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Early growth response protein 1 (EGR-1) (AT225) (Nerve growth factor-induced protein A) (NGFI-A) (Transcription factor ETR103) (Transcription factor Zif268) (Zinc finger protein 225) (Zinc finger protein Krox-24)

 EGR1_HUMAN              Reviewed;         543 AA.
P18146;
01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
01-NOV-1990, sequence version 1.
25-OCT-2017, entry version 177.
RecName: Full=Early growth response protein 1 {ECO:0000303|PubMed:2377485};
Short=EGR-1 {ECO:0000303|PubMed:2377485};
AltName: Full=AT225;
AltName: Full=Nerve growth factor-induced protein A;
Short=NGFI-A;
AltName: Full=Transcription factor ETR103;
AltName: Full=Transcription factor Zif268;
AltName: Full=Zinc finger protein 225 {ECO:0000303|PubMed:2110381};
AltName: Full=Zinc finger protein Krox-24;
Name=EGR1; Synonyms=KROX24, ZNF225 {ECO:0000303|PubMed:2110381};
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Foreskin;
PubMed=2377485; DOI=10.1093/nar/18.14.4283;
Suggs S.V., Katzowitz J.L., Tsai-Morris C.-H., Sukhatme V.P.;
"cDNA sequence of the human cellular early growth response gene Egr-
1.";
Nucleic Acids Res. 18:4283-4283(1990).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=1569051;
Shimizu N., Ohta M., Fujiwara C., Sagara J., Mochizuki N., Oda T.,
Utiyama H.;
"A gene coding for a zinc finger protein is induced during 12-O-
tetradecanoylphorbol-13-acetate-stimulated HL-60 cell
differentiation.";
J. Biochem. 111:272-277(1992).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2110381; DOI=10.1126/science.2110381;
Wright J.J., Gunter K.C., Mitsuya H., Irving S.G., Kelly K.,
Siebenlist U.;
"Expression of a zinc finger gene in HTLV-I- and HTLV-II-transformed
cells.";
Science 248:588-591(1990).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=PNS;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[6]
INTERACTION WITH SNAI1 AND SP1, AND FUNCTION.
PubMed=20121949; DOI=10.1111/j.1742-4658.2009.07553.x;
Hu C.T., Chang T.Y., Cheng C.C., Liu C.S., Wu J.R., Li M.C., Wu W.S.;
"Snail associates with EGR-1 and SP-1 to upregulate transcriptional
activation of p15INK4b.";
FEBS J. 277:1202-1218(2010).
[7]
SUBCELLULAR LOCATION, AND INDUCTION BY GROWTH FACTORS.
PubMed=20363028; DOI=10.1016/j.molimm.2010.03.003;
Cullen E.M., Brazil J.C., O'Connor C.M.;
"Mature human neutrophils constitutively express the transcription
factor EGR-1.";
Mol. Immunol. 47:1701-1709(2010).
[8]
SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-305, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=28112733; DOI=10.1038/nsmb.3366;
Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
Nielsen M.L.;
"Site-specific mapping of the human SUMO proteome reveals co-
modification with phosphorylation.";
Nat. Struct. Mol. Biol. 24:325-336(2017).
[9] {ECO:0000244|PDB:4R2A, ECO:0000244|PDB:4R2C, ECO:0000244|PDB:4R2D}
X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 335-423 IN COMPLEX WITH ZINC
AND TARGET DNA, FUNCTION, DOMAIN, AND SITES OF INTERACTION WITH DNA.
PubMed=25258363; DOI=10.1101/gad.250746.114;
Hashimoto H., Olanrewaju Y.O., Zheng Y., Wilson G.G., Zhang X.,
Cheng X.;
"Wilms tumor protein recognizes 5-carboxylcytosine within a specific
DNA sequence.";
Genes Dev. 28:2304-2313(2014).
[10] {ECO:0000244|PDB:4X9J}
X-RAY CRYSTALLOGRAPHY (1.41 ANGSTROMS) OF 335-423 IN COMPLEX WITH ZINC
AND TARGET DNA, FUNCTION, DOMAIN, AND SITES OF INTERACTION WITH DNA.
