Target Information

Target General Information

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Target ID

T10844 (Former ID: TTDR00311)

Target Name

Immunoglobulin gamma Fc receptor I (FCGR1)

Synonyms

IgG Fc receptor I; FcRI; Fc-gamma RI; FCGR1A; CD64 antigen; CD64

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Gene Name

FCGR1A

Target Type

Literature-reported target

[1]

Function

High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.

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BioChemical Class

Immunoglobulin

UniProt ID

FCGR1_HUMAN

Sequence

MWFLTTLLLWVPVDGQVDTTKAVITLQPPWVSVFQEETVTLHCEVLHLPGSSSTQWFLNG
TATQTSTPSYRITSASVNDSGEYRCQRGLSGRSDPIQLEIHRGWLLLQVSSRVFTEGEPL
ALRCHAWKDKLVYNVLYYRNGKAFKFFHWNSNLTILKTNISHNGTYHCSGMGKHRYTSAG
ISVTVKELFPAPVLNASVTSPLLEGNLVTLSCETKLLLQRPGLQLYFSFYMGSKTLRGRN
TSSEYQILTARREDSGLYWCEAATEDGNVLKRSPELELQVLGLQLPTPVWFHVLFYLAVG
IMFLVNTVLWVTIRKELKRKKKWDLEISLDSGHEKKVISSLQEDRHLEEELKCQEQKEEQ
LQEGVHRKEPQGAT

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3D Structure

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AlphaFold

HIT2.0 ID

T17LB4

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: 3,6,9,12,15,18-Hexaoxaicosane-1,20-diol

Ligand Info

Structure Description

Crystal structure of Fc RI and its implication to high affinity immunoglobulin G binding

PDB:3RJD

Method

X-ray diffraction

Resolution

2.65 Å

Mutation

[2]

PDB Sequence

KAVITLQPPW

³⁰

VSVFQEETVT

⁴⁰

LHCEVLHLPG

⁵⁰

SSSTQWFLNG

⁶⁰

TATQTSTPSY

⁷⁰

RITSASVNDS

⁸⁰

GEYRCQRGLS

⁹⁰

GRSDPIQLEI

¹⁰⁰

HRGWLLLQVS

¹¹⁰

SRVFTEGEPL

¹²⁰

ALRCHAWKDK

¹³⁰

LVYNVLYYRN

¹⁴⁰

GKAFKFFHWN

¹⁵⁰

SNLTILKTNI

¹⁶⁰

SHNGTYHCSG

¹⁷⁰

MGKHRYTSAG

¹⁸⁰

ISVTVKELFP

¹⁹⁰

APVLNASVTS

²⁰⁰

PLLEGNLVTL

²¹⁰

SCETKLLLQL

²²⁵

YFSFYMGSKT

²³⁵

LRGRNTSSEY

²⁴⁵

QILTARREDS

²⁵⁵

GLYWCEAATE

²⁶⁵

DGNVLKRSPE

²⁷⁵

LELQVLG

Residue

Distance (Å)

ASN59

3.593

GLY60

3.409

Residue

Distance (Å)

THR61

4.268

ARG92

2.940

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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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Titin (TTN)		24.390 (70/287)	2.72E-09
Obscurin (OBSCN)	PF00041 ; PF07679 ; PF00612 ; PF00069 ; PF00621 More >>	25.243 (52/206)	2.10E-04
Myosin light kinase (MYLK)	PF16620 ; PF00041 ; PF07679 ; PF00069 More >>	21.534 (73/339)	1.00E-03


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
Phagosome	hsa04145	Affiliated Target
Class: Cellular Processes => Transport and catabolism	Pathway Hierarchy
Osteoclast differentiation	hsa04380	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy
Neutrophil extracellular trap formation	hsa04613	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Hematopoietic cell lineage	hsa04640	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Fc gamma R-mediated phagocytosis	hsa04666	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	6	Degree centrality	6.45E-04	Betweenness centrality	3.03E-05
Closeness centrality	2.12E-01	Radiality	1.37E+01	Clustering coefficient	2.00E-01
Neighborhood connectivity	3.20E+01	Topological coefficient	2.39E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

References

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REF 1

Neutrophil Fc gamma RI as target for immunotherapy of invasive candidiasis. J Immunol. 2001 Jun 15;166(12):7019-22.

REF 2

Crystal structure of FcGamma receptor I and its implication in high affinity Gamma-immunoglobulin binding. J Biol Chem. 2011 Nov 25;286(47):40608-13.

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