EGR1 early growth response 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EGR1provided by HGNC
Official Full Name: early growth response 1provided by HGNC
Primary source: HGNC:HGNC:3238
See related: Ensembl:ENSG00000120738 MIM:128990
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TIS8; AT225; G0S30; NGFI-A; ZNF225; KROX-24; ZIF-268
Summary: The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentitation and mitogenesis. Studies suggest this is a cancer suppressor gene. [provided by RefSeq, Dec 2014]
Expression: Ubiquitous expression in ovary (RPKM 449.0), thyroid (RPKM 344.9) and 23 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 5q31.2

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	5	NC_000005.10 (138465479..138469303)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (137801181..137805004)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Endometrial EGR1 levels are decreased in women with recurrent implantation failure. Priming of endometrial cells for decidualization requires EGR1 function.
Title: Early growth response 1 transcriptionally primes the human endometrial stromal cell for decidualization.
miR-181b-5p contributes to glycogen synthesis by targeting EGR1, thereby regulating PTEN expression to mediate hepatic insulin resistance.
Title: Hepatic miR-181b-5p Contributes to Glycogen Synthesis Through Targeting EGR1.
EGR1-activated HNF1A-AS1 regulates various pro- and antigrowth factors to promote the development of gastric cancer
Title: EGR1-Mediated Transcription of lncRNA-HNF1A-AS1 Promotes Cell-Cycle Progression in Gastric Cancer.
ChIP-seq data showed that EGR1 (early growth response gene-1) may play an important role in the transcriptional regulation of SOCS1 (suppressor of cytokine signaling 1), SOCS3 (suppressor of cytokine signaling 3), and Fos gene family in the liver, as the low expression of EGR1 in patients with insulin resistance may promote the occurrence and development of NAFLD.
Title: Transcriptional Regulation of Early Growth Response Gene-1 (EGR1) is Associated with Progression of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients with Insulin Resistance.
This research highlights the importance of MAPK signaling in response to ER stress and identifies ELK1 as a transcriptional mediator and the EGR1 gene as a target.
Title: Induction of early growth response gene 1 (EGR1) by endoplasmic reticulum stress is mediated by the extracellular regulated kinase (ERK) arm of the MAPK pathways.
miR-181 serves an important role during renal fibrosis by targeting Egr1.
Title: MicroRNA‑181 exerts an inhibitory role during renal fibrosis by targeting early growth response factor‑1 and attenuating the expression of profibrotic markers.
This study describes the identification of a splicing isoform for the human EGR1 gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.
Title: Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform.
miR-181a-5p is a negative regulator of Egr1 that can suppress tumor proliferation in HCC through targeting Egr1/TGF-beta1/Smad pathway, which may be a potential therapeutic approach of HCC.
Title: MicroRNA-181a-5p suppresses cell proliferation by targeting Egr1 and inhibiting Egr1/TGF-β/Smad pathway in hepatocellular carcinoma.
these data demonstrated the negative effect of up-regulated GCN5 in IL-6-induced metastasis and EMT in prostate cancer (PCa) cells through PI3K/PTEN/Akt signaling pathway down-regulating Egr-1 expression.
Title: GCN5 inhibition prevents IL-6-induced prostate cancer metastases through PI3K/PTEN/Akt signaling by inactivating Egr-1.
The results reveal a novel role for ZF3 domain in the interaction of Egr-1 with other proteins and the DNA, providing insight on the regulation of other genes by Egr-1.
Title: Single-molecule DNA unzipping reveals asymmetric modulation of a transcription factor by its binding site sequence and context.