PubMed=25999311; DOI=10.1016/j.febslet.2015.05.022;
Zandarashvili L., White M.A., Esadze A., Iwahara J.;
"Structural impact of complete CpG methylation within target DNA on
specific complex formation of the inducible transcription factor Egr-
1.";
FEBS Lett. 589:1748-1753(2015).
-!- FUNCTION: Transcriptional regulator (PubMed:20121949). Recognizes
and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the
promoter region of target genes (By similarity). Binds double-
stranded target DNA, irrespective of the cytosine methylation
status (PubMed:25258363, PubMed:25999311). Regulates the
transcription of numerous target genes, and thereby plays an
important role in regulating the response to growth factors, DNA
damage, and ischemia. Plays a role in the regulation of cell
survival, proliferation and cell death. Activates expression of
p53/TP53 and TGFB1, and thereby helps prevent tumor formation.
Required for normal progress through mitosis and normal
proliferation of hepatocytes after partial hepatectomy. Mediates
responses to ischemia and hypoxia; regulates the expression of
proteins such as IL1B and CXCL2 that are involved in inflammatory
processes and development of tissue damage after ischemia.
Regulates biosynthesis of luteinizing hormone (LHB) in the
pituitary (By similarity). {ECO:0000250|UniProtKB:P08046,
ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:25258363,
ECO:0000269|PubMed:25999311}.
-!- SUBUNIT: Interacts with SNAI1 and SP1 upon 12-O-
tetradecanoylphorbol-13-acetate (TPA) induction.
{ECO:0000269|PubMed:20121949}.
-!- INTERACTION:
Q8N726:CDKN2A; NbExp=4; IntAct=EBI-2834611, EBI-625922;
P35222:CTNNB1; NbExp=7; IntAct=EBI-2834611, EBI-491549;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20363028}.
Cytoplasm {ECO:0000269|PubMed:20363028}.
-!- TISSUE SPECIFICITY: Detected in neutrophils (at protein level).
{ECO:0000269|PubMed:20363028}.
-!- INDUCTION: By growth factors. {ECO:0000269|PubMed:20363028}.
-!- DOMAIN: Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3'
via its C2H2-type zinc fingers (PubMed:25258363, PubMed:25999311).
The first, most N-terminal zinc finger binds to the 3'-GCG motif,
the middle zinc finger interacts with the central TGG motif, and
the C-terminal zinc finger binds to the 5'-GCG motif. Binds
double-stranded target DNA, irrespective of the cytosine
methylation status. Has reduced affinity for target DNA where the
cytosines have been oxidized to 5-hydroxymethylcytosine. Does not
bind target DNA where the cytosines have been oxidized to 5-
formylcytosine or 5-carboxylcytosine (PubMed:25258363).
{ECO:0000269|PubMed:25258363, ECO:0000269|PubMed:25999311}.
-!- SIMILARITY: Belongs to the EGR C2H2-type zinc-finger protein
family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/EGR1ID496ch5q31.html";
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EMBL; X52541; CAA36777.1; -; mRNA.
EMBL; M62829; AAA35815.1; -; mRNA.
EMBL; M80583; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; BC073983; AAH73983.1; -; mRNA.
CCDS; CCDS4206.1; -.
PIR; A41211; A41211.
RefSeq; NP_001955.1; NM_001964.2.
UniGene; Hs.326035; -.
UniGene; Hs.708393; -.
PDB; 4R2A; X-ray; 1.59 A; A=335-423.
PDB; 4R2C; X-ray; 1.89 A; A=335-423.
PDB; 4R2D; X-ray; 2.09 A; A=335-423.
PDB; 4X9J; X-ray; 1.41 A; A=335-423.
PDB; 5N14; NMR; -; A=395-408.
PDBsum; 4R2A; -.
PDBsum; 4R2C; -.
PDBsum; 4R2D; -.
PDBsum; 4X9J; -.
PDBsum; 5N14; -.
ProteinModelPortal; P18146; -.
