Q9N2Z7
SS
Gene name |
wwp-1 (Y65B4BR.4) |
Protein name |
E3 ubiquitin-protein ligase wwp-1 |
Names |
EC 2.3.2.26 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
cel:CELE_Y65B4BR.4 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
WNK family protein kinases are large enzymes that contain the catalytic lysine in a unique position compared with all other protein kinases. Rat WNK1 (Q9JIH7) contains an autoinhibitory region C-terminal to the catalytic kinase domain.
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
39 regional properties for Q9N2Z7
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| repeat | Thrombospondin type-1 (TSP1) repeat | 57 - 111 | IPR000884-1 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 338 - 397 | IPR000884-2 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 399 - 463 | IPR000884-3 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 461 - 521 | IPR000884-4 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 524 - 577 | IPR000884-5 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 576 - 640 | IPR000884-6 |
| repeat | Thrombospondin type-1 (TSP1) repeat | 639 - 694 | IPR000884-7 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 1610 - 1663 | IPR002223-1 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 1668 - 1722 | IPR002223-2 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 1728 - 1781 | IPR002223-3 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 1788 - 1841 | IPR002223-4 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 1847 - 1900 | IPR002223-5 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 1920 - 1973 | IPR002223-6 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 1999 - 2052 | IPR002223-7 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 2069 - 2122 | IPR002223-8 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 2126 - 2179 | IPR002223-9 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 2192 - 2245 | IPR002223-10 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 2251 - 2304 | IPR002223-11 |
| domain | Pancreatic trypsin inhibitor Kunitz domain | 2316 - 2372 | IPR002223-12 |
| domain | Immunoglobulin subtype 2 | 2534 - 2599 | IPR003598-1 |
| domain | Immunoglobulin subtype 2 | 2631 - 2694 | IPR003598-2 |
| domain | Immunoglobulin subtype 2 | 2766 - 2831 | IPR003598-3 |
| domain | Immunoglobulin subtype | 2528 - 2611 | IPR003599-1 |
| domain | Immunoglobulin subtype | 2625 - 2701 | IPR003599-2 |
| domain | Immunoglobulin subtype | 2760 - 2842 | IPR003599-3 |
| domain | Immunoglobulin-like domain | 2523 - 2607 | IPR007110-1 |
| domain | Immunoglobulin-like domain | 2617 - 2697 | IPR007110-2 |
| domain | Immunoglobulin-like domain | 2749 - 2840 | IPR007110-3 |
| domain | WAP-type 'four-disulfide core' domain | 2452 - 2498 | IPR008197 |
| domain | ADAMTS/ADAMTS-like, Spacer 1 | 217 - 329 | IPR010294 |
| domain | PLAC | 2847 - 2886 | IPR010909 |
| domain | Immunoglobulin I-set | 2766 - 2840 | IPR013098 |
| conserved_site | Proteinase inhibitor I2, Kunitz, conserved site | 1640 - 1658 | IPR020901-1 |
| conserved_site | Proteinase inhibitor I2, Kunitz, conserved site | 1758 - 1776 | IPR020901-2 |
| conserved_site | Proteinase inhibitor I2, Kunitz, conserved site | 1877 - 1895 | IPR020901-3 |
| conserved_site | Proteinase inhibitor I2, Kunitz, conserved site | 2099 - 2117 | IPR020901-4 |
| conserved_site | Proteinase inhibitor I2, Kunitz, conserved site | 2222 - 2240 | IPR020901-5 |
| conserved_site | Proteinase inhibitor I2, Kunitz, conserved site | 2281 - 2299 | IPR020901-6 |
| conserved_site | Proteinase inhibitor I2, Kunitz, conserved site | 2349 - 2367 | IPR020901-7 |
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 | |
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 |
| MDGDGGRRDA | PGALMEAGRG | TGSAGMAEPR | ARAARLGPQR | FLRRSVVESD | QEEPPGLEAA |
| 70 | 80 | 90 | 100 | 110 | 120 |
| ETPSAQPPQP | LQRRVLLLCK | TRRLIAERAR | GRPAAPAPAA | PAAPPGSPSV | PSDPGPERAG |
| 130 | 140 | 150 | 160 | 170 | 180 |
| TQEPSPDPTT | ASAAATQVPD | GGPRQEEAPA | PTQEDAGTTE | AKPEPGRARK | DEPEEEEDDE |
