ID   ETV4_HUMAN              Reviewed;         484 AA.
AC   P43268; A8K314; Q96AW9;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   12-APR-2005, sequence version 3.
DT   25-JAN-2012, entry version 97.
DE   RecName: Full=ETS translocation variant 4;
DE   AltName: Full=Adenovirus E1A enhancer-binding protein;
DE   AltName: Full=E1A-F;
DE   AltName: Full=Polyomavirus enhancer activator 3 homolog;
DE            Short=Protein PEA3;
GN   Name=ETV4; Synonyms=E1AF, PEA3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=95293380; PubMed=7774926; DOI=10.1016/0888-7543(95)80133-7;
RA   Friedman L.S., Ostermeyer E.A., Lynch E.D., Szabo C.I., Meza J.E.,
RA   Anderson L.A., Dowd P., Lee M.K., Rowell S.E., Ellison J., Boyd J.,
RA   King M.-C.;
RT   "22 genes from chromosome 17q21: cloning, sequencing, and
RT   characterization of mutations in breast cancer families and tumors.";
RL   Genomics 25:256-263(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=20033563; PubMed=10564827; DOI=10.1016/S0378-1119(99)00400-X;
RA   Coutte L., Monte D., Baert J.-L., de Launoit Y.;
RT   "Genomic organization of the human e1af gene, a member of Ets
RT   transcription factors.";
RL   Gene 240:201-207(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 23-484.
RX   MEDLINE=93181246; PubMed=8441666; DOI=10.1093/nar/21.3.547;
RA   Higashino F., Yoshida K., Fujinaga K., Kamio K., Fujinaga K.;
RT   "Isolation of a cDNA encoding the adenovirus E1A enhancer binding
RT   protein: a new human member of the ets oncogene family.";
RL   Nucleic Acids Res. 21:547-553(1993).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140 AND SER-149, AND
RP   MASS SPECTROMETRY.
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   [7]
RP   FUNCTION, SUMOYLATION AT LYS-96; LYS-226 AND LYS-260, DESUMOYLATION BY
RP   SENP1, UBIQUITINATION BY RNF4, DEUBIQUITINATION BY UPS2, AND
RP   MUTAGENESIS OF LYS-96; GLU-98; SER-101; PRO-102; LYS-226; GLU-228;
RP   LYS-260; GLU-262; GLU-324 AND GLU-443.
RX   PubMed=19307308; DOI=10.1128/MCB.01128-08;
RA   Guo B., Sharrocks A.D.;
RT   "Extracellular signal-regulated kinase mitogen-activated protein
RT   kinase signaling initiates a dynamic interplay between sumoylation and
RT   ubiquitination to regulate the activity of the transcriptional
RT   activator PEA3.";
RL   Mol. Cell. Biol. 29:3204-3218(2009).
CC   -!- FUNCTION: Transcriptional activator that binds to the enhancer of
CC       the adenovirus E1A gene; the core-binding sequence is
CC       5'[AC]GGA[AT]GT-3'.
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- PTM: Sumoylated; enhanced upon ERK/MAP kinase pathway activation,
CC       it positively regulates the transcriptional activator capacity.
CC       Sumoylation at Lys-96 probably requires phosphorylation at Ser-
CC       101. Transiently polysumoylated and desumoylated by SENP1.
CC       Sumoylation is a prerequisite to polyubiquitination which in turn
CC       increases proteasomal-mediated degradation. Probably
CC       polyubiquitinated by RNF4 and deubiquitinated by USP2.
CC   -!- SIMILARITY: Belongs to the ETS family.
CC   -!- SIMILARITY: Contains 1 ETS DNA-binding domain.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA95991.1; Type=Erroneous initiation;
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DR   EMBL; U18018; AAA95991.1; ALT_INIT; mRNA.
DR   EMBL; AF095890; AAD09186.1; -; Genomic_DNA.
DR   EMBL; AF095887; AAD09186.1; JOINED; Genomic_DNA.
DR   EMBL; AF095888; AAD09186.1; JOINED; Genomic_DNA.
DR   EMBL; AF095889; AAD09186.1; JOINED; Genomic_DNA.
DR   EMBL; AK290429; BAF83118.1; -; mRNA.
DR   EMBL; BC016623; AAH16623.1; -; mRNA.
DR   EMBL; D12765; BAA02234.1; -; mRNA.
DR   IPI; IPI00017382; -.
DR   PIR; S35534; S35534.
DR   RefSeq; NP_001073143.1; NM_001079675.1.
DR   RefSeq; NP_001977.1; NM_001986.2.
DR   UniGene; Hs.434059; -.
DR   ProteinModelPortal; P43268; -.
DR   SMR; P43268; 354-427.
DR   DIP; DIP-748N; -.
DR   STRING; P43268; -.
DR   PhosphoSite; P43268; -.
DR   DMDM; 62512145; -.
DR   PRIDE; P43268; -.
DR   Ensembl; ENST00000319349; ENSP00000321835; ENSG00000175832.
DR   Ensembl; ENST00000393664; ENSP00000377273; ENSG00000175832.
DR   GeneID; 2118; -.
DR   KEGG; hsa:2118; -.
DR   UCSC; uc002idw.1; human.
DR   CTD; 2118; -.
DR   GeneCards; GC17M041615; -.
DR   H-InvDB; HIX0019239; -.
DR   HGNC; HGNC:3493; ETV4.
DR   HPA; HPA005768; -.
DR   MIM; 600711; gene.
DR   neXtProt; NX_P43268; -.
DR   Orphanet; 319; Ewing sarcoma.
