Target Information

Target General Information

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Target ID

T33425 (Former ID: TTDI01986)

Target Name

Epidermal growth factor (EGF)

Synonyms

Proepidermal growth factor; Pro-epidermal growth factor

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Gene Name

EGF

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Unspecific body region injury [ICD-11: ND56]

Function

Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. Can induce neurite outgrowth in motoneurons of the pond snail Lymnaea stagnalis in vitro. EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.

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BioChemical Class

Growth factor

UniProt ID

EGF_HUMAN

Sequence

MLLTLIILLPVVSKFSFVSLSAPQHWSCPEGTLAGNGNSTCVGPAPFLIFSHGNSIFRID
TEGTNYEQLVVDAGVSVIMDFHYNEKRIYWVDLERQLLQRVFLNGSRQERVCNIEKNVSG
MAINWINEEVIWSNQQEGIITVTDMKGNNSHILLSALKYPANVAVDPVERFIFWSSEVAG
SLYRADLDGVGVKALLETSEKITAVSLDVLDKRLFWIQYNREGSNSLICSCDYDGGSVHI
SKHPTQHNLFAMSLFGDRIFYSTWKMKTIWIANKHTGKDMVRINLHSSFVPLGELKVVHP
LAQPKAEDDTWEPEQKLCKLRKGNCSSTVCGQDLQSHLCMCAEGYALSRDRKYCEDVNEC
AFWNHGCTLGCKNTPGSYYCTCPVGFVLLPDGKRCHQLVSCPRNVSECSHDCVLTSEGPL
CFCPEGSVLERDGKTCSGCSSPDNGGCSQLCVPLSPVSWECDCFPGYDLQLDEKSCAASG
PQPFLLFANSQDIRHMHFDGTDYGTLLSQQMGMVYALDHDPVENKIYFAHTALKWIERAN
MDGSQRERLIEEGVDVPEGLAVDWIGRRFYWTDRGKSLIGRSDLNGKRSKIITKENISQP
RGIAVHPMAKRLFWTDTGINPRIESSSLQGLGRLVIASSDLIWPSGITIDFLTDKLYWCD
AKQSVIEMANLDGSKRRRLTQNDVGHPFAVAVFEDYVWFSDWAMPSVMRVNKRTGKDRVR
LQGSMLKPSSLVVVHPLAKPGADPCLYQNGGCEHICKKRLGTAWCSCREGFMKASDGKTC
LALDGHQLLAGGEVDLKNQVTPLDILSKTRVSEDNITESQHMLVAEIMVSDQDDCAPVGC
SMYARCISEGEDATCQCLKGFAGDGKLCSDIDECEMGVPVCPPASSKCINTEGGYVCRCS
EGYQGDGIHCLDIDECQLGEHSCGENASCTNTEGGYTCMCAGRLSEPGLICPDSTPPPHL
REDDHHYSVRNSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWW
ELRHAGHGQQQKVIVVAVCVVVLVMLLLLSLWGAHYYRTQKLLSKNPKNPYEESSRDVRS
RRPADTEDGMSSCPQPWFVVIKEHQDLKNGGQPVAGEDGQAADGSMQPTSWRQEPQLCGM
GTEQGCWIPVSSDKGSCPQVMERSFHMPSYGTQTLEGGVEKPHSLLSANPLWQQRALDPP
HQMELTQ

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3D Structure

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AlphaFold

HIT2.0 ID

T52CKD

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

Epidermal growth factor

Drug Info

Approved

Vulnerary

[2]

Mode of Action

[+] 1 Modes of Action

Modulator

[+] 2 Modulator drugs

Epidermal growth factor

Drug Info

[1]

Hebervis

Drug Info

[3]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Stabilin-2 (STAB2)	PF12947 ; PF02469 ; PF00193 More >>	27.551 (54/196)	9.18E-12
Stabilin-1 (STAB1)	PF12947 ; PF02469 ; PF00193 More >>	33.077 (43/130)	1.16E-08
Epiregulin (EREG)		26.724 (31/116)	3.54E-08
Transforming growth factor alpha (TGFA)		32.990 (32/97)	2.73E-07
Epigen (EPGN)		29.787 (28/94)	2.35E-05
Pro-neuregulin-2, membrane-bound isoform (NRG2)	PF07679 ; PF02158	30.120 (25/83)	8.14E-05
Probetacellulin (BTC)		27.451 (28/102)	9.02E-05
Thrombospondin-1 (THBS1)	PF00090 ; PF02412 ; PF05735 ; PF00093 More >>	27.044 (43/159)	4.94E-04
Proto-oncogene c-Ros (ROS1)	PF00041 ; PF07714	25.258 (49/194)	5.00E-03
Tomoregulin-1 (TMEFF1)	PF07648	22.609 (26/115)	5.00E-03
Click to Show/Hide the Information of Human Similarity Proteins


