SCAMP1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006887 exocytosis	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for exocytosis is well-supported by the role of SCAMPs in regulated secretion pathways. Studies have shown that SCAMP proteins, including SCAMP1, participate in dense-core granule release and fusion pore dynamics. SCAMP1 localizes to secretory granules and participates in post-Golgi vesicle-mediated transport, contributing to exocytotic processes. Deep research (SCAMP1-deep-research-falcon.md) cites family-level evidence for SCAMP involvement in exocytosis and fusion pore regulation. Reason: The IBA annotation is consistent with experimental evidence showing SCAMP family involvement in exocytosis. The phylogenetic inference is supported by the conserved role of SCAMPs in vesicular transport and the conservation of the E peptide domain implicated in fusion pore dynamics. This represents a core function of the SCAMP family. Supporting Evidence: GO_REF:0000033 Phylogenetic annotation from IBA pipeline based on PANTHER family file:human/SCAMP1/SCAMP1-deep-research-falcon.md Overexpression of the SCAMP E peptide inhibits dense-core granule release, and SCAMP1 knockout studies indicate altered fusion dynamics with increased transient fusion events
GO:0032588 trans-Golgi network membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for trans-Golgi network membrane is strongly supported by direct experimental evidence. PMID:15840657 demonstrated that SCAMP1 localizes to the trans-Golgi network where it interacts with the Na+/H+ exchanger NHE7. Reason: The IBA annotation is supported by IDA evidence from PMID:15840657 showing SCAMP1 co-immunolocalization with TGN markers and co-sedimentation with TGN fractions. This represents a primary localization site for SCAMP1. Supporting Evidence: PMID:15840657 The majority of the NHE7-SCAMP complexes accumulated at the TGN
GO:0055038 recycling endosome membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation for recycling endosome membrane is well-supported. PMID:15840657 showed that SCAMP1 localizes to recycling vesicles. Reason: This annotation is supported by IDA evidence showing SCAMP1 in recycling vesicles. The recycling endosome is a key site for SCAMP1 function in cargo shuttling between TGN and plasma membrane. Supporting Evidence: PMID:15840657 a minor fraction also resided in recycling vesicles
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	ACCEPT	Summary: IEA annotation for Golgi apparatus is correct but less specific than the IDA annotation for trans-Golgi network. This is a parent term that encompasses the more specific TGN localization. Reason: The annotation is accurate as the TGN is part of the Golgi apparatus, and this IEA annotation serves as an appropriate broader annotation consistent with the experimental data. Supporting Evidence: PMID:15840657 The majority of the NHE7-SCAMP complexes accumulated at the TGN
GO:0015031 protein transport	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation for protein transport is supported by the IDA evidence from PMID:15840657 showing that SCAMP1 regulates trafficking of NHE7 between recycling vesicles and the TGN. Reason: SCAMP1 participates in protein transport by regulating shuttling of cargo proteins like NHE7 between organellar compartments. This is a core function of the protein. Supporting Evidence: PMID:15840657 We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN
GO:0016020 membrane	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation for membrane is accurate but very general. SCAMP1 is an integral membrane protein with four transmembrane domains. Reason: The annotation is correct; SCAMP1 is a multi-pass membrane protein. More specific membrane localizations (TGN membrane, recycling endosome membrane) are also annotated. Supporting Evidence: UniProt:O15126 Multi-pass membrane protein
GO:0055038 recycling endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Duplicate IEA annotation for recycling endosome membrane, paralleling the IBA annotation. This is consistent with experimental evidence. Reason: The annotation is supported by experimental evidence from PMID:15840657 showing SCAMP1 in recycling vesicles. Supporting Evidence: PMID:15840657 a minor fraction also resided in recycling vesicles
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: High-throughput interactome study (HI-II-14) identifying protein-protein interactions. The term 'protein binding' is uninformative for a protein whose function depends on protein-protein interactions. Reason: While SCAMP1 clearly binds proteins as part of its trafficking function, the generic 'protein binding' term does not capture the specific nature of these interactions. More informative terms describing the functional context of interactions would be preferred. Supporting Evidence: PMID:25416956 Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Another high-throughput interactome study identifying SCAMP1 interactions. Reason: Same rationale as above; 'protein binding' is too generic for meaningful annotation. Supporting Evidence: PMID:28514442 BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Reference map of human binary protein interactome detecting SCAMP1 interactions. Reason: Same rationale; 'protein binding' lacks specificity about the functional context. Supporting Evidence: PMID:32296183 we refer to HI-III-20 as a reference map of the human binary protein interactome
