Q9CUN6
PR
Gene name |
Smurf1 |
Protein name |
E3 ubiquitin-protein ligase SMURF1 |
Names |
HECT-type E3 ubiquitin transferase SMURF1, SMAD ubiquitination regulatory factor 1, SMAD-specific E3 ubiquitin-protein ligase 1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:75788 |
EC number |
2.3.2.26: Aminoacyltransferases |
Protein Class |
|
Descriptions
(Annotation based on sequence homology with Q9HAU4)
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 |
|
Relief mechanism |
|
Assay |
cis-regPred |
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for Q9CUN6
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q9CUN6-F1 | Predicted | AlphaFoldDB |
34 variants for Q9CUN6
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs36694826 | 63 | N>S | No | EVA | |
| rs3388798270 | 103 | N>I | No | EVA | |
| rs3388803342 | 112 | G>D | No | EVA | |
| rs3388793957 | 139 | T>I | No | EVA | |
| rs3388793950 | 140 | R>* | No | EVA | |
| rs3388808880 | 142 | R>I | No | EVA | |
| rs3388793946 | 154 | G>W | No | EVA | |
| rs3388810476 | 187 | G>D | No | EVA | |
| rs3388816120 | 190 | A>G | No | EVA | |
| rs3388816068 | 203 | Q>R | No | EVA | |
| rs3388798242 | 210 | Q>* | No | EVA | |
| rs3388798255 | 262 | W>C | No | EVA | |
| rs3388790112 | 266 | R>K | No | EVA | |
| rs3388813879 | 285 | G>D | No | EVA | |
| rs3388803031 | 291 | T>I | No | EVA | |
| rs3388804977 | 292 | V>A | No | EVA | |
| rs3388810003 | 301 | H>R | No | EVA | |
| rs3388808809 | 392 | K>N | No | EVA | |
| rs3388793963 | 396 | K>Q | No | EVA | |
| rs3388813836 | 415 | G>D | No | EVA | |
| rs3388777299 | 444 | I>T | No | EVA | |
| rs3388808802 | 478 | H>R | No | EVA | |
| rs3388810513 | 522 | T>A | No | EVA | |
| rs3388803043 | 532 | E>V | No | EVA | |
| rs3388803072 | 541 | Q>H | No | EVA | |
| rs3388816098 | 552 | P>H | No | EVA | |
| rs3388804954 | 565 | Y>F | No | EVA | |
| rs3388810218 | 608 | G>E | No | EVA | |
| rs3388805030 | 609 | L>R | No | EVA | |
| rs3388809082 | 631 | N>K | No | EVA | |
| rs3388801169 | 640 | V>* | No | EVA | |
| rs3388810187 | 640 | V>G | No | EVA | |
| rs3388790082 | 658 | S>P | No | EVA | |
| rs3388803027 | 675 | A>S | No | EVA |
No associated diseases with Q9CUN6
4 regional properties for Q9CUN6
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | C2 domain | 1 - 120 | IPR000008 |
| domain | HECT domain | 373 - 731 | IPR000569 |
| domain | WW domain | 234 - 267 | IPR001202-1 |
| domain | WW domain | 280 - 313 | IPR001202-2 |
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 | |
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| axon | The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter. |
| 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. |
| mitochondrion | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. |
| neuronal cell body | The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
4 GO annotations of molecular function
| Name | Definition |
|---|---|
| I-SMAD binding | Binding to an inhibitory SMAD signaling protein. |
| R-SMAD binding | Binding to a receptor-regulated SMAD signaling protein. |
| 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: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues. |
| 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. |
20 GO annotations of biological process
| Name | Definition |
|---|---|
| BMP signaling pathway | The series of molecular signals initiated by the binding of a member of the BMP (bone morphogenetic protein) family to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| cell differentiation | The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| engulfment of target by autophagosome | The membrane invagination process by which an autophagosomal membrane surrounds an object that will be degraded by macroautophagy. |
| 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 ossification | Any process that stops, prevents, or reduces the frequency, rate or extent of ossification, the formation of bone or of a bony substance or the conversion of fibrous tissue or of cartilage into bone or a bony substance. |
| negative regulation of transforming growth factor beta receptor signaling pathway | Any process that stops, prevents, or reduces the frequency, rate or extent of any TGF-beta receptor signaling pathway. |
| parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization | A positive regulation of the macromitophagy pathway that is triggered by mitochondrial depolarization and requires the function of a parkin-family molecule. |
