P43268 (ETV4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ETS translocation variant 4

Alternative name(s):
Adenovirus E1A enhancer-binding protein
E1A-F
Polyomavirus enhancer activator 3 homolog
Short name=Protein PEA3

Gene names

Name:	ETV4
Synonyms:	E1AF, PEA3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	484 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator that binds to the enhancer of the adenovirus E1A gene; the core-binding sequence is 5'[AC]GGA[AT]GT-3'. Ref.8
Subcellular location	Nucleus.
Post-translational modification	Sumoylated; enhanced upon ERK/MAP kinase pathway activation, it positively regulates the transcriptional activator capacity. Sumoylation at Lys-96 probably requires phosphorylation at Ser-101. Transiently polysumoylated and desumoylated by SENP1. Sumoylation is a prerequisite to polyubiquitination which in turn increases proteasomal-mediated degradation. Probably polyubiquitinated by RNF4 and deubiquitinated by USP2. Ref.8
Sequence similarities	Belongs to the ETS family. Contains 1 ETS DNA-binding domain.
Sequence caution	The sequence AAA95991.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	branching involved in mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara motor neuron axon guidance Inferred from electronic annotation. Source: Compara negative regulation of mammary gland epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Non-traceable author statement. Source: UniProtKB regulation of branching involved in mammary gland duct morphogenesis Inferred from electronic annotation. Source: Compara stem cell differentiation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleolus Inferred from direct assay. Source: HPA
Molecular_function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P43268-1)

