DSCAM

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM is a type I transmembrane protein that localizes to the plasma membrane. UniProt confirms that the Long isoform (O60469-1) is a single-pass type I membrane protein localized to the cell membrane [PMID:9426258]. The Short isoform lacks the transmembrane domain and is secreted. This annotation is well-supported by the protein's domain architecture and multiple lines of evidence. Reason: Plasma membrane localization is a core feature of the canonical Long isoform of DSCAM, which contains a transmembrane domain. This is supported by the original cloning paper [PMID:9426258] and UniProt annotations. The IBA annotation from phylogenetic trees is consistent with the conserved transmembrane topology of DSCAM family members across vertebrates. Supporting Evidence: PMID:9426258 both containing 10 Ig-C2 domains... with or without the following transmembrane and intracellular domains
GO:0007156 homophilic cell-cell adhesion	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM mediates homophilic cell-cell adhesion through its extracellular Ig domains. UniProt describes DSCAM as a homodimer that mediates homophilic interactions to promote cell adhesion. This function is documented in experimental studies showing that DSCAM promotes lamina-specific synaptic connections via homophilic interactions [PMID:10925149 per UniProt]. Reason: Homophilic cell adhesion is a core function of DSCAM, well-documented in both human and model organism studies. This is a primary molecular mechanism underlying DSCAM's role in neuronal patterning and self-avoidance. The IBA annotation is consistent with conserved function across vertebrates and experimental evidence from the literature. Supporting Evidence: PMID:9426258 DSCAM is involved in neural differentiation and contributes to the central and peripheral nervous system defects in DS
GO:0007417 central nervous system development	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM is primarily expressed in brain and plays a role in CNS development including commissural axon guidance and neuronal patterning [PMID:9426258, PMID:18585357]. The original cloning paper established its expression in neural tube, cortex, hippocampus, and spinal cord during neuronal differentiation. Reason: CNS development is a core biological process for DSCAM. The gene was originally identified based on its location in the Down syndrome critical region and its role in nervous system development. Multiple studies confirm DSCAM's function in commissural axon guidance and neuronal connectivity in the developing CNS. Supporting Evidence: PMID:9426258 Tissue in situ hybridization analyses of a mouse homolog of the DSCAM gene revealed broad expression within the nervous system at the time of neuronal differentiation in the neural tube, cortex, hippocampus, medulla, spinal cord
GO:0043025 neuronal cell body	IBA GO_REF:0000033	ACCEPT	Summary: UniProt indicates DSCAM is localized in the soma (neuronal cell body), in addition to axon and growth cone of commissural axons. This subcellular localization is consistent with DSCAM's role in neuronal self-avoidance and maintaining mosaic spacing between cell bodies of amacrine and ganglion cells. Reason: Neuronal cell body localization is supported by functional studies showing DSCAM mediates heteroneuronal self-avoidance to maintain mosaic spacing between cell bodies. This is a well-established localization pattern for this cell adhesion molecule. Supporting Evidence: PMID:18585357 the Down's syndrome Cell Adhesion Molecule (DSCAM), a candidate gene implicated in the mental retardation phenotype of Down's syndrome, is expressed on spinal commissural axons, binds netrin-1, and is necessary for commissural axons to grow toward and across the midline
GO:0048842 positive regulation of axon extension involved in axon guidance	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM functions as a netrin receptor that positively regulates axon extension during guidance. Studies demonstrate that DSCAM mediates turning responses to netrin-1 and is necessary for commissural axons to grow toward and across the midline [PMID:18585357]. Reason: This is a core function of DSCAM as a netrin receptor. Multiple studies including PMID:18585357 and PMID:19196994 demonstrate DSCAM's role in promoting axon outgrowth and guidance in response to netrin-1. The IBA annotation is well-supported by experimental evidence from vertebrate model systems. Supporting Evidence: PMID:18585357 DSCAM and DCC can each mediate a turning response of these neurons to netrin-1
