GRB2_PONAB
ID GRB2_PONAB Reviewed; 217 AA.
AC Q5R4J7;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Growth factor receptor-bound protein 2;
DE AltName: Full=Adapter protein GRB2;
DE AltName: Full=SH2/SH3 adapter GRB2;
GN Name=GRB2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Adapter protein that provides a critical link between cell
CC surface growth factor receptors and the Ras signaling pathway.
CC {ECO:0000250|UniProtKB:P62993}.
CC -!- SUBUNIT: Associates (via SH2 domain) with activated EGF and PDGF
CC receptors (tyrosine phosphorylated) (By similarity). Interacts with
CC PDGFRA (tyrosine phosphorylated); the interaction may be indirect (By
CC similarity). Also associates to other cellular Tyr-phosphorylated
CC proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via the
CC concerted action of both its SH2 and SH3 domains. It also seems to
CC interact with RAS in the signaling pathway leading to DNA synthesis.
CC Interacts with SOS1. Forms a complex with MUC1 and SOS1, through
CC interaction of the SH3 domains with SOS1 and the SH2 domain with
CC phosphorylated MUC1. Interacts with phosphorylated MET (By similarity).
CC Interacts with phosphorylated TOM1L1 (By similarity). Interacts with
CC the phosphorylated C-terminus of SH2B2 (By similarity). Interacts with
CC phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR
CC activation (By similarity). Interacts with NISCH, PTPNS1 and REPS2 (By
CC similarity). Interacts with syntrophin SNTA1 (By similarity). Interacts
CC (via SH3 domains) with REPS1 (By similarity). Interacts (via SH3
CC domains) with PIK3C2B. Interacts with CBL and CBLB (By similarity).
CC Interacts with AJUBA and CLNK (By similarity). Interacts (via SH2
CC domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).
CC Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (By similarity).
CC Interacts with PTPN11 (By similarity). Interacts with PRNP (By
CC similarity). Interacts with RALGPS1. Interacts with HCST (By
CC similarity). Interacts with KDR (By similarity). Interacts with FLT1
CC (tyrosine-phosphorylated) (By similarity). Interacts with GAPT and
CC PTPRE. Interacts (via SH2 domain) with KIF26A. Interacts (via SH3 2)
CC with GAB2. Interacts with ADAM15 (By similarity). Interacts with
CC THEMIS2 (By similarity). Interacts (via SH2 domain) with AXL
CC (phosphorylated). Interacts (via SH2 domain) with KIT (phosphorylated).
CC Interacts with PTPRJ and BCR. Interacts with PTPN23. Interacts with
CC FLT4 (tyrosine phosphorylated). Interacts with EPHB1 and SHC1;
CC activates the MAPK/ERK cascade to regulate cell migration. Part of a
CC complex including TNK2, GRB2, LTK and one receptor tyrosine kinase
CC (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by
CC TNK2. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated).
CC Interacts with ERBB4. Interacts with NTRK1 (phosphorylated upon ligand-
CC binding). Interacts with PTK2/FAK1 (tyrosine phosphorylated). Interacts
CC with PTK2B/PYK2 (tyrosine phosphorylated). Interacts (via SH2-domain)
CC with SCIMP; this interaction is dependent on phosphorylation on SCIMP
CC 'Tyr-69' (By similarity). Interacts (via SH3 domains) with GAREM1
CC isoform 1 (via proline-rich domain and tyrosine phosphorylated); the
CC interaction occurs upon EGF stimulation (By similarity). Interacts with
CC DAB2 (By similarity). Interacts with TESPA1 (By similarity). Interacts
CC with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the
CC association is weaker in the absence of TESPA1 (By similarity).