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 2 (identifier: P43268-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-39: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 484	484	ETS translocation variant 4		PRO_0000204116
Regions
	DNA binding	341 – 421	81	ETS
	Compositional bias	49 – 75	27	Asp/Glu-rich (acidic)
	Compositional bias	148 – 244	97	Gln-rich
Amino acid modifications
	Cross-link	96		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.8
	Cross-link	226		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.8
	Cross-link	260		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.8
Natural variations
	Alternative sequence	1 – 39	39	Missing in isoform 2.		VSP_046036
	Natural variant	195	1	F → I. Ref.3 Corresponds to variant rs150119757 [ dbSNP | Ensembl ].		VAR_069110
	Natural variant	437	1	R → C. Corresponds to variant rs34260468 [ dbSNP | Ensembl ].		VAR_048950
Experimental info
	Mutagenesis	96	1	K → R: Altered sumoylation pattern. Loss of sumoylation, ubiquitination and transcriptional activator function; when associated with R-226 and R-260. Ref.8
	Mutagenesis	98	1	E → A: Loss of polysumoylation and ubiquitination; when associated with A-228; A-262; A-324 and A-443. Ref.8
	Mutagenesis	101	1	S → A: Loss of sumoylation at K-96. Ref.8
	Mutagenesis	101	1	S → E: Normal sumoylation at K-96. Ref.8
	Mutagenesis	102	1	P → A: Loss of sumoylation at K-96. Ref.8
	Mutagenesis	226	1	K → R: Altered sumoylation pattern. Loss of sumoylation, ubiquitination and transcriptional activator function; when associated with R-96 and R-260. Ref.8
	Mutagenesis	228	1	E → A: Loss of polysumoylation and ubiquitination; when associated with A-98; A-262; A-324 and A-443. Ref.8
	Mutagenesis	260	1	K → R: Altered sumoylation pattern. Loss of sumoylation, ubiquitination and transcriptional activator function; when associated with R-96 and R-226. Ref.8
	Mutagenesis	262	1	E → A: Loss of polysumoylation and ubiquitination; when associated with A-98; A-228; A-324 and A-443. Ref.8
	Mutagenesis	324	1	E → A: Loss of polysumoylation and ubiquitination; when associated with A-98; A-228; A-262 and A-443. Ref.8
	Mutagenesis	443	1	E → A: Loss of polysumoylation and ubiquitination; when associated with A-98; A-228; A-262 and A-324. Ref.8
	Sequence conflict	24 – 27	4	GNGS → EMSD in BAA02234. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 12, 2005. Version 3. Checksum: BA9864F3C690A8C1	FASTA	484	53,938
	10 20 30 40 50 60 MERRMKAGYL DQQVPYTFSS KSPGNGSLRE ALIGPLGKLM DPGSLPPLDS EDLFQDLSHF 70 80 90 100 110 120 QETWLAEAQV PDSDEQFVPD FHSENLAFHS PTTRIKKEPQ SPRTDPALSC SRKPPLPYHH 130 140 150 160 170 180 GEQCLYSSAY DPPRQIAIKS PAPGALGQSP LQPFPRAEQR NFLRSSGTSQ PHPGHGYLGE 190 200 210 220 230 240 HSSVFQQPLD ICHSFTSQGG GREPLPAPYQ HQLSEPCPPY PQQSFKQEYH DPLYEQAGQP 250 260 270 280 290 300 AVDQGGVNGH RYPGAGVVIK QEQTDFAYDS DVTGCASMYL HTEGFSGPSP GDGAMGYGYE 310 320 330 340 350 360 KPLRPFPDDV CVVPEKFEGD IKQEGVGAFR EGPPYQRRGA LQLWQFLVAL LDDPTNAHFI 370 380 390 400 410 420 AWTGRGMEFK LIEPEEVARL WGIQKNRPAM NYDKLSRSLR YYYEKGIMQK VAGERYVYKF 430 440 450 460 470 480 VCEPEALFSL AFPDNQRPAL KAEFDRPVSE EDTVPLSHLD ESPAYLPELA GPAQPFGPKG GYSY
	Isoform 2 [UniParc]. Checksum: 391745C2ADC1C064	FASTA	445	49,659
	10 20 30 40 50 60 MDPGSLPPLD SEDLFQDLSH FQETWLAEAQ VPDSDEQFVP DFHSENLAFH SPTTRIKKEP 70 80 90 100 110 120 QSPRTDPALS CSRKPPLPYH HGEQCLYSSA YDPPRQIAIK SPAPGALGQS PLQPFPRAEQ 130 140 150 160 170 180 RNFLRSSGTS QPHPGHGYLG EHSSVFQQPL DICHSFTSQG GGREPLPAPY QHQLSEPCPP 190 200 210 220 230 240 YPQQSFKQEY HDPLYEQAGQ PAVDQGGVNG HRYPGAGVVI KQEQTDFAYD SDVTGCASMY 250 260 270 280 290 300 LHTEGFSGPS PGDGAMGYGY EKPLRPFPDD VCVVPEKFEG DIKQEGVGAF REGPPYQRRG 310 320 330 340 350 360 ALQLWQFLVA LLDDPTNAHF IAWTGRGMEF KLIEPEEVAR LWGIQKNRPA MNYDKLSRSL 370 380 390 400 410 420 RYYYEKGIMQ KVAGERYVYK FVCEPEALFS LAFPDNQRPA LKAEFDRPVS EEDTVPLSHL 430 440 DESPAYLPEL AGPAQPFGPK GGYSY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"22 genes from chromosome 17q21: cloning, sequencing, and characterization of mutations in breast cancer families and tumors." Friedman L.S., Ostermeyer E.A., Lynch E.D., Szabo C.I., Meza J.E., Anderson L.A., Dowd P., Lee M.K., Rowell S.E., Ellison J., Boyd J., King M.-C. Genomics 25:256-263(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Genomic organization of the human e1af gene, a member of Ets transcription factors." Coutte L., Monte D., Baert J.-L., de Launoit Y. Gene 240:201-207(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-195. Tissue: Amygdala.
