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

194-373 (DH domain)

Relief mechanism

PTM

Assay

Target domain

194-373 (DH domain)

Relief mechanism

PTM

Assay

Target domain

194-373 (DH domain)

Relief mechanism

Partner binding, PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for P54100

Entry ID Method Resolution Chain Position Source
AF-P54100-F1 Predicted AlphaFoldDB

No variants for P54100

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P54100

No associated diseases with P54100

12 regional properties for P54100

Type Name Position InterPro Accession
domain Dbl homology (DH) domain 194 - 373 IPR000219
domain SH2 domain 667 - 763 IPR000980
conserved_site Guanine-nucleotide dissociation stimulator, CDC24, conserved site 322 - 347 IPR001331
domain SH3 domain 590 - 658 IPR001452-1
domain SH3 domain 780 - 840 IPR001452-2
domain Pleckstrin homology domain 402 - 506 IPR001849
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 515 - 565 IPR002219
domain Calmodulin-regulated spectrin-associated protein-like, Calponin-homology domain 19 - 102 IPR022613
domain VAV1 protein, second SH3 domain 784 - 837 IPR035729
domain VAV1 protein, first SH3 domain 594 - 656 IPR035730
domain VAV1, SH2 domain 663 - 765 IPR035879
domain Vav, PH domain 385 - 508 IPR037832

Functions

Description
EC Number
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

1 GO annotations of cellular component

Name Definition
cell-cell junction A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.

4 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.
phosphorylation-dependent protein binding Binding to a protein upon phosphorylation of the target protein.
phosphotyrosine residue binding Binding to a phosphorylated tyrosine residue within a protein.

17 GO annotations of biological process

Name Definition
cell development The process whose specific outcome is the progression of the cell over time, from its formation to the mature structure. Cell development does not include the steps involved in committing a cell to a specific fate.
G protein-coupled receptor signaling pathway The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
immune response Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat.
immune response-regulating cell surface receptor signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell capable of activating, perpetuating, or inhibiting an immune response.
integrin-mediated signaling pathway The series of molecular signals initiated by an extracellular ligand binding to an integrin on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
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.
neutrophil chemotaxis The directed movement of a neutrophil cell, the most numerous polymorphonuclear leukocyte found in the blood, in response to an external stimulus, usually an infection or wounding.
phagocytosis A vesicle-mediated transport process that results in the engulfment of external particulate material by phagocytes and their delivery to the lysosome. The particles are initially contained within phagocytic vacuoles (phagosomes), which then fuse with primary lysosomes to effect digestion of the particles.
positive regulation of cell adhesion Any process that activates or increases the frequency, rate or extent of cell adhesion.
positive regulation of GTPase activity Any process that activates or increases the activity of a GTPase.
positive regulation of natural killer cell mediated cytotoxicity Any process that activates or increases the frequency, rate or extent of natural killer cell mediated cytotoxicity.
reactive oxygen species metabolic process The chemical reactions and pathways involving a reactive oxygen species, any molecules or ions formed by the incomplete one-electron reduction of oxygen. They contribute to the microbicidal activity of phagocytes, regulation of signal transduction and gene expression, and the oxidative damage to biopolymers.
regulation of cell size Any process that modulates the size of a cell.
regulation of GTPase activity Any process that modulates the rate of GTP hydrolysis by a GTPase.
small GTPase mediated signal transduction The series of molecular signals in which a small monomeric GTPase relays a signal.
T cell activation The change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
T cell differentiation The process in which a precursor cell type acquires characteristics of a more mature T-cell. A T cell is a type of lymphocyte whose definin characteristic is the expression of a T cell receptor complex.

9 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q08DN7 VAV1 Proto-oncogene vav Bos taurus (Bovine) SS
Q9NHV9 Vav Protein vav Drosophila melanogaster (Fruit fly) SS
Q9UKW4 VAV3 Guanine nucleotide exchange factor VAV3 Homo sapiens (Human) SS
P52735 VAV2 Guanine nucleotide exchange factor VAV2 Homo sapiens (Human) SS
P15498 VAV1 Proto-oncogene vav Homo sapiens (Human) EV SS
Q9R0C8 Vav3 Guanine nucleotide exchange factor VAV3 Mus musculus (Mouse) SS
Q60992 Vav2 Guanine nucleotide exchange factor VAV2 Mus musculus (Mouse) SS
P27870 Vav1 Proto-oncogene vav Mus musculus (Mouse) EV
Q45FX5 vav-1 Protein vav-1 Caenorhabditis elegans SS
10 20 30 40 50 60
MELWRQCTHW LIQCRVLPPS HRVTWEGAQV CELAQALRDG VLLCQLLNNL LPHAINLREV
70 80 90 100 110 120
NLRPQMSQFL CLKNIRTFLS TCCEKFGLKR SELFEAFDLF DVQDFGKVIY TLSALSWTPI
130 140 150 160 170 180
AQNKGIMPFP TEDSALGDED IYSGLSDQID DTAEEDEDLY DCVENEEAEG DEIYEDLMRS
190 200 210 220 230 240
ESVPTPPKMT EYDKRCCCLR EIQQTEEKYT DTLGSIQQHF MKPLQRFLKP QDMETIFVNI
250 260 270 280 290 300
EELLSVHTHF LKELKDALSG PGATMLYQVF IKYKERFLVY GRYCSQVESA IKHLDQVATA
310 320 330 340 350 360
REDVQMKLEE CSQRANNGRF TLRDLLMVPM QRVLKYHLLL QELVKHTQDT TEKENLRLAL
370 380 390 400 410 420
DAMRDLAQCV NEVKRDNETL RQITNFQLSI ENLDQSLANY GRPKIDGELK ITSVERRSKT
430 440 450 460 470 480
DRYAFLLDKA LLICKRRGDS YDLKASVNLH SFQVRDDSSG ERDNKKWSHM FLLIEDQGAQ
490 500 510 520 530 540
GYELFFKTRE LKKKWMEQFE MAISNIYPEN ATANGHDFQM FSFEETTSCK ACQMLLRGTF
550 560 570 580 590 600
YQGYRCYRCR APAHKECLGR VPPCGRQDFS GTMKKDKLHR RAQDKKRNEL GLPKMEVCQE
610 620 630 640 650 660
YYGIPPPPGA FGPFLRLNPG DIVELTKAEA EHTWWEGRNT ATNEVGWFPC NRVRPYVHGP
670 680 690 700 710 720
PQDLSVHLWY AGPMERAGAE GILTNRSDGT YLVRQRVKDT AEFAISIKYN VEVKHIKIMT
730 740 750 760 770 780
SEGLYRITEK KAFRGLPELV EFYQQNSLKD CFKSLDTTLQ FPYKEPERRA INKPPVGSTK
790 800 810 820 830 840
YFGTAKARYD FCARDRSELS LKEGDIIKIL NKKGQQGWWR GEIYGRIGWF PSNYVEEDYS
EYC