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Interactome mapping in neurodegenerative disease context. Reason: 'Protein binding' is uninformative; SCAMP1 interactions should be annotated with more specific functional terms where evidence supports. Supporting Evidence: PMID:32814053 an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Cell-specific interactome remodeling study. Reason: Same rationale regarding uninformative nature of 'protein binding'. Supporting Evidence: PMID:33961781 we have created two proteome-scale, cell-line-specific interaction networks
GO:0005515 protein binding	IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy...	MARK AS OVER ANNOTATED	Summary: CFTR interactome study identifying SCAMP1-CFTR interaction. Reason: While the SCAMP1-CFTR interaction is interesting given both are involved in membrane trafficking, 'protein binding' is too generic to capture this relationship meaningfully. Supporting Evidence: PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system
GO:0005515 protein binding	IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ...	MARK AS OVER ANNOTATED	Summary: CFTR proximity labeling study identifying enrichment of SLC transporters. Reason: 'Protein binding' is uninformative; the CFTR-SCAMP1 proximity relationship may be biologically relevant for CFTR trafficking but requires more specific annotation. Supporting Evidence: PMID:36012204 The two proximity labeling approaches identified both known and additional CFTR protein partners, including multiple SLC transporters
GO:0006897 endocytosis	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for endocytosis based on ortholog inference. SCAMP1 is involved in recycling pathways that are coupled to endocytosis, particularly compensatory endocytosis after exocytosis. Reason: SCAMP1 participates in recycling pathways that intersect with endocytic machinery. The NPF motifs recruit EH-domain proteins like Eps15 and intersectin, which are endocytic scaffolds. While SCAMP1 may not directly drive initial clathrin-coated vesicle formation, it functions in endocytic recycling. Supporting Evidence: file:human/SCAMP1/SCAMP1-deep-research-falcon.md SCAMP1/2 localize to recycling endosomes, where NPF motifs recruit EH-domain proteins (Eps15/intersectin)
GO:0019904 protein domain specific binding	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for protein domain specific binding. SCAMP1 contains NPF motifs that specifically bind EH domains in proteins like Eps15 and intersectin. Reason: The NPF-EH domain interaction is well-established for SCAMP proteins, representing a specific domain-based interaction mechanism for coupling to endocytic machinery. Supporting Evidence: file:human/SCAMP1/SCAMP1-deep-research-falcon.md SCAMP1 contains multiple NPF motifs in its N-terminus that bind EH-domain proteins (Eps15, intersectin)
GO:0030136 clathrin-coated vesicle	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for clathrin-coated vesicle localization based on ortholog inference. Reason: SCAMP1 interacts with EH-domain proteins that are components of clathrin-associated endocytic machinery, supporting transient localization to clathrin-coated vesicles. Supporting Evidence: file:human/SCAMP1/SCAMP1-deep-research-falcon.md NPF motifs recruit EH-domain proteins (Eps15/intersectin), linking SCAMP1 to clathrin-associated endocytic scaffolds
GO:0030659 cytoplasmic vesicle membrane	IEA GO_REF:0000107	ACCEPT	Summary: IEA annotation for cytoplasmic vesicle membrane is accurate but less specific than annotations for recycling endosome membrane or TGN membrane. Reason: SCAMP1 localizes to various cytoplasmic vesicle membranes including recycling endosomes and post-Golgi vesicles. This is a valid parent term. Supporting Evidence: PMID:15840657 a minor fraction also resided in recycling vesicles
GO:0030672 synaptic vesicle membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: IEA annotation for synaptic vesicle membrane based on ortholog inference. SCAMP1 is expressed in brain and has been found in synaptic vesicle preparations. Reason: While SCAMP1 is highly expressed in brain and localizes to synaptic vesicles in neurons, this is not its primary or core localization. SCAMP1 is widely expressed and its core function is in general post-Golgi recycling pathways. Supporting Evidence: UniProt:O15126 Widely expressed, with highest expression in brain
GO:0042589 zymogen granule membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation for zymogen granule membrane based on ortholog inference. Zymogen granules are specialized secretory granules in pancreatic acinar cells. Reason: SCAMPs have been detected in secretory granules including zymogen granules, consistent with their role in regulated secretion. However, this represents tissue-specific localization rather than a core function. Supporting Evidence: file:human/SCAMP1/SCAMP1-deep-research-falcon.md SCAMPs concentrate in endomembrane systems that recycle between plasma membrane and internal compartments (early/recycling endosomes, trans-Golgi network, secretory granules)
GO:0045202 synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA annotation for synapse localization based on ortholog inference. Reason: SCAMP1 localizes to synapses in neurons due to its presence on synaptic vesicles and recycling compartments. This is tissue-specific and not a core localization. Supporting Evidence: UniProt:O15126 Widely expressed, with highest expression in brain
