ID GAB2_RAT Reviewed; 665 AA. AC Q9EQH1; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2001, sequence version 2. DT 24-JAN-2024, entry version 123. DE RecName: Full=GRB2-associated-binding protein 2; DE AltName: Full=GRB2-associated binder 2; DE AltName: Full=Growth factor receptor bound protein 2-associated protein 2; GN Name=Gab2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Kong M., Mounier C., Wu J., Posner B.I.; RT "Identification of Gab2 as the major molecule responsible for EGF-induced RT PI3-kinase activation and DNA synthesis in rat hepatocytes."; RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases. RN [2] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Adapter protein which acts downstream of several membrane CC receptors including cytokine, antigen, hormone, cell matrix and growth CC factor receptors to regulate multiple signaling pathways. Regulates CC osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In CC allergic response, it plays a role in mast cells activation and CC degranulation through PI-3-kinase regulation. Also involved in the CC regulation of cell proliferation and hematopoiesis (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, CC GAB2, TEC and BTK; complex formation increases in the presence of CC TNFSF11/RANKL (By similarity). Interacts with HCK. Interacts with SHC1; CC may mediate interaction with receptors (By similarity). Interacts with CC SYK (By similarity). Interacts with PI-3 kinase (By similarity). CC Interacts with GRB2 (via SH3 2 domain) (By similarity). Interacts CC (phosphorylated) with PTPN11 (By similarity). Interacts with TNFRSF11A CC (via cytoplasmic domain) (By similarity). Interacts (phosphorylated) CC with 14-3-3 family proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and CC YWHAZ; prevents interaction with GRB2 and attenuates GAB2 signaling (By CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q9Z1S8}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UQC2}. Cell CC membrane {ECO:0000250|UniProtKB:Q9UQC2}. Membrane raft CC {ECO:0000250|UniProtKB:Q9Z1S8}. CC -!- DOMAIN: The SH3-binding motifs mediate interaction with SHC1 and GRB2. CC {ECO:0000250}. CC -!- DOMAIN: The PH domain mediates phosphatidylinositol 3,4,5-trisphosphate CC and phosphatidylinositol 3,4-bisphosphate binding. {ECO:0000250}. CC -!- PTM: Phosphorylated upon EGF stimulation. Phosphorylated on tyrosine CC residues by HCK upon IL6 signaling (By similarity). Phosphorylated on CC tyrosine residue(s) by the thrombopoietin receptor (TPOR), stem cell CC factor receptor (SCFR), and T-cell and B-cell antigen receptors, gp130, CC IL-2R and IL-3R (By similarity). Phosphorylated upon stimulation of CC TNFRSF11A/RANK by TNFSF11/RANKL (By similarity). {ECO:0000250}. CC -!- PTM: Dephosphorylated by PTPN11. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the GAB family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF230367; AAG44268.2; -; mRNA. DR RefSeq; NP_445869.1; NM_053417.1. DR AlphaFoldDB; Q9EQH1; -. DR SMR; Q9EQH1; -. DR BioGRID; 249977; 1. DR CORUM; Q9EQH1; -. DR IntAct; Q9EQH1; 3. DR MINT; Q9EQH1; -. DR STRING; 10116.ENSRNOP00000016361; -. DR iPTMnet; Q9EQH1; -. DR PhosphoSitePlus; Q9EQH1; -. DR PaxDb; 10116-ENSRNOP00000016361; -. DR GeneID; 84477; -. DR KEGG; rno:84477; -. DR UCSC; RGD:621367; rat. DR AGR; RGD:621367; -. DR CTD; 9846; -. DR RGD; 621367; Gab2. DR eggNOG; ENOG502QTS1; Eukaryota. DR InParanoid; Q9EQH1; -. DR OrthoDB; 2904117at2759; -. DR PhylomeDB; Q9EQH1; -. DR Reactome; R-RNO-109704; PI3K Cascade. DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling. DR Reactome; R-RNO-1433557; Signaling by SCF-KIT. DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-RNO-8853659; RET signaling. DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling. DR Reactome; R-RNO-9607240; FLT3 Signaling. DR Reactome; R-RNO-9674555; Signaling by CSF3 (G-CSF). DR PRO; PR:Q9EQH1; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:RGD. DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISS:UniProtKB. DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD. DR GO; GO:0019903; F:protein phosphatase binding; IPI:RGD. DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; ISS:UniProtKB. DR GO; GO:0016477; P:cell migration; ISO:RGD. DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD. DR GO; GO:0030316; P:osteoclast differentiation; ISS:UniProtKB. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB. DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISO:RGD. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR046355; Gab1-4-like. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR001849; PH_domain. DR PANTHER; PTHR45960; GRB2-ASSOCIATED-BINDING PROTEIN; 1. DR PANTHER; PTHR45960:SF1; GRB2-ASSOCIATED-BINDING PROTEIN 2; 1. DR Pfam; PF00169; PH; 1. DR SMART; SM00233; PH; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. PE 1: Evidence at protein level; KW Cell membrane; Cytoplasm; Membrane; Phosphoprotein; Reference proteome. FT CHAIN 1..665 FT /note="GRB2-associated-binding protein 2" FT /id="PRO_0000050287" FT DOMAIN 8..119 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT REGION 131..183 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 340..442 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 491..517 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 548..631 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 646..665 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 348..355 FT /note="SH3-binding" FT /evidence="ECO:0000250" FT MOTIF 499..508 FT /note="SH3-binding" FT /evidence="ECO:0000250" FT COMPBIAS 131..150 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 160..183 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 360..383 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 394..442 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 548..597 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 614..629 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 135 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 142 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 143 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 150 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 160 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 165 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 211 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 220 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 261 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 262 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 263 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 275 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 278 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 282 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 284 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 290 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 328 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 382 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 388 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 402 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 405 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 420 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 423 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 441 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1S8" FT MOD_RES 532 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 612 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" FT MOD_RES 632 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9UQC2" SQ SEQUENCE 665 AA; 73328 MW; BEB170B69406063E CRC64; MSGGGGDDVV CTGWLRKSPP EKKLRRYAWK KRWFILRSGR MSGDPDVLEY YKNEHSKKPL RIINLNFCEQ VDAGLTFNKK ELQDSFVFDI KTSERTFYLV AETEADMNKW VQSICQICGF NQAEESTDSL RNLSSASHGP RSSPAEFSSS QHLLRERKSS APSHSSQPTL FTFEPPMTSH MQPALSTSAP QEYLYLHQCI SRRTENSRSA SFSQGTRQKS DTAVQKLAQS NGHCINGVSN QVHGFYSLPK PSRHNTEFKD STYDLPRSLA SHGHTKSSLT GSETDNEDVY TFKMPSNTLC REFGDLLVDN MDVPTTPLSA YQIPRTFTLD KNHNAMTVAT SGDSAIAPPP RPPKPSQAET PRWGSPQQKP PIGENSRSVA ATIPRRNTLP AMDNSRLHRA SSCETYEYPT RGSGESASWS AESPGKTAVG RSDSASSDEN YVPMNPGSST LLAMERAGDN SQSAYIPMGP GPHHFDPLGY PSTALPIHRG PSRGSEIQPP PVNRNLKPDR KAKPTPLDLR NNTVIDELPF KSPVTKSWSR INHTFNSSSS QYCRPISTQS ITSTDSGDSE ENYVPMQNPV SASPVPSGTN SPAPRKSTGS VDYLALDFQP GSPSPHRKPS TSSVTSDEKV DYVQVDKEKT QALQNTMQEW TDVRQSSEPS KGAKL //