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Protein

GRB2-associated-binding protein 2

Gene

Gab2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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.5 Publications

GO - Molecular functioni

GO - Biological processi

  • cell migration Source: MGI
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • integrin-mediated signaling pathway Source: MGI
  • osteoclast differentiation Source: UniProtKB
  • phosphatidylinositol-mediated signaling Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of epithelial cell migration Source: CACAO
  • positive regulation of mast cell degranulation Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.

Names & Taxonomyi

Protein namesi
Recommended name:
GRB2-associated-binding protein 2
Alternative name(s):
GRB2-associated binder 2
Growth factor receptor bound protein 2-associated protein 2
PH domain-containing adaptor molecule p97
Gene namesi
Name:Gab2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1333854. Gab2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are viable and healthy for up to 15 months. However, they have reduced number of mast cells and develop osteopetrosis.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi32 – 321R → C: Impairs EGF-induced phosphorylation at S-211 and T-388 and binding to phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 665665GRB2-associated-binding protein 2PRO_0000050286Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21PhosphoserineBy similarity
Modified residuei135 – 1351PhosphoserineBy similarity
Modified residuei142 – 1421PhosphoserineBy similarity
Modified residuei143 – 1431PhosphoserineBy similarity
Modified residuei149 – 1491PhosphoserineBy similarity
Modified residuei150 – 1501PhosphoserineBy similarity
Modified residuei160 – 1601PhosphoserineBy similarity
Modified residuei165 – 1651PhosphoserineBy similarity
Modified residuei211 – 2111Phosphoserine1 Publication
Modified residuei220 – 2201PhosphoserineBy similarity
Modified residuei261 – 2611PhosphoserineCombined sources
Modified residuei262 – 2621PhosphothreonineCombined sources
Modified residuei263 – 2631PhosphotyrosineCombined sources
Modified residuei275 – 2751PhosphothreonineBy similarity
Modified residuei278 – 2781PhosphoserineBy similarity
Modified residuei282 – 2821PhosphoserineBy similarity
Modified residuei284 – 2841PhosphothreonineBy similarity
Modified residuei290 – 2901PhosphotyrosineCombined sources
Modified residuei328 – 3281PhosphothreonineBy similarity
Modified residuei365 – 3651PhosphoserineBy similarity
Modified residuei382 – 3821PhosphothreonineBy similarity
Modified residuei388 – 3881Phosphothreonine1 Publication
Modified residuei402 – 4021PhosphoserineBy similarity
Modified residuei405 – 4051PhosphothreonineCombined sources
Modified residuei420 – 4201PhosphoserineBy similarity
Modified residuei441 – 4411Phosphotyrosine1 Publication
Modified residuei469 – 4691PhosphoserineBy similarity
Modified residuei532 – 5321PhosphoserineBy similarity
Modified residuei612 – 6121PhosphoserineBy similarity
Modified residuei632 – 6321PhosphotyrosineBy similarity

Post-translational modificationi

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.By similarity4 Publications
Dephosphorylated by PTPN11.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9Z1S8.
PaxDbiQ9Z1S8.
PRIDEiQ9Z1S8.

PTM databases

iPTMnetiQ9Z1S8.
PhosphoSiteiQ9Z1S8.

Expressioni

Tissue specificityi

Ubiquitously expressed.2 Publications

Interactioni

Subunit structurei

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.By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-41351N.
IntActiQ9Z1S8. 10 interactions.
MINTiMINT-244287.
STRINGi10090.ENSMUSP00000004622.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1S8.
SMRiQ9Z1S8. Positions 29-114.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 119112PHPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi348 – 3558SH3-bindingBy similarity
Motifi499 – 50810SH3-bindingBy similarity