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6799350	ACCEPT	Summary: TAS annotation for plasma membrane from Reactome neutrophil degranulation pathway. SCAMP1 cycles between intracellular compartments and the plasma membrane. Reason: SCAMP1 functions in recycling pathways that deliver cargo to the plasma membrane, and a fraction of SCAMP1 transiently localizes to the surface during this cycling. Supporting Evidence: Reactome:R-HSA-6799350 Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances UniProt:O15126 Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.
GO:0035579 specific granule membrane	TAS Reactome:R-HSA-6799350	KEEP AS NON CORE	Summary: TAS annotation for specific granule membrane from Reactome. Specific granules are secondary granules in neutrophils containing antimicrobial substances. Reason: This is a neutrophil-specific localization related to degranulation. While SCAMP1 is involved, this represents cell-type-specific function rather than core function. Supporting Evidence: Reactome:R-HSA-6799350 Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances
GO:0030136 clathrin-coated vesicle	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation for clathrin-coated vesicle localization based on sequence similarity. Reason: Consistent with the IEA annotation; SCAMP1 interacts with clathrin-associated machinery through NPF-EH domain interactions. Supporting Evidence: GO_REF:0000024 Manual transfer of experimentally-verified manual GO annotation data to orthologs
GO:0005515 protein binding	IPI PMID:15840657 Secretory carrier membrane proteins interact and regulate tr...	MODIFY	Summary: IPI annotation for protein binding based on interaction with NHE7 (SLC9A7). This is from a focused study showing functional interaction between SCAMP1 and NHE7. Reason: While the SCAMP1-NHE7 interaction is experimentally validated, 'protein binding' is uninformative. A more specific term describing the functional relationship would be preferred. SCAMP1 interacts with NHE7 through a conserved cytoplasmic loop to regulate NHE7 trafficking. Proposed replacements: protein domain specific binding Supporting Evidence: PMID:15840657 the C-terminal cytoplasmic tail of NHE7 bound preferentially to a highly conserved cytoplasmic loop between the second and the third transmembrane segments (TM2-TM3 loop) of SCAMP2
GO:0005802 trans-Golgi network	IDA PMID:15840657 Secretory carrier membrane proteins interact and regulate tr...	ACCEPT	Summary: IDA annotation for trans-Golgi network localization based on direct experimental evidence from Lin et al. 2005. Reason: Strong experimental evidence from co-immunolocalization and sucrose gradient fractionation demonstrating SCAMP1 accumulation at the TGN. This is a core localization site. Supporting Evidence: PMID:15840657 The majority of the NHE7-SCAMP complexes accumulated at the TGN, but a minor fraction also resided in recycling vesicles
GO:0015031 protein transport	IDA PMID:15840657 Secretory carrier membrane proteins interact and regulate tr...	ACCEPT	Summary: IDA annotation for protein transport based on functional studies showing SCAMP1 regulates NHE7 trafficking between TGN and recycling vesicles. Reason: The experimental evidence demonstrates that SCAMP1 participates in shuttling cargo proteins between compartments, representing a core function. Supporting Evidence: PMID:15840657 We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN
GO:0016020 membrane	IDA PMID:15840657 Secretory carrier membrane proteins interact and regulate tr...	ACCEPT	Summary: IDA annotation for membrane localization from the same study. Reason: SCAMP1 is an integral membrane protein demonstrated by fractionation studies. Supporting Evidence: PMID:15840657 co-sedimentation in membrane fractions resolved on sucrose density gradients
GO:0055038 recycling endosome membrane	IDA PMID:15840657 Secretory carrier membrane proteins interact and regulate tr...	ACCEPT	Summary: IDA annotation for recycling endosome membrane based on localization studies. Reason: Experimental evidence shows SCAMP1 in recycling vesicles, representing a core localization for its function in cargo recycling. Supporting Evidence: PMID:15840657 a minor fraction also resided in recycling vesicles
GO:0006892 post-Golgi vesicle-mediated transport	TAS PMID:9378760 Three mammalian SCAMPs (secretory carrier membrane proteins)...	ACCEPT	Summary: TAS annotation for post-Golgi vesicle-mediated transport based on the original characterization of mammalian SCAMPs. Reason: This term accurately captures the core function of SCAMP1 in mediating transport from the Golgi to other cellular destinations via carrier vesicles. Supporting Evidence: PMID:9378760 SCAMPs may largely function at the same sites during vesicular transport rather than in separate post-Golgi recycling pathways
GO:0032456 endocytic recycling	TAS file:human/SCAMP1/SCAMP1-deep-research-falcon.md	NEW	Summary: Annotation for endocytic recycling based on deep research review of SCAMP1 literature showing SCAMP1 participates in recycling pathways that return cargo from endosomes to plasma membrane. Reason: SCAMP1 localizes to recycling endosomes and contains NPF motifs that recruit EH-domain endocytic scaffolds (Eps15, intersectin), coupling SCAMP1-containing carriers to the endocytic machinery. Supporting Evidence: file:human/SCAMP1/SCAMP1-deep-research-falcon.md SCAMP1 participates in recycling pathways rather than initial clathrin-coated vesicle formation

