Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T58924
(Former ID: TTDI03561)
|
|||||
| Target Name |
SRSF protein kinase 2 (SRPK2)
|
|||||
| Synonyms |
Serine/arginine-rich protein-specific kinase 2; SR-protein-specific kinase 2; SFRS protein kinase 2
Click to Show/Hide
|
|||||
| Gene Name |
SRPK2
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression. This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression. Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation. Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28. Can mediate hepatitis B virus (HBV) core protein phosphorylation. Plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing.
Click to Show/Hide
|
|||||
| BioChemical Class |
Kinase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
|
|||||
| Sequence |
MSVNSEKSSSSERPEPQQKAPLVPPPPPPPPPPPPPLPDPTPPEPEEEILGSDDEEQEDP
ADYCKGGYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTE TALDEIKLLKCVRESDPSDPNKDMVVQLIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKS NYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRMAAEATEWQ KAGAPPPSGSAVSTAPQQKPIGKISKNKKKKLKKKQKRQAELLEKRLQEIEELEREAERK IIEENITSAAPSNDQDGEYCPEVKLKTTGLEEAAEAETAKDNGEAEDQEEKEDAEKENIE KDEDDVDQELANIDPTWIESPKTNGHIENGPFSLEQQLDDEDDDEEDCPNPEEYNLDEPN AESDYTYSSSYEQFNGELPNGRHKIPESQFPEFSTSLFSGSLEPVACGSVLSEGSPLTEQ EESSPSHDRSRTVSASSTGDLPKAKTRAADLLVNPLDPRNADKIRVKIADLGNACWVHKH FTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGEDYSRDEDHIA HIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFT DFLIPMLEMVPEKRASAGECLRHPWLNS Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: L-751250 | Ligand Info | |||||
| Structure Description | Structure of human serine-arginine-rich protein-specific kinase 2 (SRPK2) bound to purvalanol B | PDB:2X7G | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [2] |
| PDB Sequence |
PVKIGDLFNG
90 RYHVIRKLGW100 GHFSTVWLCW110 DMQGKRFVAM120 KVVKSAQHYT130 ETALDEIKLL 140 KCVRESDPSD150 PNKDMVVQLI160 DDFKISGMNG170 IHVCMVFEVL180 GHHLLKWIIK 190 SNYQGLPVRC200 VKSIIRQVLQ210 GLDYLHSKCK220 IIHTDIKPEN230 ILMCVDDAYV 240 RRMAAELLVN525 PLDPRNADKI535 RVKIADLGNA545 CWVHKHFTED555 IQTRQYRSIE 565 VLIGAGYSTP575 ADIWSTACMA585 FELATGDYLF595 EPHSGEDYSR605 DEDHIAHIIE 615 LLGSIPRHFA625 LSGKYSREFF635 NRRGELRHIT645 KLKPWSLFDV655 LVEKYGWPHE 665 DAAQFTDFLI675 PMLEMVPEKR685 ASAGECLRHP695 WLNS
|
|||||
|
|
||||||
| Ligand Name: 5-Methyl-~{n}-[2-(4-Methylpiperazin-1-Yl)-5-(Trifluoromethyl)phenyl]furan-2-Carboxamide | Ligand Info | |||||
| Structure Description | Crystal structure of SRPK2 in complex with compound 1 | PDB:5MYV | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [3] |
| PDB Sequence |
YHPVKIGDLF
88 NGRYHVIRKL98 GWGHFSTVWL108 CWDMQGKRFV118 AMKVVKSAQH128 YTETALDEIK 138 LLKCVRESDP148 SDPNKDMVVQ158 LIDDFKISGM168 NGIHVCMVFE178 VLGHHLLKWI 188 IKSNYQGLPV198 RCVKSIIRQV208 LQGLDYLHSK218 CKIIHTDIKP228 ENILMCVDDA 238 YVRRMAAEAT248 EWQKLLVNPL527 DPRNADKIRV537 KIADLGNACW547 VHKHFTEDIQ 557 TRQYRSIEVL567 IGAGYSTPAD577 IWSTACMAFE587 LATGDYLFEP597 HSGEDYSRDE 607 DHIAHIIELL617 GSIPRHFALS627 GKYSREFFNR637 RGELRHITKL647 KPWSLFDVLV 657 EKYGWPHEDA667 AQFTDFLIPM677 LEMVPEKRAS687 AGECLRHPWL697 NS |
|||||
|
|
||||||
| 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 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
|
|
|
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 | 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 | 5.00E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3. J Med Chem. 2013 Oct 24;56(20):8032-48. | |||||
| REF 2 | Structure of Human Serine-Arginine-Rich Protein- Specific Kinase 2 (Srpk2) Bound to Purvalanol B | |||||
| REF 3 | Development of Potent, Selective SRPK1 Inhibitors as Potential Topical Therapeutics for Neovascular Eye Disease. ACS Chem Biol. 2017 Mar 17;12(3):825-832. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.