sem-5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001784 phosphotyrosine residue binding	IBA GO_REF:0000033	ACCEPT	Summary: IBA: phosphotyrosine residue binding by the conserved SEM-5/GRB2 SH2 domain. Reason: SEM-5 is an SH2/SH3 adaptor in the GRB2 family; the central SH2 domain is the conserved phosphotyrosine-recognition module that allows these adaptors to couple activated receptor tyrosine kinases to downstream Ras/MAPK signaling. The PAINT placement on the GRB2/Sem-5/Drk node is consistent with direct Sem-5 sequence and functional-rescue evidence. Supporting Evidence: PMID:1372395 SH2 and SH3 domains are present in many signalling proteins regulated by receptor and non-receptor tyrosine kinases.
GO:0005154 epidermal growth factor receptor binding	IBA GO_REF:0000033	ACCEPT	Summary: IBA: epidermal growth factor receptor binding by the conserved SEM-5/GRB2 adaptor family. Reason: EGFR binding is a core activity of SEM-5/GRB2-family SH2/SH3 adaptors. Worm SEM-5 itself was shown to bind activated human EGFR in vitro, and human GRB2 and fly Drk can functionally replace SEM-5 in vivo, supporting the PAINT inference across this family node. Supporting Evidence: PMID:8305738 We also show that Sem-5, like GRB2, can bind to the activated hEGFR in vitro.
GO:0005154 epidermal growth factor receptor binding	IEA GO_REF:0000117	ACCEPT	Summary: IEA/ARBA: epidermal growth factor receptor binding. Reason: The electronic ARBA assertion agrees with direct SEM-5 evidence for activated EGFR binding and with the conserved GRB2-family adaptor role. Supporting Evidence: PMID:8305738 We also show that Sem-5, like GRB2, can bind to the activated hEGFR in vitro.
GO:0005154 epidermal growth factor receptor binding	IPI PMID:8305738 The human GRB2 and Drosophila Drk genes can functionally rep...	ACCEPT	Summary: IPI: SEM-5 binding to activated human EGFR. Reason: This is the direct biochemical basis for EGFR-binding by SEM-5; the paper also showed that GRB2 and Drk functionally substitute for SEM-5 in C. elegans, so activated EGFR binding is an informative molecular-function assertion rather than a generic interaction call. Supporting Evidence: PMID:8305738 We also show that Sem-5, like GRB2, can bind to the activated hEGFR in vitro.
GO:0005515 protein binding	IPI PMID:14978303 Directed discovery of bivalent peptide ligands to an SH3 dom...	MODIFY	Summary: IPI: SEM-5 C-terminal SH3-domain binding to a proline-rich Sos-derived peptide. Reason: The experiment is a peptide-selection and structural study of the SEM-5 SH3 domain rather than a demonstration of a native SEM-5:SOS1 signaling complex. It does, however, directly support the more informative SH3-domain activity of proline-rich region binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:14978303 The Caenorhabditis elegans SEM-5 SH3 domains recognize proline-rich peptide segments with modest affinity.
GO:0005654 nucleoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA: nucleoplasmic activity inferred for a GRB2-family adaptor. Reason: Nucleoplasm is plausible as a secondary localization for this adaptor family but is not the canonical SEM-5 site of action in C. elegans; SEM-5 is best established as a cytosolic and membrane-recruited SH2/SH3 adaptor in receptor tyrosine kinase signaling. Supporting Evidence: PMID:1372395 On the basis of its DNA sequence, sem-5 encodes a novel 228-amino-acid protein which consists almost entirely of one SH2 (SH, src homology region) and two SH3 domains.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: IBA: cytoplasmic SEM-5/GRB2-family activity. Reason: SEM-5 is a soluble adaptor recruited to activated receptors and scaffolds, so cytoplasm is a correct site for the core RTK-to-Ras/MAPK adaptor function. Supporting Evidence: PMID:8305738 The sem-5 sequence encodes a protein comprised almost exclusively of SH2 and SH3 domains (SH, src homology region) that are found together in many signaling proteins and nonreceptor tyrosine kinases.
GO:0005886 plasma membrane	EXP PMID:27780040 Functional Coordination of WAVE and WASP in C. elegans Neuro...	ACCEPT	Summary: EXP: SEM-5 localization at the plasma membrane in migrating neuroblasts. Reason: UniProt records SEM-5 cell-membrane targeting to the leading edge of Q neuroblasts from this study, consistent with MIG-13-dependent recruitment of SEM-5/Grb2 to activate the WASP branch during migration. Supporting Evidence: UniProt:P29355 SUBCELLULAR LOCATION: Cell membrane {ECO:0000269\|PubMed:27780040}. Note=Targeted to the leading edge of Q neuroblasts by mig-13.
