Target Information

Target General Information

Target ID

T98635 (Former ID: TTDR00795)

Target Name

Angiopoietin-related protein 4 (ANGPTL4)

Synonyms

UNQ171/PRO197; PSEC0166; PP1158; PGAR; Hepatic fibrinogen/angiopoietin-related protein; HFARP; Angiopoietin-like protein PP1158; Angiopoietin-like protein 4; Angiopoietin-like 4; ARP4

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Gene Name

ANGPTL4

Target Type

Literature-reported target

[1]

Function

May also play a role in regulating glucose homeostasis and insulin sensitivity. Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. Upon heterologous expression, inhibits the adhesion of endothelial cell to the extracellular matrix (ECM), and inhibits the reorganization of the actin cytoskeleton, formation of actin stress fibers and focal adhesions in endothelial cells that have adhered to ANGPTL4-containing ECM (in vitro). Depending on context, may modulate tumor-related angiogenesis. Mediates inactivation of the lipoprotein lipase LPL, and thereby plays a role in the regulation of triglyceride clearance from the blood serum and in lipid metabolism.

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BioChemical Class

Fibrinogen protein

UniProt ID

ANGL4_HUMAN

Sequence

MSGAPTAGAALMLCAATAVLLSAQGGPVQSKSPRFASWDEMNVLAHGLLQLGQGLREHAE
RTRSQLSALERRLSACGSACQGTEGSTDLPLAPESRVDPEVLHSLQTQLKAQNSRIQQLF
HKVAQQQRHLEKQHLRIQHLQSQFGLLDHKHLDHEVAKPARRKRLPEMAQPVDPAHNVSR
LHRLPRDCQELFQVGERQSGLFEIQPQGSPPFLVNCKMTSDGGWTVIQRRHDGSVDFNRP
WEAYKAGFGDPHGEFWLGLEKVHSITGDRNSRLAVQLRDWDGNAELLQFSVHLGGEDTAY
SLQLTAPVAGQLGATTVPPSGLSVPFSTWDQDHDLRRDKNCAKSLSGGWWFGTCSHSNLN
GQYFRSIPQQRQKLKKGIFWKTWRGRYYPLQATTMLIQPMAAEAAS

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3D Structure

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AlphaFold

ADReCS ID

BADD_A00753 ; BADD_A02982

HIT2.0 ID

T11O8V

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: Myristic acid

Ligand Info

Structure Description

Human Angiopoietin-Like 4 C-Terminal Domain (cANGPTL4) with Myristic Acid

PDB:6U73

Method

X-ray diffraction

Resolution

2.38 Å

Mutation

[2]

PDB Sequence

PRDCQELFQV

¹⁹⁴

GERQSGLFEI

²⁰⁴

QPQGSPPFLV

²¹⁴

NCKMTSDGGW

²²⁴

TVIQRRHDGS

²³⁴

VDFNRPWEAY

²⁴⁴

KAGFGDPHGE

²⁵⁴

FWLGLEKVHS

²⁶⁴

ITGDRNSRLA

²⁷⁴

VQLRDWDGNA

²⁸⁴

ELLQFSVHLG

²⁹⁴

GEDTAYSLQL

³⁰⁴

TAPVAGQLGA

³¹⁴

TTVPPSGLSV

³²⁴

PFSTWDQDHD

³³⁴

LRRDKNCAKS

³⁴⁴

LSGGWWFGTC

³⁵⁴

SHSNLNGQYF

³⁶⁴

RSIPQQRQKL

³⁷⁴

KKGIFWKTWR

³⁸⁴

GRYYPLQATT

³⁹⁴

MLIQPM

Residue

Distance (Å)

LEU273

3.889

VAL275

4.453

PHE289

4.348

LEU302

4.027

LEU304

4.609

LEU312

3.833

GLY313

4.182

ALA314

3.908

LEU322

3.992

VAL324

4.408

Residue

Distance (Å)

TRP349

4.088

TRP350

3.297

GLY352

4.521

THR353

2.990

SER355

3.944

HIS356

3.682

SER357

4.101

TRP380

4.021

LYS381

2.485

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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

There is no similarity protein (E value < 0.005) for this target


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
PPAR signaling pathway	hsa03320	Affiliated Target
Class: Organismal Systems => Endocrine system	Pathway Hierarchy
Cholesterol metabolism	hsa04979	Affiliated Target
Class: Organismal Systems => Digestive system	Pathway Hierarchy

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	6.61E-05
Closeness centrality	2.11E-01	Radiality	1.37E+01	Clustering coefficient	5.00E-01
Neighborhood connectivity	2.68E+01	Topological coefficient	2.79E-01	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

References

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REF 1

Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway. PPAR Res. 2017;2017:8187235.

REF 2

Crystal Structures of Angiopoietin-Like 4s C-Terminal Domain (cANGPTL4) Reveal a Binding Site for Various Ligands

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