).
RN [13]
RP REVIEW.
RX PubMed=15203199; DOI=10.1016/j.ygeno.2004.02.011;
RA Rossetti S., Hoogeveen A.T., Sacchi N.;
RT "The MTG proteins: chromatin repression players with a passion for
RT networking.";
RL Genomics 84:1-9(2004).
RN [14]
RP INTERACTION WITH PDE4A AND PDE7A.
RX PubMed=15470020; DOI=10.4049/jimmunol.173.8.4806;
RA Asirvatham A.L., Galligan S.G., Schillace R.V., Davey M.P., Vasta V.,
RA Beavo J.A., Carr D.W.;
RT "A-kinase anchoring proteins interact with phosphodiesterases in T
RT lymphocyte cell lines.";
RL J. Immunol. 173:4806-4814(2004).
RN [15]
RP INDUCTION.
RX PubMed=15676213; DOI=10.1016/j.exphem.2004.10.011;
RA Lindberg S.R., Olsson A., Persson A.-M., Olsson I.;
RT "The leukemia-associated ETO homologues are differently expressed during
RT hematopoietic differentiation.";
RL Exp. Hematol. 33:189-198(2005).
RN [16]
RP INTERACTION WITH AML1-MTG8/ETO.
RX PubMed=16616331; DOI=10.1016/j.ccr.2006.03.012;
RA Liu Y., Cheney M.D., Gaudet J.J., Chruszcz M., Lukasik S.M., Sugiyama D.,
RA Lary J., Cole J., Dauter Z., Minor W., Speck N.A., Bushweller J.H.;
RT "The tetramer structure of the Nervy homology two domain, NHR2, is critical
RT for AML1/ETO's activity.";
RL Cancer Cell 9:249-260(2006).
RN [17]
RP INTERACTION WITH ERBB4.
RX PubMed=16815842; DOI=10.1074/jbc.m603998200;
RA Linggi B., Carpenter G.;
RT "ErbB-4 s80 intracellular domain abrogates ETO2-dependent transcriptional
RT repression.";
RL J. Biol. Chem. 281:25373-25380(2006).
RN [18]
RP FUNCTION, AND INTERACTION WITH ZNF652.
RX PubMed=16966434; DOI=10.1158/1541-7786.mcr-05-0249;
RA Kumar R., Manning J., Spendlove H.E., Kremmidiotis G., McKirdy R., Lee J.,
RA Millband D.N., Cheney K.M., Stampfer M.R., Dwivedi P.P., Morris H.A.,
RA Callen D.F.;
RT "ZNF652, a novel zinc finger protein, interacts with the putative breast
RT tumor suppressor CBFA2T3 to repress transcription.";
RL Mol. Cancer Res. 4:655-665(2006).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [20]
RP INTERACTION WITH PLXNA1; PLXNA3 AND PRKAR1A.
RX PubMed=20138877; DOI=10.1016/j.febslet.2010.02.007;
RA Fiedler S.E., Schillace R.V., Daniels C.J., Andrews S.F., Carr D.W.;
RT "Myeloid translocation gene 16b is a dual A-kinase anchoring protein that
RT interacts selectively with plexins in a phospho-regulated manner.";
RL FEBS Lett. 584:873-877(2010).
RN [21]
RP FUNCTION, AND INTERACTION WITH ZBTB4; ZBTB33 AND ZBTB38.
RX PubMed=23251453; DOI=10.1371/journal.pone.0051205;
RA Barrett C.W., Smith J.J., Lu L.C., Markham N., Stengel K.R., Short S.P.,
RA Zhang B., Hunt A.A., Fingleton B.M., Carnahan R.H., Engel M.E., Chen X.,
RA Beauchamp R.D., Wilson K.T., Hiebert S.W., Reynolds A.B., Williams C.S.;
RT "Kaiso directs the transcriptional corepressor MTG16 to the Kaiso binding
RT site in target promoters.";
RL PLoS ONE 7:E51205-E51205(2012).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457; SER-459 AND THR-479, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP FUNCTION, AND REGIONS NHR2 AND NHR3.
