Descriptions
Dbl-related oncoproteins are guanine nucleotide exchange factors specific for Rho-family GTPases and typically possess tandem Dbl homology (DH) and pleckstrin homology (PH) domains that act in concert to catalyze exchange. The ability of many Dbl-family proteins to catalyze exchange is constitutively activated by truncations N-terminal to their DH domains. The Dbl-family protein Tim, called ARHGEF5, is autoinhibited by a short, helical motif immediately N-terminal to its DH domain, which directly occludes the catalytic surface of the DH domain to prevent GTPase activation.
Autoinhibitory domains (AIDs)
Target domain |
1158-1342 (DH domain) |
Relief mechanism |
PTM |
Assay |
|
Target domain |
1158-1342 (DH domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Yohe ME et al. (2007) "Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif", The Journal of biological chemistry, 282, 13813-23
- Yohe ME et al. (2008) "Role of the C-terminal SH3 domain and N-terminal tyrosine phosphorylation in regulation of Tim and related Dbl-family proteins", Biochemistry, 47, 6827-39
Autoinhibited structure
Activated structure
1 structures for E9Q7D5
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-E9Q7D5-F1 | Predicted | AlphaFoldDB |
111 variants for E9Q7D5
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs258152457 | 48 | Y>C | No | EVA | |
| rs3396705894 | 50 | W>C | No | EVA | |
| rs3396752636 | 51 | T>SVHL* | No | EVA | |
| rs264111687 | 85 | D>A | No | EVA | |
| rs229515092 | 97 | A>D | No | EVA | |
| rs3412564242 | 123 | E>V | No | EVA | |
| rs36955757 | 128 | A>D | No | EVA | |
| rs226516164 | 156 | T>S | No | EVA | |
| rs37115323 | 159 | V>A | No | EVA | |
| rs215574366 | 166 | E>G | No | EVA | |
| rs3388826090 | 169 | S>Y | No | EVA | |
| rs237553073 | 172 | T>A | No | EVA | |
| rs259831011 | 192 | T>S | No | EVA | |
| rs3388794461 | 241 | E>G | No | EVA | |
| rs217675060 | 246 | N>K | No | EVA | |
| rs3388807427 | 257 | E>* | No | EVA | |
| rs237022745 | 257 | E>D | No | EVA | |
| rs248401550 | 258 | Q>E | No | EVA | |
| rs220295901 | 266 | N>H | No | EVA | |
| rs3388822254 | 271 | E>V | No | EVA | |
| rs3388810140 | 274 | Q>E | No | EVA | |
| rs252294884 | 275 | G>E | No | EVA | |
| rs3388814065 | 294 | G>W | No | EVA | |
| rs3388820358 | 297 | E>G | No | EVA | |
| rs3388827275 | 325 | D>E | No | EVA | |
| rs224234741 | 326 | Q>R | No | EVA | |
| rs248408719 | 341 | T>A | No | EVA | |
| rs265955899 | 354 | K>R | No | EVA | |
| rs221789056 | 362 | Q>K | No | EVA | |
| rs237430558 | 370 | R>G | No | EVA | |
| rs226445154 | 386 | G>W | No | EVA | |
| rs36501956 | 405 | P>S | No | EVA | |
| rs254364910 | 409 | V>M | No | EVA | |
| rs3388820368 | 412 | V>I | No | EVA | |
| rs37258677 | 414 | P>L | No | EVA | |
| rs3388822299 | 449 | A>V | No | EVA | |
| rs3388824839 | 477 | R>T | No | EVA | |
| rs235234374 | 488 | L>Q | No | EVA | |
| rs38198468 | 492 | I>N | No | EVA | |
| rs38198468 | 492 | I>T | No | EVA | |
| rs214634933 | 498 | S>R | No | EVA | |
| rs36810416 | 507 | R>Q | No | EVA | |
| rs224557658 | 520 | S>N | No | EVA | |
| rs243542367 | 527 | V>A | No | EVA | |
| rs260314133 | 537 | T>N | No | EVA | |
| rs221217948 | 542 | A>V | No | EVA | |
