O01965
Gene name |
ari-1.1 (C27A12.8) |
Protein name |
E3 ubiquitin-protein ligase ari-1.1 |
Names |
EC 2.3.2.31 |
Species |
Homo sapiens (Human) |
KEGG Pathway |
cel:CELE_C27A12.8 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
MAP KAP kinase 2 (MK2), a Ser/Thr kinase, plays a crucial role in the inflammatory process. MK2 contains an autoinhibitory domain within its C-terminal region. This domain regulates the enzyme by acting as a pseudosubstrate, blocking substrate binding and thus inhibiting activity. The autoinhibitory domain affects the catalytic kinase domain of MK2, specifically influencing the binding of peptide substrates and ATP, which are crucial for the enzyme’s activity. Phosphorylation by p38 MAP kinase alleviates autoinhibition. It induces conformational changes in MK2, particularly in the autoinhibitory domain and the activation segment, allowing efficient substrate binding and restoring enzymatic activity.
Autoinhibitory domains (AIDs)
Target domain |
214-285 (RING2 domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Duda DM et al. (2013) "Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism", Structure (London, England : 1993), 21, 1030-41
- Kelsall IR et al. (2013) "TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes", The EMBO journal, 32, 2848-60
- Kostrhon S et al. (2021) "CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation", Nature chemical biology, 17, 1075-1083
Autoinhibited structure
Activated structure
1 structures for O01965
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O01965-F1 | Predicted | AlphaFoldDB |
No variants for O01965
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for O01965 | |||||
No associated diseases with O01965
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| ubiquitin ligase complex | A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex. |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| ubiquitin conjugating enzyme binding | Binding to a ubiquitin conjugating enzyme, any of the E2 proteins. |
| ubiquitin protein ligase activity | Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond |
| zinc ion binding | Binding to a zinc ion (Zn). |
3 GO annotations of biological process
| Name | Definition |
|---|---|
| positive regulation of proteasomal ubiquitin-dependent protein catabolic process | Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome. |
| protein polyubiquitination | Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain. |
| ubiquitin-dependent protein catabolic process | The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein. |
11 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A2VEA3 | ARIH1 | E3 ubiquitin-protein ligase ARIH1 | Bos taurus (Bovine) | SS |
| Q94981 | ari-1 | E3 ubiquitin-protein ligase ariadne-1 | Drosophila melanogaster (Fruit fly) | SS |
| O76924 | ari-2 | Potential E3 ubiquitin-protein ligase ariadne-2 | Drosophila melanogaster (Fruit fly) | SS |
| Q9Y4X5 | ARIH1 | E3 ubiquitin-protein ligase ARIH1 | Homo sapiens (Human) | EV |
| O95376 | ARIH2 | E3 ubiquitin-protein ligase ARIH2 | Homo sapiens (Human) | EV |
| Q9Z1K5 | Arih1 | E3 ubiquitin-protein ligase ARIH1 | Mus musculus (Mouse) | SS |
| Q9Z1K6 | Arih2 | E3 ubiquitin-protein ligase ARIH2 | Mus musculus (Mouse) | SS |
| Q22431 | ari-2 | Potential E3 ubiquitin-protein ligase ariadne-2 | Caenorhabditis elegans | SS |
| B1H1E4 | arih1 | E3 ubiquitin-protein ligase arih1 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | SS |
| Q6NW85 | arih1l | E3 ubiquitin-protein ligase arih1l | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q6PFJ9 | arih1 | E3 ubiquitin-protein ligase arih1 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MLSNSQGQSP | PVPFPAPAPP | PQPPTPALPH | PPAQPPPPPP | QQFPQFHVKS | GLQIKKNAII |
| 70 | 80 | 90 | 100 | 110 | 120 |
| DDYKVTSQVL | GLGINGKVLQ | IFNKRTQEKF | ALKMLQDCPK | ARREVELHWR | ASQCPHIVRI |
| 130 | 140 | 150 | 160 | 170 | 180 |
| VDVYENLYAG | RKCLLIVMEC | LDGGELFSRI | QDRGDQAFTE | REASEIMKSI | GEAIQYLHSI |
| 190 | 200 | 210 | 220 | 230 | 240 |
| NIAHRDVKPE | NLLYTSKRPN | AILKLTDFGF | AKETTSHNSL | TTPCYTPYYV | APEVLGPEKY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| DKSCDMWSLG | VIMYILLCGY | PPFYSNHGLA | ISPGMKTRIR | MGQYEFPNPE | WSEVSEEVKM |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LIRNLLKTEP | TQRMTITEFM | NHPWIMQSTK | VPQTPLHTSR | VLKEDKERWE | DVKEEMTSAL |
| 370 | 380 | 390 | |||
| ATMRVDYEQI | KIKKIEDASN | PLLLKRRKKA | RALEAAALAH |