RX PubMed=23840896; DOI=10.1371/journal.pone.0068502;
RA Kumar P., Sharoyko V.V., Spegel P., Gullberg U., Mulder H., Olsson I.,
RA Ajore R.;
RT "The transcriptional co-repressor myeloid translocation gene 16 inhibits
RT glycolysis and stimulates mitochondrial respiration.";
RL PLoS ONE 8:E68502-E68502(2013).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-637; SER-641 AND THR-650, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [25]
RP FUNCTION, AND INTERACTION WITH HIF1A AND EGLN1.
RX PubMed=25974097; DOI=10.1371/journal.pone.0123725;
RA Kumar P., Gullberg U., Olsson I., Ajore R.;
RT "Myeloid translocation gene-16 co-repressor promotes degradation of
RT hypoxia-inducible factor 1.";
RL PLoS ONE 10:E0123725-E0123725(2015).
RN [26]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-306; LYS-518 AND VAL-534.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Transcriptional corepressor which facilitates transcriptional
CC repression via its association with DNA-binding transcription factors
CC and recruitment of other corepressors and histone-modifying enzymes
CC (PubMed:12559562, PubMed:15203199). Can repress the expression of MMP7
CC in a ZBTB33-dependent manner (PubMed:23251453). Reduces the protein
CC levels and stability of the transcriptinal regulator HIF1A; interacts
CC with EGLN1 and promotes the HIF1A prolyl hydroxylation-dependent
CC ubiquitination and proteasomal degradation pathway (PubMed:25974097).
CC Contributes to inhibition of glycolysis and stimulation of
CC mitochondrial respiration by down-regulating the expression of
CC glycolytic genes including PFKFB3, PFKFB4, PDK1, PFKP, LDHA and HK1
CC which are direct targets of HIF1A (PubMed:23840896, PubMed:25974097).
CC Regulates the proliferation and the differentiation of erythroid
CC progenitors by repressing the expression of TAL1 target genes (By
CC similarity). Plays a role in granulocyte differentiation
CC (PubMed:15231665). {ECO:0000250|UniProtKB:O54972,
CC ECO:0000269|PubMed:12183414, ECO:0000269|PubMed:15231665,
CC ECO:0000269|PubMed:16966434, ECO:0000269|PubMed:23251453,
CC ECO:0000269|PubMed:23840896, ECO:0000269|PubMed:25974097,
CC ECO:0000303|PubMed:12559562, ECO:0000303|PubMed:15203199}.
CC -!- FUNCTION: Isoform 2 functions as an A-kinase-anchoring protein
CC (PubMed:11823486). {ECO:0000269|PubMed:11823486}.
CC -!- SUBUNIT: Homooligomer. Homotetramerization is mediated by nervy
CC homology region 2 (NRH2) (By similarity). Can interact with RUNX1T1 and
CC CBFA2T2; heterotetramerization between members of the CBFA2T family is
CC proposed (PubMed:12242670). Component of a TAL-1 complex composed at
CC least of CBFA2T3, LDB1, TAL1 and TCF3 (By similarity). Interacts with
CC ERBB4, HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, NCOR1, NCOR2, and ZNF652.
CC According to PubMed:12242670, may not interact with HDAC6. Interacts
CC with PLXNA1, PLXNA3 and PRKAR1A. Isoform 2 interacts with PRKAR2A,
CC PDE7A and probably PDE4A. Interacts with ZBTB4, ZBTB38 and ZBTB33.
CC Interacts with HIF1A and EGLN1. Interacts with the AML1-MTG8/ETO fusion
CC protein. {ECO:0000250|UniProtKB:O54972, ECO:0000250|UniProtKB:Q06455,
CC ECO:0000269|PubMed:11533236, ECO:0000269|PubMed:11823486,
CC ECO:0000269|PubMed:12242670, ECO:0000269|PubMed:15231665,
CC ECO:0000269|PubMed:15470020, ECO:0000269|PubMed:16616331,
CC ECO:0000269|PubMed:16815842, ECO:0000269|PubMed:16966434,
CC ECO:0000269|PubMed:20138877, ECO:0000269|PubMed:23251453,
CC ECO:0000269|PubMed:25974097}.