SMR; P18146; -.
BioGrid; 108278; 39.
CORUM; P18146; -.
IntAct; P18146; 23.
MINT; MINT-234136; -.
STRING; 9606.ENSP00000239938; -.
ChEMBL; CHEMBL3616355; -.
iPTMnet; P18146; -.
PhosphoSitePlus; P18146; -.
BioMuta; EGR1; -.
DMDM; 119242; -.
EPD; P18146; -.
PaxDb; P18146; -.
PeptideAtlas; P18146; -.
PRIDE; P18146; -.
DNASU; 1958; -.
Ensembl; ENST00000239938; ENSP00000239938; ENSG00000120738.
GeneID; 1958; -.
KEGG; hsa:1958; -.
CTD; 1958; -.
DisGeNET; 1958; -.
EuPathDB; HostDB:ENSG00000120738.7; -.
GeneCards; EGR1; -.
HGNC; HGNC:3238; EGR1.
HPA; CAB019427; -.
HPA; HPA029937; -.
HPA; HPA029938; -.
MIM; 128990; gene.
neXtProt; NX_P18146; -.
OpenTargets; ENSG00000120738; -.
PharmGKB; PA27673; -.
eggNOG; KOG1721; Eukaryota.
eggNOG; COG5048; LUCA.
GeneTree; ENSGT00550000074455; -.
HOGENOM; HOG000036856; -.
HOVERGEN; HBG003909; -.
InParanoid; P18146; -.
KO; K09203; -.
OMA; FATQTGS; -.
OrthoDB; EOG091G06VX; -.
PhylomeDB; P18146; -.
TreeFam; TF318980; -.
Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
Reactome; R-HSA-909733; Interferon alpha/beta signaling.
SignaLink; P18146; -.
SIGNOR; P18146; -.
ChiTaRS; EGR1; human.
GeneWiki; EGR1; -.
GenomeRNAi; 1958; -.
PRO; PR:P18146; -.
Proteomes; UP000005640; Chromosome 5.
Bgee; ENSG00000120738; -.
CleanEx; HS_EGR1; -.
CleanEx; HS_ZNF225; -.
ExpressionAtlas; P18146; baseline and differential.
Genevisible; P18146; HS.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
GO; GO:0010385; F:double-stranded methylated DNA binding; IDA:UniProtKB.
GO; GO:0044729; F:hemi-methylated DNA-binding; IDA:UniProtKB.
GO; GO:0035035; F:histone acetyltransferase binding; IPI:BHF-UCL.
GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl.
GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
GO; GO:0071504; P:cellular response to heparin; ISS:UniProtKB.
GO; GO:0098759; P:cellular response to interleukin-8; IDA:UniProtKB.
GO; GO:0071506; P:cellular response to mycophenolic acid; ISS:UniProtKB.
GO; GO:0044849; P:estrous cycle; ISS:UniProtKB.
GO; GO:0072110; P:glomerular mesangial cell proliferation; ISS:UniProtKB.
GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:BHF-UCL.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0045080; P:positive regulation of chemokine biosynthetic process; ISS:UniProtKB.
GO; GO:0072303; P:positive regulation of glomerular metanephric mesangial cell proliferation; ISS:UniProtKB.
GO; GO:0046886; P:positive regulation of hormone biosynthetic process; ISS:UniProtKB.
GO; GO:0050725; P:positive regulation of interleukin-1 beta biosynthetic process; ISS:UniProtKB.
GO; GO:1901216; P:positive regulation of neuron death; ISS:ARUK-UCL.
GO; GO:1902949; P:positive regulation of tau-protein kinase activity; ISS:ARUK-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0042981; P:regulation of apoptotic process; IEA:Ensembl.
GO; GO:2000182; P:regulation of progesterone biosynthetic process; ISS:UniProtKB.
GO; GO:0033233; P:regulation of protein sumoylation; IDA:BHF-UCL.
GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; IEA:Ensembl.
GO; GO:0009749; P:response to glucose; IEA:Ensembl.
GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
GO; GO:0032868; P:response to insulin; IEA:Ensembl.
