P62994 (GRB2_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified June 11, 2014. Version 103. History...
Names and origin
|Protein names||Recommended name:|
Growth factor receptor-bound protein 2
Adapter protein GRB2
SH2/SH3 adapter GRB2
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||217 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway By similarity. Ref.2
Associates with activated Tyr-phosphorylated EGF receptor/EGFR and PDGF receptors via its SH2 domain. Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS4, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Binds to and translocates the guanine nucleotide exchange factors SOS. Interacts with phosphorylated TOM1L1 and MET. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with PTPNS1, REPS2 and the syntrophin SNTA1. Interacts with REPS1 and PIK3C2B via its SH3 domains. Interacts with CBL and CBLB. Interacts with AJUBA By similarity. Interacts with SHB, INPP5D/SHIP1, SKAP1, SKAP2 and CLNK By similarity. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains SH2 domain with phosphorylated MUC1. Interacts with PRNP By similarity. Interacts with NISCH, RALGPS1 and with HCST By similarity. Interacts with GAPT, THEMIS and PTPRE By similarity. Interacts (via SH3 2) with GAB2 By similarity. Interacts with ADAM15. Interacts with PTPRJ and BCR By similarity. Interacts with THEMIS2. Interacts (via SH2 domain) with AXL and KIT (phosphorylated). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) By similarity. Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PTPN23 By similarity. Interacts with FLT1, KDR and FLT4 (tyrosine phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) By similarity. Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL, in which GRB2 promotes RTK recruitment by TNK2 By similarity. Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect By similarity. Interacts with PTPN11. Interacts with NTRK1 (phosphorylated upon ligand-binding) By similarity. Interacts with ERBB4. Interacts with PTK2/FAK1 (tyrosine phosphorylated). Interacts with SCIMP By similarity. Interacts with PLCG1, LAT, THEMIS and TESPA1 upon TCR activation in thymocytes. Interacts with DAB2 By similarity. Interacts (via SH3 domains) with GAREM (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation By similarity. Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA. Interacts with ASAP3 (phosphorylated form). Interacts with CD28 By similarity. Interacts (via SH2 domain) with CSF1R and IRS1 (tyrosine phosphorylated). Ref.5 Ref.6
Wide tissue distribution. Ref.1
The SH3 domains mediate interaction with RALGPS1 and SHB By similarity.
Belongs to the GRB2/sem-5/DRK family.
Contains 1 SH2 domain.
Contains 2 SH3 domains.
|This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]|
Note: Additional isoforms seem to exist.
|Isoform 1 (identifier: P62994-1) |
Also known as: Ash-L;
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: P62994-2) |
Also known as: Ash-M;
The sequence of this isoform differs from the canonical sequence as follows:
|Isoform 3 (identifier: P62994-3) |
Also known as: Ash-S;
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 217||217||Growth factor receptor-bound protein 2||PRO_0000088201|
|Domain||1 – 58||58||SH3 1|
|Domain||60 – 152||93||SH2|
|Domain||156 – 215||60||SH3 2|
Amino acid modifications
|Modified residue||1||1||N-acetylmethionine By similarity|
|Modified residue||6||1||N6-acetyllysine By similarity|
|Modified residue||50||1||N6-acetyllysine By similarity|
|Modified residue||109||1||N6-acetyllysine By similarity|
|Modified residue||211||1||Phosphothreonine By similarity|
|Alternative sequence||60 – 217||158||Missing in isoform 3.||VSP_001838|
|Alternative sequence||157 – 170||14||Missing in isoform 2.||VSP_001840|
|||"Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries."|
Matuoka K., Yamakawa A., Shibata M., Takenawa T.
Proc. Natl. Acad. Sci. U.S.A. 89:9015-9019(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Strain: Fischer 344.
|||"Splicing isoforms of rat Ash/Grb2. Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms."|
Watanabe K., Fukuchi T., Hosoya H., Shirasawa T., Matsuoka K., Miki H., Takenawa T.
J. Biol. Chem. 270:13733-13739(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
|||Lubec G., Afjehi-Sadat L., Chen W.-Q.|
Submitted (APR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 11-21; 77-86; 101-109; 125-136; 143-149 AND 208-215, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Hippocampus and Spinal cord.
|||"Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts."|
van der Geer P., Hunter T.
EMBO J. 12:5161-5172(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CSF1R.
|||"Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2."|
Tobe K., Matuoka K., Tamemoto H., Ueki K., Kaburagi Y., Asai S., Noguchi T., Matsuda M., Tanaka S., Hattori S., Fukui Y., Akanuma Y., Yazaki Y., Takenawa T., Kadowaki T.
J. Biol. Chem. 268:11167-11171(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IRS1.
|+||Additional computationally mapped references.|
|X62853 mRNA. Translation: CAA44665.1.|
D49846 mRNA. Translation: BAA08645.1.
D49847 mRNA. Translation: BAA08646.1.
BC091144 mRNA. Translation: AAH91144.1.
|RefSeq||NP_110473.2. NM_030846.2. [P62994-1]|
3D structure databases
|SMR||P62994. Positions 1-217. |
Protein-protein interaction databases
|BioGrid||249501. 10 interactions.|
|IntAct||P62994. 14 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000005347; ENSRNOP00000005347; ENSRNOG00000003990. [P62994-1]|
|RGD||619758. Grb2. |
Enzyme and pathway databases
|Reactome||REACT_212996. Signal Transduction. |
REACT_227097. Immune System.
Gene expression databases
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
|InterPro||IPR000980. SH2. |
|Pfam||PF00017. SH2. 1 hit. |
PF00018. SH3_1. 2 hits.
|PRINTS||PR00401. SH2DOMAIN. |
|SMART||SM00252. SH2. 1 hit. |
SM00326. SH3. 2 hits.
|SUPFAM||SSF50044. SSF50044. 2 hits. |
SSF55550. SSF55550. 2 hits.
|PROSITE||PS50001. SH2. 1 hit. |
PS50002. SH3. 2 hits.
|Accession||Primary (citable) accession number: P62994|
Secondary accession number(s): P29354 Q63059
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families