GAB2_RAT
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 03-AUG-2022, entry version 116.
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: Interacts with HCK. Interacts with SHC1; may mediate
CC interaction with receptors (By similarity). Interacts with SYK (By
CC similarity). Interacts with PI-3 kinase (By similarity). Interacts with
CC GRB2 (via SH3 2 domain) (By similarity). Interacts (phosphorylated)
CC with PTPN11 (By similarity). Interacts with TNFRSF11A (via cytoplasmic
CC domain) (By similarity). Interacts (phosphorylated) with 14-3-3 family
CC proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; prevents
CC interaction with GRB2 and attenuates GAB2 signaling (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}.
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}.
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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; Q9EQH1; -.
DR PRIDE; Q9EQH1; -.
DR GeneID; 84477; -.
DR KEGG; rno:84477; -.
DR UCSC; RGD:621367; rat.
DR CTD; 9846; -.
DR RGD; 621367; Gab2.
DR eggNOG; ENOG502QTS1; Eukaryota.
DR InParanoid; Q9EQH1; -.
DR OrthoDB; 1153633at2759; -.
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: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:0035591; F:signaling adaptor activity; IBA:GO_Central.
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:0048015; P:phosphatidylinositol-mediated signaling; 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; -; 1.
DR InterPro; IPR046355; Gab1-4-like.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR45960; PTHR45960; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00233; PH; 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