GO; GO:0002931; P:response to ischemia; ISS:UniProtKB.
GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
GO; GO:0030217; P:T cell differentiation; IEA:Ensembl.
GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0060337; P:type I interferon signaling pathway; TAS:Reactome.
Gene3D; 3.30.40.10; -; 1.
InterPro; IPR021849; EGR.
InterPro; IPR021839; EGR1_C.
InterPro; IPR036236; Znf_C2H2_sf.
InterPro; IPR013087; Znf_C2H2_type.
InterPro; IPR013083; Znf_RING/FYVE/PHD.
Pfam; PF11914; DUF3432; 2.
Pfam; PF11928; DUF3446; 1.
SMART; SM00355; ZnF_C2H2; 3.
SUPFAM; SSF57667; SSF57667; 2.
PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
1: Evidence at protein level;
3D-structure; Activator; Complete proteome; Cytoplasm; DNA-binding;
Isopeptide bond; Metal-binding; Nucleus; Polymorphism;
Reference proteome; Repeat; Transcription; Transcription regulation;
Ubl conjugation; Zinc; Zinc-finger.
CHAIN 1 543 Early growth response protein 1.
/FTId=PRO_0000047109.
ZN_FING 338 362 C2H2-type 1. {ECO:0000244|PDB:4R2A,
ECO:0000244|PDB:4R2C,
ECO:0000244|PDB:4R2D,
ECO:0000244|PDB:4X9J,
ECO:0000255|PROSITE-ProRule:PRU00042,
ECO:0000269|PubMed:25258363,
ECO:0000269|PubMed:25999311}.
ZN_FING 368 390 C2H2-type 2. {ECO:0000244|PDB:4R2A,
ECO:0000244|PDB:4R2C,
ECO:0000244|PDB:4R2D,
ECO:0000244|PDB:4X9J,
ECO:0000255|PROSITE-ProRule:PRU00042,
ECO:0000269|PubMed:25258363,
ECO:0000269|PubMed:25999311}.
ZN_FING 396 418 C2H2-type 3. {ECO:0000244|PDB:4R2A,
ECO:0000244|PDB:4R2C,
ECO:0000244|PDB:4R2D,
ECO:0000244|PDB:4X9J,
ECO:0000255|PROSITE-ProRule:PRU00042,
ECO:0000269|PubMed:25258363,
ECO:0000269|PubMed:25999311}.
COMPBIAS 57 84 Gly/Ser-rich.
SITE 336 336 Interaction with DNA.
{ECO:0000244|PDB:4R2A,
ECO:0000269|PubMed:25258363}.
SITE 347 347 Interaction with DNA.
{ECO:0000250|UniProtKB:P08046}.
SITE 351 351 Interaction with DNA.
{ECO:0000250|UniProtKB:P08046}.
SITE 357 357 Interaction with DNA.
{ECO:0000244|PDB:4R2A,
ECO:0000269|PubMed:25258363}.
SITE 375 375 Interaction with DNA.
{ECO:0000250|UniProtKB:P08046}.
SITE 379 379 Interaction with DNA.
{ECO:0000244|PDB:4R2A,
ECO:0000269|PubMed:25258363}.
SITE 403 403 Interaction with DNA.
{ECO:0000244|PDB:4X9J,
ECO:0000269|PubMed:25999311}.
SITE 407 407 Interaction with DNA.
{ECO:0000244|PDB:4R2A,
ECO:0000269|PubMed:25258363}.
SITE 413 413 Interaction with DNA.
{ECO:0000244|PDB:4R2A,
ECO:0000244|PDB:4X9J,
ECO:0000269|PubMed:25258363,
ECO:0000269|PubMed:25999311}.
CROSSLNK 305 305 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000244|PubMed:28112733}.
VARIANT 28 28 T -> I (in dbSNP:rs13181973).
/FTId=VAR_052712.
VARIANT 144 144 N -> K (in dbSNP:rs28365166).
/FTId=VAR_029330.
VARIANT 145 145 S -> R (in dbSNP:rs28365164).