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA: plasma-membrane activity of the conserved SEM-5/GRB2 adaptor family. Reason: Activated cell-surface receptor tyrosine kinases recruit SEM-5/GRB2 adaptors to the cytoplasmic face of the plasma membrane, and direct SEM-5 localization evidence also places it at the membrane in C. elegans neuroblasts. Supporting Evidence: UniProt:P29355 SUBCELLULAR LOCATION: Cell membrane {ECO:0000269\|PubMed:27780040}. Note=Targeted to the leading edge of Q neuroblasts by mig-13.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA/UniProt: SEM-5 plasma-membrane localization. Reason: The UniProt subcellular-location mapping is consistent with the curated SEM-5 cell-membrane annotation from the MIG-13/WASP neuroblast-migration study and with the receptor-proximal role of the adaptor. Supporting Evidence: UniProt:P29355 SUBCELLULAR LOCATION: Cell membrane {ECO:0000269\|PubMed:27780040}. Note=Targeted to the leading edge of Q neuroblasts by mig-13.
GO:0007165 signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: IBA: signal transduction by the SEM-5/GRB2 adaptor family. Reason: Although broad, signal transduction is accurate for SEM-5 because genetic and functional-rescue evidence place it in conserved RTK pathways that couple activated receptors to Ras/MAPK outputs. Supporting Evidence: PMID:8305738 These data indicate that GRB2 and Drk are functional homologues of Sem-5 and demonstrate the high degree of conservation of both structure and function between signaling systems throughout evolution.
GO:0007173 epidermal growth factor receptor signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: IEA/ARBA: epidermal growth factor receptor signaling pathway. Reason: The electronic assertion is consistent with direct WormBase perturbation annotations placing SEM-5 downstream of the LET-23 EGFR-like receptor during vulval induction. Supporting Evidence: PMID:1372395 Many genes required for vulval induction have been identified, including the let-23 receptor tyrosine kinase gene and the let-60 ras gene.
GO:0007173 epidermal growth factor receptor signaling pathway	IGI PMID:1372395 C. elegans cell-signalling gene sem-5 encodes a protein with...	ACCEPT	Summary: IGI: SEM-5 in LET-23/EGFR signaling. Reason: Genetic-interaction evidence from the founding sem-5 study supports SEM-5 function in the LET-23 receptor tyrosine kinase pathway that induces vulval fates; the EGFR-pathway term captures this core worm RTK signaling role. Supporting Evidence: PMID:1372395 We report here the identification and characterization of a new gene, sem-5 (sem, sex muscle abnormal), that acts both in vulval induction and in sex myoblast migration.
GO:0007173 epidermal growth factor receptor signaling pathway	IMP PMID:1372395 C. elegans cell-signalling gene sem-5 encodes a protein with...	ACCEPT	Summary: IMP: SEM-5 in LET-23/EGFR signaling. Reason: SEM-5 mutant phenotypes place this SH2/SH3 adaptor in the LET-23 to LET-60/Ras signaling pathway for vulval induction, supporting the worm EGFR-signaling annotation. Supporting Evidence: PMID:1372395 We report here the identification and characterization of a new gene, sem-5 (sem, sex muscle abnormal), that acts both in vulval induction and in sex myoblast migration.
GO:0007517 muscle organ development	IMP PMID:16495308 FGF negatively regulates muscle membrane extension in Caenor...	KEEP AS NON CORE	Summary: IMP: SEM-5 in body-wall muscle development downstream of EGL-15/FGFR. Reason: SEM-5 acts with EGL-15 in body-wall muscles to restrain ectopic membrane extension during neuromuscular junction development. This is a real developmental output of an RTK adaptor, but it is contextual rather than the core molecular function. Supporting Evidence: PMID:16495308 We discovered that an FGF pathway, including let-756(FGF), egl-15(FGF receptor), sem-5(GRB2) and other genes negatively regulates plasma membrane extension from muscles.
GO:0008180 COP9 signalosome	IBA GO_REF:0000033	REMOVE	Summary: IBA: COP9 signalosome membership. Reason: COP9 signalosome is a defined GPS1/COPS1-8 complex, not a complex of SEM-5/GRB2 SH2/SH3 adaptors. This family-wide PAINT inference is biologically implausible as structural complex membership and appears to be the same GRB2-clade over-propagation already seen for GRB2 and Drk. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN005273574 · GRB2/Sem-5/DRK family node SUPPORTS SOURCE BUT NOT TARGET SEM-5/GRB2 proteins are receptor-proximal SH2/SH3 adaptors, not stable subunits of the COPS1-8 COP9 signalosome.