| rs3388828208 | 545 | D>N | No | EVA | |
| rs3388817043 | 547 | P>S | No | EVA | |
| rs36544969 | 548 | H>Y | No | EVA | |
| rs3388807358 | 561 | K>N | No | EVA | |
| rs238717264 | 575 | P>S | No | EVA | |
| rs3388831305 | 576 | H>Y | No | EVA | |
| rs3412986796 | 577 | S>I | No | EVA | |
| rs3388827336 | 590 | R>I | No | EVA | |
| rs36935979 | 613 | F>S | No | EVA | |
| rs3388834482 | 617 | E>V | No | EVA | |
| rs3388820323 | 620 | Q>H | No | EVA | |
| rs3388821749 | 643 | I>F | No | EVA | |
| rs3388814066 | 645 | F>L | No | EVA | |
| rs3388828227 | 688 | I>K | No | EVA | |
| rs37335525 | 691 | P>S | No | EVA | |
| rs3388827320 | 700 | V>A | No | EVA | |
| rs3388827320 | 700 | V>D | No | EVA | |
| rs3388821826 | 704 | M>I | No | EVA | |
| rs263854854 | 706 | I>M | No | EVA | |
| rs3388810894 | 707 | R>P | No | EVA | |
| rs3388814102 | 708 | E>Q | No | EVA | |
| rs3388822302 | 709 | A>P | No | EVA | |
| rs3388827785 | 710 | L>S | No | EVA | |
| rs3388827352 | 712 | P>T | No | EVA | |
| rs214180524 | 716 | E>G | No | EVA | |
| rs3388827315 | 738 | L>Q | No | EVA | |
| rs3388827351 | 740 | R>W | No | EVA | |
| rs3388831274 | 801 | P>R | No | EVA | |
| rs246217034 | 806 | M>V | No | EVA | |
| rs216552232 | 822 | M>I | No | EVA | |
| rs3388814036 | 822 | M>R | No | EVA | |
| rs3388828229 | 842 | P>S | No | EVA | |
| rs240681690 | 857 | I>M | No | EVA | |
| rs212855661 | 897 | L>P | No | EVA | |
| rs3396677175 | 933 | R>S | No | EVA | |
| rs3388827332 | 947 | E>K | No | EVA | |
| rs3388828189 | 958 | A>T | No | EVA | |
| rs3388827803 | 978 | E>G | No | EVA | |
| rs252156828 | 980 | P>T | No | EVA | |
| rs241437574 | 1008 | V>I | No | EVA | |
| rs259291193 | 1013 | V>I | No | EVA | |
| rs3388821841 | 1126 | Q>R | No | EVA | |
| rs3388807375 | 1132 | S>P | No | EVA | |
| rs3413113901 | 1164 | F>L | No | EVA | |
| rs3388810839 | 1186 | H>Q | No | EVA | |
| rs3388826015 | 1217 | L>I | No | EVA | |
| rs3388825818 | 1235 | D>E | No | EVA | |
| rs38556647 | 1242 | A>T | No | EVA | |
| rs3388828184 | 1275 | V>I | No | EVA | |
| rs3388807352 | 1280 | E>D | No | EVA | |
| rs37980996 | 1287 | R>C | No | EVA | |
| rs3388826069 | 1315 | T>I | No | EVA | |
| rs3388820386 | 1347 | R>W | No | EVA | |
| rs3388807412 | 1348 | R>Q | No | EVA | |
| rs3388828228 | 1350 | E>K | No | EVA | |
| rs3388810849 | 1354 | Y>F | No | EVA | |
| rs3388794503 | 1402 | H>Q | No | EVA | |
| rs3388821794 | 1435 | E>K | No | EVA | |
| rs37134203 | 1457 | A>T | No | EVA | |
| rs3395927137 | 1462 | V>E | No | EVA | |
| rs3396285130 | 1465 | L>H | No | EVA | |
| rs3388831332 | 1499 | V>L | No | EVA | |
| rs3388822283 | 1504 | A>V | No | EVA | |
| rs3388794463 | 1509 | E>G | No | EVA | |
| rs3388826051 | 1536 | R>G | No | EVA |
No associated diseases with E9Q7D5
6 regional properties for E9Q7D5
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Dbl homology (DH) domain | 1158 - 1342 | IPR000219 |
| conserved_site | Guanine-nucleotide dissociation stimulator, CDC24, conserved site | 1290 - 1315 | IPR001331 |
| domain | SH3 domain | 1494 - 1555 | IPR001452 |
| domain | Pleckstrin homology domain | 1375 - 1488 | IPR001849 |
| domain | Rho guanine nucleotide exchange factor 5/35, N-terminal | 1 - 477 | IPR029212 |
