Q9Z1S8 · GAB2_MOUSE
- ProteinGRB2-associated-binding protein 2
- GeneGab2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids665 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling (PubMed:15750601).
In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis
In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | membrane raft | |
Cellular Component | plasma membrane | |
Cellular Component | protein-containing complex | |
Molecular Function | phosphatidylinositol-3,4,5-trisphosphate binding | |
Molecular Function | phosphatidylinositol-3,4-bisphosphate binding | |
Molecular Function | protein domain specific binding | |
Molecular Function | protein phosphatase binding | |
Molecular Function | transmembrane receptor protein tyrosine kinase adaptor activity | |
Biological Process | cell migration | |
Biological Process | integrin-mediated signaling pathway | |
Biological Process | intracellular signal transduction | |
Biological Process | osteoclast differentiation | |
Biological Process | phosphatidylinositol 3-kinase/protein kinase B signal transduction | |
Biological Process | positive regulation of cell population proliferation | |
Biological Process | positive regulation of epithelial cell migration | |
Biological Process | positive regulation of mast cell degranulation | |
Biological Process | signal transduction |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGRB2-associated-binding protein 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9Z1S8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Mice are viable and healthy for up to 15 months. However, they have reduced number of mast cells and develop osteopetrosis.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 32 | Impairs EGF-induced phosphorylation at S-211 and T-388 and binding to phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate. | ||||
Sequence: R → C |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000050286 | 1-665 | GRB2-associated-binding protein 2 | |||
Sequence: MSGGGGDDVVCTGWLRKSPPEKKLRRYAWKKRWFILRSGRMSGDPDVLEYYKNEHSKKPLRIINLNLCEQVDAGLTFNKKELQDSFVFDIKTSERTFYLVAETEADMNKWVQSICQICGFNQAEESTDSLRNLSSASHGPRSSPAEFSSSQHLLRERKSSAPSHSSQPTLFTFEPPVSSHMQPTLSTSAPQEYLYLHQCISRRTENARSASFSQGTRQKSDTAVQKLAQSNGHCINGVGGQVHGFYSLPKPSRHNTEFKDSTYDLPRSLASHGHTKSSLTGSETDNEDVYTFKMPSNTLCRELGDLLVDNMDVPTTPLSAYQIPRTFTLDKNHNAMTVATPGDSAIAPPPRPPKPSQAETSQWGSIQQRPPISENSRSVAATIPRRNTLPAMDNSRLHRASSCETYEYPARGSGESASWSAEPPGKTAVGRSNSASSDDNYVPMNPGSSTLLAMERPGDNSQSVYIPMSPGPHHFDPLGYPSTALPIHRGPSRGSEIQPPPVNRNLKPDRKAKPTPLDLRNNTVIDELPFKSPVTKSWSRINHTFNSSSSQYCRPISTQSITSTDSGDSEENYVPMQNPVSASPVPSGTNSPAPKKSTGSVDYLALDFQPGSPSPHRKPSTSSVTSDEKVDYVQVDKEKTQALQNTMQEWTDVRQSSEPSKGAKL | ||||||
Modified residue | 2 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 135 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 142 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 143 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 149 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 150 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 160 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 165 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 211 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 220 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 261 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 262 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 263 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 275 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 278 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 282 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 284 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 290 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 328 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 365 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 382 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 388 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 402 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 405 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 420 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 441 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 469 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 532 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 612 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 632 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated upon EGF stimulation. Phosphorylated on tyrosine residues by HCK upon IL6 signaling (By similarity).
Phosphorylated on tyrosine residue(s) by the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors, gp130, IL-2R and IL-3R. Phosphorylated upon stimulation of TNFRSF11A/RANK by TNFSF11/RANKL
Phosphorylated on tyrosine residue(s) by the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors, gp130, IL-2R and IL-3R. Phosphorylated upon stimulation of TNFRSF11A/RANK by TNFSF11/RANKL
Dephosphorylated by PTPN11.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitously expressed.
Interaction
Subunit
Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294).
Interacts with HCK (By similarity).
Interacts with SHC1; may mediate interaction with receptors. Interacts with SYK. Interacts with PI-3 kinase. Interacts with GRB2 (via SH3 2 domain). Interacts (phosphorylated) with PTPN11. Interacts with TNFRSF11A (via cytoplasmic domain). Interacts (phosphorylated) with 14-3-3 family proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; prevents interaction with GRB2 and attenuates GAB2 signaling
Interacts with HCK (By similarity).
