ETV6_HUMAN
ID ETV6_HUMAN Reviewed; 452 AA.
AC P41212; A3QVP6; A8K076; Q9UMF6; Q9UMF7; Q9UMG0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Transcription factor ETV6;
DE AltName: Full=ETS translocation variant 6;
DE AltName: Full=ETS-related protein Tel1;
DE Short=Tel;
GN Name=ETV6; Synonyms=TEL, TEL1;
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 [MRNA], AND CHROMOSOMAL TRANSLOCATION WITH PDGFRB.
RX PubMed=8168137; DOI=10.1016/0092-8674(94)90322-0;
RA Golub T.R., Barker G.F., Lovett M., Gilliland D.G.;
RT "Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic
RT myelomonocytic leukemia with t(5;12) chromosomal translocation.";
RL Cell 77:307-316(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Urinary bladder;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-109; 111-336 AND 338-452.
RX PubMed=8743990; DOI=10.1101/gr.6.5.404;
RA Baens M., Peeters P., Guo C., Aerssens J., Marynen P.;
RT "Genomic organization of TEL: the human ETS-variant gene 6.";
RL Genome Res. 6:404-413(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 56-452, AND CHROMOSOMAL TRANSLOCATION WITH
RP PAX5.
RX PubMed=17344859; DOI=10.1038/nature05690;
RA Mullighan C.G., Goorha S., Radtke I., Miller C.B., Coustan-Smith E.,
RA Dalton J.D., Girtman K., Mathew S., Ma J., Pounds S.B., Su X., Pui C.-H.,
RA Relling M.V., Evans W.E., Shurtleff S.A., Downing J.R.;
RT "Genome-wide analysis of genetic alterations in acute lymphoblastic
RT leukaemia.";
RL Nature 446:758-764(2007).
RN [7]
RP CHROMOSOMAL TRANSLOCATION WITH MN1.
RX PubMed=7731705;
RA Buijs A., Sherr S., van Baal S., van Bezouw S., van der Plas D.,
RA Geurts van Kessel A., Riegman P., Lekanne Deprez R., Zwarthoff E.,
RA Hagemeijer A.;
RT "Translocation (12;22) (p13;q11) in myeloproliferative disorders results in
RT fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11.";
RL Oncogene 10:1511-1519(1995).
RN [8]
RP CHROMOSOMAL TRANSLOCATION WITH AML1.
RX PubMed=7761424; DOI=10.1073/pnas.92.11.4917;
RA Golub T.R., Barker G.F., Bohlander S.K., Hiebert S.W., Ward D.C.,
RA Bray-Ward P., Morgan E., Raimondi S.C., Rowley J.D., Gilliland D.G.;
RT "Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute
RT lymphoblastic leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4917-4921(1995).
RN [9]
RP CHROMOSOMAL TRANSLOCATION WITH AML1.
RX PubMed=7780150;
RA Romana S.P., Mauchauffe M., le Coniat M., Chumakov I., le Paslier D.,
RA Berger R., Bernard O.A.;
RT "The t(12;21) of acute lymphoblastic leukemia results in a tel-AML1 gene
RT fusion.";
RL Blood 85:3662-3670(1995).
RN [10]
RP CHROMOSOMAL TRANSLOCATIONS WITH JAK2.
RX PubMed=9326218;
RA Peeters P., Raynaud S.D., Cools J., Wlodarska I., Grosgeorge J., Philip P.,
RA Monpoux F., Van Rompaey L., Baens M., Van Den Berghe H., Marynen P.;
RT "Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated
RT kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a
RT myeloid leukemia.";
RL Blood 90:2535-2540(1997).
RN [11]
RP CHROMOSOMAL TRANSLOCATION WITH ACSL6.
RX PubMed=10502316;
RX DOI=10.1002/(sici)1098-2264(199911)26:3<192::aid-gcc2>3.0.co;2-e;
RA Yagasaki F., Jinnai I., Yoshida S., Yokoyama Y., Matsuda A., Kusumoto S.,
RA Kobayashi H., Terasaki H., Ohyashiki K., Asou N., Murohashi I., Bessho M.,
RA Hirashima K.;
RT "Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute
RT myelogenous leukemia with t(5;12)(q31;p13).";
RL Genes Chromosomes Cancer 26:192-202(1999).
RN [12]
RP CHROMOSOMAL TRANSLOCATION WITH CHIC2.
