SHC1 (P29353) curation notes

Identity and isoforms

Human SHC1 / ShcA; three major isoforms p46Shc, p52Shc (alternative translation start) and p66Shc (alternative promoter, extra N-terminal CH2). Domain order PTB (PID) - CH1 - SH2. [UniProt:P29353 "Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex"]
All GOA rows are on the canonical accession P29353; none are isoform-specific in the GOA file, so no isoform fields were added. Isoform differences are handled in review reasons (p46 mitochondrial matrix; p66 oxidative stress).

PTB domain binds NPXpY: PMID:7542744
SH2 domain binds EGFR pY1173/pY992: PMID:7518560
INSR and IGF1R NPEY motifs via the N-terminal PTB region: PMID:7537849; PMID:7541045
Receptor-to-GRB2-SOS bridging (adaptor activity): PMID:9544989; Y239/240 and Y317 are the GRB2 docking sites PMID:8939605
Insulin: PMID:8491186
Late-phase scaffold switching: PEAK1/SgK269 binds SHC1 PTB via phosphorylated NPXY PMID:23846654
GO-CAM: mouse insulin receptor model (gocams index) types Shc1 p52 as GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity, consistent with the review.

p66shc knockout mice: stress resistance and longer life span PMID:10580504
Proposed redox activity PMID:16051147 (contested; left as a suggested question, no NEW annotation).
p46Shc mitochondrial matrix PMID:14573619
Deep research notes that much apparent mitochondrial p66Shc may be at MAMs [file:human/SHC1/SHC1-deep-research-falcon.md "p66Shc is mainly cytosolic/ER/MAM-associated, with a smaller or condition-dependent mitochondrial pool"].

82 IPI rows, grouped by partner and paper:

Phosphotyrosine recognition shown in the cited paper (EGFR site mapping, ErbB SH2/PTB microarray, INSR NPEY, JAK2, CEACAM1 pY488, APP pY682, PEAK1, MET/KIT/GAB1/AR FP interactome, ALK MaMTH, EGFR phosphopeptide pulldown) -> MODIFY to GO:0001784.
Receptor-SHC1-GRB2(-SOS) bridging shown (insulin/GRB2, Y239/240 mutagenesis, PTB-bound SHC1 with GRB2-SOS, p66 knockdown reducing EGFR-GRB2 association) -> MODIFY to GO:0005068.
GRB2 SH2 structural/biophysical studies with SHC1-derived peptides: the binding activity is GRB2's; SHC1 only supplies the motif -> REMOVE.
High-throughput AP-MS / Y2H / proximity / complex co-IP without a defined SHC1 activity (CALCOCO2, CBLC, SMAD4, CFTR, NS1, PTPN12, GAB2, CPNE3, ESR1, many GRB2/EGFR rows) -> REMOVE; removal does not assert the interaction is false.
EGFR crystal structure with primed Shc1 peptide (PMID:26551075): SHC1 is the kinase substrate -> REMOVE.

GO:0048408 epidermal growth factor binding (IEA from mouse): mouse source is IPI with mouse Egfr as WITH/FROM, so the intended claim is receptor binding -> MODIFY to GO:0005154.
GO:0042742 defense response to bacterium (IMP, Tarp paper): full text shows SHC1 is not needed for bacterial propagation and is exploited for host-cell survival PMID:20624904 -> MARK_AS_OVER_ANNOTATED (not REMOVE, deferring to curator on an experimental row).
Transcription regulation IMP rows (same paper): indirect transcriptome effects -> MARK_AS_OVER_ANNOTATED.
PMID:19593445 (known batch miscitation) is not cited in the SHC1 GOA set.