GRB2
Growth factor receptor-bound protein 2
Also known as: GRB2_HUMAN, NCKAP2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P62993
- Gene
- GRB2
- Ensembl
- ENSG00000177885
- Chromosome
- 17
- Canonical length
- 217 aa
- Protein class
- Cancer-related genes, Plasma proteins, Predicted intracellular proteins, RAS pathway related proteins
- Subcellular location
- Primary cilium,Centrosome,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
217 residues, UniProt reviewed canonical sequence.
>P62993|GRB2
1 MEAIAKYDFK ATADDELSFK RGDILKVLNE ECDQNWYKAE LNGKDGFIPK NYIEMKPHPW
61 FFGKIPRAKA EEMLSKQRHD GAFLIRESES APGDFSLSVK FGNDVQHFKV LRDGAGKYFL
121 WVVKFNSLNE LVDYHRSTSV SRNQQIFLRD IEQVPQQPTY VQALFDFDPQ EDGELGFRRG
181 DFIHVMDNSD PNWWKGACHG QTGMFPRNYV TPVNRNVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against GRB2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.32
- Highest tissue expression
- 120 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 120 nTPM
- lymph node: 109 nTPM
- tonsil: 101 nTPM
- appendix: 93 nTPM
- spleen: 87 nTPM
- thymus: 78 nTPM
Single-cell type
- neutrophils: 2,324 nCPM
- monocytes: 836 nCPM
- neutrophil progenitors: 694 nCPM
- extravillous trophoblasts: 580 nCPM
- cdc: 523 nCPM
- macrophages: 480 nCPM
Immune cell
- neutrophil: 276 nTPM
- non-classical monocyte: 186 nTPM
- eosinophil: 166 nTPM
- intermediate monocyte: 161 nTPM
- classical monocyte: 137 nTPM
- basophil: 135 nTPM
Brain region
- white matter: 99 nTPM
- hippocampal formation: 95 nTPM
- hypothalamus: 90 nTPM
- spinal cord: 89 nTPM
- midbrain: 84 nTPM
- amygdala: 84 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.36
- gnomAD pLI
- 0.94
- gnomAD missense Z
- 2.85
- DepMap mean gene effect
- -0.9
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- actin cytoskeleton organization
- B cell receptor signaling pathway
- branching involved in labyrinthine layer morphogenesis
- cellular response to ionizing radiation
- endodermal cell differentiation
- epidermal growth factor receptor signaling pathway
- fibroblast growth factor receptor signaling pathway
- insulin receptor signaling pathway
- insulin-like growth factor receptor signaling pathway
- myelination
- natural killer cell mediated cytotoxicity
- negative regulation of epidermal growth factor receptor signaling pathway
- negative regulation of natural killer cell mediated cytotoxicity
- positive regulation of actin filament polymerization
- positive regulation of Rac protein signal transduction
- positive regulation of reactive oxygen species metabolic process
- Ras protein signal transduction
- receptor internalization
- regulation of MAPK cascade
- Schwann cell development
- signal transduction
- signal transduction in response to DNA damage
- T cell activation
Molecular functions
- ephrin receptor binding
- epidermal growth factor receptor binding
- identical protein binding
- insulin receptor substrate binding
- neurotrophin TRKA receptor binding
- phosphotyrosine residue binding
- protein kinase binding
- protein phosphatase binding
- protein-macromolecule adaptor activity
- RNA binding
- SH3 domain binding
- transmembrane receptor protein tyrosine kinase adaptor activity
- guanyl-nucleotide exchange factor adaptor activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- SH2 domain
- SH3 domain
- SH3-like domain superfamily
- SH2 domain superfamily
- Grb2-like
- SH2 domain
- SH3 domain
- GRB2, N-terminal SH3 domain
- GRB2, C-terminal SH3 domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of GRB2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads GRB2 as an antibody target. Whether an autoantibody or antibody against GRB2 could matter depends on whether native GRB2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
GRB2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label GRB2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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