Q99607 (ELF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ETS-related transcription factor Elf-4

Alternative name(s):
E74-like factor 4
Myeloid Elf-1-like factor

Gene names

Name:	ELF4
Synonyms:	ELFR, MEF

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	663 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator that binds to DNA sequences containing the consensus 5'-WGGA-3'. Transactivates promoters of the hematopoietic growth factor genes CSF2, IL3, IL8, and of the bovine lysozyme gene. Acts synergistically with RUNX1 to transactivate the IL3 promoter By similarity. Also transactivates the PRF1 promoter in natural killer (NK) cells. Plays a role in the development and function of NK and NK T-cells and in innate immunity. Controls the proliferation and homing of CD8+ T cells via the Kruppel-like factors KLF4 and KLF2 By similarity. Controls cell senescence in a p53-dependent manner. Can also promote celular transformation through inhibition of the p16 pathway. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.12 UniProtKB Q9Z2U4
Subunit structure	Interacts with RUNX1 (via the Runt domain); the interaction transactivates the IL3 promoter. Interacts (via its C-terminus) with PML; the interaction translocates ELF4 to PML nuclear bodies and enhances transactivation of LYZ. Ref.6 Ref.8
Subcellular location	Nucleus › PML body. Note: Accumulation into PML nuclear bodies is mediated by PML. Ref.8
Tissue specificity	Abundantly expressed in the placenta and in a variety of myeloid leukemia cell lines. Moderate levels of expression in heart, lung, spleen, thymus, peripheral blood lymphocytes, ovary and colon. Lower levels of expression in Jurkat T-cells and other T-cell lines and no expression in brain. Ref.1 Ref.2
Induction	By ponisterone A in erythroleukemia cells. Ref.7
Involvement in disease	Note=A chromosomal aberration involving ELF4 has been found in a case of acute myeloid leukemia (AML). Translocation t(X;21)(q25-26;q22) with ERG.
Sequence similarities	Belongs to the ETS family. Contains 1 ETS DNA-binding domain.
Sequence caution	The sequence AAC17452.1 differs from that shown. Reason: Frameshift at positions 334 and 412.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	NK T cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB natural killer cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.7Ref.1Ref.2. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	PML body Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction Ref.6Ref.8. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 663	663	ETS-related transcription factor Elf-4		PRO_0000204089
Regions
	DNA binding	209 – 291	83	ETS
	Region	87 – 206	120	RUNX1-binding Ref.6
Sites
	Site	25 – 26	2	Breakpoint for translocation to form ELF4-ERG oncogene
Amino acid modifications
	Modified residue	151	1	Phosphoserine Ref.10
	Modified residue	187	1	Phosphothreonine Ref.11
	Modified residue	188	1	Phosphoserine Ref.11
	Modified residue	643	1	Phosphothreonine Ref.10
	Modified residue	648	1	Phosphoserine Ref.10 Ref.13
Experimental info
	Sequence conflict	293 – 294	2	MP → IA in AAC17452. Ref.2
	Sequence conflict	499	1	P → L in AAC17452. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q99607 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 1696085D31B09BC5	FASTA	663	70,730
	10 20 30 40 50 60 MAITLQPSDL IFEFASNGMD DDIHQLEDPS VFPAVIVEQV PYPDLLHLYS GLELDDVHNG 70 80 90 100 110 120 IITDGTLCMT QDQILEGSFL LTDDNEATSH TMSTAEVLLN MESPSDILDE KQIFSTSEML 130 140 150 160 170 180 PDSDPAPAVT LPNYLFPASE PDALNRAGDT SDQEGHSLEE KASREESAKK TGKSKKRIRK 190 200 210 220 230 240 TKGNRSTSPV TDPSIPIRKK SKDGKGSTIY LWEFLLALLQ DRNTCPKYIK WTQREKGIFK 250 260 270 280 290 300 LVDSKAVSKL WGKQKNKPDM NYETMGRALR YYYQRGILAK VEGQRLVYQF KEMPKDLVVI 310 320 330 340 350 360 EDEDESSEAT AAPPQASTAS VASASTTRRT SSRVSSRSAP QGKGSSSWEK PKIQHVGLQP 370 380 390 400 410 420 SASLELGPSL DEEIPTTSTM LVSPAEGQVK LTKAVSASSV PSNIHLGVAP VGSGSALTLQ 430 440 450 460 470 480 TIPLTTVLTN GPPASTTAPT QLVLQSVPAA STFKDTFTLQ ASFPLNASFQ DSQVAAPGAP 490 500 510 520 530 540 LILSGLPQLL AGANRPTNPA PPTVTGAGPA GPSSQPPGTV IAAFIRTSGT TAAPRVKEGP 550 560 570 580 590 600 LRSSSYVQGM VTGAPMEGLL VPEETLRELL RDQAHLQPLP TQVVSRGSHN PSLLGNQTLS 610 620 630 640 650 660 PPSRPTVGLT PVAELELSSG SGSLLMAEPS VTTSGSLLTR SPTPAPFSPF NPTSLIKMEP HDI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MEF, a novel transcription factor with an Elf-1 like DNA binding domain but distinct transcriptional activating properties." Miyazaki Y., Sun X., Uchida H., Zhang J., Nimer S. Oncogene 13:1721-1729(1996) [PubMed: 8895518] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Promyelocytic leukemia.