Submit: New GeneRIF Correction See all GeneRIFs (373)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	The gene expression of early growth response 1 is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells	PubMed
	tat	HIV-1 Tat-induced upregulation and phosphorylation of STAT3 expression results in increased GFAP, Egr-1, and p300 transcription and protein expression in both Tat-expressing astrocytes, and HIV-infected astrocytes	PubMed
	tat	HIV-1 Tat increases Egr-1 expression in human astrocytoma cells by transactivating the Egr-1 promoter and involving specific serum response elements within the promoter	PubMed
	tat	HIV-1 Tat decreases the levels of Egr-1 and p35 expression in nerve growth factor (NGF)-treated neural cells	PubMed
	tat	HIV-1-Tat-mediated upregulation of platelet-derived growth factor (PDGF) B chain in astrocytes is regulated by activation of ERK1/2 and JNK MAPK signaling pathways and the downstream transcription factor early growth response 1 (Egr1)	PubMed
	tat	HIV-1 Tat upregulates EGR1 expression in Tat-infected Jurkat T cells	PubMed
	tat	HIV-1 Tat-induced upregulation of p300 occurs at the transcriptional level through the cis-acting elements of early growth response 1 (egr-1) within its promoter	PubMed
	tat	HIV-1 Tat binds to Egr-1, an interaction that is mediated through Tat amino acids 30-40	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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AGE-RAGE signaling pathway in diabetic complications, organism-specific biosystem (from KEGG)
AGE-RAGE signaling pathway in diabetic complications, organism-specific biosystemAdvanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and un...
AGE-RAGE signaling pathway in diabetic complications, conserved biosystem (from KEGG)
AGE-RAGE signaling pathway in diabetic complications, conserved biosystemAdvanced glycation end products (AGEs) are a complex group of compounds produced through the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids, primarily due to aging and un...
Apelin signaling pathway, organism-specific biosystem (from KEGG)
Apelin signaling pathway, organism-specific biosystemApelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various ti...
Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystem (from WikiPathways)
Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystemBrain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, b...
Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem (from Pathway Interaction Database)
Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
Downstream signaling in naive CD8+ T cells, organism-specific biosystem (from Pathway Interaction Database)
Downstream signaling in naive CD8+ T cells, organism-specific biosystem
Downstream signaling in naive CD8+ T cells
ErbB1 downstream signaling, organism-specific biosystem (from Pathway Interaction Database)
ErbB1 downstream signaling, organism-specific biosystem
ErbB1 downstream signaling
Glucocorticoid receptor regulatory network, organism-specific biosystem (from Pathway Interaction Database)
Glucocorticoid receptor regulatory network, organism-specific biosystem
Glucocorticoid receptor regulatory network
HTLV-I infection, organism-specific biosystem (from KEGG)
HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
HTLV-I infection, conserved biosystem (from KEGG)
HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
Human Thyroid Stimulating Hormone (TSH) signaling pathway, organism-specific biosystem (from WikiPathways)
Human Thyroid Stimulating Hormone (TSH) signaling pathway, organism-specific biosystemHuman thyroid stimulating hormone (TSH) is a glycoprotein hormone secreted from the anterior pituitary lobe, which plays an important physiological role in regulation of the hypothalamus-pituitary-th...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Insulin Signaling, organism-specific biosystem (from WikiPathways)
Insulin Signaling, organism-specific biosystemInsulin signaling influences energy metabolism as well as growth. The presence of insulin signals the fed state, and this signal is passed via the AKT branch, which leads to the uptake of glucose fro...
Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
Interferon Signaling, organism-specific biosystem (from REACTOME)
Interferon Signaling, organism-specific biosystemInterferons (IFNs) are cytokines that play a central role in initiating immune responses, especially antiviral and antitumor effects. There are three types of IFNs:Type I (IFN-alpha, -beta and others...
Interferon alpha/beta signaling, organism-specific biosystem (from REACTOME)
Interferon alpha/beta signaling, organism-specific biosystemType I interferons (IFNs) are composed of various genes including IFN alpha (IFNA), beta (IFNB), omega, epsilon, and kappa. In humans the IFNA genes are composed of more than 13 subfamily genes, wher...
NRF2 pathway, organism-specific biosystem (from WikiPathways)
NRF2 pathway, organism-specific biosystemNRF2 is part of a group of transcription factors called nuclear receptors. It is activated under oxidative stress conditions and subsequently activates several antioxidative genes and proteins.
Oncostatin M Signaling Pathway, organism-specific biosystem (from WikiPathways)
Oncostatin M Signaling Pathway, organism-specific biosystemOncostatin M (OSM) is a member of the multifunctional cytokine interleukin 6 (IL6) - type cytokine family. It is mainly produced in cell types such as activated T lymphocytes, macrophages, monocytes,...
Ovarian Infertility Genes, organism-specific biosystem (from WikiPathways)
Ovarian Infertility Genes, organism-specific biosystemOvarian bottleneck genes associated with infertility. A valuable approach to the study of infertility is the comparison of mutations of individual human and mouse genes associated with infertility ph...
Preimplantation Embryo, organism-specific biosystem (from WikiPathways)
Preimplantation Embryo, organism-specific biosystemThe source of this pathway is RNA-Seq data from single-cell pre-implantation embryos (Supplemental Table 1): http://www.nature.com/nsmb/journal/v20/n9/full/nsmb.2660.html Analysis options for runnin...
Prion diseases, organism-specific biosystem (from KEGG)
Prion diseases, organism-specific biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
Prion diseases, conserved biosystem (from KEGG)
Prion diseases, conserved biosystemPrion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of ...
Regulation of Androgen receptor activity, organism-specific biosystem (from Pathway Interaction Database)
Regulation of Androgen receptor activity, organism-specific biosystem
Regulation of Androgen receptor activity
Serotonin Receptor 4/6/7 and NR3C Signaling, organism-specific biosystem (from WikiPathways)
Serotonin Receptor 4/6/7 and NR3C Signaling, organism-specific biosystemThis pathway is courtesy of Ariadne Genomics Pathway Studio.
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
Signaling events mediated by PRL, organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by PRL, organism-specific biosystem
Signaling events mediated by PRL
Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways, organism-specific biosystem (from WikiPathways)
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways, organism-specific biosystemIn this model, we provide an integrated view of Sudden Infant Death Syndrome (SIDS) at the level of implicated tissues, signaling networks and genetics. The purpose of this model is to serve as an ov...
Trk receptor signaling mediated by PI3K and PLC-gamma, organism-specific biosystem (from Pathway Interaction Database)
Trk receptor signaling mediated by PI3K and PLC-gamma, organism-specific biosystem
Trk receptor signaling mediated by PI3K and PLC-gamma
Trk receptor signaling mediated by the MAPK pathway, organism-specific biosystem (from Pathway Interaction Database)
Trk receptor signaling mediated by the MAPK pathway, organism-specific biosystem
Trk receptor signaling mediated by the MAPK pathway

