Target Information

Target General Information

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Target ID

T02532 (Former ID: TTDS00368)

Target Name

T-cell surface antigen CD2 (CD2)

Synonyms

T-cell surface antigen T11/Leu-5; SRBC; Rosette receptor; LFA-3 receptor; LFA-2; Erythrocyte receptor

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Gene Name

CD2

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Lymphoma [ICD-11: 2A80-2A86]

Function

CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function. CD2 interacts with lymphocyte function-associated antigen CD58 (LFA-3) and CD48/BCM1 to mediate adhesion between T-cells and other cell types.

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UniProt ID

CD2_HUMAN

Sequence

MSFPCKFVASFLLIFNVSSKGAVSKEITNALETWGALGQDINLDIPSFQMSDDIDDIKWE
KTSDKKKIAQFRKEKETFKEKDTYKLFKNGTLKIKHLKTDDQDIYKVSIYDTKGKNVLEK
IFDLKIQERVSKPKISWTCINTTLTCEVMNGTDPELNLYQDGKHLKLSQRVITHKWTTSL
SAKFKCTAGNKVSKESSVEPVSCPEKGLDIYLIIGICGGGSLLMVFVALLVFYITKRKKQ
RSRRNDEELETRAHRVATEERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSHRPPPP
GHRVQHQPQKRPPAPSGTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

Siplizumab

Drug Info

Phase 2

Lymphoma

[2]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 6 Inhibitor drugs

Alpha-D-Mannose

Drug Info

[3]

Cyclo(1,10)EIYDPGDDIK

Drug Info

[4]

Cyclo(1,10)H-EIYDPGDDIK-OH

Drug Info

[4]

Cyclo(1,11)H-ESIYDPGDDIK-OH

Drug Info

[4]

Cyclo(1,12)PenIYDTKGKNVLC-OH

Drug Info

[5]

Pen(Acm)AQFRKEKETFC(Acm)-OH

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). 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	Percentage of Identity (%)	E value
T-lymphocyte surface antigen Ly-9 (LY9)	25.000 (60/240)	5.05E-06
SLAM family member 5 (CD84)	26.012 (45/173)	1.00E-03
SLAM family member 7 SLAMF7 (CS1)	29.600 (37/125)	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
Cell adhesion molecules	hsa04514	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Hematopoietic cell lineage	hsa04640	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	15	Degree centrality	1.61E-03	Betweenness centrality	9.00E-04
Closeness centrality	2.12E-01	Radiality	1.37E+01	Clustering coefficient	1.33E-01
Neighborhood connectivity	1.53E+01	Topological coefficient	1.13E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Target Regulators

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Target-interacting Proteins

Target-interacting Proteins Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 2 KEGG Pathways

Cell adhesion molecules (CAMs)

Hematopoietic cell lineage

NetPath Pathway

[+] 2 NetPath Pathways

TCR Signaling Pathway

IL2 Signaling Pathway

Reactome

[+] 1 Reactome Pathways

Cell surface interactions at the vascular wall

WikiPathways

[+] 1 WikiPathways

Cell surface interactions at the vascular wall

References

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REF 1

Emerging drugs for moderate-to-severe psoriasis. Expert Opin Emerg Drugs. 2005 Feb;10(1):35-52.

REF 2

Safety profile of intravenous and subcutaneous siplizumab, an anti-CD2 monoclonal antibody, for the treatment of plaque psoriasis: results of two randomized, double-blind, placebo-controlled studies.Int J Dermatol. 2010 Jul;49(7):818-28.

REF 3

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 4

Design of beta-hairpin peptides for modulation of cell adhesion by beta-turn constraint. J Med Chem. 2009 Feb 12;52(3):726-36.

REF 5

Structure-activity studies of peptides from the "hot-spot" region of human CD2 protein: development of peptides for immunomodulation. J Med Chem. 2005 Oct 6;48(20):6236-49.

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