Interacts with SHC1; may mediate interaction with receptors. Interacts with SYK. Interacts with PI-3 kinase. Interacts with GRB2 (via SH3 2 domain). Interacts (phosphorylated) with PTPN11. Interacts with TNFRSF11A (via cytoplasmic domain). Interacts (phosphorylated) with 14-3-3 family proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; prevents interaction with GRB2 and attenuates GAB2 signaling
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Z1S8 | Lyn P25911 | 2 | EBI-641738, EBI-643537 | |
BINARY | Q9Z1S8 | Ptpn6 P29351 | 2 | EBI-641738, EBI-2620699 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-119 | PH | ||||
Sequence: DVVCTGWLRKSPPEKKLRRYAWKKRWFILRSGRMSGDPDVLEYYKNEHSKKPLRIINLNLCEQVDAGLTFNKKELQDSFVFDIKTSERTFYLVAETEADMNKWVQSICQICG | ||||||
Compositional bias | 131-150 | Polar residues | ||||
Sequence: RNLSSASHGPRSSPAEFSSS | ||||||
Region | 131-184 | Disordered | ||||
Sequence: RNLSSASHGPRSSPAEFSSSQHLLRERKSSAPSHSSQPTLFTFEPPVSSHMQPT | ||||||
Compositional bias | 160-184 | Polar residues | ||||
Sequence: SAPSHSSQPTLFTFEPPVSSHMQPT | ||||||
Region | 338-396 | Disordered | ||||
Sequence: VATPGDSAIAPPPRPPKPSQAETSQWGSIQQRPPISENSRSVAATIPRRNTLPAMDNSR | ||||||
Motif | 348-355 | SH3-binding | ||||
Sequence: PPPRPPKP | ||||||
Compositional bias | 357-383 | Polar residues | ||||
Sequence: QAETSQWGSIQQRPPISENSRSVAATI | ||||||
Region | 408-445 | Disordered | ||||
Sequence: YPARGSGESASWSAEPPGKTAVGRSNSASSDDNYVPMN | ||||||
Compositional bias | 427-445 | Polar residues | ||||
Sequence: TAVGRSNSASSDDNYVPMN | ||||||
Region | 491-517 | Disordered | ||||
Sequence: PSRGSEIQPPPVNRNLKPDRKAKPTPL | ||||||
Motif | 499-508 | SH3-binding | ||||
Sequence: PPPVNRNLKP | ||||||
Compositional bias | 548-597 | Polar residues | ||||
Sequence: SSSQYCRPISTQSITSTDSGDSEENYVPMQNPVSASPVPSGTNSPAPKKS | ||||||
Region | 548-632 | Disordered | ||||
Sequence: SSSQYCRPISTQSITSTDSGDSEENYVPMQNPVSASPVPSGTNSPAPKKSTGSVDYLALDFQPGSPSPHRKPSTSSVTSDEKVDY | ||||||
Compositional bias | 614-629 | Polar residues | ||||
Sequence: SPHRKPSTSSVTSDEK | ||||||
Region | 646-665 | Disordered | ||||
Sequence: TMQEWTDVRQSSEPSKGAKL |
Domain
The SH3-binding motifs mediate interaction with SHC1 and GRB2.
The PH domain mediates phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate binding.
Sequence similarities
Belongs to the GAB family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length665
- Mass (Da)73,208
- Last updated2004-04-13 v2
- ChecksumE8955EE638174085
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 131-150 | Polar residues | ||||
Sequence: RNLSSASHGPRSSPAEFSSS | ||||||
Compositional bias | 160-184 | Polar residues | ||||
Sequence: SAPSHSSQPTLFTFEPPVSSHMQPT | ||||||
Compositional bias | 357-383 | Polar residues | ||||
Sequence: QAETSQWGSIQQRPPISENSRSVAATI | ||||||
Compositional bias | 427-445 | Polar residues | ||||
Sequence: TAVGRSNSASSDDNYVPMN | ||||||
Sequence conflict | 542 | in Ref. 1; AAD05166 | ||||
Sequence: N → NS | ||||||
Compositional bias | 548-597 | Polar residues | ||||
Sequence: SSSQYCRPISTQSITSTDSGDSEENYVPMQNPVSASPVPSGTNSPAPKKS | ||||||
Compositional bias | 614-629 | Polar residues | ||||
Sequence: SPHRKPSTSSVTSDEK |
Keywords
- Technical term