Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T90628
|
|||||
Target Name |
Rab proteins geranylgeranyltransferase component A 1 (CHM)
|
|||||
Synonyms |
Choroideremia protein; Rab escort protein 1; REP-1; TCD protein
Click to Show/Hide
|
|||||
Gene Name |
CHM
|
|||||
Target Type |
Clinical trial target
|
[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Choroidal dystrophy ICD-11: 9B61 | |||||
Function |
Substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B composed of RABGGTA and RABGGTB, and remains bound to it after the geranylgeranyl transfer reaction. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane. Besides, a pre-formed complex consisting of CHM and the Rab GGTase dimer (RGGT or component B) can bind to and prenylate Rab proteins; this alternative pathway is proposed to be the predominant pathway for Rab protein geranylgeranylation.
Click to Show/Hide
|
|||||
UniProt ID | ||||||
Sequence |
MADTLPSEFDVIVIGTGLPESIIAAACSRSGRRVLHVDSRSYYGGNWASFSFSGLLSWLK
EYQENSDIVSDSPVWQDQILENEEAIALSRKDKTIQHVEVFCYASQDLHEDVEEAGALQK NHALVTSANSTEAADSAFLPTEDESLSTMSCEMLTEQTPSSDPENALEVNGAEVTGEKEN HCDDKTCVPSTSAEDMSENVPIAEDTTEQPKKNRITYSQIIKEGRRFNIDLVSKLLYSRG LLIDLLIKSNVSRYAEFKNITRILAFREGRVEQVPCSRADVFNSKQLTMVEKRMLMKFLT FCMEYEKYPDEYKGYEEITFYEYLKTQKLTPNLQYIVMHSIAMTSETASSTIDGLKATKN FLHCLGRYGNTPFLFPLYGQGELPQCFCRMCAVFGGIYCLRHSVQCLVVDKESRKCKAII DQFGQRIISEHFLVEDSYFPENMCSRVQYRQISRAVLITDRSVLKTDSDQQISILTVPAE EPGTFAVRVIELCSSTMTCMKGTYLVHLTCTSSKTAREDLESVVQKLFVPYTEMEIENEQ VEKPRILWALYFNMRDSSDISRSCYNDLPSNVYVCSGPDCGLGNDNAVKQAETLFQEICP NEDFCPPPPNPEDIILDGDSLQPEASESSAIPEANSETFKESTNLGNLEESSE Click to Show/Hide
|
|||||
3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | BIIB111 | Drug Info | Phase 3 | Choroideremia | [2] | |
2 | SPK-7001 | Drug Info | Phase 1/2 | Choroidal dystrophy | [1] | |
3 | 4D-110 | Drug Info | Phase 1 | Choroideremia | [3] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Replacement | [+] 1 Replacement drugs | + | ||||
1 | SPK-7001 | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
---|---|---|---|---|---|---|
Cell-based Target Expression Variations |
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
|
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.
|
Degree | 5 | Degree centrality | 5.37E-04 | Betweenness centrality | 8.55E-05 |
---|---|---|---|---|---|
Closeness centrality | 1.76E-01 | Radiality | 1.29E+01 | Clustering coefficient | 2.00E-01 |
Neighborhood connectivity | 1.18E+01 | Topological coefficient | 2.58E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
References | Top | |||||
---|---|---|---|---|---|---|
REF 1 | Clinical pipeline report, company report or official report of Spark Therapeutics. | |||||
REF 2 | ClinicalTrials.gov (NCT03496012) A Randomised, Open Label, Outcomes-Assessor Masked, Prospective, Parallel Controlled Group, Phase 3 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1). U.S.National Institutes of Health. | |||||
REF 3 | ClinicalTrials.gov (NCT04483440) Phase 1 Open-Label, Dose-Escalation Study of the Safety, Tolerability and Preliminary Efficacy of Intravitreal 4D-110 in Patients With Choroideremia. U.S.National Institutes of Health. | |||||
REF 4 | Clinical pipeline report, company report or official report of 4D Molecular Therapeutics |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.