Q8BTM9
Gene name |
Rasgrp4 |
Protein name |
RAS guanyl-releasing protein 4 |
Names |
|
Species |
Homo sapiens (Human) |
KEGG Pathway |
mmu:233046 |
EC number |
2.3.2.27: Aminoacyltransferases |
Protein Class |
CBL (PTHR23007) |
Descriptions
The E3 ubiquitin-protein ligase CBL-B (CBL-B) is an E3 ubiquitin-protein ligase that functions as a negative regulator of T-cell activation. The expression of CBL-B in T cells causes ligand-induced down-modulation of T-cell receptors, thereby controlling the activation degree of T-cells during antigen presentation. Autoinhibition of Cbl-b involves the masking of the E2 binding site due to an interaction between the RING domain and the tyrosine kinase binding domain (TKB). The phosphorylation of Y363 results in a structural rearrangement that unblocks the E2 binding site, thereby activating the E3 ligase activity.
Autoinhibitory domains (AIDs)
Target domain |
197-433 (Ras guanine-nucleotide exchange factors catalytic domain) |
Relief mechanism |
Ligand binding, PTM |
Assay |
|
Target domain |
459-501 (EF domain) |
Relief mechanism |
Ligand binding, PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Czikora A et al. (2016) "Structural Basis for the Failure of the C1 Domain of Ras Guanine Nucleotide Releasing Protein 2 (RasGRP2) to Bind Phorbol Ester with High Affinity", The Journal of biological chemistry, 291, 11133-47
- Canault M et al. (2020) "RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology", International journal of molecular sciences, 21,
- Iwig JS et al. (2013) "Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1", eLife, 2, e00813
Autoinhibited structure
Activated structure
1 structures for Q8BTM9
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q8BTM9-F1 | Predicted | AlphaFoldDB |
38 variants for Q8BTM9
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388887175 | 5 | D>Y | No | EVA | |
| rs32155624 | 24 | S>P | No | EVA | |
| rs3388883616 | 25 | R>C | No | EVA | |
| rs3388889172 | 26 | Q>R | No | EVA | |
| rs3397308548 | 33 | C>* | No | EVA | |
| rs3388855548 | 46 | M>T | No | EVA | |
| rs3388891970 | 57 | S>C | No | EVA | |
| rs32107664 | 72 | A>S | No | EVA | |
| rs46375256 | 92 | V>G | No | EVA | |
| rs3388883618 | 96 | S>L | No | EVA | |
| rs3388855534 | 128 | W>R | No | EVA | |
| rs45673726 | 182 | M>I | No | EVA | |
| rs3545426092 | 235 | R>K | No | EVA | |
| rs248946222 | 276 | R>H | No | EVA | |
| rs3412865575 | 299 | H>Q | No | EVA | |
| rs31372739 | 342 | G>S | No | EVA | |
| rs3397317067 | 346 | F>C | No | EVA | |
| rs3396934574 | 346 | F>I | No | EVA | |
| rs3397317078 | 348 | L>M | No | EVA | |
| rs3397773208 | 348 | L>Q | No | EVA | |
| rs46371097 | 362 | Y>H | No | EVA | |
| rs240065004 | 390 | M>T | No | EVA | |
| rs32365817 | 443 | K>R | No | EVA | |
| rs3388898366 | 444 | A>S | No | EVA | |
| rs3388869733 | 450 | W>R | No | EVA | |
| rs3388896486 | 458 | P>S | No | EVA | |
| rs48706891 | 468 | E>G | No | EVA | |
| rs3388877376 | 508 | P>H | No | EVA | |