Core Functions

SCAMP1 functions as a trafficking factor that mediates transport of cargo proteins from the trans-Golgi network to other cellular destinations including the plasma membrane and recycling endosomes. The protein contains NPF motifs that specifically bind EH domains in endocytic scaffold proteins, and interacts with cargo proteins like NHE7 through its conserved TM2-TM3 cytoplasmic loop. This is supported by experimental evidence showing SCAMP1 regulates trafficking of NHE7 between TGN and recycling vesicles (PMID:15840657) and the original characterization of SCAMPs as secretory carrier-associated membrane proteins involved in post-Golgi recycling pathways (PMID:9378760).

Molecular Function:

protein domain specific binding

Directly Involved In:

post-Golgi vesicle-mediated transport endocytic recycling

Cellular Locations:

trans-Golgi network membrane recycling endosome membrane

Supporting Evidence:

PMID:15840657
We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN
PMID:9378760
SCAMPs may largely function at the same sites during vesicular transport rather than in separate post-Golgi recycling pathways

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:15840657

Secretory carrier membrane proteins interact and regulate trafficking of the organellar (Na+,K+)/H+ exchanger NHE7.

SCAMP1 interacts with NHE7 at the TGN and recycling vesicles

"The majority of the NHE7-SCAMP complexes accumulated at the TGN, but a minor fraction also resided in recycling vesicles"
SCAMP1 regulates shuttling of NHE7 between compartments

"We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN"
Interaction is mediated by the conserved TM2-TM3 cytoplasmic loop

"the C-terminal cytoplasmic tail of NHE7 bound preferentially to a highly conserved cytoplasmic loop between the second and the third transmembrane segments (TM2-TM3 loop) of SCAMP2"

PMID:25416956

A proteome-scale map of the human interactome network.

High-throughput binary protein-protein interaction mapping

"Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions"

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

Interactome mapping study

"BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins"

PMID:32296183

A reference map of the human binary protein interactome.

Systematic binary interactome mapping

"we refer to HI-III-20 as a reference map of the human binary protein interactome"

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Neurodegenerative disease protein interaction network

"an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions"

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

Cell-type-specific interactome analysis

"we have created two proteome-scale, cell-line-specific interaction networks"

PMID:35156780

CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.

SCAMP1 identified as CFTR interactor

"CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system"

PMID:36012204

Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters.

CFTR proximity labeling identifies trafficking factors

"The two proximity labeling approaches identified both known and additional CFTR protein partners, including multiple SLC transporters"

PMID:9378760

Three mammalian SCAMPs (secretory carrier membrane proteins) are highly related products of distinct genes having similar subcellular distributions.

SCAMP1-3 are products of distinct genes

"The structures indicated that SCAMPs are highly related products of distinct genes"
SCAMPs have similar subcellular distributions in post-Golgi compartments

"Examination of the codistribution of the three forms within individual cells using double label immunofluorescence indicates extensive colocalization"
SCAMPs function together at same sites during vesicular transport

"SCAMPs may largely function at the same sites during vesicular transport rather than in separate post-Golgi recycling pathways"

Reactome:R-HSA-6799350

Exocytosis of specific granule membrane proteins

SCAMP1 involved in neutrophil specific granule exocytosis

"Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances"

file:human/SCAMP1/SCAMP1-deep-research-falcon.md

Deep research review of SCAMP1 literature

SCAMP family structural and functional analysis from multiple studies

"NPF motifs recruit EH-domain proteins (Eps15/intersectin), and E peptide is conserved and membrane-active"

Suggested Experiments

Experiment: Live-cell imaging of SCAMP1 dynamics during regulated secretion in neuroendocrine cells to characterize its role in exocytosis and compensatory endocytosis. Would clarify the temporal relationship between SCAMP1 localization and fusion pore dynamics.

Experiment: Proximity labeling (BioID/APEX) of SCAMP1 to comprehensively identify cargo proteins and trafficking machinery that co-localize with SCAMP1 carriers. Would expand understanding of SCAMP1 cargo specificity and interaction partners beyond NHE7 and CFTR.

