Q9V853
SS
Gene name |
Smurf (lack, Smurf1, CG4943) |
Protein name |
E3 ubiquitin-protein ligase Smurf1 |
Names |
EC 2.3.2.26 , HECT-type E3 ubiquitin transferase Smurf1 , Lethal with a checkpoint kinase protein , SMAD ubiquitination regulatory factor 1 homolog , DSmurf |
Species |
Drosophila melanogaster (Fruit fly) |
KEGG Pathway |
dme:Dmel_CG4943 |
EC number |
2.3.2.26: Aminoacyltransferases |
Protein Class |
|
Descriptions
Ubiquitination of proteins is an abundant modification that controls numerous cellular processes. The C2-WW-HECT-domain E3 Smurf2 downregulates transforming growth factor-β (TGF-β) signaling by targeting itself, the adaptor protein Smad7, and TGF-β receptor kinases for degradation. The intramolecular interaction between C2 phospholipid binding domain and HECT domain inhibits the catalytic activity of the HECT domain by obstructing accessibility of the catalytic cysteine of the HECT domain and thus blocking Smurf2-Ub thioester formation. The autoinhibition is relieved by the binding of HECT-binding domain of Smad7.
Autoinhibitory domains (AIDs)
Target domain |
702-1061 (HECT domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Wiesner S et al. (2007) "Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain", Cell, 130, 651-62
- Lu K et al. (2011) "Pivotal role of the C2 domain of the Smurf1 ubiquitin ligase in substrate selection", The Journal of biological chemistry, 286, 16861-70
- Ogunjimi AA et al. (2005) "Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain", Molecular cell, 19, 297-308
Autoinhibited structure
Activated structure
1 structures for Q9V853
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q9V853-F1 | Predicted | AlphaFoldDB |
No variants for Q9V853
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q9V853 | |||||
No associated diseases with Q9V853
11 regional properties for Q9V853
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | SH3 domain | 507 - 577 | IPR001452 |
| domain | PDZ domain | 153 - 240 | IPR001478-1 |
| domain | PDZ domain | 246 - 335 | IPR001478-2 |
| domain | PDZ domain | 391 - 474 | IPR001478-3 |
| domain | L27 domain | 4 - 60 | IPR004172 |
| domain | Guanylate kinase-like domain | 610 - 786 | IPR008144 |
| domain | Guanylate kinase/L-type calcium channel beta subunit | 609 - 789 | IPR008145 |
| domain | L27-1 | 6 - 59 | IPR015143 |
| domain | Disks large homolog 1-4, PDZ-associated domain | 339 - 392 | IPR019583 |
| domain | Disks large homologue 1, N-terminal PEST domain | 70 - 152 | IPR019590 |
| conserved_site | Guanylate kinase, conserved site | 642 - 659 | IPR020590 |
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 | |
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. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| 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. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| 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 |
| ubiquitin-protein transferase activity | Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages. |
14 GO annotations of biological process
| Name | Definition |
|---|---|
| embryonic development via the syncytial blastoderm | The process whose specific outcome is the progression of the embryo over time, from zygote formation through syncytial blastoderm to the hatching of the first instar larva. An example of this process is found in Drosophila melanogaster. |
| embryonic hindgut morphogenesis | The process in which the anatomical structures of the hindgut are generated and organized, during the embryonic phase. |
| germarium-derived egg chamber formation | Construction of a stage-1 egg chamber in the anterior part of the germarium, from the progeny of germ-line and somatic stem cells. An example of this is found in Drosophila melanogaster. |
| male gamete generation | Generation of the male gamete; specialised haploid cells produced by meiosis and along with a female gamete takes part in sexual reproduction. |
| negative regulation of BMP signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of the BMP signaling pathway. |
| negative regulation of hippo signaling | Any process that stops, prevents, or reduces the frequency, rate or extent of hippo signaling. |
