ETS1

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
1GVJ, 2NNY, 2STT, 2STW, 3MFK, 3RI4, 3WTS, 3WTT, 3WTU, 3WTV, 3WTW, 3WTX, 3WTY, 3WTZ, 3WU0, 3WU1, 4L0Y, 4L0Z, 4L18, 4LG0

Identifiers

Aliases

ETS1, ETS-1, EWSR2, p54, c-ets-1, ETS proto-oncogene 1, transcription factor

External IDs

MGI: 95455 HomoloGene: 3837 GeneCards: ETS1

Genetically Related Diseases

obesity, celiac disease, systemic lupus erythematosus^[1]

Gene ontology
Molecular function	• DNA binding • sequence-specific DNA binding • transcription factor activity, sequence-specific DNA binding • transcription factor binding • protein binding • histone acetyltransferase binding • identical protein binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
Cellular component	• cytoplasm • transcription factor complex • nucleoplasm • nucleus
Biological process	• regulation of apoptotic process • pituitary gland development • response to estradiol • response to interleukin-1 • response to hypoxia • regulation of transcription, DNA-templated • positive regulation of erythrocyte differentiation • cell motility • estrous cycle • immune system process • regulation of transcription from RNA polymerase II promoter • response to antibiotic • female pregnancy • angiogenesis involved in wound healing • positive regulation of cell migration • response to mechanical stimulus • response to laminar fluid shear stress • negative regulation of cell cycle • regulation of angiogenesis • transcription from RNA polymerase II promoter • regulation of extracellular matrix disassembly • transcription, DNA-templated • positive regulation of angiogenesis • positive regulation of endothelial cell migration • positive regulation of transcription, DNA-templated • PML body organization • response to wounding • immune response • positive regulation of cell proliferation • hypothalamus development • positive regulation of cellular component movement • negative regulation of inflammatory response • positive regulation of transcription from RNA polymerase II promoter • negative regulation of cell proliferation • cellular response to hydrogen peroxide • positive regulation of inflammatory response • pri-miRNA transcription from RNA polymerase II promoter • positive regulation of leukocyte adhesion to vascular endothelial cell
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


2113


23871

Ensembl


ENSG00000134954


ENSMUSG00000032035

UniProt


P14921


P27577

RefSeq (mRNA)


NM_001143820 NM_001162422 NM_005238


NM_001038642 NM_011808

RefSeq (protein)


NP_001137292.1 NP_001155894.1 NP_005229.1


NP_035938.2

Location (UCSC)

Chr 11: 128.46 – 128.59 Mb

Chr 9: 32.64 – 32.76 Mb

PubMed search

^[2]

^[3]

Wikidata

View/Edit Human

View/Edit Mouse

Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene.^[4] The protein encoded by this gene belongs to the ETS family of transcription factors.^[5]

Function

There are 28 ETS genes in humans and 27 genes – in mice. They bind the DNA via their winged-helix-turn-helix DNA binding motif known as the Ets domain that specifically recognizes DNA sequences that contain a GGAA/T core element. However, Ets proteins differ significantly in their preference for the sequence flanking the GGAA/T core motif. For instance, the consensus sequence for Ets1 is PuCC/a-GGAA/T-GCPy. On the other hand, many natural Ets1-responsive GGAA/T elements differ from this consensus sequence. The later suggests that several other transcription factors may facilitate Ets1 binding to unfavorable DNA sequences.

Ets1 binds to DNA as a monomer. Phosphorylation of serine residues of the C-terminal domain (in the nucleotide sequence they belong to exon VII) known as autoinhibition makes Ets1 inactive. There are several ways to activate Ets1. First, Ets1 can be dephosphorylated. Second, two Ets1 can be activated If two Ets molecules homodimerize. The homodimerization occurs if DNA binding sites are present in the correct orientation and spacing. Thus, the exact layout of binding sites within an enhancer or promoter segment to either relieve or allow autoinhibition of Ets1 to occur may strongly influence whether or not Ets1 actually binds to particular site. Third, Ets1 can be activated by Erk2 and Ras at Thr38. The truncated isoform cannot be phosphorylated by the Erk2. It is localized in the cytoplasm and acts as a dominant negative isoform. Contrary, another isoform that misses exon VII is constitutively active. Many Ras responsive genes harbor combinatorial Ets/AP1 recognition motifs through which Ets1 and AP1 synergistically activate transcription when stimulated by Ras.^[6]