[4]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon.
[6]	"Isolation of a cDNA encoding the adenovirus E1A enhancer binding protein: a new human member of the ets oncogene family." Higashino F., Yoshida K., Fujinaga K., Kamio K., Fujinaga K. Nucleic Acids Res. 21:547-553(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-484 (ISOFORM 1).
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Extracellular signal-regulated kinase mitogen-activated protein kinase signaling initiates a dynamic interplay between sumoylation and ubiquitination to regulate the activity of the transcriptional activator PEA3." Guo B., Sharrocks A.D. Mol. Cell. Biol. 29:3204-3218(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUMOYLATION AT LYS-96; LYS-226 AND LYS-260, DESUMOYLATION BY SENP1, UBIQUITINATION BY RNF4, DEUBIQUITINATION BY UPS2, MUTAGENESIS OF LYS-96; GLU-98; SER-101; PRO-102; LYS-226; GLU-228; LYS-260; GLU-262; GLU-324 AND GLU-443.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U18018 mRNA. Translation: AAA95991.1. Different initiation. AF095890 , AF095887, AF095888, AF095889 Genomic DNA. Translation: AAD09186.1. AK290429 mRNA. Translation: BAF83118.1. AK299019 mRNA. Translation: BAH12929.1. AK315961 mRNA. Translation: BAH14332.1. AC068675 Genomic DNA. No translation available. BC016623 mRNA. Translation: AAH16623.1. D12765 mRNA. Translation: BAA02234.1.
IPI	IPI00017382. IPI01011611.
PIR	S35534.
RefSeq	NP_001073143.1. NM_001079675.2. NP_001248366.1. NM_001261437.1. NP_001248367.1. NM_001261438.1. NP_001977.1. NM_001986.2.
UniGene	Hs.434059.
3D structure databases
ProteinModelPortal	P43268.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-748N.
IntAct	P43268. 2 interactions.
STRING	9606.ENSP00000321835.
PTM databases
PhosphoSite	P43268.
Polymorphism databases
DMDM	62512145.
Proteomic databases
PaxDb	P43268.
PRIDE	P43268.
Protocols and materials databases
DNASU	2118.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000319349; ENSP00000321835; ENSG00000175832. ENST00000393664; ENSP00000377273; ENSG00000175832. ENST00000538265; ENSP00000443846; ENSG00000175832. ENST00000545954; ENSP00000440023; ENSG00000175832. ENST00000591713; ENSP00000465718; ENSG00000175832.
GeneID	2118.
KEGG	hsa:2118.
UCSC	uc002idw.3. human.
Organism-specific databases
CTD	2118.
GeneCards	GC17M041605.
HGNC	HGNC:3493. ETV4.
HPA	HPA005768.
MIM	600711. gene.
neXtProt	NX_P43268.
Orphanet	319. Ewing sarcoma.
PharmGKB	PA27907.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG258471.
HOGENOM	HOG000230986.
HOVERGEN	HBG000231.
InParanoid	P43268.
KO	K15592.
OMA	PFPRAEQ.
OrthoDB	EOG4W0XCT.
Gene expression databases
ArrayExpress	P43268.
Bgee	P43268.
CleanEx	HS_ETV4.
Genevestigator	P43268.
GermOnline	ENSG00000175832. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR000418. Ets_dom. IPR006715. ETS_PEA3_N. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00178. Ets. 1 hit. PF04621. ETS_PEA3_N. 1 hit. [Graphical view]
PRINTS	PR00454. ETSDOMAIN.
SMART	SM00413. ETS. 1 hit. [Graphical view]
PROSITE	PS00345. ETS_DOMAIN_1. 1 hit. PS00346. ETS_DOMAIN_2. 1 hit. PS50061. ETS_DOMAIN_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ETV4. human.
GenomeRNAi	2118.
NextBio	8559.
SOURCE	Search...

Entry information

Entry name

ETV4_HUMAN

Accession

Primary (citable) accession number: P43268
Secondary accession number(s): A8K314 , B7Z5J3, B7Z9J6, Q96AW9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	April 12, 2005
Last modified:	May 1, 2013
This is version 111 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.