| 190 | 200 | 210 | 220 | 230 | 240 |
| DDLKAVATSL | DGRFLKFDIE | LGRGSFKTVY | KGLDTETWVE | VAWCELQDRK | LTKLERQRFK |
| 250 | 260 | 270 | 280 | 290 | 300 |
| EEAEMLKGLQ | HPNIVRFYDF | WESSAKGKRC | IVLVTELMTS | GTLKTYLKRF | KVMKPKVLRS |
| 310 | 320 | 330 | 340 | 350 | 360 |
| WCRQILKGLL | FLHTRTPPII | HRDLKCDNIF | ITGPTGSVKI | GDLGLATLKR | ASFAKSVIGT |
| 370 | 380 | 390 | 400 | 410 | 420 |
| PEFMAPEMYE | EHYDESVDVY | AFGMCMLEMA | TSEYPYSECQ | NAAQIYRKVT | CGIKPASFEK |
| 430 | 440 | 450 | 460 | 470 | 480 |
| VHDPEIKEII | GECICKNKEE | RYEIKDLLSH | AFFAEDTGVR | VELAEEDHGR | KSTIALRLWV |
| 490 | 500 | 510 | 520 | 530 | 540 |
| EDPKKLKGKP | KDNGAIEFTF | DLEKETPDEV | AQEMIDSGFF | HESDVKIVAK | SIRDRVALIQ |
| 550 | 560 | 570 | 580 | 590 | 600 |
| WRRERIWPAL | QSQEPKDSGS | PDKARGLPAP | LQVQVTYHAQ | SGQPGQPEPE | EPEADQHLLP |
| 610 | 620 | 630 | 640 | 650 | 660 |
| PTLPASVTSL | ASDSTFDSGQ | GSTVYSDSQS | SQQSMVLSSL | VDTAPTPASC | VCSPPVSEGP |
| 670 | 680 | 690 | 700 | 710 | 720 |
| GLTHSLPTLG | AFQQPATVPG | LSVGPVPPPA | RPPLLQQHFP | ESSMSFTPVL | PPPSTPVPTG |
| 730 | 740 | 750 | 760 | 770 | 780 |
| PSQPAPPVQQ | PLPMAQPPTL | PQVLAPQPMG | TVQPVPSHLP | PYLAPTSQVV | APAQLKPLQM |
| 790 | 800 | 810 | 820 | 830 | 840 |
| PQPPLQPLAQ | VPPQMPQMPV | VPPITPLTGL | DGLPQTLTDL | PAANVAPVPP | PQYFSPAVIL |
| 850 | 860 | 870 | 880 | 890 | 900 |
| PSLTTPLPTS | PALPMQAVKL | PHPPGTPLAV | PCQTIVPNAP | AAIPLLAVAP | QGVAALSIHP |
| 910 | 920 | 930 | 940 | 950 | 960 |
| AVAQIPAQPV | YPAAFPQMVP | GDIPPSPHHT | VQSLRATPPQ | LASPVPPQPV | QPSVIHLPEQ |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| AAPTAASGTQ | VLLGHPPSYT | ADVAAPVSAV | SLPPAVLSPP | LPDTLLPTVP | DLLPKVPSSL |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| APTVVAASQS | APAQTSSLLL | PTNPPLPTGP | AVAGPCPAVQ | LMVEVAQEEQ | VSQDKPPGPP |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| QSSESFGGSD | VTSGRDLSDS | CEGTFGGGRL | EGRTARKHHR | RSTRARSRQE | RASRPRLTIL |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| NVCNTGDKMV | ECQLETHNHK | MVTFKFDLDG | DAPDEIATYM | VEHDFILPAE | RETFIEQMKD |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| VMDKAEDMLS | EDTDADHGSD | TGTSPPHLGT | CGLATGEENR | QSQANAPVYQ | QNVLHTGKRW |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| FIICPVAEHP | ATDTSESSPP | LPLSSLQPEA | SQDPAPYPDQ | LSLTDKPSFP | AAQQLLSQAG |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| SSNPPGGASA | PLAPSSPPVT | TVIPAAPATS | TVPESAAGTA | MQAGGPGTHQ | GPASVHETLQ |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| PLAETRSAQC | TAQPLSTGQG | PCTPALEASR | CSTGLGEPIS | TREVSTQGEP | LPASVPEPSP |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| PTGATQSVPG | QPPPPLPITV | GAISLAAPQL | PSPPLGPTAP | PPPPSALESD | GEGPPPRVGF |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| VDNTIKSLDE | KLRTLLYQEH | VPTSSASAGT | PMEASDRDFT | LEPLRGDLPS | ALSDKTPSLT |
| 1570 | 1580 | 1590 | 1600 | 1610 | 1620 |
| QQTQPSLEKS | ETAPAGWALA | QREQGASSPM | TAESSSSNTL | GCDSDAGQVA | SDSSTAPSVP |
| 1630 | 1640 | 1650 | 1660 | 1670 | 1680 |
| QDASGSSVPT | HMDPKDQNSS | VPREALAAPM | QSGPGSFTVG | SPAQLRGARD | SGSPHKRPGQ |
| 1690 | 1700 | 1710 | 1720 | 1730 | 1740 |
| QDNSSPAKTV | GRFSVVSTQD | EWTLASPHSL | RYSAPPDVYL | DEIPSSPEVK | LAVRRVQTAS |
| 1750 | 1760 | 1770 | 1780 | 1790 | 1800 |
| SIEVGVEEPA | SSDSGDERPR | RRSQVQKQSS | LPGTGGVASD | FVKKATAFLH | RSSRAGSLGP |
| 1810 | 1820 | 1830 | 1840 | 1850 | 1860 |
| ETPSRAGVKV | PTISITSFHS | QSSYISSDND | SEFEDADIKK | ELRSLREKHL | KEISELQSQQ |
| 1870 | 1880 | 1890 | 1900 | 1910 | 1920 |
| KQEIEALYRR | LGKPLPPNVG | FFHTAPPMGR | RRKTSKSKLK | AGKLLNPLVQ | QLKVVASSTG |
| 1930 | 1940 | 1950 | 1960 | 1970 | 1980 |
| HLSDSSRGPP | TKDPRGTKAV | QTQQPCSVRA | SLSTDICSGL | ASDGGGARGQ | GWTVYHPTSE |
| 1990 | 2000 | 2010 | 2020 | 2030 | 2040 |
| RGAYKSSSKP | RARFLSGPVS | VSIWSALKRL | CLGKEHSSSL | YDSPGSSTSS | LAPGPEPGPQ |
| 2050 | 2060 | 2070 | 2080 | 2090 | 2100 |
| PTLHVQAQVN | NSNNKKGTFT | DDLHKLVDEW | TTKTVGAAQV | KPTLNQLKQT | QKLHDMEASG |
| 2110 | 2120 | 2130 | 2140 | ||
| DARATSVPRA | AVGASCLAPA | PGPLSTTATP | GATPALPVPI | PDPESEKPD |