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
MAPK signaling pathway	hsa04010	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
ErbB signaling pathway	hsa04012	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Ras signaling pathway	hsa04014	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Rap1 signaling pathway	hsa04015	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
HIF-1 signaling pathway	hsa04066	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
FoxO signaling pathway	hsa04068	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Phospholipase D signaling pathway	hsa04072	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
PI3K-Akt signaling pathway	hsa04151	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Focal adhesion	hsa04510	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Gap junction	hsa04540	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Regulation of actin cytoskeleton	hsa04810	Affiliated Target
Class: Cellular Processes => Cell motility	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	48	Degree centrality	5.16E-03	Betweenness centrality	5.18E-03
Closeness centrality	2.67E-01	Radiality	1.46E+01	Clustering coefficient	2.06E-01
Neighborhood connectivity	5.68E+01	Topological coefficient	4.87E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target-interacting Proteins

Target-interacting Proteins Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 22 KEGG Pathways	+
1	MAPK signaling pathway
2	ErbB signaling pathway
3	Ras signaling pathway
4	Rap1 signaling pathway
5	Cytokine-cytokine receptor interaction
6	HIF-1 signaling pathway
7	FoxO signaling pathway
8	Endocytosis
9	PI3K-Akt signaling pathway
10	Focal adhesion
11	Gap junction
12	Regulation of actin cytoskeleton
13	Hepatitis C
14	Pathways in cancer
15	Pancreatic cancer
16	Endometrial cancer
17	Glioma
18	Prostate cancer
19	Melanoma
20	Bladder cancer
21	Non-small cell lung cancer
22	Choline metabolism in cancer
Panther Pathway	[+] 1 Panther Pathways	+
1	EGF receptor signaling pathway
PID Pathway	[+] 15 PID Pathways	+
1	Signaling events mediated by PTP1B
2	Arf6 signaling events
3	Signaling events mediated by TCPTP
4	Thromboxane A2 receptor signaling
5	SHP2 signaling
6	Regulation of Telomerase
7	EGF receptor (ErbB1) signaling pathway
8	EGFR-dependent Endothelin signaling events
9	Posttranslational regulation of adherens junction stability and dissassembly
10	Ceramide signaling pathway
11	ErbB1 downstream signaling
12	ErbB receptor signaling network
13	Internalization of ErbB1
14	Stabilization and expansion of the E-cadherin adherens junction
15	a6b1 and a6b4 Integrin signaling
Reactome	[+] 14 Reactome Pathways	+
1	Platelet degranulation
2	Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
3	SHC1 events in ERBB2 signaling
4	PLCG1 events in ERBB2 signaling
5	PIP3 activates AKT signaling
6	GRB2 events in EGFR signaling
7	GAB1 signalosome
8	SHC1 events in EGFR signaling
9	EGFR downregulation
10	GRB2 events in ERBB2 signaling
11	PI3K events in ERBB2 signaling
12	Constitutive Signaling by Aberrant PI3K in Cancer
13	Constitutive Signaling by EGFRvIII
14	RAF/MAP kinase cascade
WikiPathways	[+] 19 WikiPathways	+
1	ErbB Signaling Pathway
2	TGF Beta Signaling Pathway
3	Regulation of Actin Cytoskeleton
4	EGF/EGFR Signaling Pathway
5	MAPK Signaling Pathway
6	Focal Adhesion
7	Hematopoietic Stem Cell Differentiation
8	Differentiation Pathway
9	Bladder Cancer
10	Hair Follicle Development: Induction (Part 1 of 3)
11	Cardiac Hypertrophic Response
12	Signaling by ERBB4
13	Signaling by ERBB2
14	PIP3 activates AKT signaling
15	JAK/STAT
16	Polycystic Kidney Disease Pathway
17	Integrated Pancreatic Cancer Pathway
18	Signaling by EGFR
19	MicroRNAs in cardiomyocyte hypertrophy

References

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REF 1

Repurposing of the epidermal growth factor. Journal of Commercial Biotechnology (2011) 17, 45-52.

REF 2

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 3

Leadership in BioBusiness. Dr Gurinder S Shahi. Page(36).

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