CC -!- INTERACTION:
CC O75081; P51805: PLXNA3; NbExp=2; IntAct=EBI-1190217, EBI-7135904;
CC O75081; Q9Y2D9: ZNF652; NbExp=2; IntAct=EBI-1190217, EBI-1190229;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus. Note=The RUNX1-
CC CBFA2T3 fusion protein localizes to the nucleoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:11823486}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:11823486}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=CBFA2T3A, MTG16a;
CC IsoId=O75081-1; Sequence=Displayed;
CC Name=2; Synonyms=CBFA2T3B, MTG16b;
CC IsoId=O75081-2; Sequence=VSP_028620, VSP_028624;
CC Name=3; Synonyms=MTG16c;
CC IsoId=O75081-4; Sequence=VSP_028621;
CC Name=4; Synonyms=MTG16HEL;
CC IsoId=O75081-5; Sequence=VSP_028622, VSP_028623;
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in heart,
CC pancreas, skeletal muscle, spleen, thymus and peripheral blood
CC leukocytes. Expressed in hematopoietic cells (at protein level).
CC {ECO:0000269|PubMed:15231665, ECO:0000269|PubMed:9596646,
CC ECO:0000269|PubMed:9790752}.
CC -!- INDUCTION: Down-regulated by all-trans retinoic acid (ATRA).
CC {ECO:0000269|PubMed:15676213}.
CC -!- DOMAIN: Nervy homology region 2 (NHR2) mediates homo- and possibly
CC heterotypic oligomerization by forming a four-helix bundle tetrameric
CC structure. {ECO:0000250|UniProtKB:Q06455}.
CC -!- DISEASE: Note=A chromosomal aberration involving CBFA2T3 is found in
CC therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22)
CC that forms a RUNX1-CBFA2T3 fusion protein.
CC {ECO:0000269|PubMed:10995019, ECO:0000269|PubMed:11224496,
CC ECO:0000269|PubMed:9596646}.
CC -!- SIMILARITY: Belongs to the CBFA2T family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH62624.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
CC Sequence=BAA31276.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA31277.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CBFA2T3ID428ch16q24.html";
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DR EMBL; AB010419; BAA29061.1; -; mRNA.
DR EMBL; AB010420; BAA29062.1; -; mRNA.
DR EMBL; AB013286; BAA31276.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB013286; BAA31277.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471184; EAW66748.1; -; Genomic_DNA.
DR EMBL; CH471184; EAW66752.1; -; Genomic_DNA.
DR EMBL; BC047019; AAH47019.1; -; mRNA.
DR EMBL; BC062624; AAH62624.1; ALT_SEQ; mRNA.
DR EMBL; AF052217; AAC64701.1; -; Genomic_DNA.
DR EMBL; AF052216; AAC64701.1; JOINED; Genomic_DNA.
DR EMBL; AF052215; AAC64702.1; -; Genomic_DNA.
DR EMBL; AF052213; AAC64702.1; JOINED; Genomic_DNA.
DR EMBL; AF052214; AAC64702.1; JOINED; Genomic_DNA.
DR EMBL; AF052220; AAC64698.1; -; mRNA.
DR CCDS; CCDS10972.1; -. [O75081-1]
DR CCDS; CCDS10973.1; -. [O75081-2]
DR RefSeq; NP_005178.4; NM_005187.5. [O75081-1]
DR RefSeq; NP_787127.1; NM_175931.2. [O75081-2]
DR AlphaFoldDB; O75081; -.
DR BMRB; O75081; -.
DR SMR; O75081; -.
DR BioGRID; 107311; 81.
DR DIP; DIP-48898N; -.
DR IntAct; O75081; 18.
DR MINT; O75081; -.
DR STRING; 9606.ENSP00000268679; -.
DR iPTMnet; O75081; -.
DR PhosphoSitePlus; O75081; -.
DR BioMuta; CBFA2T3; -.
DR EPD; O75081; -.
DR jPOST; O75081; -.
DR MassIVE; O75081; -.
DR MaxQB; O75081; -.
DR PaxDb; O75081; -.
DR PeptideAtlas; O75081; -.
DR PRIDE; O75081; -.
DR ProteomicsDB; 49745; -. [O75081-1]
DR ProteomicsDB; 49746; -. [O75081-2]
DR ProteomicsDB; 49747; -. [O75081-4]
DR ProteomicsDB; 49748; -. [O75081-5]
DR Antibodypedia; 30813; 136 antibodies from 27 providers.
DR DNASU; 863; -.
DR Ensembl; ENST00000268679.9; ENSP00000268679.4; ENSG00000129993.15. [O75081-1]
DR Ensembl; ENST00000327483.9; ENSP00000332122.5; ENSG00000129993.15. [O75081-2]
DR GeneID; 863; -.
