Target Information

Target General Information

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Target ID

T42974 (Former ID: TTDR01221)

Target Name

AXL receptor tyrosine kinase ligand (GAS6)

Synonyms

Growth arrest-specific protein 6; GAS-6; AXLLG

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Gene Name

GAS6

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Ovarian cancer [ICD-11: 2C73]

Function

Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses.

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UniProt ID

GAS6_HUMAN

Sequence

MAPSLSPGPAALRRAPQLLLLLLAAECALAALLPAREATQFLRPRQRRAFQVFEEAKQGH
LERECVEELCSREEAREVFENDPETDYFYPRYLDCINKYGSPYTKNSGFATCVQNLPDQC
TPNPCDRKGTQACQDLMGNFFCLCKAGWGGRLCDKDVNECSQENGGCLQICHNKPGSFHC
SCHSGFELSSDGRTCQDIDECADSEACGEARCKNLPGSYSCLCDEGFAYSSQEKACRDVD
ECLQGRCEQVCVNSPGSYTCHCDGRGGLKLSQDMDTCEDILPCVPFSVAKSVKSLYLGRM
FSGTPVIRLRFKRLQPTRLVAEFDFRTFDPEGILLFAGGHQDSTWIVLALRAGRLELQLR
YNGVGRVTSSGPVINHGMWQTISVEELARNLVIKVNRDAVMKIAVAGDLFQPERGLYHLN
LTVGGIPFHEKDLVQPINPRLDGCMRSWNWLNGEDTTIQETVKVNTRMQCFSVTERGSFY
PGSGFAFYSLDYMRTPLDVGTESTWEVEVVAHIRPAADTGVLFALWAPDLRAVPLSVALV
DYHSTKKLKKQLVVLAVEHTALALMEIKVCDGQEHVVTVSLRDGEATLEVDGTRGQSEVS
AAQLQERLAVLERHLRSPVLTFAGGLPDVPVTSAPVTAFYRGCMTLEVNRRLLDLDEAAY
KHSDITAHSCPPVEPAAA

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

Batiraxcept

Drug Info

Phase 3

Ovarian cancer

[2]

AVB-500

Drug Info

Phase 2

IgA nephropathy

[3]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 2 Inhibitor drugs

Batiraxcept

Drug Info

[4]

AVB-500

Drug Info

[5]

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). 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 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).

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

Biological Network Descriptors

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Matrilin-3 (MATN3)	PF14670 ; PF10393 ; PF00092 More >>	33.333 (57/171)	4.17E-17
Endosialin (CD248)	PF14670 ; PF00059	36.170 (51/141)	1.08E-12
Sushi, nidogen and EGF-like domain-containing protein 1 (SNED1)	PF00008 ; PF00041 ; PF12661 ; PF06119 More >>	33.113 (50/151)	3.30E-11
Low-density lipoprotein receptor-related protein 8 (LRP8)	PF14670 ; PF00057 ; PF00058 More >>	41.176 (35/85)	6.10E-11
Oncoprotein-induced transcript 3 protein (OIT3)	PF14670 ; PF00100	37.805 (31/82)	1.46E-10
Delta-like protein 1 (DLL1)	PF01414 ; PF00008 ; PF12661 ; PF07657 More >>	33.721 (58/172)	5.80E-10
Delta and Notch-like epidermal growth factor-related receptor (DNER)	PF19330 ; PF00008 ; PF12661 More >>	32.692 (51/156)	1.50E-07
Stabilin-1 (STAB1)	PF12947 ; PF02469 ; PF00193 More >>	28.090 (50/178)	3.71E-07
Delta-like protein 3 (DLL3)	PF00008 ; PF12661 ; PF07657 More >>	27.717 (51/184)	1.05E-06
Stabilin-2 (STAB2)	PF12947 ; PF02469 ; PF00193 More >>	34.722 (50/144)	3.99E-06
Cartilage matrix protein (MATN1)	PF14670 ; PF10393 ; PF00092 More >>	50.000 (18/36)	4.97E-06
Protein delta homolog 2 (DLK2)	PF00008 ; PF12661	26.797 (41/153)	1.44E-05
LDL receptor related protein-6 (LRP-6)	PF14670 ; PF00057 ; PF00058 More >>	50.000 (19/38)	2.93E-05
Mannan-binding lectin serine protease 1 (MASP1)	PF00431 ; PF00084 ; PF00089 More >>	30.000 (33/110)	5.51E-05
Protein delta homolog 1 (DLK1)	PF00008	30.657 (42/137)	6.82E-05
Delta-like protein 4 (DLL4)	PF01414 ; PF00008 ; PF07657 More >>	30.579 (37/121)	2.01E-04
EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3)	PF00008 ; PF00754 ; PF12661 More >>	35.632 (31/87)	2.71E-04
Versican core protein (VCAN)	PF00008 ; PF00059 ; PF00084 ; PF07686 ; PF00193 More >>	30.488 (25/82)	2.90E-04
Astrotactin-1 (ASTN1)	PF18411 ; PF19743 ; PF19441 ; PF14670 More >>	32.530 (27/83)	6.36E-04
Complement C1r subcomponent (C1R)	PF00431 ; PF14670 ; PF00084 ; PF00089 More >>	33.333 (25/75)	1.00E-03
Low-density lipoprotein receptor-related protein 5 (LRP5)	PF14670 ; PF00057 ; PF00058 More >>	43.590 (17/39)	4.00E-03
Neurocan core protein (NCAN)	PF00008 ; PF00059 ; PF00084 ; PF07686 ; PF00193 More >>	40.000 (18/45)	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.

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	4.71E-04
Closeness centrality	1.97E-01	Radiality	1.34E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.16E+01	Topological coefficient	2.08E-01	Eccentricity	13
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Management of fetal endocrine disorders. Growth Horm IGF Res. 2003 Aug;13 Suppl A:S55-61.

REF 2

ClinicalTrials.gov (NCT04729608) A Phase 3, Randomized, Double-Blind, Placebo/Paclitaxel-Controlled Study of Batiraxcept (AVB-S6-500) in Combination With Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer (AXLerate-OC). U.S.National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT04042623) Study of Safety and Efficacy of AVB-S6-500 in Patients With IgA Nephropathy. U.S. National Institutes of Health.

REF 4

Target-Mediated Drug Disposition Pharmacokinetic/Pharmacodynamic Model-Informed Dose Selection for the First-in-Human Study of AVB-S6-500. Clin Transl Sci. 2020 Jan;13(1):204-211.

REF 5

Clinical pipeline report, company report or official report of Aravive.

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