In adult humans, Ets1 is expressed at high levels mainly in immune tissues such as thymus, spleen, and lymph node (B cells, T cells, NK cells, and NK T cells and non-lymphoid immune cells). An enforced expression of Ets1 blocks differentiation of B- and T-cells. Contrary, knocking Ets1 down is causing multiple defects in the immune system.

Knockout mice

Ets1 knockout mice have aberrant thymic differentiation, reduced peripheral T cell numbers, reduced IL-2 production, a skewing towards a memory/effector phenotype and impairments in the production of Th1 and Th2 cytokines. Although Ets1 knockout mice have an impaired development of Th1, Th2, and Treg cells, they have higher numbers of Th17 cells. There are also partial defects in bone marrow B cell development with reduced cellularity and inefficient transition from pro-B to pre-B cell stages.

Clinical significance

Meta-analyses of multiple genome-wide association studies has suggested an association of SNPs in the ETS1locus with psoriasis in European populations. This is not surprising because Ets1 is a negative regulator of Th17 cells.

Ets1 overexpression in stratified squamous epithelial cells causes pro-oncogenic changes, such as suspension of terminal differentiation, high secretion of matrix metalloproteases (Mmps), epidermal growth factor ligands, and inflammatory mediators.

Interactions

Ets1 directly interacts with various transcription factors. Their interaction results in formation of multiprotein complexes. When Ets1 interacts with other transcription factors (Runx1, Pax5, TFE3, and USF1) its final effect on transcription depends on whether C-terminal domain is phosphorylated. Acetyltransferases CBP and p300 bind to the transactivation domain. AP1, STAT5 and VDR bind to C-terminal domain.

Also, ETS1 has been shown to interact with TTRAP,^[7] UBE2I^[8] and Death associated protein 6.^[9]

References

↑ "Diseases that are genetically associated with ETS1 view/edit references on wikidata".
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G (Sep 1992). "Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours". Nature. 359 (6391): 162–5. doi:10.1038/359162a0. PMID 1522903.
↑ Dwyer J, Li H, Xu D, Liu JP (Oct 2007). "Transcriptional regulation of telomerase activity: roles of the Ets transcription factor family". Annals of the New York Academy of Sciences. 1114 (1): 36–47. doi:10.1196/annals.1396.022. PMID 17986575.
↑ Wasylyk B, Hagman J, Gutierrez-Hartmann A (1998). "Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway". Trends Biochem. Sci. 23 (6): 213–6. doi:10.1016/S0968-0004(98)01211-0. PMID 9644975.
↑ Pei H, Yordy JS, Leng Q, Zhao Q, Watson DK, Li R (May 2003). "EAPII interacts with ETS1 and modulates its transcriptional function". Oncogene. 22 (18): 2699–709. doi:10.1038/sj.onc.1206374. PMID 12743594.
↑ Hahn SL, Wasylyk B, Criqui-Filipe P, Criqui P (Sep 1997). "Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-conjugating enzyme". Oncogene. 15 (12): 1489–95. doi:10.1038/sj.onc.1201301. PMID 9333025.
↑ Li R, Pei H, Watson DK, Papas TS (Feb 2000). "EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes". Oncogene. 19 (6): 745–53. doi:10.1038/sj.onc.1203385. PMID 10698492.