DR KEGG; hsa:863; -.
DR MANE-Select; ENST00000268679.9; ENSP00000268679.4; NM_005187.6; NP_005178.4.
DR UCSC; uc002fml.3; human. [O75081-1]
DR CTD; 863; -.
DR DisGeNET; 863; -.
DR GeneCards; CBFA2T3; -.
DR HGNC; HGNC:1537; CBFA2T3.
DR HPA; ENSG00000129993; Tissue enhanced (brain, lymphoid tissue, pancreas).
DR MalaCards; CBFA2T3; -.
DR MIM; 603870; gene.
DR neXtProt; NX_O75081; -.
DR OpenTargets; ENSG00000129993; -.
DR Orphanet; 329469; Acute megakaryoblastic leukemia without Down syndrome.
DR PharmGKB; PA26113; -.
DR VEuPathDB; HostDB:ENSG00000129993; -.
DR eggNOG; ENOG502QTD6; Eukaryota.
DR GeneTree; ENSGT00950000183176; -.
DR HOGENOM; CLU_022077_2_0_1; -.
DR InParanoid; O75081; -.
DR OMA; GPCLPTG; -.
DR OrthoDB; 334242at2759; -.
DR PhylomeDB; O75081; -.
DR TreeFam; TF106303; -.
DR PathwayCommons; O75081; -.
DR SignaLink; O75081; -.
DR SIGNOR; O75081; -.
DR BioGRID-ORCS; 863; 26 hits in 1079 CRISPR screens.
DR ChiTaRS; CBFA2T3; human.
DR GeneWiki; CBFA2T3; -.
DR GenomeRNAi; 863; -.
DR Pharos; O75081; Tbio.
DR PRO; PR:O75081; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O75081; protein.
DR Bgee; ENSG00000129993; Expressed in endometrium epithelium and 119 other tissues.
DR ExpressionAtlas; O75081; baseline and differential.
DR Genevisible; O75081; HS.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0030851; P:granulocyte differentiation; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:1903715; P:regulation of aerobic respiration; IDA:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR Gene3D; 1.20.120.1110; -; 1.
DR InterPro; IPR013289; CBFA2T1/2/3.
DR InterPro; IPR013292; CBFA2T3.
DR InterPro; IPR014896; NHR2.
DR InterPro; IPR037249; TAFH/NHR1_dom_sf.
DR InterPro; IPR003894; TAFH_NHR1.
DR InterPro; IPR002893; Znf_MYND.
DR PANTHER; PTHR10379; PTHR10379; 1.
DR Pfam; PF08788; NHR2; 1.
DR Pfam; PF07531; TAFH; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR PRINTS; PR01875; ETOFAMILY.
DR PRINTS; PR01878; MTG16PROTEIN.
DR SMART; SM00549; TAFH; 1.
DR SUPFAM; SSF158553; SSF158553; 1.
DR PROSITE; PS51119; TAFH; 1.
DR PROSITE; PS01360; ZF_MYND_1; 1.
