Q60992
SS
Gene name |
Vav2 |
Protein name |
Guanine nucleotide exchange factor VAV2 |
Names |
VAV-2 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:22325 |
EC number |
|
Protein Class |
|
Descriptions
The Vav family is a group of tyrosine phosphorylation-dependent guanine nucleotide exchange factors (GEFs) that activate members of the Rac and Rho families of guanosine triphosphatases (GTPases) downstream of protein tyrosine kinases. When the tyrosine residues within the acidic (Ac) region are non-phosphorylated, the CH domain and Ac region occlude the GTPase-binding site within DH domain. The interaction is stabilized by the interaction between the hydroxyl group of Tyr174 within Ac region and GTPase binding site as well as the interaction between CH domain and DH-PH domains. The Y174F mutant displays constitutive and phosphorylation-independent catalytic activity. In addition to the N-terminal autoinhibitory regions, the truncation of C-terminal SH3 domain also relives the autoinhibition. C-terminal SH3 domain interacts with DH-PH domains and the intramolecular interaction occludes the GTPase-binding site of DH domain.
Autoinhibitory domains (AIDs)
Target domain |
193-371 (DH domain) |
Relief mechanism |
Partner binding, PTM |
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
- Aghazadeh B et al. (2000) "Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation", Cell, 102, 625-33
- Barreira M et al. (2014) "The C-terminal SH3 domain contributes to the intramolecular inhibition of Vav family proteins", Science signaling, 7, ra35
- Yu B et al. (2010) "Structural and energetic mechanisms of cooperative autoinhibition and activation of Vav1", Cell, 140, 246-56
- Rapley J et al. (2008) "Crucial structural role for the PH and C1 domains of the Vav1 exchange factor", EMBO reports, 9, 655-61
Autoinhibited structure
Activated structure
1 structures for Q60992
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q60992-F1 | Predicted | AlphaFoldDB |
44 variants for Q60992
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3388535652 | 75 | I>S | No | EVA | |
| rs3388540851 | 77 | T>I | No | EVA | |
| rs3388538827 | 81 | V>F | No | EVA | |
| rs3388542112 | 138 | D>V | No | EVA | |
| rs3388540550 | 141 | V>I | No | EVA | |
| rs3388538922 | 157 | D>N | No | EVA | |
| rs3388537903 | 169 | D>G | No | EVA | |
| rs3388537797 | 179 | E>* | No | EVA | |
| rs3388537916 | 181 | Q>K | No | EVA | |
| rs3388540552 | 189 | T>I | No | EVA | |
| rs3388538232 | 200 | E>V | No | EVA | |
| rs3388532265 | 235 | V>I | No | EVA | |
| rs3388532211 | 246 | H>Y | No | EVA | |
| rs3388532205 | 255 | V>M | No | EVA | |
| rs3388542086 | 265 | A>D | No | EVA | |
| rs3388537835 | 283 | S>N | No | EVA | |
| rs3388540862 | 287 | H>Y | No | EVA | |
| rs261140679 | 295 | L>V | No | EVA | |
| rs3388532221 | 350 | E>K | No | EVA | |
| rs3388538786 | 404 | D>E | No | EVA | |
| rs229567277 | 449 | F>L | No | EVA | |
| rs3391247590 | 451 | K>T | No | EVA | |
| rs3391377053 | 454 | D>N | No | EVA | |
| rs3388538193 | 508 | K>N | No | EVA | |
| rs3388537807 | 520 | T>I | No | EVA | |
| rs3388537949 | 524 | T>S | No | EVA | |
| rs3388538602 | 552 | H>D | No | EVA | |
| rs3388538602 | 552 | H>Y | No | EVA | |
| rs3388538872 | 558 | V>A | No | EVA | |
| rs3388537909 | 559 | I>F | No | EVA | |
| rs3388537888 | 593 | P>L | No | EVA | |
| rs3388538223 | 596 | K>R | No | EVA | |
| rs3388540548 | 626 | T>I | No | EVA | |
| rs3388540849 | 628 | K>R | No | EVA | |
| rs3388537814 | 678 | K>N | No | EVA | |
| rs3388537866 | 712 | V>SDG* | No | EVA | |
| rs3388538207 | 740 | H>Y | No | EVA | |
| rs3388532262 | 745 | S>R | No | EVA | |
| rs864293105 | 763 | T>S | No | EVA | |
| rs3388538824 | 773 | A>T | No | EVA | |
| rs3391310758 | 788 | L>P | No | EVA | |
| rs3388538239 | 807 | V>G | No | EVA | |
| rs3388538628 | 812 | V>M | No | EVA | |
| rs3388541181 | 824 | E>G | No | EVA |
No associated diseases with Q60992
19 regional properties for Q60992
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | FERM domain | 35 - 378 | IPR000299 |
| domain | Protein kinase domain | 542 - 806 | IPR000719-1 |
| domain | Protein kinase domain | 846 - 1123 | IPR000719-2 |
| domain | SH2 domain | 395 - 499 | IPR000980 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 543 - 802 | IPR001245-1 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 846 - 1119 | IPR001245-2 |
