Q5E9A7
SS
Gene name |
KLHDC2 |
Protein name |
Kelch domain-containing protein 2 |
Names |
|
Species |
Bos taurus (Bovine) |
KEGG Pathway |
bta:535436 |
EC number |
|
Protein Class |
|
Descriptions
The ubiquitin-proteasome system (UPS) is a major pathway regulating eukaryotic protein levels. Selectivity for UPS protein substrates, containing terminal destabilizing motifs (degrons), is largely governed by E3 ligases, which modify proteins with ubiquitin (UB) to target them for degradation.<br>KLHDC2 is a substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation.<br>Autoinhibition of KLHDC2 involves the self-assembly of its C-terminal Gly-Ser motif, which mimics a C-degron and engages the substrate-binding domain of another protomer in the homotetramer. This autoinhibited state prevents the binding of diGly substrates, ensuring that only true substrates that can displace the C-degron mimic can bind and activate the E3 ligase for ubiquitylation.
Autoinhibitory domains (AIDs)
Target domain |
1-362 (Substrate binding domain) |
Relief mechanism |
|
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for Q5E9A7
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q5E9A7-F1 | Predicted | AlphaFoldDB |
66 variants for Q5E9A7
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs470506532 | 7 | D>A | No | EVA | |
| rs437465982 | 8 | L>P | No | EVA | |
| rs474359025 | 11 | D>A | No | EVA | |
| rs434876312 | 12 | E>A | No | EVA | |
| rs453476871 | 13 | L>P | No | EVA | |
| rs438819479 | 15 | G>W | No | EVA | |
| rs461783872 | 18 | Y>* | No | EVA | |
| rs443448454 | 18 | Y>D | No | EVA | |
| rs443448454 | 18 | Y>H | No | EVA | |
| rs440964324 | 19 | E>G | No | EVA | |
| rs480173261 | 19 | E>K | No | EVA | |
| rs459418579 | 20 | G>V | No | EVA | |
| rs469766771 | 21 | Y>* | No | EVA | |
| rs477926174 | 21 | Y>D | No | EVA | |
| rs444818012 | 21 | Y>S | No | EVA | |
| rs482525919 | 22 | E>D | No | EVA | |
| rs449556863 | 23 | S>P | No | EVA | |
| rs468069140 | 24 | A>G | No | EVA | |
| rs435019214 | 25 | E>A | No | EVA | |
| rs453466816 | 25 | E>D | No | EVA | |
| rs435019214 | 25 | E>G | No | EVA | |
| rs465452161 | 26 | L>P | No | EVA | |
| rs432428487 | 27 | A>P | No | EVA | |
| rs457284995 | 29 | P>S | No | EVA | |
| rs475565928 | 34 | G>R | No | EVA | |
| rs442508541 | 80 | K>* | No | EVA | |
| rs472986538 | 80 | K>N | No | EVA | |
| rs460950533 | 80 | K>T | No | EVA | |
| rs439986310 | 93 | G>A | No | EVA | |
| rs477739582 | 94 | S>I | No | EVA | |
| rs467879930 | 100 | D>A | No | EVA | |
| rs720393567 | 126 | T>M | No | EVA | |
| rs478932778 | 131 | H>D | No | EVA | |
| rs445712315 | 151 | W>* | No | EVA | |
| rs464111617 | 155 | N>I | No | EVA | |
| rs470336171 | 164 | G>R | No | EVA | |
| rs437296247 | 169 | D>A | No | EVA | |
| rs455869220 | 169 | D>E | No | EVA | |
| rs453252976 | 186 | S>G | No | EVA | |
| rs472500422 | 191 | W>C | No | EVA | |
| rs439447501 | 192 | N>K | No | EVA | |
| rs457784635 | 196 | H>Y | No | EVA | |
| rs482673253 | 197 | I>V | No | EVA | |
| rs443372824 | 198 | L>F | No | EVA | |
| rs461712260 | 199 | D>N | No | EVA | |
| rs447217942 | 200 | T>N | No | EVA | |
| rs480323257 | 200 | T>P | No | EVA | |
| rs478556482 | 201 | E>* | No | EVA | |
| rs470472676 | 201 | E>D | No | EVA | |
| rs445512190 | 201 | E>V | No | EVA | |
| rs437427374 | 203 | F>Y | No | EVA | |
| rs455907899 | 204 | I>F | No | EVA | |
| rs467865736 | 205 | W>L | No | EVA | |
| rs450850780 | 234 | G>R | No | EVA | |
| rs458862117 | 263 | I>R | No | EVA | |
| rs469128362 | 286 | G>R | No | EVA | |
| rs436091011 | 289 | T>P | No | EVA | |
| rs448132021 | 290 | D>G | No | EVA | |