RX PubMed=10477709;
RA Cools J., Bilhou-Nabera C., Wlodarska I., Cabrol C., Talmant P.,
RA Bernard P., Hagemeijer A., Marynen P.;
RT "Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a
RT t(4;12)(q11-q12;p13).";
RL Blood 94:1820-1824(1999).
RN [13]
RP PHOSPHORYLATION AT SER-22 AND SER-257, AND MUTAGENESIS OF SER-213; SER-238
RP AND SER-257.
RX PubMed=12435397; DOI=10.1016/s0006-291x(02)02588-3;
RA Arai H., Maki K., Waga K., Sasaki K., Nakamura Y., Imai Y., Kurokawa M.,
RA Hirai H., Mitani K.;
RT "Functional regulation of TEL by p38-induced phosphorylation.";
RL Biochem. Biophys. Res. Commun. 299:116-125(2002).
RN [14]
RP CHROMOSOMAL TRANSLOCATION WITH MDS2.
RX PubMed=12203785; DOI=10.1002/gcc.10090;
RA Odero M.D., Vizmanos J.L., Roman J.P., Lahortiga I., Panizo C.,
RA Calasanz M.J., Zeleznik-Le N.J., Rowley J.D., Novo F.J.;
RT "A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a
RT patient with myelodysplastic syndrome.";
RL Genes Chromosomes Cancer 35:11-19(2002).
RN [15]
RP INVOLVEMENT IN MPE, AND CHROMOSOMAL TRANSLOCATION WITH PDGFRB.
RX PubMed=12181402; DOI=10.1056/nejmoa020150;
RA Apperley J.F., Gardembas M., Melo J.V., Russell-Jones R., Bain B.J.,
RA Baxter E.J., Chase A., Chessells J.M., Colombat M., Dearden C.E.,
RA Dimitrijevic S., Mahon F.-X., Marin D., Nikolova Z., Olavarria E.,
RA Silberman S., Schultheis B., Cross N.C.P., Goldman J.M.;
RT "Response to imatinib mesylate in patients with chronic myeloproliferative
RT diseases with rearrangements of the platelet-derived growth factor receptor
RT beta.";
RL N. Engl. J. Med. 347:481-487(2002).
RN [16]
RP INTERACTION WITH L3MBTL1.
RX PubMed=12588862; DOI=10.1074/jbc.m300592200;
RA Boccuni P., MacGrogan D., Scandura J.M., Nimer S.D.;
RT "The human L(3)MBT Polycomb group protein is a transcriptional repressor
RT and interacts physically and functionally with TEL (ETV6).";
RL J. Biol. Chem. 278:15412-15420(2003).
RN [17]
RP INTERACTION WITH HDAC9.
RX PubMed=12590135; DOI=10.1074/jbc.m212935200;
RA Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M.,
RA Zelent A.;
RT "The histone deacetylase 9 gene encodes multiple protein isoforms.";
RL J. Biol. Chem. 278:16059-16072(2003).
RN [18]
RP INVOLVEMENT IN AML, VARIANT GLY-344 INS, AND CHARACTERIZATION OF VARIANT
RP GLY-344 INS.
RX PubMed=15806161; DOI=10.1038/sj.onc.1208588;
RA Barjesteh van Waalwijk van Doorn-Khosrovani S., Spensberger D.,
RA de Knegt Y., Tang M., Loewenberg B., Delwel R.;
RT "Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6
RT protein in acute myeloid leukemia.";
RL Oncogene 24:4129-4137(2005).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-18 AND SER-22, AND
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 [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-11 AND LYS-302, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22 AND SER-213, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [25]
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 [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-11, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-11, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-11 AND LYS-288, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [29]
RP FUNCTION, INVOLVEMENT IN THC5, VARIANTS THC5 LEU-214; GLN-369 AND CYS-399,
RP AND CHARACTERIZATION OF VARIANTS THC5 LEU-214; GLN-369 AND CYS-399.
