O70481
EV
Gene name |
Ubr1 |
Protein name |
E3 ubiquitin-protein ligase UBR1 |
Names |
N-recognin-1, RING-type E3 ubiquitin transferase UBR1, Ubiquitin-protein ligase E3-alpha-1, Ubiquitin-protein ligase E3-alpha-I |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:22222 |
EC number |
2.3.2.27: Aminoacyltransferases |
Protein Class |
UBIQUITIN LIGASE E3 ALPHA-RELATED (PTHR21497) |
Descriptions
In Saccharomyces cerevisiae, RING domain-containing Ub ligase UBR1 recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Binding of dipeptides with destabilizing N-terminal residues to two substrate-binding sites of UBR1 causes dissociation of the C-terminal autoinhibitory domain of UBR1 from its N-terminal region that contains all three substrate-binding sites. This dissociation allows the interaction between UBR1 and CUP9, a transcriptional repressor of the peptide transporter PTR2, thereby accelerating the UBR1-dependent degradation of CUP9 and increasing the cell's capacity to import peptides. An aspect of autoinhibition characteristic of yeast UBR1 also is observed with mouse UBR1.
Autoinhibitory domains (AIDs)
Target domain |
1-1031 (N-terminal region containing three substrate-binding sites) |
Relief mechanism |
Ligand binding |
Assay |
Split protein assay |
Accessory elements
No accessory elements
References
- Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100
- Du F et al. (2002) "Pairs of dipeptides synergistically activate the binding of substrate by ubiquitin ligase through dissociation of its autoinhibitory domain", Proceedings of the National Academy of Sciences of the United States of America, 99, 14110-5
Autoinhibited structure
Activated structure
1 structures for O70481
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-O70481-F1 | Predicted | AlphaFoldDB |
80 variants for O70481
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3392068037 | 64 | E>* | No | EVA | |
| rs3392148615 | 65 | S>I | No | EVA | |
| rs3388587057 | 130 | S>N | No | EVA | |
| rs3388586344 | 132 | V>I | No | EVA | |
| rs3388582424 | 156 | A>S | No | EVA | |
| rs27423157 | 165 | D>E | No | EVA | |
| rs3388582805 | 190 | A>V | No | EVA | |
| rs3388579729 | 192 | R>* | No | EVA | |
| rs3388578014 | 192 | R>I | No | EVA | |
| rs3388587745 | 195 | P>L | No | EVA | |
| rs3388583965 | 211 | K>R | No | EVA | |
| rs3388587076 | 247 | R>K | No | EVA | |
| rs3388587765 | 300 | V>G | No | EVA | |
| rs3388579743 | 337 | Q>H | No | EVA | |
| rs3388582762 | 395 | Y>C | No | EVA | |
| rs3388576634 | 445 | L>M | No | EVA | |
| rs3388583960 | 449 | L>S | No | EVA | |
| rs3388583288 | 476 | I>K | No | EVA | |
| rs3388587038 | 477 | C>Y | No | EVA | |
| rs3388580369 | 478 | D>E | No | EVA | |
| rs3388584202 | 490 | W>* | No | EVA | |
| rs3392114339 | 512 | M>I | No | EVA | |
| rs3388578033 | 519 | R>K | No | EVA | |
| rs3388586322 | 521 | Q>H | No | EVA | |
| rs3388587085 | 531 | D>N | No | EVA | |
| rs3388582765 | 535 | A>V | No | EVA | |
| rs3388583959 | 539 | Q>* | No | EVA | |
| rs3388576629 | 562 | V>E | No | EVA | |
| rs3388583314 | 572 | M>L | No | EVA | |
| rs27438817 | 639 | G>S | No | EVA | |
| rs3388583896 | 715 | Y>C | No | EVA | |
| rs3388582733 | 735 | Q>H | No | EVA | |
| rs3388583311 | 772 | I>N | No | EVA | |
| rs3388587738 | 868 | P>H | No | EVA | |
| rs49215462 | 888 | M>I | No | EVA | |
| rs27438849 | 888 | M>L | No | EVA | |
| rs3388586374 | 897 | R>W | No | EVA | |
| rs3388586340 | 898 | A>T | No | EVA | |
| rs27438850 | 901 | M>T | No | EVA | |
| rs3388587042 | 902 | E>V | No | EVA | |
| rs3388583394 | 910 | M>I | No | EVA | |
| rs235951634 | 926 | K>Q | No | EVA | |
| rs3392068027 | 942 | Y>F | No | EVA | |
| rs27438865 | 964 | K>R | No | EVA | |
| rs51051976 | 973 | S>G | No | EVA | |
| rs3388576636 | 1001 | T>I | No | EVA | |
| rs27438871 | 1008 | V>I | No | EVA | |