| rs3388875297 | 536 | G>D | No | EVA | |
| rs3388869783 | 590 | C>R | No | EVA | |
| rs243429647 | 596 | T>I | No | EVA | |
| rs3388900363 | 608 | P>S | No | EVA | |
| rs3388883652 | 626 | T>I | No | EVA | |
| rs3388889099 | 628 | S>F | No | EVA | |
| rs3388855554 | 645 | E>K | No | EVA | |
| rs3388875254 | 657 | P>T | No | EVA | |
| rs3388889097 | 664 | P>Q | No | EVA | |
| rs48237048 | 669 | S>L | No | EVA |
No associated diseases with Q8BTM9
Functions
| Description | ||
|---|---|---|
| EC Number | 2.3.2.27 | Aminoacyltransferases |
| Subcellular Localization |
|
|
| PANTHER Family | PTHR23007 | CBL |
| PANTHER Subfamily | PTHR23007:SF3 | E3 UBIQUITIN-PROTEIN LIGASE CBL-B |
| PANTHER Protein Class |
ligase
metabolite interconversion enzyme |
|
| PANTHER Pathway Category |
EGF receptor signaling pathway c-Cbl |
|
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
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. |
| metal ion binding | Binding to a metal ion. |
5 GO annotations of biological process
| Name | Definition |
|---|---|
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| cell population proliferation | The multiplication or reproduction of cells, resulting in the expansion of a cell population. |
| positive regulation of Ras protein signal transduction | Any process that activates or increases the frequency, rate or extent of Ras protein signal transduction. |
| Ras protein signal transduction | The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state. |
| response to extracellular stimulus | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an extracellular stimulus. |
28 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A6N9I4 | RASGRP2 | RAS guanyl-releasing protein 2 | Bos taurus (Bovine) | SS |
| Q1LZ97 | RASGRP4 | RAS guanyl-releasing protein 4 | Bos taurus (Bovine) | SS |
| A0A3S5ZPR1 | RASGRP3 | RAS guanyl releasing protein 3 | Gallus gallus (Chicken) | SS |
| P26675 | Sos | Protein son of sevenless | Drosophila melanogaster (Fruit fly) | SS |
| Q07890 | SOS2 | Son of sevenless homolog 2 | Homo sapiens (Human) | SS |
| Q5JS13 | RALGPS1 | Ras-specific guanine nucleotide-releasing factor RalGPS1 | Homo sapiens (Human) | PR |
| O95267 | RASGRP1 | RAS guanyl-releasing protein 1 | Homo sapiens (Human) | EV |
| Q7LDG7 | RASGRP2 | RAS guanyl-releasing protein 2 | Homo sapiens (Human) | EV SS |
| Q86X27 | RALGPS2 | Ras-specific guanine nucleotide-releasing factor RalGPS2 | Homo sapiens (Human) | PR |
| Q13905 | RAPGEF1 | Rap guanine nucleotide exchange factor 1 | Homo sapiens (Human) | PR |
| Q8IV61 | RASGRP3 | Ras guanyl-releasing protein 3 | Homo sapiens (Human) | SS |
| Q07889 | SOS1 | Son of sevenless homolog 1 | Homo sapiens (Human) | EV |
| Q8TDF6 | RASGRP4 | RAS guanyl-releasing protein 4 | Homo sapiens (Human) | SS |
| Q02384 | Sos2 | Son of sevenless homolog 2 | Mus musculus (Mouse) | SS |
| Q62245 | Sos1 | Son of sevenless homolog 1 | Mus musculus (Mouse) | SS |
| Q8VCC8 | Rapgef3 | Rap guanine nucleotide exchange factor 3 | Mus musculus (Mouse) | SS |
