Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T60433
(Former ID: TTDS00472)
|
|||||
| Target Name |
T-cell surface glycoprotein CD1a (CD1A)
|
|||||
| Synonyms |
hTa1 thymocyteantigen; hTa1 thymocyte antigen; T-cell surfaceantigen T6/Leu-6; T-cell surface antigen T6/Leu-6; CD1a
Click to Show/Hide
|
|||||
| Gene Name |
CD1A
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Aplastic anaemia [ICD-11: 3A70] | |||||
| Function |
Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.
Click to Show/Hide
|
|||||
| BioChemical Class |
Immunoglobulin
|
|||||
| UniProt ID | ||||||
| Sequence |
MLFLLLPLLAVLPGDGNADGLKEPLSFHVTWIASFYNHSWKQNLVSGWLSDLQTHTWDSN
SSTIVFLCPWSRGNFSNEEWKELETLFRIRTIRSFEGIRRYAHELQFEYPFEIQVTGGCE LHSGKVSGSFLQLAYQGSDFVSFQNNSWLPYPVAGNMAKHFCKVLNQNQHENDITHNLLS DTCPRFILGLLDAGKAHLQRQVKPEAWLSHGPSPGPGHLQLVCHVSGFYPKPVWVMWMRG EQEQQGTQRGDILPSADGTWYLRATLEVAAGEAADLSCRVKHSSLEGQDIVLYWEHHSSV GFIILAVIVPLLLLIGLALWFRKRCFC Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T87Y6K | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Antithymocyte globulin | Drug Info | Approved | Aplastic anemia | [2] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | PF-07242813 | Drug Info | Phase 1 | Atopic dermatitis | [3] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Antithymocyte globulin | Drug Info | [1] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | PF-07242813 | Drug Info | [4] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Farnesol | Ligand Info | |||||
| Structure Description | CD1a-lipid binary complex | PDB:6NUX | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [5] |
| PDB Sequence |
SFHVIWIASF
18 YNHSWKQNLV28 SGWLSDLQTH38 TWDSNSSTIV48 FLWPWSRGNF58 SNEWKELETL 69 FRIRTIRSFE79 GIRRYAHELQ89 FEYPFEIQVT99 GGCESGSFLQ115 LAYQGSDFVS 125 FQNNSWLPYP135 VAGNMAKHFC145 KVLNQNQHEN155 DITHNLLSDT165 CPRFILGLLD 175 AGKAHLQRQV185 KPEAWLSHGP195 SPGPGHLQLV205 CHVSGFYPKP215 VWVMWMRGEQ 225 EQQGTQRGDI235 LPSADGTWYL245 RATLEVAAGE255 AADLSCRVKH265 SSLEGQDIVL 275 YWEGSLVPRG285
|
|||||
|
|
||||||
| Ligand Name: Oleic acid | Ligand Info | |||||
| Structure Description | CD1a ternary complex with endogenous lipids and BK6 TCR | PDB:4X6D | ||||
| Method | X-ray diffraction | Resolution | 2.98 Å | Mutation | Yes | [6] |
| PDB Sequence |
PLSFHVIWIA
16 SFKQNLVSGW31 LSDLQTHTWD41 SNSSTIVFLW51 PWSRGNFSNE61 EWKELETLFR 71 IRTIRSFEGI81 RRYAHELQFE91 YPFEIQVTGG101 CELHSGKVSG111 SFLQLAYQGS 121 DFVSFQNNSW131 LPYPVAGNMA141 KHFCKVLNQN151 QHENDITHNL161 LSDTCPRFIL 171 GLLDAGKAHL181 QRQVKPEAWL191 SHGPSPGPGH201 LQLVCHVSGF211 YPKPVWVMWM 221 RGEQEQQGTQ231 RGDILPSADG241 TWYLRATLEV251 AAGEAADLSC261 RVKHSSLEGQ 271 DIVLYWE
|
|||||
|
|
PHE10
4.070
VAL12
3.724
TRP14
3.825
VAL28
4.493
GLY30
4.735
HIS38
3.874
TRP40
4.804
ILE47
3.915
TRP63
3.802
LEU66
4.470
PHE70
4.117
ARG73
3.591
|
|||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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 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 Pathway Affiliation
Biological Network Descriptors
|
|
| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
|---|---|---|---|
| Butyrophilin-like protein 2 (BTNL2) | 34.615 (27/78) | 4.00E-03 |
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Tight junction | hsa04530 | Affiliated Target |
|
| Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
| Hematopoietic cell lineage | hsa04640 | Affiliated Target |
|
| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.72E-01 | Radiality | 1.27E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 3.40E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Hematopoietic cell lineage | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Acute sensory neuropathy associated with rabbit antithymocyte globulin. Am J Transplant. 2007 Feb;7(2):484-6. | |||||
| REF 2 | Approval information for Divalproex Sodium (approved in 1996). 1996. | |||||
| REF 3 | ClinicalTrials.gov (NCT04668066) A PHASE 1 FIRST IN HUMAN, RANDOMIZED, DOUBLE BLIND, SPONSOR OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE DOSE ESCALATION, PARALLEL GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF PF 07242813 IN HEALTHY PARTICIPANTS AND PARTICIPANTS WITH ATOPIC DERMATITIS. U.S.National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of Pfizer | |||||
| REF 5 | Human T cell response to CD1a and contact dermatitis allergens in botanical extracts and commercial skin care products. Sci Immunol. 2020 Jan 3;5(43):eaax5430. | |||||
| REF 6 | Alphabeta T cell antigen receptor recognition of CD1a presenting self lipid ligands. Nat Immunol. 2015 Mar;16(3):258-66. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.