DR PROSITE; PS50865; ZF_MYND_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosomal rearrangement; Coiled coil;
KW Differentiation; Golgi apparatus; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..653
FT /note="Protein CBFA2T3"
FT /id="PRO_0000307173"
FT DOMAIN 171..266
FT /note="TAFH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00440"
FT ZN_FING 556..592
FT /note="MYND-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT REGION 1..435
FT /note="Mediates localization to the nucleus"
FT /evidence="ECO:0000250"
FT REGION 1..430
FT /note="Mediates interaction with PDE7A (in isoform 2)"
FT REGION 1..127
FT /note="Required for nucleolar targeting (in isoform 1)"
FT REGION 1..109
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..242
FT /note="Interaction with ZBTB33"
FT /evidence="ECO:0000269|PubMed:23251453"
FT REGION 176..268
FT /note="Interaction with HIF1A"
FT /evidence="ECO:0000269|PubMed:25974097"
FT REGION 284..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..412
FT /note="Nervy homology region 2 (NHR2); essential for down-
FT regulation of PFKFB3, PFKFB4 and PDK1 expression"
FT /evidence="ECO:0000269|PubMed:23840896"
FT REGION 434..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 485..533
FT /note="Nervy homology region 3 (NHR3); essential for down-
FT regulation of PFKFB3, PFKFB4 and PDK1 expression"
FT /evidence="ECO:0000269|PubMed:23840896"
FT REGION 485..506
FT /note="Mediates interaction with PRKAR2A"
FT /evidence="ECO:0000269|PubMed:11823486"
FT REGION 603..653
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 488..543
FT /evidence="ECO:0000255"
FT COMPBIAS 10..30
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 75..90
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..314
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 434..449
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 638..653
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 556
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 559
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 567
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 570
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 576
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 580
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 588
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 592
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT SITE 51..52
FT /note="Breakpoint for translocation to form type-1 RUNX1-
FT CBFA2T3 fusion protein"
FT SITE 127..128
FT /note="Breakpoint for translocation to form type-2 RUNX1-
FT CBFA2T3 fusion protein"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 459
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 641
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 650
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..61
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9596646"
FT /id="VSP_028620"
FT VAR_SEQ 51..127
FT /note="APVDRKAKASAMPDSPAEVKTQPRSTPPSMPPPPPAASQGATRPPSFTPHTH
FT REDGPATLPHGRFHGCLKWSMVCLL -> V (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_028621"
FT VAR_SEQ 51
FT /note="A -> GKPALAAAGAPALCTPGQADARPVLGPA (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_028622"
FT VAR_SEQ 52..653
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_028623"
FT VAR_SEQ 102..126
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9596646"
FT /id="VSP_028624"
FT VARIANT 306
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs745972870)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035447"
FT VARIANT 429
FT /note="E -> G (in dbSNP:rs1053526)"
FT /evidence="ECO:0000269|PubMed:9596646"
FT /id="VAR_035374"
FT VARIANT 518
FT /note="E -> K (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs774310781)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035448"
FT VARIANT 534
FT /note="A -> V (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs553618592)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035449"
FT MUTAGEN 494
FT /note="V->P,A: Loss of interaction with PRKAR2A."
FT /evidence="ECO:0000269|PubMed:11823486"
FT CONFLICT 231
FT /note="F -> L (in Ref. 3; AAH47019)"
FT /evidence="ECO:0000305"
FT CONFLICT 295
FT /note="T -> S (in Ref. 4; AAC64702)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="D -> E (in Ref. 1; BAA29061)"
FT /evidence="ECO:0000305"
FT CONFLICT 370
FT /note="R -> P (in Ref. 4; AAC64698)"
FT /evidence="ECO:0000305"
FT CONFLICT 420
FT /note="L -> V (in Ref. 4; AAC64698)"
FT /evidence="ECO:0000305"
FT CONFLICT 542
FT /note="A -> D (in Ref. 4; AAC64701)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 653 AA; 71192 MW; 0B72B602120FA5DE CRC64;
MPASRLRDRA ASSASGSTCG SMSQTHPVLE SGLLASAGCS APRGPRKGGP APVDRKAKAS
AMPDSPAEVK TQPRSTPPSM PPPPPAASQG ATRPPSFTPH THREDGPATL PHGRFHGCLK
WSMVCLLMNG SSHSPTAING APCTPNGFSN GPATSSTASL STQHLPPACG ARQLSKLKRF
LTTLQQFGSD ISPEIGERVR TLVLGLVNST LTIEEFHSKL QEATNFPLRP FVIPFLKANL
PLLQRELLHC ARLAKQTPAQ YLAQHEQLLL DASASSPIDS SELLLEVNEN GKRRTPDRTK
ENGSDRDPLH PEHLSKRPCT LNPAQRYSPS NGPPQPTPPP HYRLEDIAMA HHFRDAYRHP
DPRELRERHR PLVVPGSRQE EVIDHKLTER EWAEEWKHLN NLLNCIMDMV EKTRRSLTVL
RRCQEADREE LNHWARRYSD AEDTKKGPAP AAARPRSSSA GPEGPQLDVP REFLPRTLTG
YVPEDIWRKA EEAVNEVKRQ AMSELQKAVS DAERKAHELI TTERAKMERA LAEAKRQASE
DALTVINQQE DSSESCWNCG RKASETCSGC NAARYCGSFC QHRDWEKHHH VCGQSLQGPT
AVVADPVPGP PEAAHSLGPS LPVGAASPSE AGSAGPSRPG SPSPPGPLDT VPR