| Q9EQZ6 | Rapgef4 | Rap guanine nucleotide exchange factor 4 | Mus musculus (Mouse) | EV |
| Q9D300 | Rasgef1c | Ras-GEF domain-containing family member 1C | Mus musculus (Mouse) | PR |
| Q03385 | Ralgds | Ral guanine nucleotide dissociation stimulator | Mus musculus (Mouse) | PR |
| Q9Z1S3 | Rasgrp1 | RAS guanyl-releasing protein 1 | Mus musculus (Mouse) | SS |
| Q9QUG9 | Rasgrp2 | RAS guanyl-releasing protein 2 | Mus musculus (Mouse) | SS |
| Q9ERD6 | Ralgps2 | Ras-specific guanine nucleotide-releasing factor RalGPS2 | Mus musculus (Mouse) | PR |
| A2AR50 | Ralgps1 | Ras-specific guanine nucleotide-releasing factor RalGPS1 | Mus musculus (Mouse) | PR |
| Q9R1K8 | Rasgrp1 | RAS guanyl-releasing protein 1 | Rattus norvegicus (Rat) | SS |
| P0C643 | Rasgrp2 | RAS guanyl-releasing protein 2 | Rattus norvegicus (Rat) | SS |
| Q8R5I4 | Rasgrp4 | RAS guanyl-releasing protein 4 | Rattus norvegicus (Rat) | SS |
| Q9N5D3 | sos-1 | Son of sevenless homolog | Caenorhabditis elegans | EV |
| A4IJ06 | rasgrp1 | RAS guanyl-releasing protein 1 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MANSMNGRNP | GGRGGNPRKG | RILGIIDAIQ | DAVGPPKQAA | ADRRTVEKTW | KLMDKVVRLC |
| 70 | 80 | 90 | 100 | 110 | 120 |
| QNPKLQLKNS | PPYILDILPD | TYQHLRLILS | KYDDNQKLAQ | LSENEYFKIY | IDSLMKKSKR |
| 130 | 140 | 150 | 160 | 170 | 180 |
| AIRLFKEGKE | RMYEEQSQDR | RNLTKLSLIF | SHMLAEIKAI | FPNGQFQGDN | FRITKADAAE |
| 190 | 200 | 210 | 220 | 230 | 240 |
| FWRKFFGDKT | IVPWKVFRQC | LHEVHQISSG | LEAMALKSTI | DLTCNDYISV | FEFDIFTRLF |
| 250 | 260 | 270 | 280 | 290 | 300 |
| QPWGSILRNW | NFLAVTHPGY | MAFLTYDEVK | ARLQKYSTKP | GSYIFRLSCT | RLGQWAIGYV |
| 310 | 320 | 330 | 340 | 350 | 360 |
| TGDGNILQTI | PHNKPLFQAL | IDGSREGFYL | YPDGRSYNPD | LTGLCEPTPH | DHIKVTQEQY |
| 370 | 380 | 390 | 400 | 410 | 420 |
| ELYCEMGSTF | QLCKICAEND | KDVKIEPCGH | LMCTSCLTAW | QESDGQGCPF | CRCEIKGTEP |
| 430 | 440 | 450 | 460 | 470 | 480 |
| IIVDPFDPRD | EGSRCCSIID | PFGMPMLDLD | DDDDREESLM | MNRLANVRKC | TDRQNSPVTS |
| 490 | 500 | 510 | 520 | 530 | 540 |
| PGSSPLAQRR | KPQPDPLQIP | HLSLPPVPPR | LDLIQKGIVR | SPCGSPTGSP | KSSPCMVRKQ |
| 550 | 560 | 570 | 580 | 590 | 600 |
| DKPLPAPPPP | LRDPPPPPPE | RPPPIPPDNR | LSRHIHHVES | VPSRDPPMPL | EAWCPRDVFG |
| 610 | 620 | 630 | 640 | 650 | 660 |
| TNQLVGCRLL | GEGSPKPGIT | ASSNVNGRHS | RVGSDPVLMR | KHRRHDLPLE | GAKVFSNGHL |
| 670 | 680 | 690 | 700 | 710 | 720 |
| GSEEYDVPPR | LSPPPPVTTL | LPSIKCTGPL | ANSLSEKTRD | PVEEDDDEYK | IPSSHPVSLN |
| 730 | 740 | 750 | 760 | 770 | 780 |
| SQPSHCHNVK | PPVRSCDNGH | CMLNGTHGPS | SEKKSNIPDL | SIYLKGDVFD | SASDPVPLPP |
| 790 | 800 | 810 | 820 | 830 | 840 |
| ARPPTRDNPK | HGSSLNRTPS | DYDLLIPPLG | EDAFDALPPS | LPPPPPPARH | SLIEHSKPPG |
| 850 | 860 | 870 | 880 | 890 | 900 |
| SSSRPSSGQD | LFLLPSDPFV | DLASGQVPLP | PARRLPGENV | KTNRTSQDYD | QLPSCSDGSQ |
| 910 | 920 | 930 | 940 | 950 | 960 |
| APARPPKPRP | RRTAPEIHHR | KPHGPEAALE | NVDAKIAKLM | GEGYAFEEVK | RALEIAQNNV |
| 970 | 980 | ||||
| EVARSILREF | AFPPPVSPRL | NL |