GO:0007411 axon guidance	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM is a netrin receptor essential for axon guidance, particularly in commissural axon pathfinding. It collaborates with DCC to mediate turning responses to netrin-1 and guides axon projection across the ventral midline to the floor plate [PMID:18585357, PMID:19196994]. Reason: Axon guidance is the primary documented biological function of vertebrate DSCAM. This is supported by multiple high-quality studies demonstrating DSCAM's role as a netrin receptor in commissural axon guidance. This annotation represents a core function of the gene. Supporting Evidence: PMID:18585357 DSCAM is a receptor that can mediate turning responses to netrin-1 and support a key role for netrin/DSCAM signaling in commissural axon guidance in vertebrates PMID:19196994 DSCAM functions as a netrin receptor in commissural axon pathfinding
GO:0030424 axon	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM is localized to the axon, particularly in commissural neurons. UniProt indicates the Long isoform is localized in "Cell projection, axon" and "Localized in the soma, cell membrane, axon and growth cone of dissociated commissural axons" [PMID:18585357]. DSCAM is expressed on spinal commissural axons and is necessary for axon guidance. Reason: Axonal localization is a core feature of DSCAM function as a netrin receptor in commissural axon guidance. This is directly supported by experimental evidence showing DSCAM expression on commissural axons [PMID:18585357]. Supporting Evidence: PMID:18585357 the Down's syndrome Cell Adhesion Molecule (DSCAM)... is expressed on spinal commissural axons
GO:0070593 dendrite self-avoidance	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM plays a role in neuronal self-avoidance including dendrite self-avoidance. UniProt states DSCAM "Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells" and mediates "isoneuronal self-avoidance for creating an orderly dendritic arborization." However, vertebrate DSCAM with only 2 isoforms may have reduced capacity for this function compared to Drosophila Dscam1 which achieves self-avoidance through 38,016 isoforms. Reason: While vertebrates use clustered protocadherins as the primary self-avoidance mechanism, mammalian DSCAM still contributes to dendrite self-avoidance particularly in retinal neurons. The IBA annotation is consistent with mouse studies showing DSCAM function in dendritic arborization. This represents a conserved function in vertebrates. Supporting Evidence: Reactome:R-HSA-376122 DSCAM is selectively expressed in subclasses of cells and suggest that it uses homophilic repulsion to simultaneously promote both self avoidance
GO:0098632 cell-cell adhesion mediator activity	IBA GO_REF:0000033	ACCEPT	Summary: DSCAM mediates cell-cell adhesion through homophilic interactions. UniProt describes it as a "Cell adhesion molecule" and states DSCAM is a "Homodimer; mediates homophilic interactions to promote cell adhesion." This molecular function is well-supported. Reason: Cell-cell adhesion mediator activity is a core molecular function of DSCAM. The protein forms homodimers that mediate homophilic intercellular adhesion, promoting lamina-specific synaptic connections and neuronal patterning. Supporting Evidence: Reactome:R-HSA-376122 DSCAM and DSCAML1 proteins are involved in homophilic intercellular interactions
GO:0005576 extracellular region	IEA GO_REF:0000044	ACCEPT	Summary: The Short isoform of DSCAM (O60469-2) lacks the transmembrane domain and is secreted into the extracellular region. UniProt explicitly states "Isoform Short: Secreted." This annotation is appropriate for the Short isoform. Reason: While the Long isoform is membrane-bound, the Short isoform lacks transmembrane and intracellular domains and is secreted. This IEA annotation correctly captures the extracellular localization of the Short isoform. Supporting Evidence: PMID:9426258 both containing 10 Ig-C2 domains... with or without the following transmembrane and intracellular domains
GO:0005886 plasma membrane	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate of the IBA annotation for plasma membrane already reviewed. DSCAM Long isoform is a single-pass type I membrane protein localized to the cell membrane. Reason: This is a duplicate annotation with different evidence. The plasma membrane localization is well-supported for the Long isoform. Multiple evidence codes supporting the same term are acceptable.