| positive regulation of axon extension | Any process that activates or increases the frequency, rate or extent of axon extension. |
| positive regulation of dendrite extension | Any process that activates or increases the frequency, rate or extent of dendrite extension. |
| positive regulation of ubiquitin-dependent protein catabolic process | Any process that activates or increases the frequency, rate or extent of ubiquitin-dependent protein catabolic process. |
| 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 export from nucleus | The directed movement of a protein from the nucleus into the cytoplasm. |
| protein localization to cell surface | A process in which a protein is transported to, or maintained in, a location within the external part of the cell wall and/or plasma membrane. |
| protein polyubiquitination | Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain. |
| protein targeting to vacuole involved in autophagy | The process of directing proteins towards the vacuole using signals contained within the protein, occurring as part of autophagy, the process in which cells digest parts of their own cytoplasm. |
| protein ubiquitination | The process in which one or more ubiquitin groups are added to a protein. |
| receptor catabolic process | The chemical reactions and pathways resulting in the breakdown of a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. |
| substrate localization to autophagosome | The localization process by which an autophagic substrate is delivered to a forming autophagosome. |
| 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. |
| ubiquitin-dependent SMAD protein catabolic process | The chemical reactions and pathways resulting in the breakdown of SMAD signaling proteins by ubiquitination and targeting to the proteasome. |
23 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 |
| Q9V853 | Smurf | E3 ubiquitin-protein ligase Smurf1 | Drosophila melanogaster (Fruit fly) | SS |
| Q9HAU4 | SMURF2 | E3 ubiquitin-protein ligase SMURF2 | Homo sapiens (Human) | EV |
| 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 |
| Q9HCE7 | SMURF1 | E3 ubiquitin-protein ligase SMURF1 | Homo sapiens (Human) | PR |
| Q60780 | Gas7 | Growth arrest-specific protein 7 | Mus musculus (Mouse) | 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 |
| Q9DBH0 | Wwp2 | NEDD4-like E3 ubiquitin-protein ligase WWP2 | Mus musculus (Mouse) | SS |
| A2A5Z6 | Smurf2 | E3 ubiquitin-protein ligase SMURF2 | Mus musculus (Mouse) | SS |
| Q8C863 | Itch | E3 ubiquitin-protein ligase Itchy | Mus musculus (Mouse) | EV |
| Q3U0D9 | Hace1 | E3 ubiquitin-protein ligase HACE1 | Mus musculus (Mouse) | SS |
| Q8CFI0 | Nedd4l | E3 ubiquitin-protein ligase NEDD4-like | Mus musculus (Mouse) | PR |
| 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 |
| MSNPGTRRNG | SSIKIRLTVL | CAKNLAKKDF | FRLPDPFAKI | VVDGSGQCHS | TDTVKNTLDP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KWNQHYDLYV | GKTDSITISV | WNHKKIHKKQ | GAGFLGCVRL | LSNAISRLKD | TGYQRLDLCK |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LNPSDTDAVR | GQIVVSLQTR | DRIGGGGSVV | DCRGLLENEG | TVYEDSGPGR | PLSCLMEEPA |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PYTDGTGAAA | GGGNCRFVES | PSQDQRLLVQ | RLRNPEVRGP | LQTPQNRPHG | HQSPELPEGY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| EQRTTVQGQV | YFLHTQTGVS | TWHDPRIPRD | LNSVNCDELG | PLPPGWEVRS | TVSGRIYFVD |
| 310 | 320 | 330 | 340 | 350 | 360 |
| HNNRTTQFTD | PRLHHIMNHQ | CQLKEPSQPL | QLPSEGSVED | EELPAQRYER | DLVQKLKVLR |
| 370 | 380 | 390 | 400 | 410 | 420 |
| HELSLQQPQA | GHCRIEVSRE | EIFEESYRQI | MKMRPKDLKK | RLMVKFRGEE | GLDYGGVARE |
| 430 | 440 | 450 | 460 | 470 | 480 |
| WLYLLCHEML | NPYYGLFQYS | TDNIYTLQIN | PDSSINPDHL | SYFHFVGRIM | GLAVFHGHYI |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NGGFTVPFYK | QLLGKPIQLS | DLESVDPELH | KSLVWILEND | ITPVLDHTFC | VEHNAFGRIL |
| 550 | 560 | 570 | 580 | 590 | 600 |
| QHELKPNGRN | VPVTEENKKE | YVRLYVNWRF | MRGIEAQFLA | LQKGFNELIP | QHLLKPFDQK |
| 610 | 620 | 630 | 640 | 650 | 660 |
| ELELIIGGLD | KIDLNDWKSN | TRLKHCVADS | NIVRWFWQAV | ETFDEERRAR | LLQFVTGSTR |
| 670 | 680 | 690 | 700 | 710 | 720 |
| VPLQGFKALQ | GSTGAAGPRL | FTIHLIDANT | DNLPKAHTCF | NRIDIPPYES | YEKLYEKLLT |
| 730 | |||||
| AVEETCGFAV | E |