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5S2415 (e-PCR)
- UniSTS:34569

PMC98754P1 (e-PCR)
- UniSTS:273678

PMC64850P3 (e-PCR)
- UniSTS:273423

SHGC-11945 (e-PCR)
- UniSTS:48525

WI-12096 (e-PCR)
- UniSTS:81337

EGR1_437 (e-PCR)
- UniSTS:277192

PMC321436P3 (e-PCR)
- UniSTS:273108

Homology

Homologs of the EGR1 gene: The EGR1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 263 organisms have orthologs with human gene EGR1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA-binding transcription activator activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
RNA polymerase II regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
double-stranded methylated DNA binding	IDA Inferred from Direct Assay more info	PubMed
hemi-methylated DNA-binding	IDA Inferred from Direct Assay more info	PubMed
histone acetyltransferase binding	IPI Inferred from Physical Interaction more info	PubMed
promoter-specific chromatin binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
BMP signaling pathway	IEA Inferred from Electronic Annotation more info
T cell differentiation	IEA Inferred from Electronic Annotation more info
cellular response to gamma radiation	IEA Inferred from Electronic Annotation more info
cellular response to heparin	ISS Inferred from Sequence or Structural Similarity more info
cellular response to interleukin-8	IDA Inferred from Direct Assay more info	PubMed
cellular response to mycophenolic acid	ISS Inferred from Sequence or Structural Similarity more info
circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
circadian temperature homeostasis	ISS Inferred from Sequence or Structural Similarity more info
estrous cycle	ISS Inferred from Sequence or Structural Similarity more info
glomerular mesangial cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
interleukin-1-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
locomotor rhythm	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
positive regulation of chemokine biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of glomerular metanephric mesangial cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of hormone biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-1 beta biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuron death	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of tau-protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
regulation of progesterone biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
regulation of protein sumoylation	IDA Inferred from Direct Assay more info	PubMed
regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of transcription from RNA polymerase II promoter in response to hypoxia	IEA Inferred from Electronic Annotation more info
response to glucose	IEA Inferred from Electronic Annotation more info
response to hypoxia	ISS Inferred from Sequence or Structural Similarity more info
response to insulin	IEA Inferred from Electronic Annotation more info
response to ischemia	ISS Inferred from Sequence or Structural Similarity more info
skeletal muscle cell differentiation	IEA Inferred from Electronic Annotation more info
transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
type I interferon signaling pathway	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
nuclear chromatin	ISA Inferred from Sequence Alignment more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: early growth response protein 1

Names: EGR-1; nerve growth factor-induced protein A; transcription factor ETR103; transcription factor Zif268; zinc finger protein 225; zinc finger protein Krox-24

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_021374.1 RefSeqGene

Range

4988..8812

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001964.3 → NP_001955.1 early growth response protein 1

See identical proteins and their annotated locations for NP_001955.1

Status: REVIEWED

Source sequence(s)

AC113403

Consensus CDS

CCDS4206.1

UniProtKB/Swiss-Prot

P18146

UniProtKB/TrEMBL

Q546S1

Related

ENSP00000239938.4, ENST00000239938.5

Conserved Domains (5) summary

sd00017
Location:340 → 362

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam11914
Location:447 → 530

DUF3432; Domain of unknown function (DUF3432)

pfam00096
Location:338 → 362

zf-C2H2; Zinc finger, C2H2 type

pfam11928
Location:135 → 209

DUF3446; Domain of unknown function (DUF3446)

pfam13465
Location:382 → 407

zf-H2C2_2; Zinc-finger double domain