DR   PharmGKB; PA27907; -.
DR   eggNOG; prNOG09615; -.
DR   GeneTree; ENSGT00600000083997; -.
DR   HOGENOM; HBG443839; -.
DR   HOVERGEN; HBG000231; -.
DR   InParanoid; P43268; -.
DR   OMA; PFPRAEQ; -.
DR   OrthoDB; EOG4W0XCT; -.
DR   PhylomeDB; P43268; -.
DR   NextBio; 8559; -.
DR   ArrayExpress; P43268; -.
DR   Bgee; P43268; -.
DR   CleanEx; HS_ETV4; -.
DR   Genevestigator; P43268; -.
DR   GermOnline; ENSG00000175832; Homo sapiens.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR   GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR   InterPro; IPR000418; Ets.
DR   InterPro; IPR006715; ETS_PEA3_N.
DR   InterPro; IPR011991; WHTH_trsnscrt_rep_DNA-bd.
DR   Gene3D; G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 1.
DR   KO; K15592; -.
DR   Pfam; PF00178; Ets; 1.
DR   Pfam; PF04621; ETS_PEA3_N; 1.
DR   PRINTS; PR00454; ETSDOMAIN.
DR   SMART; SM00413; ETS; 1.
DR   PROSITE; PS00345; ETS_DOMAIN_1; 1.
DR   PROSITE; PS00346; ETS_DOMAIN_2; 1.
DR   PROSITE; PS50061; ETS_DOMAIN_3; 1.
PE   1: Evidence at protein level;
KW   Activator; Complete proteome; DNA-binding; Isopeptide bond; Nucleus;
KW   Phosphoprotein; Polymorphism; Reference proteome; Transcription;
KW   Transcription regulation; Ubl conjugation.
FT   CHAIN         1    484       ETS translocation variant 4.
FT                                /FTId=PRO_0000204116.
FT   DNA_BIND    341    421       ETS.
FT   COMPBIAS     49     75       Asp/Glu-rich (acidic).
FT   COMPBIAS    148    244       Gln-rich.
FT   MOD_RES     140    140       Phosphoserine.
FT   MOD_RES     149    149       Phosphoserine.
FT   CROSSLNK     96     96       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT   CROSSLNK    226    226       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT   CROSSLNK    260    260       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT   VARIANT     437    437       R -> C (in dbSNP:rs34260468).
FT                                /FTId=VAR_048950.
FT   MUTAGEN      96     96       K->R: Altered sumoylation pattern. Loss
FT                                of sumoylation, ubiquitination and
FT                                transcriptional activator function; when
FT                                associated with R-226 and R-260.
FT   MUTAGEN      98     98       E->A: Loss of polysumoylation and
FT                                ubiquitination; when associated with A-
FT                                228; A-262; A-324 and A-443.
FT   MUTAGEN     101    101       S->A: Loss of sumoylation at K-96.
FT   MUTAGEN     101    101       S->E: Normal sumoylation at K-96.
FT   MUTAGEN     102    102       P->A: Loss of sumoylation at K-96.
FT   MUTAGEN     226    226       K->R: Altered sumoylation pattern. Loss
FT                                of sumoylation, ubiquitination and
FT                                transcriptional activator function; when
FT                                associated with R-96 and R-260.
FT   MUTAGEN     228    228       E->A: Loss of polysumoylation and
FT                                ubiquitination; when associated with A-
FT                                98; A-262; A-324 and A-443.
FT   MUTAGEN     260    260       K->R: Altered sumoylation pattern. Loss
FT                                of sumoylation, ubiquitination and
FT                                transcriptional activator function; when
FT                                associated with R-96 and R-226.
FT   MUTAGEN     262    262       E->A: Loss of polysumoylation and
FT                                ubiquitination; when associated with A-
FT                                98; A-228; A-324 and A-443.
FT   MUTAGEN     324    324       E->A: Loss of polysumoylation and
FT                                ubiquitination; when associated with A-
FT                                98; A-228; A-262 and A-443.
FT   MUTAGEN     443    443       E->A: Loss of polysumoylation and
FT                                ubiquitination; when associated with A-
FT                                98; A-228; A-262 and A-324.
FT   CONFLICT     24     27       GNGS -> EMSD (in Ref. 5; BAA02234).
SQ   SEQUENCE   484 AA;  53938 MW;  BA9864F3C690A8C1 CRC64;
     MERRMKAGYL DQQVPYTFSS KSPGNGSLRE ALIGPLGKLM DPGSLPPLDS EDLFQDLSHF
     QETWLAEAQV PDSDEQFVPD FHSENLAFHS PTTRIKKEPQ SPRTDPALSC SRKPPLPYHH
     GEQCLYSSAY DPPRQIAIKS PAPGALGQSP LQPFPRAEQR NFLRSSGTSQ PHPGHGYLGE
     HSSVFQQPLD ICHSFTSQGG GREPLPAPYQ HQLSEPCPPY PQQSFKQEYH DPLYEQAGQP
     AVDQGGVNGH RYPGAGVVIK QEQTDFAYDS DVTGCASMYL HTEGFSGPSP GDGAMGYGYE
     KPLRPFPDDV CVVPEKFEGD IKQEGVGAFR EGPPYQRRGA LQLWQFLVAL LDDPTNAHFI
     AWTGRGMEFK LIEPEEVARL WGIQKNRPAM NYDKLSRSLR YYYEKGIMQK VAGERYVYKF
     VCEPEALFSL AFPDNQRPAL KAEFDRPVSE EDTVPLSHLD ESPAYLPELA GPAQPFGPKG
     GYSY
//