| negative regulation of smoothened signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of smoothened signaling. |
| positive regulation of receptor-mediated endocytosis | Any process that activates or increases the frequency, rate or extent of receptor mediated endocytosis, the uptake of external materials by cells, utilizing receptors to ensure specificity of transport. |
| positive regulation of smoothened signaling pathway | Any process that activates or increases the frequency, rate or extent of smoothened signaling. |
| 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 growth | Any process that modulates the frequency, rate or extent of the growth of all or part of an organism so that it occurs at its proper speed, either globally or in a specific part of the organism's development. |
| 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. |
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 |
| Q9Y0H4 | Su(dx) | E3 ubiquitin-protein ligase Su | Drosophila melanogaster (Fruit fly) | SS |
| O00308 | WWP2 | NEDD4-like E3 ubiquitin-protein ligase WWP2 | Homo sapiens (Human) | EV |
| 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 |
| Q9HAU4 | SMURF2 | E3 ubiquitin-protein ligase SMURF2 | Homo sapiens (Human) | EV |
| Q9HCE7 | SMURF1 | E3 ubiquitin-protein ligase SMURF1 | Homo sapiens (Human) | PR |
| P46935 | Nedd4 | E3 ubiquitin-protein ligase NEDD4 | Mus musculus (Mouse) | PR |
| Q8BZZ3 | Wwp1 | NEDD4-like E3 ubiquitin-protein ligase WWP1 | Mus musculus (Mouse) | SS |
| Q60780 | Gas7 | Growth arrest-specific protein 7 | Mus musculus (Mouse) | PR |
| Q8C863 | Itch | E3 ubiquitin-protein ligase Itchy | Mus musculus (Mouse) | EV |
| Q9DBH0 | Wwp2 | NEDD4-like E3 ubiquitin-protein ligase WWP2 | Mus musculus (Mouse) | SS |
| Q8CFI0 | Nedd4l | E3 ubiquitin-protein ligase NEDD4-like | 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 |
| Q62940 | Nedd4 | E3 ubiquitin-protein ligase NEDD4 | Rattus norvegicus (Rat) | PR |
| Q9N2Z7 | wwp-1 | E3 ubiquitin-protein ligase wwp-1 | Caenorhabditis elegans | SS |
| A9JRZ0 | smurf2 | E3 ubiquitin-protein ligase SMURF2 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MNKLDYPRRN | GTHKVRITIL | CARNLARKDL | FRLPDPFAKV | QVDGTGQVYS | TEISKSSLDP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KWNAHYDLFL | GIGDAITITV | WNQRKIHKGS | GFLGCVRIPA | FNIQSLKGAG | FQRLDLGKLS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| PDDDELVRGQ | IIISLLSKDG | PSSGNPLAIV | GPSGDVRGPS | EDDSSEDSLP | EGWEERRTDN |
| 190 | 200 | 210 | 220 | 230 | 240 |
| GRVYYVNHAT | KSTQWDRPRQ | PGVVGSSHAT | SPQQRHNTHN | GNSGDRQAPA | GPTRSTTCTN |
| 250 | 260 | 270 | 280 | 290 | 300 |
| LMNNGHRSRD | LSVTASDERR | HSTEILSSVG | KENTSPTTPV | SATTTPGKKT | SSSNSSSAGG |
| 310 | 320 | 330 | 340 | 350 | 360 |
| RTLEQRPTNE | PATPTSSTTS | ASVRLHSNDN | HVKTPKHQTN | GHAPPESTPT | SPTGQQNYVN |
| 370 | 380 | 390 | 400 | 410 | 420 |
| GNAQNGSTSG | NGSGQAAQPQ | SASNGWTQED | AATTTSPSTT | TSPPRHSQSP | PTPNISPPAS |
| 430 | 440 | 450 | 460 | 470 | 480 |
| VTPSANGNVH | SPNANSTPAG | SGGGSRSYTA | ATPGQRSQRR | SSRQQGEESS | TRRRSSRGTR |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NGGTSGGGGG | GGSGQRYASA | AIAAANQAAR | PFLDLPPGYE | MRTTQQGQVY | FYHIPTGVST |
| 550 | 560 | 570 | 580 | 590 | 600 |
| WHDPRIPRDF | DTQHLTLDAI | GPLPSGWEQR | KTASGRVYFV | DHNNRTTQFT | DPRLSGSILQ |
| 610 | 620 | 630 | 640 | 650 | 660 |
| MIRRGTVPPT | SAANAGTPAP | PSATPATPSA | AAAVPPQATP | ASNATPTTLT | TTTNPPHRIV |
| 670 | 680 | 690 | 700 | 710 | 720 |
| PDLPQGLLEG | ADLLPKYRRD | LVGKLRALRT | ELQTMQPQSG | HCRLEVSRNE | IFEESYRLIM |
| 730 | 740 | 750 | 760 | 770 | 780 |
| KMRAKDMRKR | LMVKFKGEEG | LDYGGVAREW | LHLLSREMLN | PQYGLFQYSR | DDHYTLQINP |
| 790 | 800 | 810 | 820 | 830 | 840 |
| DSGVNPDHLS | YFHFVGRTLG | IAVFHGHCLD | GGFTTPFYKQ | LLNKPITLGD | IEGVDPDLHR |
| 850 | 860 | 870 | 880 | 890 | 900 |
| SLTWMLESNI | SGIIESTFSV | ENNSFGALVV | HELKPGGASI | PVTEENKREY | VKLYVNYRFM |
| 910 | 920 | 930 | 940 | 950 | 960 |
| RGIEQQFLAL | QKGFCELIPS | HLLRPFDERE | LELVIGGISS | IDVNDWRNNT | RLKHCTNETT |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| QVLWFWQVVE | SYSSEMRARL | LQFVTGSSRV | PLQGFRALQG | STGAVGPRLF | TIHLTADVPT |
| 1030 | 1040 | 1050 | 1060 | ||
| QNLPKAHTCF | NRIDLPPYET | YQLLCDKLTQ | AVEETCGFAV | E |