| domain | Ephexin-like, PH domain | 1362 - 1488 | IPR047270 |
8 GO annotations of cellular component
| Name | Definition |
|---|---|
| anchoring junction | A cell junction that mechanically attaches a cell (and its cytoskeleton) to neighboring cells or to the extracellular matrix. |
| cell projection | A prolongation or process extending from a cell, e.g. a flagellum or axon. |
| 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. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| podosome | An actin-rich adhesion structure characterized by formation upon cell substrate contact and localization at the substrate-attached part of the cell, contain an F-actin-rich core surrounded by a ring structure containing proteins such as vinculin and talin, and have a diameter of 0.5 mm. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| guanyl-nucleotide exchange factor activity | Stimulates the exchange of GDP to GTP on a signaling GTPase, changing its conformation to its active form. Guanine nucleotide exchange factors (GEFs) act by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP), which is more abundant in the cell under normal cellular physiological conditions. |
| lipid binding | Binding to a lipid. |
7 GO annotations of biological process
| Name | Definition |
|---|---|
| actin cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| hematopoietic stem cell homeostasis | Any biological process involved in the maintenance of the steady-state number of hematopoietic stem cells within a population of cells. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| myeloid dendritic cell chemotaxis | The movement of a myeloid dendritic cell in response to an external stimulus. |
| positive regulation of podosome assembly | Any process that activates or increases the rate or extent of podosome assembly. |
| positive regulation of protein import | Any process that activates or increases the frequency, rate or extent of protein import. |
| positive regulation of stress fiber assembly | Any process that activates or increases the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. |
12 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q8N5V2 | NGEF | Ephexin-1 | Homo sapiens (Human) | EV |
| Q8IW93 | ARHGEF19 | Rho guanine nucleotide exchange factor 19 | Homo sapiens (Human) | SS |
| Q96DR7 | ARHGEF26 | Rho guanine nucleotide exchange factor 26 | Homo sapiens (Human) | SS |
| O94989 | ARHGEF15 | Rho guanine nucleotide exchange factor 15 | Homo sapiens (Human) | SS |
| A5YM69 | ARHGEF35 | Rho guanine nucleotide exchange factor 35 | Homo sapiens (Human) | PR |
| Q5VV41 | ARHGEF16 | Rho guanine nucleotide exchange factor 16 | Homo sapiens (Human) | PR |
| Q12774 | ARHGEF5 | Rho guanine nucleotide exchange factor 5 | Homo sapiens (Human) | EV |
| Q3U5C8 | Arhgef16 | Rho guanine nucleotide exchange factor 16 | Mus musculus (Mouse) | PR |
| Q8BWA8 | Arhgef19 | Rho guanine nucleotide exchange factor 19 | Mus musculus (Mouse) | PR |
| Q5FWH6 | Arhgef15 | Rho guanine nucleotide exchange factor 15 | Mus musculus (Mouse) | SS |
| Q8CHT1 | Ngef | Ephexin-1 | Mus musculus (Mouse) | SS |