| rs136560600 | 291 | K>N | No | EVA | |
| rs135392378 | 291 | K>T | No | EVA | |
| rs466675594 | 294 | L>Q | No | EVA | |
| rs465292803 | 323 | T>P | No | EVA | |
| rs477245293 | 323 | T>R | No | EVA | |
| rs450779225 | 324 | A>S | No | EVA | |
| rs443047119 | 395 | N>D | No | EVA | |
| rs1116314851 | 402 | N>T | No | EVA |
No associated diseases with Q5E9A7
No regional properties for Q5E9A7
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| No domain, repeats, and functional sites for Q5E9A7 | |||
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| Cul2-RING ubiquitin ligase complex | A ubiquitin ligase complex in which a cullin from the Cul2 subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by an elongin-BC adaptor and a SOCS/BC box protein. |
| nuclear body | Extra-nucleolar nuclear domains usually visualized by confocal microscopy and fluorescent antibodies to specific proteins. |
| nuclear membrane | Either of the lipid bilayers that surround the nucleus and form the nuclear envelope; excludes the intermembrane space. |
| 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. |
1 GO annotations of molecular function
| Name | Definition |
|---|---|
| ubiquitin ligase-substrate adaptor activity | The binding activity of a molecule that brings together a ubiquitin ligase and its substrate. Usually mediated by F-box BTB/POZ domain proteins. |
3 GO annotations of biological process
| Name | Definition |
|---|---|
| proteasome-mediated 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 ubiquitin, and mediated by the proteasome. |
| protein ubiquitination | The process in which one or more ubiquitin groups are added to a protein. |
| ubiquitin-dependent protein catabolic process via the C-end degron rule pathway | The chemical reactions and pathways resulting in the breakdown of a protein or peptide covalently tagged with ubiquitin, via the DesCEND (destruction via C-end degron) pathway. In the DesCEND pathway, C-terminal residues (C-end degrons) in substrates are recognized by Cul2-RING and Cul4-RING E3 ligases, whereupon the substrates are linked to ubiquitin and then delivered to the proteasome for degradation. C-end degrons can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. |
6 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q8N7A1 | KLHDC1 | Kelch domain-containing protein 1 | Homo sapiens (Human) | SS |
| Q9Y2U9 | KLHDC2 | Kelch domain-containing protein 2 | Homo sapiens (Human) | EV |
| Q8N653 | LZTR1 | Leucine-zipper-like transcriptional regulator 1 | Homo sapiens (Human) | PR |
| Q4G5Y1 | Klhdc2 | Kelch domain-containing protein 2 | Mus musculus (Mouse) | SS |
| Q80YG3 | Klhdc1 | Kelch domain-containing protein 1 | Mus musculus (Mouse) | SS |
| Q3KRE6 | Klhdc2 | Kelch domain-containing protein 2 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MADGYEDLRE | DELPGPAYEG | YESAELACPA | ERSGHVAVSD | GRHMFVWGGY | KSNQVRGLYD |
| 70 | 80 | 90 | 100 | 110 | 120 |
| FYLPREELWI | YNMETGRWKK | INTEGDVPPS | MSGSCAVCVD | RVLYLFGGHH | SRGNTNKFYM |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LDSRSTDRVL | HWERIDCQGV | PPSSKDKLGV | WVYKNKLIFF | GGYGYLPEDK | VLGTFEFDET |
| 190 | 200 | 210 | 220 | 230 | 240 |
| SFWNSSHPRG | WNDHVHILDT | ETFIWSQPIT | TGKPPSPRAA | HACATVGNKG | FVFGGRYRDA |
| 250 | 260 | 270 | 280 | 290 | 300 |
| RMNDLHYLNL | DTWEWNELIP | QGICPVGRSW | HSLTPVSSDH | LFLFGGFTTD | KQPLSDAWTY |
| 310 | 320 | 330 | 340 | 350 | 360 |
| CISKNEWIKF | NHPHTEKPRL | WHTACASDEG | EVIVFGGCAN | NLLVHHRAAH | SNEILIFSVQ |
| 370 | 380 | 390 | 400 | ||
| PKSLVRLSLE | AVICFKEMLA | NSWNCLPKHL | LHSVNQRFGS | NNTSGS |