CC Interacts with CD28 (By similarity). Interacts with RAB13; may recruit
CC RAB13 to the leading edge of migrating endothelial cells where it can
CC activate RHOA (By similarity). Interacts with ASAP3 (phosphorylated
CC form) (By similarity). Interacts (via SH2 domain) with PTPRH
CC (phosphorylated form) (By similarity). Interacts with PTPRO
CC (phosphorylated form) (By similarity). Interacts with PTPRB
CC (phosphorylated form) (By similarity). Interacts (via SH3 domain 2)
CC with PRR14 (via proline-rich region). Interacts with FCRL6 (tyrosine
CC phosphorylated form). Interacts with RHEX (via tyrosine-phosphorylated
CC form) (By similarity). Interacts with DENND2B (By similarity).
CC Interacts with SPRY2 (By similarity). Interacts with LRRC8A (By
CC similarity). {ECO:0000250|UniProtKB:P62993,
CC ECO:0000250|UniProtKB:Q60631}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P62993}. Cytoplasm
CC {ECO:0000250|UniProtKB:P62993}. Endosome
CC {ECO:0000250|UniProtKB:P62993}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q60631}.
CC -!- DOMAIN: The SH3 domains mediate interaction with RALGPS1 and SHB.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GRB2/sem-5/DRK 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; CR860761; CAH92874.1; -; mRNA.
DR EMBL; CR861250; CAH93319.1; -; mRNA.
DR RefSeq; NP_001126954.1; NM_001133482.1.
DR RefSeq; XP_009250292.1; XM_009252017.1.
DR RefSeq; XP_009250293.1; XM_009252018.1.
DR AlphaFoldDB; Q5R4J7; -.
DR BMRB; Q5R4J7; -.
DR SMR; Q5R4J7; -.
DR STRING; 9601.ENSPPYP00000009686; -.
DR Ensembl; ENSPPYT00000010071; ENSPPYP00000009686; ENSPPYG00000008626.
DR GeneID; 100173972; -.
DR KEGG; pon:100173972; -.
DR CTD; 2885; -.
DR eggNOG; KOG3601; Eukaryota.
DR GeneTree; ENSGT00940000155738; -.
DR HOGENOM; CLU_073617_1_0_1; -.
DR InParanoid; Q5R4J7; -.
DR OMA; MVPEEML; -.
DR OrthoDB; 1091250at2759; -.
DR TreeFam; TF354288; -.
DR Proteomes; UP000001595; Chromosome 17.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0008180; C:COP9 signalosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0070436; C:Grb2-EGFR complex; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0012506; C:vesicle membrane; IEA:Ensembl.
DR GO; GO:0046875; F:ephrin receptor binding; IEA:Ensembl.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0043560; F:insulin receptor substrate binding; IEA:Ensembl.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; IEA:Ensembl.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:Ensembl.
DR GO; GO:0019903; F:protein phosphatase binding; IEA:Ensembl.
DR GO; GO:0017124; F:SH3 domain binding; ISS:UniProtKB.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IEA:Ensembl.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IEA:Ensembl.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IEA:Ensembl.
DR GO; GO:0035987; P:endodermal cell differentiation; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0031623; P:receptor internalization; IEA:Ensembl.
DR GO; GO:0043408; P:regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0042770; P:signal transduction in response to DNA damage; IEA:Ensembl.
DR CDD; cd11949; SH3_GRB2_C; 1.
DR CDD; cd11946; SH3_GRB2_N; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035643; GRB2_C_SH3.
DR InterPro; IPR035641; GRB2_N_SH3.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 2.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 2.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Endosome; Golgi apparatus; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; SH2 domain; SH3 domain.
FT CHAIN 1..217
FT /note="Growth factor receptor-bound protein 2"
FT /id="PRO_0000088200"
FT DOMAIN 1..58
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 60..152
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 156..215
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT MOD_RES 6
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT MOD_RES 50
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT MOD_RES 109
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
FT MOD_RES 211
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62993"
SQ SEQUENCE 217 AA; 25206 MW; 83A4B0BA1B248DC4 CRC64;
MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK NYIEMKPHPW
FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK FGNDVQHFKV LRDGAGKYFL
WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD IEQVPQQPTY VQALFDFDPQ EDGELGFRRG
DFIHVMDNSD PNWWKGACHG QTGMFPRNYV TPVNRNV