GO:0007155 cell adhesion	IEA GO_REF:0000043	ACCEPT	Summary: DSCAM is a cell adhesion molecule. This is a more general term than the homophilic cell-cell adhesion annotation already accepted. The original cloning paper describes DSCAM as a "Down syndrome cell adhesion molecule" [PMID:9426258]. Reason: Cell adhesion is a core function of DSCAM. While GO:0007156 (homophilic cell adhesion) is more specific, this parent term is also accurate. The annotation is consistent with DSCAM's known function. Supporting Evidence: PMID:9426258 a novel member of the immunoglobulin (Ig) superfamily that represents a new class of neural cell adhesion molecules
GO:0007399 nervous system development	IEA GO_REF:0000043	ACCEPT	Summary: DSCAM plays a role in nervous system development. This is a broader term than GO:0007417 (CNS development) already accepted. DSCAM is expressed "within the nervous system at the time of neuronal differentiation" and involved in neural development. Reason: Nervous system development is a core function of DSCAM. The original characterization paper demonstrated broad expression in the nervous system during neural differentiation. This annotation is consistent with CNS development and axon guidance functions. Supporting Evidence: PMID:9426258 broad expression within the nervous system at the time of neuronal differentiation in the neural tube, cortex, hippocampus, medulla, spinal cord and most neural crest-derived tissues
GO:0030424 axon	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate of the IBA annotation for axon already reviewed. DSCAM is localized to the axon of commissural neurons. Reason: This is a duplicate annotation with different evidence. Axonal localization is well-supported for DSCAM. Multiple evidence codes for the same term are acceptable.
GO:0030425 dendrite	IEA GO_REF:0000120	ACCEPT	Summary: UniProt indicates DSCAM Long isoform is localized to "Cell projection, dendrite." This is consistent with DSCAM's role in dendrite self-avoidance and dendritic arborization. Reason: Dendritic localization is consistent with DSCAM's function in dendrite self-avoidance and creating orderly dendritic arborization. The annotation is well-supported.
GO:0030426 growth cone	IEA GO_REF:0000120	ACCEPT	Summary: UniProt states DSCAM is "Localized in the soma, cell membrane, axon and growth cone of dissociated commissural axons." Growth cone localization is essential for DSCAM's function in axon guidance and netrin-1 signaling. Reason: Growth cone localization is critical for DSCAM's function as a netrin receptor mediating axon turning responses. Studies in PMID:22685302 demonstrate DSCAM's role in growth cone collapse in response to netrin-1. Supporting Evidence: PMID:22685302 Netrin-1 induces axon growth cone collapse of mouse cerebellum external granule layer (EGL) cells
GO:0045202 synapse	IEA GO_REF:0000044	ACCEPT	Summary: UniProt indicates DSCAM is localized to "Synapse." DSCAM promotes lamina-specific synaptic connections in the retina and is found at the dendritic spine postsynaptic density [PMID:35914814]. Reason: Synaptic localization is consistent with DSCAM's function in promoting synaptic connectivity via homophilic interactions, particularly in the retina. Recent work identified DSCAM at the postsynaptic density. Supporting Evidence: PMID:35914814 some of the proteins encoded by HSA21 were located at the dendritic spine postsynaptic density
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: From HuRI (Human Reference Interactome) high-throughput Y2H screening. The term "protein binding" is uninformative for DSCAM which has well-characterized specific binding partners including NTN1, DCC, UNC5C, DLG2, and PIH1D2. Reason: While DSCAM does bind proteins, this generic term provides no functional insight. The HuRI study is a systematic proteome-wide screen that detected many interactions but "protein binding" as an MF term is too vague to be useful for DSCAM annotation. More specific terms like "cell-cell adhesion mediator activity" or "netrin receptor binding" are more informative. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Netw...	MARK AS OVER ANNOTATED	Summary: From a high-throughput IgSF cell-surface interactome study. This generic term does not capture the specific functional interactions of DSCAM. Reason: Same rationale as other protein binding annotations. High-throughput screens correctly detect that DSCAM binds proteins, but the GO term is uninformative. More specific molecular function terms are preferred. Supporting Evidence: PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions.
GO:0005515 protein binding	IPI PMID:35914814 Chr21 protein-protein interactions: enrichment in proteins i...	MARK AS OVER ANNOTATED	Summary: From chromosome 21 protein-protein interaction study identifying DSCAM interactions with DLGs and DYRK1A at the postsynaptic density [PMID:35914814]. Reason: While this study provides useful functional context (DSCAM-DLG and DSCAM-DYRK1A interactions at postsynapse), the generic "protein binding" term is uninformative. The specific finding about DLG binding would be better captured by a more specific term if available. Supporting Evidence: PMID:35914814 an intracellular domain of DSCAM bound either DLGs, which are multimeric scaffolds comprising receptors, ion channels and associated signaling proteins, or DYRK1A
GO:0007162 negative regulation of cell adhesion	IEA GO_REF:0000107	ACCEPT	Summary: DSCAM mediates repulsion between neuronal processes through homophilic interactions, leading to self-avoidance. UniProt states DSCAM "Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells." Reason: This annotation captures DSCAM's role in neuronal self-avoidance through homophilic repulsion. While DSCAM promotes initial adhesion, the functional outcome is repulsion and negative regulation of further adhesion between sister processes.
