Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T16188
(Former ID: TTDI03613)
|
|||||
| Target Name |
Unc-51 like kinase 3 (ULK3)
|
|||||
| Synonyms |
Unc-51-like kinase 3; Serine/threonine-protein kinase ULK3
Click to Show/Hide
|
|||||
| Gene Name |
ULK3
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy.
Click to Show/Hide
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 2.7.11.1
|
|||||
| Sequence |
MAGPGWGPPRLDGFILTERLGSGTYATVYKAYAKKDTREVVAIKCVAKKSLNKASVENLL
TEIEILKGIRHPHIVQLKDFQWDSDNIYLIMEFCAGGDLSRFIHTRRILPEKVARVFMQQ LASALQFLHERNISHLDLKPQNILLSSLEKPHLKLADFGFAQHMSPWDEKHVLRGSPLYM APEMVCQRQYDARVDLWSMGVILYEALFGQPPFASRSFSELEEKIRSNRVIELPLRPLLS RDCRDLLQRLLERDPSRRISFQDFFAHPWVDLEHMPSGESLGRATALVVQAVKKDQEGDS AAALSLYCKALDFFVPALHYEVDAQRKEAIKAKVGQYVSRAEELKAIVSSSNQALLRQGT SARDLLREMARDKPRLLAALEVASAAMAKEEAAGGEQDALDLYQHSLGELLLLLAAEPPG RRRELLHTEVQNLMARAEYLKEQVKMRESRWEADTLDKEGLSESVRSSCTLQ Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Bosutinib | Ligand Info | |||||
| Structure Description | Unc-51-Like Kinase 3 (ULK3) In Complex With Bosutinib | PDB:6FDY | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [2] |
| PDB Sequence |
PRLDGFILTE
18 RLGATVYKAY32 AKKDTREVVA42 IKCVAKKSLN52 KASVENLLTE62 IEILKGIRHP 72 HIVQLKDFQW82 DSDNIYLIME92 FCAGGDLSRF102 IHTRRILPEK112 VARVFMQQLA 122 SALQFLHERN132 ISHLDLKPQN142 ILLSSLEKPH152 LKLADFGFAQ162 HMSPWDEKHV 172 LRGSPLYMAP182 EMVCQRQYDA192 RVDLWSMGVI202 LYEALFGQPP212 FASRSFSELE 222 EKIRSNRVIE232 LPLRPLLSRD242 CRDLLQRLLE252 RDPSRRISFQ262 DFFAHPWVDL 272 EH
|
|||||
|
|
LEU20
3.632
GLY21
4.466
VAL28
3.862
ALA42
3.608
ILE43
4.402
LYS44
3.918
VAL75
3.624
LEU89
4.675
MET91
3.630
GLU92
3.383
PHE93
3.716
CYS94
2.938
ALA95
3.802
GLY96
4.883
GLY97
4.151
|
|||||
| Ligand Name: Momelotinib | Ligand Info | |||||
| Structure Description | Unc-51-Like Kinase 3 (ULK3) In Complex With Momelotinib | PDB:6FDZ | ||||
| Method | X-ray diffraction | Resolution | 2.55 Å | Mutation | No | [3] |
| PDB Sequence |
PPRLDGFILT
17 ERLGSGTYAT27 VYKAYAKKDT37 REVVAIKCVA47 KKSLNKASVE57 NLLTEIEILK 67 GIRHPHIVQL77 KDFQWDSDNI87 YLIMEFCAGG97 DLSRFIHTRR107 ILPEKVARVF 117 MQQLASALQF127 LHERNISHLD137 LKPQNILLSS147 LEKPHLKLAD157 FGFAQHMSPW 167 DEKHVLRGSP177 LYMAPEMVCQ189 YDARVDLWSM199 GVILYEALFG209 QPPFASRSFS 219 ELEEKIRSNR229 VIELPLRPLL239 SRDCRDLLQR249 LLERDPSRRI259 SFQDFFAHPW 269 VDLEH
|
|||||
|
|
LEU20
3.472
GLY21
4.308
SER22
3.663
GLY23
3.437
ALA26
3.361
THR27
3.894
VAL28
3.657
ALA42
3.512
LYS44
2.712
VAL75
4.458
MET91
3.855
|
|||||
| 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 | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 1.66E-07 |
|---|---|---|---|---|---|
| Closeness centrality | 1.95E-01 | Radiality | 1.33E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.97E+01 | Topological coefficient | 6.22E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Discovery of a potent inhibitor of anaplastic lymphoma kinase with in vivo antitumor activity. ACS Med Chem Lett. 2010 Sep 1;1(9):493-8. | |||||
| REF 2 | Unc-51-Like Kinase 3 (ULK3) In Complex With Bosutinib | |||||
| REF 3 | Unc-51-Like Kinase 3 (ULK3) In Complex With Momelotinib | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.