| rs29523023 | 1014 | T>S | No | EVA | |
| rs3391973972 | 1031 | L>P | No | EVA | |
| rs3392144738 | 1039 | Q>R | No | EVA | |
| rs3388580315 | 1062 | T>S | No | EVA | |
| rs261181185 | 1094 | T>I | No | EVA | |
| rs3392122462 | 1217 | Q>* | No | EVA | |
| rs3388587078 | 1314 | P>S | No | EVA | |
| rs3388572837 | 1341 | G>* | No | EVA | |
| rs3388580327 | 1355 | Q>K | No | EVA | |
| rs27438903 | 1357 | N>S | No | EVA | |
| rs27438904 | 1371 | T>A | No | EVA | |
| rs258221747 | 1379 | H>Q | No | EVA | |
| rs236768014 | 1383 | A>V | No | EVA | |
| rs3388583974 | 1440 | L>I | No | EVA | |
| rs3388582341 | 1454 | I>M | No | EVA | |
| rs213949529 | 1462 | L>V | No | EVA | |
| rs46282240 | 1464 | S>P | No | EVA | |
| rs27438924 | 1496 | A>T | No | EVA | |
| rs3388580330 | 1534 | E>* | No | EVA | |
| rs255995843 | 1542 | E>D | No | EVA | |
| rs3388583552 | 1561 | L>P | No | EVA | |
| rs3388584214 | 1566 | W>G | No | EVA | |
| rs3388583352 | 1576 | W>* | No | EVA | |
| rs3388578035 | 1584 | K>E | No | EVA | |
| rs3388583949 | 1592 | V>L | No | EVA | |
| rs3388583911 | 1642 | L>P | No | EVA | |
| rs3388580368 | 1672 | V>D | No | EVA | |
| rs3388583894 | 1686 | V>E | No | EVA | |
| rs3388587045 | 1724 | R>E* | No | EVA | |
| rs3388583581 | 1725 | K>R | No | EVA | |
| rs3388586326 | 1727 | H>P | No | EVA | |
| rs3388579753 | 1727 | H>Y | No | EVA | |
| rs3388579773 | 1735 | I>N | No | EVA |
No associated diseases with O70481
Functions
| Description | ||
|---|---|---|
| EC Number | 2.3.2.27 | Aminoacyltransferases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR21497 | UBIQUITIN LIGASE E3 ALPHA-RELATED |
| PANTHER Subfamily | PTHR21497:SF27 | E3 UBIQUITIN-PROTEIN LIGASE UBR1 |
| PANTHER Protein Class |
ubiquitin-protein ligase
protein modifying enzyme |
|
| PANTHER Pathway Category | No pathway information available | |
4 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. |
| proteasome complex | A large multisubunit complex which catalyzes protein degradation, found in eukaryotes, archaea and some bacteria. In eukaryotes, this complex consists of the barrel shaped proteasome core complex and one or two associated proteins or complexes that act in regulating entry into or exit from the core. |
| 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. |
4 GO annotations of molecular function
| Name | Definition |
|---|---|
| leucine binding | Binding to 2-amino-4-methylpentanoic acid. |
| 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. |
| zinc ion binding | Binding to a zinc ion (Zn). |
5 GO annotations of biological process
| Name | Definition |
|---|---|
| cellular response to leucine | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a leucine stimulus. |
| negative regulation of TOR signaling | Any process that stops, prevents, or reduces the frequency, rate or extent of TOR signaling. |
| protein ubiquitination | The process in which one or more ubiquitin groups are added to a protein. |
| 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 protein catabolic process via the N-end rule pathway | The chemical reactions and pathways resulting in the breakdown of a protein or peptide covalently tagged with ubiquitin, via the N-end rule pathway. In the N-end rule pathway, destabilizing N-terminal residues (N-degrons) in substrates are recognized by E3 ligases (N-recognins), whereupon the substrates are linked to ubiquitin and then delivered to the proteasome for degradation. |
5 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P19812 | UBR1 | E3 ubiquitin-protein ligase UBR1 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | EV |
| Q9VX91 | Ubr1 | E3 ubiquitin-protein ligase UBR1 | Drosophila melanogaster (Fruit fly) | PR |
| Q8IWV8 | UBR2 | E3 ubiquitin-protein ligase UBR2 | Homo sapiens (Human) | SS |