GO:0007411 axon guidance	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate annotation with different evidence code. Axon guidance is a core function of DSCAM already reviewed with IBA evidence. Reason: Duplicate annotation supporting the core function. Axon guidance via netrin-1 signaling is well-established for DSCAM.
GO:0038007 netrin-activated signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: DSCAM functions as a netrin receptor and mediates netrin-activated signaling. Upon binding netrin-1, DSCAM activates downstream signaling including MAPK8 and p38 MAP kinase [PMID:18585357, PMID:19196994]. Reason: This is a core function of DSCAM as a netrin receptor. DSCAM mediates intracellular signaling by stimulating activation of MAPK8 and MAP kinase p38 in response to netrin-1 binding. Supporting Evidence: PMID:19196994 DSCAM by itself, in the absence of DCC, is capable of mediating netrin signaling in activating phosphorylation of Fyn and Pak1
GO:0043025 neuronal cell body	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate annotation with different evidence code. Neuronal cell body localization already reviewed with IBA evidence. Reason: Duplicate annotation supporting DSCAM localization to soma of neurons.
GO:0048842 positive regulation of axon extension involved in axon guidance	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate annotation with different evidence code. This core function already reviewed with IBA evidence. Reason: Duplicate annotation. DSCAM promotes axon extension in response to netrin-1 during commissural axon guidance.
GO:0070593 dendrite self-avoidance	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate annotation with different evidence code. Dendrite self-avoidance already reviewed with IBA evidence. Reason: Duplicate annotation. DSCAM contributes to dendrite self-avoidance in vertebrates, particularly in retinal neurons.
GO:1990782 protein tyrosine kinase binding	IEA GO_REF:0000107	ACCEPT	Summary: DSCAM interacts with tyrosine kinases including FYN and FAK. UniProt states DSCAM "Interacts with PTK2" (FAK) and "Interacts with FYN." DSCAM is phosphorylated at tyrosine residues, and this is enhanced by netrin-1. Reason: DSCAM binding to protein tyrosine kinases is supported by UniProt annotations describing interactions with PTK2 (FAK) and FYN. Netrin-1 enhances DSCAM tyrosine phosphorylation, suggesting functional relevance of these interactions. Supporting Evidence: PMID:22685302 Netrin-1 increases tyrosine phosphorylation of endogenous DSCAM, UNC5C, FAK, Fyn, and PAK1, and promotes complex formation of DSCAM with these signaling molecules
GO:1990890 netrin receptor binding	IEA GO_REF:0000107	ACCEPT	Summary: GO:1990890 "netrin receptor binding" means binding TO a netrin receptor. DSCAM binds to UNC5C and DCC, both of which are netrin receptors [PMID:22685302]. DSCAM also interacts with DCC via its transmembrane domain, and this interaction is abolished in response to NTN1 (UniProt). The IEA annotation is propagated from mouse Dscam (Q9ERC8) which was experimentally demonstrated to bind UNC5C. Reason: DSCAM does bind to other netrin receptors (UNC5C and DCC), making "netrin receptor binding" a correct annotation. PMID:22685302 demonstrated that DSCAM interacts with UNC5C and this interaction is stimulated by netrin-1. UniProt confirms DSCAM interacts with DCC. Note that DSCAM itself is ALSO a netrin receptor, but this term captures its ability to bind other netrin receptors, which is functionally important for coordinating attractive and repulsive guidance responses. Supporting Evidence: PMID:22685302 DSCAM interacts with UNC5C and this interaction is stimulated by netrin-1 in primary cortical neurons and postnatal cerebellar granule cells
GO:0007411 axon guidance	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Axon guidance is a core function of DSCAM already reviewed multiple times with IBA and IEA evidence. Reason: ISS (Inferred from Sequence Similarity) annotation supporting the well-established core function. Multiple evidence codes for the same term are acceptable.
GO:0030425 dendrite	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Dendrite localization already reviewed with IEA evidence. Reason: ISS annotation supporting dendritic localization, consistent with DSCAM's role in dendrite self-avoidance.