GO:0030334 regulation of cell migration	IMP PMID:1372395 C. elegans cell-signalling gene sem-5 encodes a protein with...	KEEP AS NON CORE	Summary: IMP: SEM-5 in sex myoblast migration. Reason: The founding SEM-5 paper established a role in sex myoblast migration. This is a legitimate cell-migration output of SEM-5 signaling, but it is a developmental context rather than the core SH2/SH3 adaptor activity. Supporting Evidence: PMID:1372395 We report here the identification and characterization of a new gene, sem-5 (sem, sex muscle abnormal), that acts both in vulval induction and in sex myoblast migration.
GO:0030539 male genitalia development	IMP PMID:7607066 The lin-3/let-23 pathway mediates inductive signalling durin...	KEEP AS NON CORE	Summary: IMP: SEM-5 in LIN-3/LET-23 signaling during male spicule development. Reason: SEM-5 is one component of the LIN-3/LET-23/Ras/Raf pathway used for anterior fate specification in male spicule development. The assertion is supported, but this sex-specific developmental output is non-core relative to the conserved RTK adaptor activity. Supporting Evidence: PMID:7607066 Reduction-of-function mutations in lin-3, let-23, sem-5, let-60 or lin-45 disrupt the fate of anterior cells.
GO:0031344 regulation of cell projection organization	IMP PMID:16495308 FGF negatively regulates muscle membrane extension in Caenor...	KEEP AS NON CORE	Summary: IMP: SEM-5/FGF pathway regulation of body-wall muscle membrane extensions. Reason: The FGF pathway study directly implicated sem-5 in preventing ectopic body-wall muscle membrane extensions. This is a specific cytoskeletal and cell-projection output of EGL-15 signaling, not the central conserved molecular activity of SEM-5. Supporting Evidence: PMID:16495308 We discovered that an FGF pathway, including let-756(FGF), egl-15(FGF receptor), sem-5(GRB2) and other genes negatively regulates plasma membrane extension from muscles.
GO:0040028 regulation of vulval development	IGI PMID:1372395 C. elegans cell-signalling gene sem-5 encodes a protein with...	KEEP AS NON CORE	Summary: IGI: SEM-5 regulation of vulval development. Reason: SEM-5 functions downstream of the LET-23 RTK and upstream of LET-60/Ras in vulval induction. The vulval-development term is true, but it represents a C. elegans developmental endpoint of EGFR/Ras signaling rather than the core adaptor function. Supporting Evidence: PMID:1372395 We report here the identification and characterization of a new gene, sem-5 (sem, sex muscle abnormal), that acts both in vulval induction and in sex myoblast migration.
GO:0040028 regulation of vulval development	IMP PMID:1372395 C. elegans cell-signalling gene sem-5 encodes a protein with...	KEEP AS NON CORE	Summary: IMP: SEM-5 regulation of vulval development. Reason: SEM-5 mutant phenotypes support its role in vulval induction, a canonical LET-23/EGFR pathway output. Keep the annotation as a real but developmental, non-core biological process. Supporting Evidence: PMID:1372395 The gonadal anchor cell induces formation of the vulva from nearby hypodermal cells, and a set of somatic gonadal cells attract the migrating sex myoblasts to their final positions.
GO:0043408 regulation of MAPK cascade	IBA GO_REF:0000033	ACCEPT	Summary: IBA: SEM-5/GRB2-family regulation of the MAPK cascade. Reason: SEM-5 is the conserved SH2/SH3 adaptor that links activated receptor tyrosine kinases to Ras/MAPK signaling, so regulation of the MAPK cascade is an appropriate core process for the GRB2/Sem-5/Drk family. Supporting Evidence: PMID:8305738 These data indicate that GRB2 and Drk are functional homologues of Sem-5 and demonstrate the high degree of conservation of both structure and function between signaling systems throughout evolution.
GO:0061062 regulation of nematode larval development	IMP PMID:1372395 C. elegans cell-signalling gene sem-5 encodes a protein with...	KEEP AS NON CORE	Summary: IMP: SEM-5 regulation of nematode larval development. Reason: Multiple SEM-5-dependent events assayed in C. elegans occur during larval development, including vulval induction and sex myoblast migration. The term is broad and organismal, so it is retained as a non-core developmental consequence of the adaptor's signaling function. Supporting Evidence: PMID:1372395 Our results indicate that the sem-5 gene encodes a novel protein that functions in at least two distinct cell-signalling processes.

Gene Description

Existing Annotations Review

Core Functions

GRB2-family phosphotyrosine adaptor activity that couples LET-23/EGFR and other RTKs to Ras/MAPK signaling at cytoplasmic and plasma-membrane receptor complexes.

References

Deep Research

WormBase

📚 Additional Documentation

Notes

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