EGR1_RAT
ID EGR1_RAT Reviewed; 508 AA.
AC P08154; Q53YM5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Early growth response protein 1;
DE Short=EGR-1;
DE AltName: Full=Nerve growth factor-induced protein A {ECO:0000303|PubMed:2492104};
DE Short=NGFI-A {ECO:0000303|PubMed:2492104};
DE AltName: Full=Transcription factor Zif268;
DE AltName: Full=Zinc finger protein Krox-24;
GN Name=Egr1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3672127; DOI=10.1126/science.3672127;
RA Milbrandt J.;
RT "A nerve growth factor-induced gene encodes a possible transcriptional
RT regulatory factor.";
RL Science 238:797-799(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION BY GROWTH FACTORS.
RX PubMed=2492104; DOI=10.1073/pnas.86.1.377;
RA Changelian P.S., Feng P., King T.C., Milbrandt J.;
RT "Structure of the NGFI-A gene and detection of upstream sequences
RT responsible for its transcriptional induction by nerve growth factor.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:377-381(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Midbrain;
RA Ju S.K.;
RT "Cloning and sequencing of cDNA encoding EGR1 from rat.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY ISCHEMIA.
RX PubMed=1859855; DOI=10.1091/mbc.2.3.251;
RA Bonventre J.V., Sukhatme V.P., Bamberger M., Ouellette A.J., Brown D.;
RT "Localization of the protein product of the immediate early growth response
RT gene, Egr-1, in the kidney after ischemia and reperfusion.";
RL Cell Regul. 2:251-260(1991).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF ILE-265.
RX PubMed=8413279; DOI=10.1128/mcb.13.11.6858-6865.1993;
RA Russo M.W., Matheny C., Milbrandt J.;
RT "Transcriptional activity of the zinc finger protein NGFI-A is influenced
RT by its interaction with a cellular factor.";
RL Mol. Cell. Biol. 13:6858-6865(1993).
CC -!- FUNCTION: Transcriptional regulator (PubMed:8413279). Recognizes and
CC binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter
CC region of target genes (By similarity). Binds double-stranded target
CC DNA, irrespective of the cytosine methylation status (By similarity).
CC Regulates the transcription of numerous target genes, and thereby plays
CC an important role in regulating the response to growth factors, DNA
CC damage, and ischemia. Plays a role in the regulation of cell survival,
CC proliferation and cell death. Activates expression of p53/TP53 and
CC TGFB1, and thereby helps prevent tumor formation. Required for normal
CC progress through mitosis and normal proliferation of hepatocytes after
CC partial hepatectomy. Mediates responses to ischemia and hypoxia;
CC regulates the expression of proteins such as IL1B and CXCL2 that are
CC involved in inflammatory processes and development of tissue damage
CC after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in
CC the pituitary (By similarity). Regulates the amplitude of the
CC expression rhythms of clock genes: ARNTL/BMAL1, PER2 and NR1D1 in the
CC liver via the activation of PER1 (clock repressor) transcription.
CC Regulates the rhythmic expression of core-clock gene ARNTL/BMAL1 in the
CC suprachiasmatic nucleus (SCN) (By similarity).
CC {ECO:0000250|UniProtKB:P08046, ECO:0000250|UniProtKB:P18146,
CC ECO:0000269|PubMed:8413279}.
CC -!- SUBUNIT: Interacts with SNAI1 and SP1 upon 12-O-tetradecanoylphorbol-
CC 13-acetate (TPA) induction. {ECO:0000250|UniProtKB:P18146}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:1859855}. Cytoplasm
CC {ECO:0000250|UniProtKB:P18146}.
CC -!- TISSUE SPECIFICITY: Detected in kidney thick ascending limbs and
CC collecting ducts (at protein level). {ECO:0000269|PubMed:1859855}.
CC -!- INDUCTION: By growth factors (PubMed:2492104). Rapidly and transiently
CC up-regulated in response to oschemia (PubMed:1859855).
CC {ECO:0000269|PubMed:1859855, ECO:0000269|PubMed:2492104}.
CC -!- DOMAIN: Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via
CC its C2H2-type zinc fingers. The first, most N-terminal zinc finger
CC binds to the 3'-GCG motif, the middle zinc finger interacts with the
CC central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG
CC motif. Binds double-stranded target DNA, irrespective of the cytosine
CC methylation status. Has reduced affinity for target DNA where the
CC cytosines have been oxidized to 5-hydroxymethylcytosine. Does not bind
CC target DNA where the cytosines have been oxidized to 5-formylcytosine
CC or 5-carboxylcytosine. {ECO:0000250|UniProtKB:P18146}.
CC -!- SIMILARITY: Belongs to the EGR C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; M18416; AAA61927.1; -; mRNA.
DR EMBL; J04154; AAA60740.1; -; Genomic_DNA.
DR EMBL; AY551092; AAS58455.1; -; mRNA.
DR PIR; A32225; A32225.
DR RefSeq; NP_036683.1; NM_012551.2.
DR AlphaFoldDB; P08154; -.
DR SMR; P08154; -.
DR STRING; 10116.ENSRNOP00000026303; -.
DR PhosphoSitePlus; P08154; -.
DR PaxDb; P08154; -.
DR GeneID; 24330; -.
DR KEGG; rno:24330; -.