RX PubMed=25581430; DOI=10.1038/ng.3177;
RA Zhang M.Y., Churpek J.E., Keel S.B., Walsh T., Lee M.K., Loeb K.R.,
RA Gulsuner S., Pritchard C.C., Sanchez-Bonilla M., Delrow J.J., Basom R.S.,
RA Forouhar M., Gyurkocza B., Schwartz B.S., Neistadt B., Marquez R.,
RA Mariani C.J., Coats S.A., Hofmann I., Lindsley R.C., Williams D.A.,
RA Abkowitz J.L., Horwitz M.S., King M.C., Godley L.A., Shimamura A.;
RT "Germline ETV6 mutations in familial thrombocytopenia and hematologic
RT malignancy.";
RL Nat. Genet. 47:180-185(2015).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-11; LYS-288; LYS-302; LYS-403 AND
RP LYS-421, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [31]
RP STRUCTURE BY NMR OF 338-442.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of ets domain transcriptional factor ETV6 protein.";
RL Submitted (DEC-2006) to the PDB data bank.
CC -!- FUNCTION: Transcriptional repressor; binds to the DNA sequence 5'-
CC CCGGAAGT-3'. Plays a role in hematopoiesis and malignant
CC transformation. {ECO:0000269|PubMed:25581430}.
CC -!- SUBUNIT: Can form homodimers or heterodimers with TEL2 or FLI1.
CC Interacts with L3MBTL1 and HDAC9. {ECO:0000269|PubMed:12588862,
CC ECO:0000269|PubMed:12590135}.
CC -!- INTERACTION:
CC P41212; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-1372759, EBI-541426;
CC P41212; A0A0S2Z4M1: AXIN1; NbExp=3; IntAct=EBI-1372759, EBI-16429430;
CC P41212; Q9UKV0-3: HDAC9; NbExp=3; IntAct=EBI-1372759, EBI-765476;
CC P41212; Q16236: NFE2L2; NbExp=5; IntAct=EBI-1372759, EBI-2007911;
CC P41212; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-1372759, EBI-741158;
CC P41212; Q13526: PIN1; NbExp=3; IntAct=EBI-1372759, EBI-714158;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylation of Ser-257 by MAPK14 (p38) inhibits ETV6
CC transcriptional repression. {ECO:0000269|PubMed:12435397}.
CC -!- DISEASE: Note=A chromosomal aberration involving ETV6 is found in a
CC form of chronic myelomonocytic leukemia (CMML). Translocation
CC t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal
CC myeloid proliferation and by progression to acute myelogenous leukemia
CC (AML). {ECO:0000269|PubMed:8168137}.
CC -!- DISEASE: Note=Chromosomal aberrations involving ETV6 are found in acute
CC myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1
CC (PubMed:7731705). Translocation t(4;12)(q12;p13) with CHIC2
CC (PubMed:10477709). {ECO:0000269|PubMed:10477709,
CC ECO:0000269|PubMed:7731705}.
CC -!- DISEASE: Note=Chromosomal aberrations involving ETV6 are found in
CC childhood acute lymphoblastic leukemia (ALL). Translocations
CC t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1.
CC {ECO:0000269|PubMed:7761424}.
CC -!- DISEASE: Note=A chromosomal aberration involving ETV6 is found in a
CC form of pre-B acute lymphoid leukemia. Translocation t(9;12)(p24;p13)
CC with JAK2. {ECO:0000269|PubMed:9326218}.
CC -!- DISEASE: Note=A chromosomal aberration involving ETV6 and JAK2 is found
CC in an atypical chronic myelogenous leukemia. Translocation
CC t(9;15;12)(p24;q15;p13). {ECO:0000269|PubMed:9326218}.
CC -!- DISEASE: Note=A chromosomal aberration involving ETV6 is found in
CC myelodysplastic syndrome (MDS) with basophilia. Translocation
CC t(5;12)(q31;p13) with ACSL6. {ECO:0000269|PubMed:10502316}.
CC -!- DISEASE: Note=A chromosomal aberration involving ETV6 is found in acute
CC eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6.
CC {ECO:0000269|PubMed:10502316}.
CC -!- DISEASE: Note=A chromosomal aberration involving ETV6 is found in
CC myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with
CC MDS2. {ECO:0000269|PubMed:12203785}.
CC -!- DISEASE: Note=A chromosomal aberration involving ETV6 is found in acute
CC lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5.
CC {ECO:0000269|PubMed:17344859}.
CC -!- DISEASE: Myeloproliferative disorder chronic with eosinophilia (MPE)
CC [MIM:131440]: A hematologic disorder characterized by malignant
CC eosinophils proliferation. {ECO:0000269|PubMed:12181402}. Note=The gene
CC represented in this entry is involved in disease pathogenesis. A
CC chromosomal aberration involving ETV6 is found in many instances of
CC myeloproliferative disorder chronic with eosinophilia. Translocation
CC t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion
CC protein. {ECO:0000269|PubMed:12181402}.