| active_site | Tyrosine-protein kinase, active site | 969 - 981 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 852 - 880 | IPR017441 |
| domain | FERM central domain | 150 - 259 | IPR019748 |
| domain | Band 4.1 domain | 31 - 268 | IPR019749 |
| domain | Tyrosine-protein kinase, catalytic domain | 542 - 802 | IPR020635-1 |
| domain | Tyrosine-protein kinase, catalytic domain | 846 - 1120 | IPR020635-2 |
| domain | Janus kinase 2, pseudokinase domain | 542 - 803 | IPR035588 |
| domain | Janus kinase 2, catalytic domain | 841 - 1124 | IPR035589 |
| domain | Tyrosine-protein kinase JAK2, SH2 domain | 384 - 480 | IPR035860 |
| domain | JAK2, FERM domain C-lobe | 264 - 384 | IPR037838 |
| domain | JAK, FERM F2 lobe domain | 140 - 259 | IPR041046 |
| domain | FERM F1 lobe ubiquitin-like domain | 37 - 132 | IPR041155 |
| domain | JAK1-3/TYK2, pleckstrin homology-like domain | 305 - 379 | IPR041381 |
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. |
| 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 |
|---|---|
| epidermal growth factor receptor binding | Binding to an epidermal growth factor receptor. |
| 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. |
| phosphotyrosine residue binding | Binding to a phosphorylated tyrosine residue within a protein. |
7 GO annotations of biological process
| Name | Definition |
|---|---|
| angiogenesis | Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels. |
| cell migration | The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. |
| cell projection assembly | Formation of a prolongation or process extending from a cell, e.g. a flagellum or axon. |
| lamellipodium assembly | Formation of a lamellipodium, a thin sheetlike extension of the surface of a migrating cell. |
| positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | Any process that activates or increases the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B. |
| regulation of cell size | Any process that modulates the size of a cell. |
| small GTPase-mediated signal transduction | The series of molecular signals in which a small monomeric GTPase relays a signal. |
8 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q9NHV9 | Vav | Protein vav | Drosophila melanogaster (Fruit fly) | SS |
| P15498 | VAV1 | Proto-oncogene vav | Homo sapiens (Human) | EV SS |
| Q9UKW4 | VAV3 | Guanine nucleotide exchange factor VAV3 | Homo sapiens (Human) | SS |
| P52735 | VAV2 | Guanine nucleotide exchange factor VAV2 | Homo sapiens (Human) | SS |
| P27870 | Vav1 | Proto-oncogene vav | Mus musculus (Mouse) | EV |
| Q9R0C8 | Vav3 | Guanine nucleotide exchange factor VAV3 | Mus musculus (Mouse) | SS |
| P54100 | Vav1 | Proto-oncogene vav | Rattus norvegicus (Rat) | SS |
| Q45FX5 | vav-1 | Protein vav-1 | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MEQWRQCGRW | LIDCKVLPPN | HRVVWPSAVV | FDLAQALRDG | VLLCQLLHNL | SPGSIDLKDI |
| 70 | 80 | 90 | 100 | 110 | 120 |
| NFRPQMSQFL | CLKNIRTFLK | VCHDKFGLRN | SELFDPFDLF | DVRDFGKVIS | AVSRLSLHSI |
| 130 | 140 | 150 | 160 | 170 | 180 |
| AQSKGIRPFP | SEETAENDDD | VYRSLEELAD | EHDLGEDIYD | CVPCEDEGDD | IYEDIIKVEV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| QQPMKMGMTE | DDKRSCCLLE | IQETEAKYYR | TLEDIEKNYM | GPLRLVLSPA | DMAAVFINLE |
| 250 | 260 | 270 | 280 | 290 | 300 |
| DLIKVHHSFL | RAIDVSMMAG | GSTLAKVFLE | FKERLLIYGE | YCSHMEHAQS | TLNQLLASRE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| DFRQKVEECT | LRVQDGKFKL | QDLLVVPMQR | VLKYHLLLKE | LLSHSADRPE | RQQLKEALEA |
| 370 | 380 | 390 | 400 | 410 | 420 |
| MQDLAMYINE | VKRDKETLKK | ISEFQCSIEN | LQVKLEEFGR | PKIDGELKVR | SIVNHTKQDR |
| 430 | 440 | 450 | 460 | 470 | 480 |
| YLFLFDKVVI | VCKRKGYSYE | LKEVIELLFH | KMTDDPMHNK | DIKKWSYGFY | LIHLQGKQGF |
| 490 | 500 | 510 | 520 | 530 | 540 |
| QFFCKTEDMK | RKWMEQFEMA | MSNIKPDKAN | ANHHSFQMYT | FDKTTNCKAC | KMFLRGTFYQ |
| 550 | 560 | 570 | 580 | 590 | 600 |
| GYLCTRCGVG | AHKECLEVIP | PCKMSSPADV | DAPGAGPGPK | MVAVQNYHGN | PAPPGKPVLT |
| 610 | 620 | 630 | 640 | 650 | 660 |
| FQTGDVIELL | RGDPDSPWWE | GRLVQTRKSG | YFPSSSVKPC | PVDGRPPTGR | PPSREIDYTA |
| 670 | 680 | 690 | 700 | 710 | 720 |
| YPWFAGNMER | QQTDNLLKSH | ASGTYLIRER | PAEAERFAIS | IKFNDEVKHI | KVVEKDSWIH |
| 730 | 740 | 750 | 760 | 770 | 780 |
| ITEAKKFESL | LELVEYYQCH | SLKESFKQLD | TTLKFPYKSR | ERTTSRASSR | SPASCASYNF |
| 790 | 800 | 810 | 820 | 830 | 840 |
| SFLSPQGLSF | APQAPSAPFW | SVFTPRVIGT | AVARYNFAAR | DMRELSLREG | DVVKIYSRIG |
| 850 | 860 | ||||
| GDQGWWKGET | NGRIGWFPST | YVEEEGVQ |