| Q8IWV7 | UBR1 | E3 ubiquitin-protein ligase UBR1 | Homo sapiens (Human) | SS |
| Q6WKZ8 | Ubr2 | E3 ubiquitin-protein ligase UBR2 | Mus musculus (Mouse) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MADEEMDGAE | RMDVSPEPPL | APQRPASWWD | QQVDFYTAFL | HHLAQLVPEI | YFAEMDPDLE |
| 70 | 80 | 90 | 100 | 110 | 120 |
| KQEESVQMSI | LTPLEWYLFG | EDPDICLEKL | KHSGAFQLCG | KVFKSGETTY | SCRDCAIDPT |
| 130 | 140 | 150 | 160 | 170 | 180 |
| CVLCMDCFQS | SVHKNHRYKM | HTSTGGGFCD | CGDTEAWKTG | PFCVDHEPGR | AGTTKESLHC |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PLNEEVIAQA | RRIFPSVIKY | IVEMTIWEEE | KELPPELQIR | EKNERYYCVL | FNDEHHSYDH |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VIYSLQRALD | CELAEAQLHT | TAIDKEGRRA | VKAGVYATCQ | EAKEDIKSHS | ENVSQHPLHV |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EVLHSVVMAH | QKFALRLGSW | MNKIMSYSSD | FRQIFCQACL | VEEPGSENPC | LISRLMLWDA |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KLYKGARKIL | HELIFSSFFM | EMEYKKLFAM | EFVKYYKQLQ | KEYISDDHER | SISITALSVQ |
| 430 | 440 | 450 | 460 | 470 | 480 |
| MLTVPTLARH | LIEEQNVISV | ITETLLEVLP | EYLDRNNKFN | FQGYSQDKLG | RVYAVICDLK |
| 490 | 500 | 510 | 520 | 530 | 540 |
| YILISKPVIW | TERLRAQFLE | GFRSFLKILT | CMQGMEEIRR | QVGQHIEVDP | DWEAAIAIQM |
| 550 | 560 | 570 | 580 | 590 | 600 |
| QLKNILLMFQ | EWCACDEDLL | LVAYKECHKA | VMRCSTNFMS | STKTVVQLCG | HSLETKSYKV |
| 610 | 620 | 630 | 640 | 650 | 660 |
| SEDLVSIHLP | LSRTLAGLHV | RLSRLGAISR | LHEFVPFDGF | QVEVLVEYPL | RCLVLVAQVV |
| 670 | 680 | 690 | 700 | 710 | 720 |
| AEMWRRNGLS | LISQVFYYQD | VKCREEMYDK | DIIMLQIGAS | IMDPNKFLLL | VLQRYELTDA |
| 730 | 740 | 750 | 760 | 770 | 780 |
| FNKTISTKDQ | DLIKQYNTLI | EEMLQVLIYI | VGERYVPGVG | NVTREEVIMR | EITHLLCIEP |
| 790 | 800 | 810 | 820 | 830 | 840 |
| MPHSAIARNL | PENENNETGL | ENVINKVATF | KKPGVSGHGV | YELKDESLKD | FNMYFYHYSK |
| 850 | 860 | 870 | 880 | 890 | 900 |
| TQHSKAEHMQ | KKRRKQENKD | EALPPPPPPE | FCPAFSKVVN | LLSCDVMMYI | LRTIFERAVD |
| 910 | 920 | 930 | 940 | 950 | 960 |
| MESNLWTEGM | LQMAFHILAL | GLLEEKQQLQ | KAPEEEVAFD | FYHKASRLGS | SAMNAQNIQM |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| LLEKLKGIPQ | LESQKDMITW | ILQMFDTVKR | LREKSCLVVA | TTSGLECVKS | EEITHDKEKA |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| ERKRKAEAAR | LHRQKIMAQM | SALQKNFIET | HKLMYDNTSE | VTGKEDSIME | EESTSAVSEA |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| SRIALGPKRG | PAVTEKEVLT | CILCQEEQEV | KLENNAMVLS | ACVQKSTALT | QHRGKPVDHL |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| GETLDPLFMD | PDLAHGTYTG | SCGHVMHAVC | WQKYFEAVQL | SSQQRIHVDL | FDLESGEYLC |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| PLCKSLCNTV | IPIIPLQPQK | INSENAEALA | QLLTLARWIQ | TVLARISGYN | IKHAKGEAPA |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| VPVLFNQGMG | DSTFEFHSIL | SFGVQSSVKY | SNSIKEMVIL | FATTIYRIGL | KVPPDELDPR |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| VPMMTWSTCA | FTIQAIENLL | GDEGKPLFGA | LQNRQHNGLK | ALMQFAVAQR | TTCPQVLIHK |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| HLARLLSVIL | PNLQSENTPG | LLSVDLFHVL | VGAVLAFPSL | YWDDTVDLQP | SPLSSSYNHL |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| YLFHLITMAH | MLQILLTTDT | DLSSGPPLAE | GEEDSEEARC | ASAFFVEVSQ | HTDGLAGCGA |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| PGWYLWLSLR | NGITPYLRCA | ALLFHYLLGV | APPEELFANS | AEGEFSALCS | YLSLPTNLFL |
| 1570 | 1580 | 1590 | 1600 | 1610 | 1620 |
| LFQEYWDTIR | PLLQRWCGDP | ALLKSLKQKS | AVVRYPRKRN | SLIELPEDYS | CLLNQASHFR |
| 1630 | 1640 | 1650 | 1660 | 1670 | 1680 |
| CPRSADDERK | HPVLCLFCGA | ILCSQNICCQ | EIVNGEEVGA | CVFHALHCGA | GVCIFLKIRE |
| 1690 | 1700 | 1710 | 1720 | 1730 | 1740 |
| CRVVLVEGKA | RGCAYPAPYL | DEYGETDPGL | KRGNPLHLSR | ERYRKLHLVW | QQHCIIEEIA |
| 1750 | |||||
| RSQETNQMLF | GFNWQLL |