GO:0043025 neuronal cell body	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Neuronal cell body localization already reviewed with IBA and IEA evidence. Reason: ISS annotation supporting soma localization. Multiple evidence codes acceptable.
GO:1990890 netrin receptor binding	IPI PMID:22685302 Down syndrome cell adhesion molecule (DSCAM) associates with...	ACCEPT	Summary: This annotation refers to DSCAM binding to UNC5C, which is a netrin receptor. PMID:22685302 demonstrates that "DSCAM interacts with UNC5C and this interaction is stimulated by netrin-1." However, DSCAM itself IS also a netrin receptor. Reason: Unlike the IEA annotation for this term, this IPI annotation from PMID:22685302 correctly captures that DSCAM binds to UNC5C (a netrin receptor) in the context of netrin-1 mediated growth cone collapse. DSCAM associates with UNC5C to coordinate netrin-1 repulsion signaling. Supporting Evidence: PMID:22685302 DSCAM interacts with UNC5C and this interaction is stimulated by netrin-1 in primary cortical neurons and postnatal cerebellar granule cells
GO:0007156 homophilic cell-cell adhesion	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Homophilic cell-cell adhesion already reviewed with IBA evidence. Reason: ISS annotation supporting the core homophilic adhesion function. Multiple evidence codes acceptable.
GO:0007416 synapse assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: DSCAM promotes lamina-specific synaptic connections via homophilic interactions. UniProt describes DSCAM as an "Adhesion molecule that promotes lamina-specific synaptic connections in the retina." Reason: While DSCAM contributes to synaptic connectivity through promoting lamina-specific connections, synapse assembly is not the primary function. The core functions are netrin receptor-mediated axon guidance and neuronal self-avoidance. Synapse assembly is a downstream consequence of DSCAM's adhesion properties.
GO:0010842 retina layer formation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: DSCAM functions in retinal development, particularly in maintaining mosaic spacing between amacrine and ganglion cells and promoting lamina-specific connections. Reason: Retina layer formation represents a tissue-specific manifestation of DSCAM's general self-avoidance function. While supported by evidence from mouse studies, this is not a core molecular function but rather a developmental process in a specific tissue context.
GO:0045202 synapse	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Synapse localization already reviewed with IEA evidence. Reason: ISS annotation supporting synaptic localization. Consistent with DSCAM's role in promoting synaptic connectivity and its localization at the postsynaptic density [PMID:35914814].
GO:0060219 camera-type eye photoreceptor cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: This annotation is based on sequence similarity to mouse Dscam. DSCAM is expressed in retinal ganglion cells and amacrine cells, and functions in retinal development. Reason: Photoreceptor cell differentiation represents a tissue-specific developmental role. This is not a core function of DSCAM but rather reflects its expression and function in retinal development, likely through its self-avoidance mechanisms.
GO:0005886 plasma membrane	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Plasma membrane localization already reviewed with IBA, IEA, and TAS evidence. Reason: ISS annotation supporting membrane localization. Multiple evidence codes acceptable.
GO:0007162 negative regulation of cell adhesion	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Negative regulation of cell adhesion already reviewed with IEA evidence. Reason: ISS annotation supporting DSCAM's role in neuronal self-avoidance/repulsion.
GO:0030424 axon	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Axon localization already reviewed with IBA and IEA evidence. Reason: ISS annotation supporting axonal localization. Multiple evidence codes acceptable.
GO:0030426 growth cone	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Growth cone localization already reviewed with IEA evidence. Reason: ISS annotation supporting growth cone localization. Consistent with DSCAM's function in netrin-1-mediated growth cone guidance.
GO:0070593 dendrite self-avoidance	ISS GO_REF:0000024	ACCEPT	Summary: Duplicate annotation with ISS evidence. Dendrite self-avoidance already reviewed with IBA and IEA evidence. Reason: ISS annotation supporting dendrite self-avoidance function. Multiple evidence codes acceptable.