/FTId=VAR_029331.
VARIANT 219 219 E -> D (in dbSNP:rs28365165).
/FTId=VAR_029332.
STRAND 348 351 {ECO:0000244|PDB:4X9J}.
HELIX 352 363 {ECO:0000244|PDB:4X9J}.
TURN 371 373 {ECO:0000244|PDB:4X9J}.
STRAND 376 378 {ECO:0000244|PDB:4X9J}.
HELIX 380 391 {ECO:0000244|PDB:4X9J}.
TURN 399 401 {ECO:0000244|PDB:4X9J}.
STRAND 404 407 {ECO:0000244|PDB:4X9J}.
HELIX 408 415 {ECO:0000244|PDB:4X9J}.
HELIX 416 418 {ECO:0000244|PDB:4X9J}.
SEQUENCE 543 AA; 57507 MW; 768CE670D9743E4E CRC64;
MAAAKAEMQL MSPLQISDPF GSFPHSPTMD NYPKLEEMML LSNGAPQFLG AAGAPEGSGS
NSSSSSSGGG GGGGGGSNSS SSSSTFNPQA DTGEQPYEHL TAESFPDISL NNEKVLVETS
YPSQTTRLPP ITYTGRFSLE PAPNSGNTLW PEPLFSLVSG LVSMTNPPAS SSSAPSPAAS
SASASQSPPL SCAVPSNDSS PIYSAAPTFP TPNTDIFPEP QSQAFPGSAG TALQYPPPAY
PAAKGGFQVP MIPDYLFPQQ QGDLGLGTPD QKPFQGLESR TQQPSLTPLS TIKAFATQSG
SQDLKALNTS YQSQLIKPSR MRKYPNRPSK TPPHERPYAC PVESCDRRFS RSDELTRHIR
IHTGQKPFQC RICMRNFSRS DHLTTHIRTH TGEKPFACDI CGRKFARSDE RKRHTKIHLR
QKDKKADKSV VASSATSSLS SYPSPVATSY PSPVTTSYPS PATTSYPSPV PTSFSSPGSS
TYPSPVHSGF PSPSVATTYS SVPPAFPAQV SSFPSSAVTN SFSASTGLSD MTATFSPRTI
EIC


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EIAAB46856 c-Krox,Krueppel-related zinc finger protein cKrox,Mouse,Mus musculus,T-helper-inducing POZ_Krueppel-like factor,Thpok,Zbtb7b,Zfp67,Zfp-67,Zinc finger and BTB domain-containing protein 7B,Zinc finger p
EIAAB12625 AT591,Early growth response protein 2,EGR2,EGR-2,Homo sapiens,Human,KROX20,Zinc finger protein Krox-20
EIAAB29957 BTB_POZ domain zinc finger transcription factor,Homo sapiens,Human,PATZ,PATZ1,POZ-, AT hook-, and zinc finger-containing protein 1,Protein kinase A RI subunit alpha-associated protein,RIAZ,ZBTB19,Zinc
EIAAB47352 CT-ZFP48,EBV-induced zinc finger protein,Epstein-Barr virus-induced zinc finger protein,Homo sapiens,Human,Zinc finger protein 271,Zinc finger protein dp,Zinc finger protein HZF7,Zinc finger protein Z
EIAAB47360 GC-box-binding zinc finger protein 1,GZP1,Homo sapiens,Human,Transcription factor ZBP-99,ZBP99,Zinc finger DNA-binding protein 99,Zinc finger protein 281,ZNF281
EIAAB47890 Krox25,Krox26,Mouse,Mus musculus,Zfp422,Zinc finger protein 22,Zinc finger protein 422,Zinc finger protein Krox-25,Zinc finger protein Krox-26,Znf22
EIAAB47067 Alpha-fetoprotein enhancer-binding protein,AT motif-binding factor,ATBF1,AT-binding transcription factor 1,Homo sapiens,Human,ZFH-3,ZFHX3,Zinc finger homeobox protein 3,Zinc finger homeodomain protein


 

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