DR UCSC; RGD:2544; rat.
DR CTD; 1958; -.
DR RGD; 2544; Egr1.
DR eggNOG; KOG1721; Eukaryota.
DR HOGENOM; CLU_043235_2_0_1; -.
DR InParanoid; P08154; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; P08154; -.
DR PRO; PR:P08154; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; P08154; RN.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0010385; F:double-stranded methylated DNA binding; ISO:RGD.
DR GO; GO:0044729; F:hemi-methylated DNA-binding; ISO:RGD.
DR GO; GO:0035035; F:histone acetyltransferase binding; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071480; P:cellular response to gamma radiation; ISO:RGD.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0071504; P:cellular response to heparin; IDA:UniProtKB.
DR GO; GO:0071455; P:cellular response to hyperoxia; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0098759; P:cellular response to interleukin-8; ISS:UniProtKB.
DR GO; GO:0071317; P:cellular response to isoquinoline alkaloid; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071506; P:cellular response to mycophenolic acid; IDA:UniProtKB.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0060086; P:circadian temperature homeostasis; ISS:UniProtKB.
DR GO; GO:0044849; P:estrous cycle; ISS:UniProtKB.
DR GO; GO:0072110; P:glomerular mesangial cell proliferation; IMP:UniProtKB.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:RGD.
DR GO; GO:0007611; P:learning or memory; IMP:RGD.
DR GO; GO:0045475; P:locomotor rhythm; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; IMP:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEP:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEP:RGD.
DR GO; GO:0010942; P:positive regulation of cell death; IMP:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0072303; P:positive regulation of glomerular metanephric mesangial cell proliferation; IMP:UniProtKB.
DR GO; GO:0046886; P:positive regulation of hormone biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:2000182; P:regulation of progesterone biosynthetic process; ISS:UniProtKB.
DR GO; GO:0033233; P:regulation of protein sumoylation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0001975; P:response to amphetamine; IEP:RGD.
DR GO; GO:0034465; P:response to carbon monoxide; IEP:RGD.
DR GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; ISO:RGD.
DR GO; GO:0034698; P:response to gonadotropin; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; ISO:RGD.
DR GO; GO:0002931; P:response to ischemia; IDA:UniProtKB.
DR GO; GO:0071873; P:response to norepinephrine; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; ISO:RGD.
DR GO; GO:0030217; P:T cell differentiation; ISO:RGD.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
DR InterPro; IPR021839; EGR1_C.
DR InterPro; IPR021849; EGR_N.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF11914; DUF3432; 1.
DR Pfam; PF11928; DUF3446; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE 1: Evidence at protein level;
KW Activator; Biological rhythms; Cytoplasm; DNA-binding; Isopeptide bond;
KW Metal-binding; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..508
FT /note="Early growth response protein 1"
FT /id="PRO_0000047111"
FT REPEAT 413..420
FT /note="1"
FT REPEAT 421..428
FT /note="2"
FT REPEAT 429..436
FT /note="3"
FT REPEAT 437..444
FT /note="4"
FT REPEAT 445..452
FT /note="5"
FT REPEAT 453..460
FT /note="6"
FT REPEAT 462..468
FT /note="7"
FT ZN_FING 311..335
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 341..363
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 369..391
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 18..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 382..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 413..468
FT /note="7 X 8 AA tandem repeats of [TS](2)-[FY]-[PS]-S-P-
FT [GSAV]-X"
FT COMPBIAS 28..78
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..202
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 309
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P18146"
FT SITE 320
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P08046"
FT SITE 324
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P08046"
FT SITE 330
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P18146"
FT SITE 348
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P08046"
FT SITE 352
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P18146"
FT SITE 376
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P18146"
FT SITE 380
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P18146"
FT SITE 386
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P18146"
FT CROSSLNK 278
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P18146"
FT MUTAGEN 265
FT /note="I->F: Increases transcriptional activity."
FT /evidence="ECO:0000269|PubMed:8413279"
SQ SEQUENCE 508 AA; 53935 MW; 3947BBA871BB8FA8 CRC64;
MDNYPKLEEM MLLSNGAPQF LGAAGTPEGS GGNNSSSSSS SSSGGGGGGG SNSGSSAFNP
QGEPSEQPYE HLTTESFSDI ALNNEKALVE TSYPSQTTRL PPITYTGRFS LEPAPNSGNT
LWPEPLFSLV SGLVSMTNPP TSSSSAPSPA ASSSSSASQS PPLSCAVPSN DSSPIYSAAP
TFPTPNTDIF PEPQSQAFPG SAGTALQYPP PAYPATKGGF QVPMIPDYLF PQQQGDLSLG
TPDQKPFQGL ENRTQQPSLT PLSTIKAFAT QSGSQDLKAL NNTYQSQLIK PSRMRKYPNR
PSKTPPHERP YACPVESCDR RFSRSDELTR HIRIHTGQKP FQCRICMRNF SRSDHLTTHI
RTHTGEKPFA CDICGRKFAR SDERKRHTKI HLRQKDKKAD KSVVASSAAS SLSSYPSPVA
TSYPSPATTS FPSPVPTSYS SPGSSTYPSP AHSGFPSPSV ATTYASVPPA FPAQVSTFQS
AGVSNSFSTS TGLSDMTATF SPRTIEIC
