Gauging the signaling space of the Src homology 2 domain by peptide and protein arrays
Bibliographic record
Abstract
Different SH2 domains select for distinct phosphopeptides, and deciphering the peptide motif recognized by an SH2 domain and identifying the interactions mediated by the domain is the key to understanding its function. We have determined the phosphotyrosyl peptide‐binding properties of 76 SH2 domains by screening an oriented peptide array library (OPAL). A number of novel binding motifs have been identified, which is exemplified by the BRDG1SH2 domain that selects specifically for a bulky, hydrophobic residue at the +4 position relative to the pTyr residue. Based on the OPAL binding patterns, we developed SMALI a web‐based program for predicting binding partners for SH2‐containing proteins. When applied to SH2D1A/SAP, a protein whose mutation or deletion underlies the X‐linked lymphoproliferative syndrome, SMALI not only recapitulated known interactions but also identified a number of novel binding partners for this disease‐associated protein. By combining SMALI prediction with peptide array‐target screening (PATS), we identified a signaling network mediated by a group of SH2 domains that provides a framework upon which the functions of SH2 domains can be systematically explored.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".