CC -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of
CC acute leukemia, a cancer of the white blood cells. AML is a malignant
CC disease of bone marrow characterized by maturational arrest of
CC hematopoietic precursors at an early stage of development. Clonal
CC expansion of myeloid blasts occurs in bone marrow, blood, and other
CC tissue. Myelogenous leukemias develop from changes in cells that
CC normally produce neutrophils, basophils, eosinophils and monocytes.
CC {ECO:0000269|PubMed:15806161}. Note=The gene represented in this entry
CC is involved in disease pathogenesis.
CC -!- DISEASE: Thrombocytopenia 5 (THC5) [MIM:616216]: A form of
CC thrombocytopenia, a hematologic disorder defined by a decrease in the
CC number of platelets in circulating blood, resulting in the potential
CC for increased bleeding and decreased ability for clotting. THC5 is an
CC autosomal dominant disorder, associated with an increased
CC susceptibility to the development of hematologic and solid
CC malignancies. {ECO:0000269|PubMed:25581430}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABI30005.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ETV6ID38.html";
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DR EMBL; U11732; AAA19786.1; -; mRNA.
DR EMBL; AK289441; BAF82130.1; -; mRNA.
DR EMBL; CH471094; EAW96240.1; -; Genomic_DNA.
DR EMBL; BC043399; AAH43399.1; -; mRNA.
DR EMBL; U61375; AAC50690.1; -; Genomic_DNA.
DR EMBL; U63312; AAB17134.1; -; Genomic_DNA.
DR EMBL; U63313; AAB17135.1; -; Genomic_DNA.
DR EMBL; DQ841178; ABI30005.1; ALT_INIT; mRNA.
DR CCDS; CCDS8643.1; -.
DR RefSeq; NP_001978.1; NM_001987.4.
DR PDB; 1JI7; X-ray; 1.45 A; A/B/C=47-123.
DR PDB; 1LKY; X-ray; 2.30 A; A/B/C/D/E/F=47-123.
DR PDB; 2DAO; NMR; -; A=338-442.
DR PDB; 2QAR; X-ray; 2.40 A; A/B/D/E=47-124.
DR PDB; 2QB0; X-ray; 2.56 A; A/C=47-123.
DR PDB; 2QB1; X-ray; 2.61 A; A/B=47-121.
DR PDB; 5L0P; X-ray; 2.30 A; A=47-356.
DR PDB; 7JU2; X-ray; 1.85 A; A/B=43-125.
DR PDB; 7N1O; X-ray; 2.77 A; A=46-125.
DR PDB; 7N2B; X-ray; 3.22 A; A/B=10-36, A/B=47-132.
DR PDBsum; 1JI7; -.
DR PDBsum; 1LKY; -.
DR PDBsum; 2DAO; -.
DR PDBsum; 2QAR; -.
DR PDBsum; 2QB0; -.
DR PDBsum; 2QB1; -.
DR PDBsum; 5L0P; -.
DR PDBsum; 7JU2; -.
DR PDBsum; 7N1O; -.
DR PDBsum; 7N2B; -.
DR AlphaFoldDB; P41212; -.
DR BMRB; P41212; -.
DR SMR; P41212; -.
DR BioGRID; 108421; 98.
DR DIP; DIP-17028N; -.
DR ELM; P41212; -.
DR IntAct; P41212; 67.
DR MINT; P41212; -.
DR STRING; 9606.ENSP00000379658; -.
DR BindingDB; P41212; -.
DR ChEMBL; CHEMBL2401606; -.
DR DrugCentral; P41212; -.
DR iPTMnet; P41212; -.
DR PhosphoSitePlus; P41212; -.
DR BioMuta; ETV6; -.
DR DMDM; 730927; -.
DR EPD; P41212; -.
DR jPOST; P41212; -.
DR MassIVE; P41212; -.
DR MaxQB; P41212; -.
DR PaxDb; P41212; -.
DR PeptideAtlas; P41212; -.
DR PRIDE; P41212; -.
DR ProteomicsDB; 55416; -.
DR Antibodypedia; 634; 397 antibodies from 35 providers.
DR DNASU; 2120; -.
DR Ensembl; ENST00000396373.9; ENSP00000379658.3; ENSG00000139083.11.