| Q5BKC9 | Ngef | Ephexin-1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MEAEEPEYGV | STEVPDIEEL | KTIPEGIMRS | SQIPALDPEA | QEDRDPSYKW | TDGHRPVMNQ |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SKVLRDMGDH | TPNSMAIFFK | KESSDMETSQ | EILLAEACNT | PDQQEAVIQS | LKDRLSRTIA |
| 130 | 140 | 150 | 160 | 170 | 180 |
| APELLACAVQ | EEWLDIPSKL | DNRVGAELQS | ELMSLTLAVS | KEKEEEETSP | DTSIPRGSWP |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PCKTHPGETE | QTQGSGSELL | RQGKQLQLEA | TQENQGQEGF | LQSQEAQGLE | EQEGQEVEIQ |
| 250 | 260 | 270 | 280 | 290 | 300 |
| EEGTLNEGIC | FGGLLGEQEE | VEEGFNGNEE | EQKQGQIQSY | MLLGGQWENE | GLSGELEGLN |
| 310 | 320 | 330 | 340 | 350 | 360 |
| YSERGQENRE | RRVWVLRDSE | EEGQDQESRE | VEERRVATQY | TENQRLVEKS | EIVKRKQRDH |
| 370 | 380 | 390 | 400 | 410 | 420 |
| DQTGKVMPVR | DQKEVVDSGD | RVQGNGDSGG | QTAVEGSRPG | EDSKPSLPVA | SVDPEVLSPG |
| 430 | 440 | 450 | 460 | 470 | 480 |
| TLFPGISSSV | ADIPQIQKEP | VCEELSPQAP | ALEPTEWSHQ | PISPPASFAP | EESLDNRTHN |
| 490 | 500 | 510 | 520 | 530 | 540 |
| SQQEEFRLRK | GIEVVSASTS | VAPSGTRDSP | PFSPPNVFSS | TATLSPVSSS | VILPEETPTA |
| 550 | 560 | 570 | 580 | 590 | 600 |
| SASADTPHHC | GPCETPPLPA | KSSRYPCATS | DTANPHSPLS | SYTGVTQHLR | SNSFPGSHRT |
| 610 | 620 | 630 | 640 | 650 | 660 |
| EQTPDSLGMS | LSFSHLELPQ | RPPKPAIYGS | LTPRRNRRSR | DGIVFSDSST | ALFALKQDSE |
| 670 | 680 | 690 | 700 | 710 | 720 |
| EFTSNPERPS | SPHGSPTWGS | PQNSAFAIGS | PANVSSPPTV | SMDMTIREAL | LPIPPEKRHS |
| 730 | 740 | 750 | 760 | 770 | 780 |
| YSHIVERDGL | LHEVASTLKR | HSHPPPLTLS | SGLHRSSKGS | FSLVPDSTVA | RQHRPLPSTP |
| 790 | 800 | 810 | 820 | 830 | 840 |
| ESPNHTQTSI | PSRLRYNKPL | PPTPDMPEFY | HPSISSSYIS | RMYRPLPPVP | IIDPSSEPPP |
| 850 | 860 | 870 | 880 | 890 | 900 |
| LPPKSRGRSK | SIQGGVIHSG | GQAKPRPNNQ | DWTASTLSVG | RTSWPPATGR | STESLPLTSR |
| 910 | 920 | 930 | 940 | 950 | 960 |
| CNNEVSPGLA | FSNMTNLLSP | SSPTTPWIPD | LQRPTTKDES | GLTEESEPPV | RGSFRRSAPQ |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| EEFNNTRRSA | LGSRKNSEKP | LHHQLEKASS | WPHRRDPART | SESSSEQVVL | GQVPNKQKGW |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| NRQGLRRPSI | LPESSSDLRN | PAAGRLPGSS | DSVVFREKKP | KEGMGGFSRR | CSKLISSQLL |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| YQEYSDVVLN | KEIQSQQRLD | SLAEPHGLSS | PRHRRKALVS | SDSYLQRLSM | ASSGSLWQEI |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| PVVRNSTVLL | SMTHEDQKLQ | EAKFELIVSE | ASYLRSLNIA | VDHFQHSAQL | RGTLSNQDHQ |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| WLFSRLQDVR | DVSTTFLSDL | EENFENNIFS | FQVCDVVLNH | AADFHRVYLP | YVTNQTYQER |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| TFQSLMNSNS | SFREVLEKLE | SDPICQRLSL | KSFLILPFQR | ITRLKLLLQN | ILKRTQPGSS |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| EEAEATKAHH | ALEKLIRDCN | SNVQRMRRTE | ELIYLSQKIE | FECKIFPLIS | QSRWLVKSGE |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| LTALEFSVSP | GLRRKLTTRP | VHLHLFNDCL | LLSRPREGSR | FLVFDHAPFS | SIRGEKCEMK |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| LHGPHKNLFR | LFLLHNAQGT | QVEFLFRTET | QSEKLRWISA | LAMPREELDL | LECYDSPQVQ |
| 1510 | 1520 | 1530 | 1540 | 1550 | 1560 |
| CLRAYKPREN | DELALEKADV | VMVTQQSSDG | WLEGVRLSDG | EQGWFPVQQV | EFISNPEVRA |
| 1570 | 1580 | ||||
| QNLKEAHRVK | TAKLQLVEQQ | V |