ETS4_CAEEL
ID ETS4_CAEEL Reviewed; 437 AA.
AC A8WFJ9; H2KYS4;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Transcription factor ets-4 {ECO:0000303|PubMed:20862312};
GN Name=ets-4 {ECO:0000303|PubMed:20862312, ECO:0000312|WormBase:F22A3.1b};
GN ORFNames=F22A3.1 {ECO:0000312|WormBase:F22A3.1b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DOMAIN, AND DISRUPTION PHENOTYPE.
RX PubMed=20862312; DOI=10.1371/journal.pgen.1001125;
RA Thyagarajan B., Blaszczak A.G., Chandler K.J., Watts J.L., Johnson W.E.,
RA Graves B.J.;
RT "ETS-4 is a transcriptional regulator of life span in Caenorhabditis
RT elegans.";
RL PLoS Genet. 6:E1001125-E1001125(2010).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CEBP-1, PHOSPHORYLATION AT SER-73, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF SER-73.
RX PubMed=26484536; DOI=10.1371/journal.pgen.1005603;
RA Li C., Hisamoto N., Matsumoto K.;
RT "Axon regeneration is regulated by Ets-C/EBP transcription complexes
RT generated by activation of the cAMP/Ca2+ signaling pathways.";
RL PLoS Genet. 11:E1005603-E1005603(2015).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27746047; DOI=10.1016/j.devcel.2016.09.018;
RA Habacher C., Guo Y., Venz R., Kumari P., Neagu A., Gaidatzis D.,
RA Harvald E.B., Faergeman N.J., Gut H., Ciosk R.;
RT "Ribonuclease-mediated control of body fat.";
RL Dev. Cell 39:359-369(2016).
CC -!- FUNCTION: Transcription factor which binds to 5'-GGAA/T-3' DNA
CC consensus sequences (PubMed:20862312, PubMed:26484536). Both positively
CC and negatively regulates the expression of target genes
CC (PubMed:20862312). Plays a role in the regulation of adult lifespan,
CC which may in part be through modulation of daf-16 activity
CC (PubMed:20862312). Regulates the expression of genes such as svh-2 in
CC response to axon injury and in addition, may function downstream of the
CC cAMP signaling pathway to promote axon regeneration (PubMed:26484536).
CC Regulates the expression of lipid metabolism genes and may also control
CC the expression of the RNA-binding protein rege-1 which too has been
CC implicated in the control of fat accumulation (PubMed:27746047).
CC {ECO:0000269|PubMed:20862312, ECO:0000269|PubMed:26484536,
CC ECO:0000269|PubMed:27746047}.
CC -!- SUBUNIT: May interact with cebp-1. {ECO:0000269|PubMed:26484536}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20862312}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:F22A3.1b};
CC IsoId=A8WFJ9-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:F22A3.1a};
CC IsoId=A8WFJ9-2; Sequence=VSP_058757, VSP_058758;
CC -!- TISSUE SPECIFICITY: Expressed in cells of the anterior and posterior
CC bulbs of the pharynx, seam cells, a few unidentified cells of the
CC vulva, the hypodermis, several unidentified neurons, labial socket
CC cells of the head and rectal cells. {ECO:0000269|PubMed:20862312}.
CC -!- DEVELOPMENTAL STAGE: Expressed in intestinal cells from the 3-fold
CC stage of embryogenesis to adulthood. {ECO:0000269|PubMed:20862312}.
CC -!- DOMAIN: The N-terminal part (1-345) is responsible for activating
CC transcription, but this action may be modulated by the PNT domain which
CC acts to repress transcription. {ECO:0000269|PubMed:20862312}.
CC -!- PTM: Phosphorylation is required for axon regeneration.
CC {ECO:0000269|PubMed:26484536}.
CC -!- DISRUPTION PHENOTYPE: Delayed larval development and increased
CC lifespan, but overall resulting animals have normal morphology and
CC fecundity (PubMed:20862312). Reduced egg-laying rate, but older
CC hermaphrodites produce more progeny (PubMed:20862312). Both decreased
CC expression of genes, such as the lipoprotein vit-5, which is related to
CC life span regulation, and increased expression of genes such as lys-7,
CC which is a lysosomal protein (PubMed:20862312). Reduced expression of
CC genes such as svh-2 in response to axon injury and as a result, there
CC is reduced axon regeneration of D-type motor neurons (PubMed:26484536).