Domaini

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 similaritiesi

Belongs to the GAB family.Curated
Contains 1 PH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IEDA. Eukaryota.
ENOG4111RDE. LUCA.
HOVERGENiHBG051685.
InParanoidiQ9Z1S8.
PhylomeDBiQ9Z1S8.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z1S8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGGGGDDVV CTGWLRKSPP EKKLRRYAWK KRWFILRSGR MSGDPDVLEY
60 70 80 90 100
YKNEHSKKPL RIINLNLCEQ VDAGLTFNKK ELQDSFVFDI KTSERTFYLV
110 120 130 140 150
AETEADMNKW VQSICQICGF NQAEESTDSL RNLSSASHGP RSSPAEFSSS
160 170 180 190 200
QHLLRERKSS APSHSSQPTL FTFEPPVSSH MQPTLSTSAP QEYLYLHQCI
210 220 230 240 250
SRRTENARSA SFSQGTRQKS DTAVQKLAQS NGHCINGVGG QVHGFYSLPK
260 270 280 290 300
PSRHNTEFKD STYDLPRSLA SHGHTKSSLT GSETDNEDVY TFKMPSNTLC
310 320 330 340 350
RELGDLLVDN MDVPTTPLSA YQIPRTFTLD KNHNAMTVAT PGDSAIAPPP
360 370 380 390 400
RPPKPSQAET SQWGSIQQRP PISENSRSVA ATIPRRNTLP AMDNSRLHRA
410 420 430 440 450
SSCETYEYPA RGSGESASWS AEPPGKTAVG RSNSASSDDN YVPMNPGSST
460 470 480 490 500
LLAMERPGDN SQSVYIPMSP GPHHFDPLGY PSTALPIHRG PSRGSEIQPP
510 520 530 540 550
PVNRNLKPDR KAKPTPLDLR NNTVIDELPF KSPVTKSWSR INHTFNSSSS
560 570 580 590 600
QYCRPISTQS ITSTDSGDSE ENYVPMQNPV SASPVPSGTN SPAPKKSTGS
610 620 630 640 650
VDYLALDFQP GSPSPHRKPS TSSVTSDEKV DYVQVDKEKT QALQNTMQEW
660
TDVRQSSEPS KGAKL
Length:665
Mass (Da):73,208
Last modified:April 13, 2004 - v2
Checksum:iE8955EE638174085
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti542 – 5421N → NS in AAD05166 (PubMed:9885561).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104244 mRNA. Translation: AAD05166.1.
AB018414 mRNA. Translation: BAA76738.1.
UniGeneiMm.42033.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF104244 mRNA. Translation: AAD05166.1.
AB018414 mRNA. Translation: BAA76738.1.
UniGeneiMm.42033.

3D structure databases

ProteinModelPortaliQ9Z1S8.
SMRiQ9Z1S8. Positions 29-114.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-41351N.
IntActiQ9Z1S8. 10 interactions.
MINTiMINT-244287.
STRINGi10090.ENSMUSP00000004622.

PTM databases

iPTMnetiQ9Z1S8.
PhosphoSiteiQ9Z1S8.

Proteomic databases

MaxQBiQ9Z1S8.
PaxDbiQ9Z1S8.
PRIDEiQ9Z1S8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1333854. Gab2.

Phylogenomic databases

eggNOGiENOG410IEDA. Eukaryota.
ENOG4111RDE. LUCA.
HOVERGENiHBG051685.
InParanoidiQ9Z1S8.
PhylomeDBiQ9Z1S8.

Enzyme and pathway databases

ReactomeiR-MMU-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.

Miscellaneous databases

PROiQ9Z1S8.
SOURCEiSearch...

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
InterProiIPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation."
    Gu H., Pratt J.C., Burakoff S.J., Neel B.G.
    Mol. Cell 2:729-740(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-5; 81-91; 251-270; 277-293; 512-529; 630-635 AND 640-648, FUNCTION, PHOSPHORYLATION, INTERACTION WITH GRB2; PTPN11 AND SHC1, TISSUE SPECIFICITY.
  2. "Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors."
    Nishida K., Yoshida Y., Itoh M., Fukada T., Ohtani T., Shirogane T., Atsumi T., Takahashi-Tezuka M., Ishihara K., Hibi M., Hirano T.
    Blood 93:1809-1816(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN11, INTERACTION WITH GRB2; PTPN11 AND PI-3 KINASE.
  3. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  4. "The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis."
    Wada T., Nakashima T., Oliveira-dos-Santos A.J., Gasser J., Hara H., Schett G., Penninger J.M.
    Nat. Med. 11:394-399(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH TNFRSF11A, PHOSPHORYLATION AT TYR-441.
  5. "Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit signals from FcepsilonRI."
    Yu M., Lowell C.A., Neel B.G., Gu H.
    J. Immunol. 176:2421-2429(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SYK, LIPID-BINDING, MUTAGENESIS OF ARG-32.
  6. Cited for: FUNCTION.
  7. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
    Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
    J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261; THR-262; TYR-263 AND TYR-290, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Mast cell.
  8. "Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein."
    Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P., Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D., Guilhaus M., James D.E., Daly R.J.
    EMBO J. 27:2305-2316(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ARG-32, PHOSPHORYLATION AT SER-211 AND THR-388.
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-405, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney, Lung, Spleen and Testis.

Entry informationi

Entry nameiGAB2_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1S8
Secondary accession number(s): Q9R1X3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: July 6, 2016
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.