External links

ETS1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
Drosophila pointed - The Interactive Fly
FactorBook ETS1

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery

1bqv:

1gvj: ETS-1 DNA BINDING AND AUTOINHIBITORY DOMAINS

1k78: Pax5(1-149)+Ets-1(331-440)+DNA

1k79: Ets-1(331-440)+GGAA duplex

1k7a: Ets-1(331-440)+GGAG duplex

1md0: CRYSTAL STRUCTURE OF AN INHIBITED FRAGMENT OF Ets-1

1mdm: INHIBITED FRAGMENT OF ETS-1 AND PAIRED DOMAIN OF PAX5 BOUND TO DNA

1r36: NMR-based structure of autoinhibited murine Ets-1 deltaN301

2stt: SOLUTION NMR STRUCTURE OF THE HUMAN ETS1/DNA COMPLEX, 25 STRUCTURES

2stw: SOLUTION NMR STRUCTURE OF THE HUMAN ETS1/DNA COMPLEX, RESTRAINED REGULARIZED MEAN STRUCTURE

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1

(1.3) bHLH-ZIP	AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2

(1.4) NF-1	NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4)

(1.5) RF-X	RFX 1 2 3 4 5 6 ANK

(1.6) Basic helix-span-helix (bHSH)	AP-2 α β γ δ ε

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)

subfamily 1	Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR

subfamily 2	COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX

subfamily 3	Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ

subfamily 4	NUR NGFIB NOR1 NURR1

subfamily 5	LRH-1 SF1

subfamily 6	GCNF

subfamily 0	DAX1 SHP

(2.2) Other Cys₄

GATA
- 1
- 2
- 3
- 4
- 5
- 6
MTA
- 1
- 2
- 3
TRPS1

(2.3) Cys₂His₂

General transcription factors
- TFIIA
- TFIIB
- TFIID
- TFIIE
  - 1
  - 2
- TFIIF
- 1
- 2
  - TFIIH
  - 1
  - 2
  - 4
  - 2I
  - 3A
  - 3C1
  - 3C2

ATBF1
BCL
- 6
- 11A
- 11B
CTCF
E4F1
EGR
- 1
- 2
- 3
- 4
ERV3
GFI1
GLI-Krüppel family
- 1
- 2
- 3
- REST
- S1
- S2
- YY1
HIC
- 1
- 2
HIVEP
- 1
- 2
- 3
IKZF
- 1
- 2
- 3
ILF
- 2
- 3
KLF
- 1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 9
- 10
- 11
- 12
- 13
- 14
- 15
- 17
MTF1
MYT1
OSR1
PRDM9
SALL
- 1
- 2
- 3
- 4
SP
- 1
- 2
- 4
- 7
- 8
TSHZ3
WT1
Zbtb7
- 7A
- 7B
ZBTB
- 11
- 16
- 17
- 20
- 32
- 33
- 40
zinc finger
- 3
- 7
- 9
- 10
- 19
- 22
- 24
- 33B
- 34
- 35
- 41
- 43
- 44
- 51
- 74
- 143
- 146
- 148
- 165
- 202
- 217
- 219
- 238
- 239
- 259
- 267
- 268
- 281
- 295
- 300
- 318
- 330
- 346
- 350
- 365
- 366
- 384
- 423
- 451
- 452
- 471
- 593
- 638
- 644
- 649
- 655

(2.4) Cys₆

HIVEP1

(2.5) Alternating composition

AIRE
DIDO1
GRLF1
ING
- 1
- 2
- 4
JARID
- 1A
- 1B
- 1C
- 1D
- 2
JMJD1B

(2.6) WRKY

WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2

(3.2) Paired box	PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX

(3.3) Fork head / winged helix	E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4

(3.4) Heat shock factors	HSF 1 2 4

(3.5) Tryptophan clusters	ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2

(3.6) TEA domain	transcriptional enhancer factor 1 2 3 4

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5

(4.2) STAT	STAT 1 2 3 4 5 6

(4.3) p53	p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63

(4.4) MADS box	Mef2 A B C D SRF

(4.6) TATA-binding proteins	TBP TBPL1

(4.7) High-mobility group	BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA YBX1

(4.11) Runt	CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA 1 2 HBP1

(0.3) Pocket domain	Rb RBL1 RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 EREBP B3

(0.6) Miscellaneous	ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma

see also transcription factor/coregulator deficiencies

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