[2]	"Cloning of a novel human ELF-1-related ETS transcription factor, ELFR, its characterization and chromosomal assignment relative to ELF-1." Aryee D.N.T., Petermann R., Kos K., Henn T., Haas O.A., Kovar H. Gene 210:71-78(1998) [PubMed: 9524226] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Ewing sarcoma.
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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. , 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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"Functional and physical interactions between AML1 proteins and an ETS protein, MEF: implications for the pathogenesis of t(8;21)-positive leukemias." Mao S., Frank R.C., Zhang J., Miyazaki Y., Nimer S.D. Mol. Cell. Biol. 19:3635-3644(1999) [PubMed: 10207087] [Abstract] Cited for: FUNCTION, INTERACTION WITH RUNX1.
[7]	"Myeloid ELF1-like factor is a potent activator of interleukin-8 expression in hematopoietic cells." Hedvat C.V., Yao J., Sokolic R.A., Nimer S.D. J. Biol. Chem. 279:6395-6400(2004) [PubMed: 14625302] [Abstract] Cited for: FUNCTION, INDUCTION.
[8]	"Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates lysozyme transcription in epithelial cells through interaction with promyelocytic leukemia protein." Suico M.A., Yoshida H., Seki Y., Uchikawa T., Lu Z., Shuto T., Matsuzaki K., Nakao M., Li J.-D., Kai H. J. Biol. Chem. 279:19091-19098(2004) [PubMed: 14976184] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML.
[9]	"ELF4 is fused to ERG in a case of acute myeloid leukemia with a t(X;21)(q25-26;q22)." Moore S.D., Offor O., Ferry J.A., Amrein P.C., Morton C.C., Dal Cin P. Leuk. Res. 30:1037-1042(2006) [PubMed: 16303180] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH ERG.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151; THR-643 AND SER-648, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-187 AND SER-188, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"ELF4/MEF activates MDM2 expression and blocks oncogene-induced p16 activation to promote transformation." Sashida G., Liu Y., Elf S., Miyata Y., Ohyashiki K., Izumi M., Menendez S., Nimer S.D. Mol. Cell. Biol. 29:3687-3699(2009) [PubMed: 19380490] [Abstract] Cited for: FUNCTION.
[13]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-648, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U32645 mRNA. Translation: AAB53693.1. AF000670 mRNA. Translation: AAC17452.1. Frameshift. AL136450, Z81363 Genomic DNA. Translation: CAI42882.1. Z81363, AL136450 Genomic DNA. Translation: CAI42371.1. CH471107 Genomic DNA. Translation: EAX11813.1. CH471107 Genomic DNA. Translation: EAX11814.1. BC017194 mRNA. Translation: AAH17194.1.
IPI	IPI00170744.
RefSeq	NP_001120669.1. NM_001127197.1. NP_001412.1. NM_001421.3.
UniGene	Hs.271940.
3D structure databases
ProteinModelPortal	Q99607.
SMR	Q99607. Positions 175-291.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99607. 4 interactions.
STRING	Q99607.
PTM databases
PhosphoSite	Q99607.
Polymorphism databases
DMDM	68052244.
Proteomic databases
PRIDE	Q99607.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308167; ENSP00000311280; ENSG00000102034. ENST00000335997; ENSP00000338608; ENSG00000102034.
GeneID	2000.
KEGG	hsa:2000.
UCSC	uc004evd.2. human.
Organism-specific databases
CTD	2000.
GeneCards	GC0XM129198.
H-InvDB	HIX0017043.
HGNC	HGNC:3319. ELF4.
MIM	300775. gene.
neXtProt	NX_Q99607.
PharmGKB	PA27747.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15051.
GeneTree	ENSGT00600000084143.
HOGENOM	HBG714786.
HOVERGEN	HBG007183.
InParanoid	Q99607.
OMA	RGSHNPS.
OrthoDB	EOG4SF95X.
PhylomeDB	Q99607.
Gene expression databases
ArrayExpress	Q99607.
Bgee	Q99607.
CleanEx	HS_ELF4.
Genevestigator	Q99607.
GermOnline	ENSG00000102034. Homo sapiens.
Family and domain databases
InterPro	IPR000418. Ets. IPR022084. TF_Elf-1_N. IPR011991. WHTH_trsnscrt_rep_DNA-bd. [Graphical view]
Gene3D	G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.
KO	K09428.
Pfam	PF12310. Elf-1_N. 1 hit. PF00178. Ets. 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
NextBio	8091.
SOURCE	Search...

Entry information

Entry name

ELF4_HUMAN

Accession

Primary (citable) accession number: Q99607
Secondary accession number(s): D3DTG1, O60435

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2005
Last sequence update:	May 1, 1997
Last modified:	January 25, 2012
This is version 102 of the entry and version 1 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.