CC RNAi-mediated knockdown results in reduced expression of the RNA-
CC binding protein rege-1 (PubMed:27746047). {ECO:0000269|PubMed:20862312,
CC ECO:0000269|PubMed:26484536, ECO:0000269|PubMed:27746047}.
CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}.
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DR EMBL; BX284606; CCD64581.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD64575.1; -; Genomic_DNA.
DR RefSeq; NP_001123137.1; NM_001129665.2.
DR RefSeq; NP_509099.2; NM_076698.4. [A8WFJ9-2]
DR AlphaFoldDB; A8WFJ9; -.
DR SMR; A8WFJ9; -.
DR IntAct; A8WFJ9; 1.
DR STRING; 6239.F22A3.1b; -.
DR iPTMnet; A8WFJ9; -.
DR PaxDb; A8WFJ9; -.
DR EnsemblMetazoa; F22A3.1a.1; F22A3.1a.1; WBGene00017687. [A8WFJ9-2]
DR EnsemblMetazoa; F22A3.1b.1; F22A3.1b.1; WBGene00017687.
DR GeneID; 180927; -.
DR UCSC; F22A3.1b; c. elegans. [A8WFJ9-1]
DR CTD; 180927; -.
DR WormBase; F22A3.1a; CE34001; WBGene00017687; ets-4. [A8WFJ9-2]
DR WormBase; F22A3.1b; CE41797; WBGene00017687; ets-4. [A8WFJ9-1]
DR eggNOG; KOG3805; Eukaryota.
DR GeneTree; ENSGT00940000157549; -.
DR HOGENOM; CLU_736166_0_0_1; -.
DR InParanoid; A8WFJ9; -.
DR OMA; ARWINEM; -.
DR OrthoDB; 837296at2759; -.
DR PhylomeDB; A8WFJ9; -.
DR SignaLink; A8WFJ9; -.
DR PRO; PR:A8WFJ9; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00017687; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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; 2.
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 Alternative splicing; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..437
FT /note="Transcription factor ets-4"
FT /evidence="ECO:0000305"
FT /id="PRO_0000438864"
FT DOMAIN 120..202
FT /note="PNT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00762"
FT DNA_BIND 349..432
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 275..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..296
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:26484536"
FT VAR_SEQ 1..54
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_058757"
FT VAR_SEQ 201..207
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_058758"
FT MUTAGEN 73
FT /note="S->A: Abolishes phosphorylation."
FT /evidence="ECO:0000269|PubMed:26484536"
FT MUTAGEN 73
FT /note="S->E: Phosphomimetic mutant which may allow for
FT association with cebp-1."
FT /evidence="ECO:0000269|PubMed:26484536"
SQ SEQUENCE 437 AA; 49766 MW; 67685E3586878DB2 CRC64;
MNGTGSVGHR WNSLSPEPHS GTESTASTPF VKSEFPFDDD LFGIDQVNNV KPHPMDMPCN
LPIQPIEYNR RFSKDADHST FVKNEIEENI LNFNVNPEIA QDNGLDTQQI DIYRDLILRH
LIQDISTTCA KLGLPNDFYL WSSEHGARWI NEMCMQFNLQ PPRNCSITGI DLLGMSQKDF
EMILPAGGDT LHAQLQVWKT GTSDYVKAFE NYHPPVTVQS SGMTAAENNM QSKTNWLAST
NNQTNNMAAA ENPNHPFFNG NGGYPNMSMS SFFQQGTVLP SPSNSDTSSN GSSQDMNDDD
IDLHMNNSNC GFSNFFHNQG YMNSPIDAMC NGSEGDDDER AYTRHQGTVH LWQFIRELLD
QPKQYSACVR WVDRDEGTFK IESSLLLARY WGQRKNRSQM NYDKLSRSLR QYYKKGIIQK
PEKKQRLVYK FLPPYNL
