Q9N2Z7
SS
Gene name |
wwp-1 (Y65B4BR.4) |
Protein name |
E3 ubiquitin-protein ligase wwp-1 |
Names |
EC 2.3.2.26 |
Species |
Caenorhabditis elegans |
KEGG Pathway |
cel:CELE_Y65B4BR.4 |
EC number |
2.3.2.26: Aminoacyltransferases |
Protein Class |
|
Descriptions
E3 ubiquitin-protein ligase Itchy homolog protein (ITCH) is a HECT domain E3 ubiquitin ligase, belonging to the NEDD4 family. It plays a crucial role in regulating proteolysis and various cellular processes by targeting specific proteins for ubiquitination and subsequent degradation. Similar with other NEDD4 families such as WWP2, ITCH is autoinhibited through interactions between the WW2-WW3 linker and the HECT domain, resulting in a closed and inactive conformation. Deletion of the WW2-WW3 linker from ITCH sharply increases autoubiquitination activity compared to full-length ITCH. Binding of PPxY motif-containing proteins, such as NDFIP1, to the WW domain disrupts the autoinhibited form of ITCH and enhances its catalytic activity.
Autoinhibitory domains (AIDs)
Target domain |
439-794 (HECT domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Mund T et al. (2009) "Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP proteins", EMBO reports, 10, 501-7
- Wiesner S et al. (2007) "Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain", Cell, 130, 651-62
- Tsunoda T et al. (2022) "ENTREP/FAM189A2 encodes a new ITCH ubiquitin ligase activator that is downregulated in breast cancer", EMBO reports, 23, e51182
- Chen Z et al. (2017) "A Tunable Brake for HECT Ubiquitin Ligases", Molecular cell, 66, 345-357.e6
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Riling C et al. (2015) "Itch WW Domains Inhibit Its E3 Ubiquitin Ligase Activity by Blocking E2-E3 Ligase Trans-thiolation", The Journal of biological chemistry, 290, 23875-87
- Wang Z et al. (2019) "A multi-lock inhibitory mechanism for fine-tuning enzyme activities of the HECT family E3 ligases", Nature communications, 10, 3162
- Zhu K et al. (2017) "Allosteric auto-inhibition and activation of the Nedd4 family E3 ligase Itch", EMBO reports, 18, 1618-1630
- Jiang H et al. (2021) "Ubiquitin Ligase Activities of WWP1 Germline Variants K740N and N745S", Biochemistry, 60, 357-364
- Imamura M et al. (2024) "The R436Q missense mutation in WWP1 disrupts autoinhibition of its E3 ubiquitin ligase activity, leading to self-degradation and loss of function", In vitro cellular & developmental biology. Animal, ,
Autoinhibited structure
Activated structure
1 structures for Q9N2Z7
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q9N2Z7-F1 | Predicted | AlphaFoldDB |
No variants for Q9N2Z7
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q9N2Z7 | |||||
No associated diseases with Q9N2Z7
6 regional properties for Q9N2Z7
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | C2 domain | 10 - 124 | IPR000008 |
| domain | HECT domain | 440 - 794 | IPR000569 |
| domain | WW domain | 219 - 252 | IPR001202-1 |
| domain | WW domain | 253 - 286 | IPR001202-2 |
| domain | WW domain | 324 - 358 | IPR001202-3 |
| domain | WW domain | 366 - 399 | IPR001202-4 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.3.2.26 | Aminoacyltransferases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
1 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| ubiquitin conjugating enzyme activity | Isoenergetic transfer of ubiquitin from one protein to another via the reaction X-ubiquitin + Y -> Y-ubiquitin + X, where both the X-ubiquitin and Y-ubiquitin linkages are thioester bonds between the C-terminal glycine of ubiquitin and a sulfhydryl side group of a cysteine residue. |
| 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 |
7 GO annotations of biological process
| Name | Definition |
|---|---|
| defense response to Gram-negative bacterium | Reactions triggered in response to the presence of a Gram-negative bacterium that act to protect the cell or organism. |
| defense response to Gram-positive bacterium | Reactions triggered in response to the presence of a Gram-positive bacterium that act to protect the cell or organism. |