DR GeneID; 2120; -.
DR KEGG; hsa:2120; -.
DR MANE-Select; ENST00000396373.9; ENSP00000379658.3; NM_001987.5; NP_001978.1.
DR UCSC; uc001qzz.4; human.
DR CTD; 2120; -.
DR DisGeNET; 2120; -.
DR GeneCards; ETV6; -.
DR GeneReviews; ETV6; -.
DR HGNC; HGNC:3495; ETV6.
DR HPA; ENSG00000139083; Low tissue specificity.
DR MalaCards; ETV6; -.
DR MIM; 131440; phenotype.
DR MIM; 600618; gene.
DR MIM; 601626; phenotype.
DR MIM; 616216; phenotype.
DR neXtProt; NX_P41212; -.
DR OpenTargets; ENSG00000139083; -.
DR Orphanet; 585877; B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality.
DR Orphanet; 98823; Chronic myelomonocytic leukemia.
DR Orphanet; 2665; Congenital mesoblastic nephroma.
DR Orphanet; 146; Differentiated thyroid carcinoma.
DR Orphanet; 71290; Familial platelet disorder with associated myeloid malignancy.
DR Orphanet; 2030; Fibrosarcoma.
DR Orphanet; 314950; Primary hypereosinophilic syndrome.
DR PharmGKB; PA27909; -.
DR VEuPathDB; HostDB:ENSG00000139083; -.
DR eggNOG; KOG3804; Eukaryota.
DR GeneTree; ENSGT00940000159508; -.
DR HOGENOM; CLU_037998_1_0_1; -.
DR InParanoid; P41212; -.
DR OMA; NPRHSMD; -.
DR OrthoDB; 559763at2759; -.
DR PhylomeDB; P41212; -.
DR TreeFam; TF318679; -.
DR PathwayCommons; P41212; -.
DR Reactome; R-HSA-9673768; Signaling by membrane-tethered fusions of PDGFRA or PDGFRB.
DR Reactome; R-HSA-9703465; Signaling by FLT3 fusion proteins.
DR SignaLink; P41212; -.
DR SIGNOR; P41212; -.
DR BioGRID-ORCS; 2120; 27 hits in 1105 CRISPR screens.
DR ChiTaRS; ETV6; human.
DR EvolutionaryTrace; P41212; -.
DR GeneWiki; ETV6; -.
DR GenomeRNAi; 2120; -.
DR Pharos; P41212; Tbio.
DR PRO; PR:P41212; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P41212; protein.
DR Bgee; ENSG00000139083; Expressed in mucosa of paranasal sinus and 170 other tissues.
DR ExpressionAtlas; P41212; baseline and differential.
DR Genevisible; P41212; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IMP:UniProtKB.
DR GO; GO:0097152; P:mesenchymal cell apoptotic process; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0022008; P:neurogenesis; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007296; P:vitellogenesis; IEA:Ensembl.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR000418; Ets_dom.
DR InterPro; IPR046328; ETS_fam.
DR InterPro; IPR003118; Pointed_dom.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR11849; PTHR11849; 1.
DR Pfam; PF00178; Ets; 1.
DR Pfam; PF02198; SAM_PNT; 1.
DR PRINTS; PR00454; ETSDOMAIN.
DR SMART; SM00413; ETS; 1.
DR SMART; SM00251; SAM_PNT; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS00346; ETS_DOMAIN_2; 1.
DR PROSITE; PS50061; ETS_DOMAIN_3; 1.