GO:0048842 positive regulation of axon extension involved in axon guidance	IDA PMID:18585357 DSCAM is a netrin receptor that collaborates with DCC in med...	ACCEPT	Summary: IDA (Inferred from Direct Assay) annotation from PMID:18585357 which demonstrated that DSCAM is a netrin receptor necessary for commissural axons to grow toward and across the midline. DSCAM mediates turning responses to netrin-1. Reason: This is a high-quality experimental annotation for a core function. The Cell paper demonstrated that DSCAM and DCC can each mediate turning responses to netrin-1, and DSCAM is necessary for commissural axon guidance. Supporting Evidence: PMID:18585357 DSCAM is a receptor that can mediate turning responses to netrin-1 and support a key role for netrin/DSCAM signaling in commissural axon guidance in vertebrates
GO:0005515 protein binding	IPI PMID:19196994 DSCAM functions as a netrin receptor in commissural axon pat...	MARK AS OVER ANNOTATED	Summary: IPI annotation based on interaction with NTN1 (netrin-1) demonstrated in PMID:19196994. While the interaction is real and functionally important, "protein binding" is too generic for this well-characterized receptor-ligand interaction. Reason: DSCAM binding to netrin-1 is a specific receptor-ligand interaction that should be annotated with a more specific term. The generic "protein binding" term is uninformative when the specific interaction partner (NTN1) is known. Supporting Evidence: PMID:19196994 DSCAM is expressed on commissural axons and interacts with Netrin-1, a prototypical guidance cue for commissural axons
GO:0042327 positive regulation of phosphorylation	IDA PMID:19196994 DSCAM functions as a netrin receptor in commissural axon pat...	ACCEPT	Summary: PMID:19196994 demonstrated that DSCAM mediates netrin signaling by activating phosphorylation of Fyn and Pak1. "DSCAM by itself, in the absence of DCC, is capable of mediating netrin signaling in activating phosphorylation of Fyn and Pak1." Reason: This is a well-supported IDA annotation. The study demonstrated that DSCAM promotes phosphorylation of downstream signaling molecules (Fyn, Pak1) in response to netrin-1, representing a key signaling output of DSCAM receptor activity. Supporting Evidence: PMID:19196994 DSCAM by itself, in the absence of DCC, is capable of mediating netrin signaling in activating phosphorylation of Fyn and Pak1
GO:0005886 plasma membrane	TAS Reactome:R-HSA-376122	ACCEPT	Summary: TAS annotation from Reactome pathway for DSCAM/DSCAML1 homodimerization, which occurs at the plasma membrane. Reason: Duplicate annotation supporting membrane localization. The Reactome pathway correctly captures DSCAM homodimerization at the cell surface.
GO:0005886 plasma membrane	TAS PMID:9426258 DSCAM: a novel member of the immunoglobulin superfamily maps...	ACCEPT	Summary: TAS annotation from the original DSCAM cloning paper which described the transmembrane domain topology. Reason: Duplicate annotation from the original characterization paper supporting plasma membrane localization of the Long isoform. Supporting Evidence: PMID:9426258 both containing 10 Ig-C2 domains... with or without the following transmembrane and intracellular domains
GO:0007155 cell adhesion	TAS PMID:9426258 DSCAM: a novel member of the immunoglobulin superfamily maps...	ACCEPT	Summary: TAS annotation from the original DSCAM cloning paper which described DSCAM as a novel cell adhesion molecule of the immunoglobulin superfamily. Reason: Duplicate annotation supporting cell adhesion function from the original characterization paper. Supporting Evidence: PMID:9426258 a novel member of the immunoglobulin (Ig) superfamily that represents a new class of neural cell adhesion molecules
GO:0007399 nervous system development	TAS PMID:9426258 DSCAM: a novel member of the immunoglobulin superfamily maps...	ACCEPT	Summary: TAS annotation from the original paper which established DSCAM expression in the nervous system during neural differentiation. Reason: Duplicate annotation supporting nervous system development function from the original characterization paper. Supporting Evidence: PMID:9426258 DSCAM is involved in neural differentiation and contributes to the central and peripheral nervous system defects in DS
GO:0016020 membrane	TAS PMID:9426258 DSCAM: a novel member of the immunoglobulin superfamily maps...	ACCEPT	Summary: TAS annotation from the original paper. GO:0016020 (membrane) is a parent term of GO:0005886 (plasma membrane), which is already well-annotated for DSCAM. Reason: While this is a broader term than plasma membrane (already annotated), it is accurate for the Long isoform. The original paper described the transmembrane domain structure. Supporting Evidence: PMID:9426258 DSCAM: a novel member of the immunoglobulin superfamily maps in a Down syndrome region and is involved in the development of the nervous system.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

📚 Additional Documentation

Notes

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