| determination of adult lifespan | The pathways that regulate the duration of the adult phase of the life-cycle of an animal. |
| 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 polyubiquitination | Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain. |
| protein ubiquitination | The process in which one or more ubiquitin groups are added to a protein. |
| regulation of protein catabolic process | Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds. |
22 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P39940 | RSP5 | E3 ubiquitin-protein ligase RSP5 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| Q9V853 | Smurf | E3 ubiquitin-protein ligase Smurf1 | Drosophila melanogaster (Fruit fly) | SS |
| Q9Y0H4 | Su(dx) | E3 ubiquitin-protein ligase Su | Drosophila melanogaster (Fruit fly) | SS |
| Q9HAU4 | SMURF2 | E3 ubiquitin-protein ligase SMURF2 | Homo sapiens (Human) | EV |
| Q9HCE7 | SMURF1 | E3 ubiquitin-protein ligase SMURF1 | Homo sapiens (Human) | PR |
| O95817 | BAG3 | BAG family molecular chaperone regulator 3 | Homo sapiens (Human) | PR |
| Q96PU5 | NEDD4L | E3 ubiquitin-protein ligase NEDD4-like | Homo sapiens (Human) | PR |
| O60861 | GAS7 | Growth arrest-specific protein 7 | Homo sapiens (Human) | PR |
| P46934 | NEDD4 | E3 ubiquitin-protein ligase NEDD4 | Homo sapiens (Human) | EV |
| Q9H0M0 | WWP1 | NEDD4-like E3 ubiquitin-protein ligase WWP1 | Homo sapiens (Human) | EV |
| Q96J02 | ITCH | E3 ubiquitin-protein ligase Itchy homolog | Homo sapiens (Human) | EV |
| O00308 | WWP2 | NEDD4-like E3 ubiquitin-protein ligase WWP2 | Homo sapiens (Human) | EV |
| P46935 | Nedd4 | E3 ubiquitin-protein ligase NEDD4 | Mus musculus (Mouse) | PR |
| Q9CUN6 | Smurf1 | E3 ubiquitin-protein ligase SMURF1 | Mus musculus (Mouse) | PR |
| A2A5Z6 | Smurf2 | E3 ubiquitin-protein ligase SMURF2 | Mus musculus (Mouse) | SS |
| Q60780 | Gas7 | Growth arrest-specific protein 7 | Mus musculus (Mouse) | PR |
| Q8CFI0 | Nedd4l | E3 ubiquitin-protein ligase NEDD4-like | Mus musculus (Mouse) | PR |
| Q8BZZ3 | Wwp1 | NEDD4-like E3 ubiquitin-protein ligase WWP1 | Mus musculus (Mouse) | SS |
| Q8C863 | Itch | E3 ubiquitin-protein ligase Itchy | Mus musculus (Mouse) | EV |
| Q9DBH0 | Wwp2 | NEDD4-like E3 ubiquitin-protein ligase WWP2 | Mus musculus (Mouse) | SS |
| Q62940 | Nedd4 | E3 ubiquitin-protein ligase NEDD4 | Rattus norvegicus (Rat) | PR |
| A9JRZ0 | smurf2 | E3 ubiquitin-protein ligase SMURF2 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MARNEPSSQQ | PSSSGSNGTP | AQQNGSAKPS | KVTVKVVNAS | FTKAADCYVE | ITSDTSSAAP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KKTTVKKKTM | APEWNEHLNV | HANESSTISF | RLLQKAKLFD | DTCLGMAKLK | LSSLTRNENG |
| 130 | 140 | 150 | 160 | 170 | 180 |
| EFKNDINNIS | LLAKDSSKIG | TLNIIFSGYP | ERKRRSAGVR | AETAASASSE | ASTSNGVATS |
| 190 | 200 | 210 | 220 | 230 | 240 |
| SSARRPATAK | RDTLAAPTST | AAAAAAATAG | GTPAAGAEEQ | LPDGWEMRFD | QYGRKYYVDH |
| 250 | 260 | 270 | 280 | 290 | 300 |
| TTKSTTWERP | STQPLPQGWE | MRRDPRGRVY | YVDHNTRTTT | WQRPTADMLE | AHEQWQSGRD |
| 310 | 320 | 330 | 340 | 350 | 360 |
| QAMLQWEQRF | LLQQNNFSAD | DPLGPLPEGW | EKRQDPNTSR | MYFVNHVNRT | TQWEDPRTQG |
| 370 | 380 | 390 | 400 | 410 | 420 |
| FRGSDQPLPD | GWEMRFTEQG | VPFFIDHQSK | TTTYNDPRTG | KPVGPLGVVG | VQMAMEKSFR |
| 430 | 440 | 450 | 460 | 470 | 480 |
| WKIAQFRYLC | LSNSVPNHVK | ITVSRNNVFE | DSFQEIMRKN | AVDLRRRLYI | QFRGEEGLDY |
| 490 | 500 | 510 | 520 | 530 | 540 |
| GGVAREWFFL | LSHEVLNPMY | CLFMYAGNNN | YSLQINPASF | VNPDHLKYFE | YIGRFIAMAL |
| 550 | 560 | 570 | 580 | 590 | 600 |
| FHGKFIYSGF | TMPFYKKMLN | KKIVLKDIEQ | VDSEIYNSLM | WIKDNNIDEC | DMELYFVADY |
| 610 | 620 | 630 | 640 | 650 | 660 |
| ELLGELKTYE | LKEGGTEIAV | TEENKLEYIE | LLVEWRFNRG | VEQQTKAFFT | GFNSVFPLEW |
| 670 | 680 | 690 | 700 | 710 | 720 |
| MQYFDERELE | LLLCGMQDVD | VDDWQRNTVY | RHYAPQSKQV | TWFWQWVRSL | DQEKRARLLQ |
| 730 | 740 | 750 | 760 | 770 | 780 |
| FVTGTCRVPV | GGFSELMGST | GPQLFCIERV | GKENWLPRSH | TCFNRLDLPP | YRSYDQLVEK |
| 790 | |||||
| LSMAIEMTEG | FGNE |