DR PROSITE; PS51433; PNT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosomal rearrangement; Disease variant;
KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..452
FT /note="Transcription factor ETV6"
FT /id="PRO_0000204121"
FT DOMAIN 40..124
FT /note="PNT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00762"
FT DNA_BIND 339..420
FT /note="ETS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00237"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 158..262
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..262
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 11..12
FT /note="Breakpoint for translocation to form CHIC2-ETV6 in
FT AML"
FT SITE 54..55
FT /note="Breakpoint for translocation to form ETV6-MDS2 in
FT MDS"
FT SITE 55..56
FT /note="Breakpoint for translocation to form PAX5-ETV6"
FT SITE 336..337
FT /note="Breakpoint for translocation to form ETV6-AML1 in
FT ALL"
FT MOD_RES 11
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 18
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12435397,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97360"
FT MOD_RES 257
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:12435397"
FT MOD_RES 302
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97360"
FT CROSSLNK 11
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 288
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 421
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 214
FT /note="P -> L (in THC5; abrogates DNA binding; alters
FT subcellular location; decreases transcriptional repression
FT in a dominant-negative fashion; dbSNP:rs724159947)"
FT /evidence="ECO:0000269|PubMed:25581430"
FT /id="VAR_073322"
FT VARIANT 344
FT /note="Y -> YG (in one individual with AML; somatic
FT mutation; unable to repress transcription)"
FT /evidence="ECO:0000269|PubMed:15806161"
FT /id="VAR_034600"
FT VARIANT 369
FT /note="R -> Q (in THC5; abrogates DNA binding; alters
FT subcellular location; decreases transcriptional repression
FT in a dominant-negative fashion; dbSNP:rs724159946)"
FT /evidence="ECO:0000269|PubMed:25581430"
FT /id="VAR_073323"
FT VARIANT 399
FT /note="R -> C (in THC5; abrogates DNA binding; alters
FT subcellular location; decreases transcriptional repression
FT in a dominant-negative fashion; dbSNP:rs724159945)"
FT /evidence="ECO:0000269|PubMed:25581430"
FT /id="VAR_073324"
FT MUTAGEN 22
FT /note="S->A: No effect."
FT MUTAGEN 213
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:12435397"
FT MUTAGEN 238
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:12435397"
FT MUTAGEN 257
FT /note="S->A: No phosphorylation by MAPK14."
FT /evidence="ECO:0000269|PubMed:12435397"
FT HELIX 12..18
FT /evidence="ECO:0007829|PDB:5L0P"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:5L0P"
FT HELIX 23..27
FT /evidence="ECO:0007829|PDB:5L0P"
FT HELIX 30..38
FT /evidence="ECO:0007829|PDB:5L0P"
FT HELIX 52..54
FT /evidence="ECO:0007829|PDB:1JI7"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:1JI7"
FT HELIX 63..76
FT /evidence="ECO:0007829|PDB:1JI7"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:1JI7"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:1JI7"
FT HELIX 99..105
FT /evidence="ECO:0007829|PDB:1JI7"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:1JI7"
FT HELIX 110..122
FT /evidence="ECO:0007829|PDB:1JI7"
FT HELIX 341..350
FT /evidence="ECO:0007829|PDB:2DAO"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:2DAO"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:2DAO"
FT STRAND 358..362
FT /evidence="ECO:0007829|PDB:2DAO"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:2DAO"
FT STRAND 367..371
FT /evidence="ECO:0007829|PDB:2DAO"
FT HELIX 373..383
FT /evidence="ECO:0007829|PDB:2DAO"
FT HELIX 391..403
FT /evidence="ECO:0007829|PDB:2DAO"
FT STRAND 406..408
FT /evidence="ECO:0007829|PDB:2DAO"
FT STRAND 411..419
FT /evidence="ECO:0007829|PDB:2DAO"
FT HELIX 424..426
FT /evidence="ECO:0007829|PDB:2DAO"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:2DAO"
FT HELIX 434..438
FT /evidence="ECO:0007829|PDB:2DAO"
SQ SEQUENCE 452 AA; 53000 MW; DEC45682ECADECBB CRC64;
MSETPAQCSI KQERISYTPP ESPVPSYASS TPLHVPVPRA LRMEEDSIRL PAHLRLQPIY
WSRDDVAQWL KWAENEFSLR PIDSNTFEMN GKALLLLTKE DFRYRSPHSG DVLYELLQHI
LKQRKPRILF SPFFHPGNSI HTQPEVILHQ NHEEDNCVQR TPRPSVDNVH HNPPTIELLH
RSRSPITTNH RPSPDPEQRP LRSPLDNMIR RLSPAERAQG PRPHQENNHQ ESYPLSVSPM
ENNHCPASSE SHPKPSSPRQ ESTRVIQLMP SPIMHPLILN PRHSVDFKQS RLSEDGLHRE
GKPINLSHRE DLAYMNHIMV SVSPPEEHAM PIGRIADCRL LWDYVYQLLS DSRYENFIRW
EDKESKIFRI VDPNGLARLW GNHKNRTNMT YEKMSRALRH YYKLNIIRKE PGQRLLFRFM
KTPDEIMSGR TDRLEHLESQ ELDEQIYQED EC