Deep Research

Falcon

(SCAMP1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 22 citations 2025-12-27T23:35:30.366655

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan and scope
We verified the target as human SCAMP1 (UniProt O15126): a tetraspanning integral membrane protein of the SCAMP family with cytosolic N- and C-termini, conserved four-pass membrane core, and N‑terminal cytosolic motifs including NPF repeats and proline-rich segments, consistent with foundational structural/topology studies of SCAMPs (URL: https://doi.org/10.1091/mbc.11.9.2933; published Sep 2000) (hubbard2000thesecretorycarrier pages 1-2). We then synthesized functional, mechanistic, and disease-linked evidence with emphasis on precise roles in trafficking and recent findings where available, noting that SCAMP1-specific primary literature in 2023–2024 is limited in the retrieved evidence.

Key concepts and definitions
• Protein family and domains: SCAMPs are evolutionarily conserved secretory carrier-associated membrane proteins; mammalian genomes encode five isoforms (SCAMP1–5). SCAMPs share a central four-transmembrane “core,” minimal luminal loops, and cytosolic N- and C-termini. SCAMP1 (like SCAMP2/3) possesses N‑terminal NPF motifs (EH-binding) and proline-rich segments; an internal amphipathic “E peptide” between TM2–TM3 is conserved and membrane-active. Limited proteolysis and biophysical studies mapped these features and showed both termini are cytosolic (URL: https://doi.org/10.1091/mbc.11.9.2933; Sep 2000) (hubbard2000thesecretorycarrier pages 1-2). A family synopsis further highlights NPF–EH interactions (Eps15/intersectin) and E‑peptide function (URL: n/a; 2012) (stevens2012geneticanalysisof pages 31-36).
• Cellular localization: SCAMPs concentrate in endomembrane systems that recycle between plasma membrane and internal compartments (early/recycling endosomes, trans‑Golgi network, secretory granules). Live-cell imaging localized GFP‑SCAMP1 to motile early/recycling endosomes with limited constitutive surface exchange (URL: https://doi.org/10.1242/jcs.02503; Aug 2005) (hubbard2000thesecretorycarrier pages 1-2) (hubbard2000thesecretorycarrier pages 1-2).

Primary functions and mechanisms
• Exocytosis and fusion pore regulation: Overexpression of the SCAMP “E peptide” inhibits dense-core granule release, and SCAMP1 knockout studies indicate altered fusion dynamics with increased transient fusion events, consistent with a role in stabilizing the fusion pore and coordinating compensatory endocytosis after exocytosis (URL: n/a; 2012 review synopsis) (stevens2012geneticanalysisof pages 31-36).
• Endocytosis and recycling: SCAMP1 participates in recycling pathways rather than initial clathrin-coated vesicle formation. SCAMP1/2 localize to recycling endosomes, where NPF motifs recruit EH-domain proteins (Eps15/intersectin), facilitating cargo sorting and endosome-to-plasma-membrane traffic. Family-level mechanisms implicate ARF6-regulated steps in endosomal recycling and surface delivery; SCAMP2 has direct ARF6 links and promotes vesicle formation, providing a pathway context applicable to SCAMP1-bearing recycling carriers (URL: https://doi.org/10.14288/1.0071692; Jan 2011) (diering2011exploringthephysiological pages 130-134). Broad endocytosis frameworks place SCAMPs among adaptors/effectors that organize internalization–recycling circuits underlying signaling spatial restriction (URL: https://doi.org/10.1016/j.molonc.2009.05.008; Aug 2009) (diering2011exploringthephysiological pages 130-134, hubbard2000thesecretorycarrier pages 1-2).
• Lipid interactions: The conserved amphipathic segments in SCAMPs (including SCAMP1) bind phospholipid membranes; the inter-TM2/3 segment forms an α-helix on membranes. Electrostatic interactions between SCAMP1/2 cytosolic peptides and PI(4,5)P2 have been reported in family-level analyses, consistent with localization to PI(4,5)P2-rich recycling domains (URL: https://doi.org/10.1091/mbc.11.9.2933; Sep 2000; and oncology integrative study referencing PI(4,5)P2–E‑peptide interactions, Jan 2021) (hubbard2000thesecretorycarrier pages 1-2, mao2021expressionandprognostic pages 6-10).
• Interaction motifs and partners: SCAMP1 contains multiple NPF motifs in its N‑terminus that bind EH-domain proteins (Eps15, intersectin), linking SCAMP1 to clathrin-associated endocytic scaffolds and to coupling of exo–endocytosis cycles (URL: n/a; 2012) (stevens2012geneticanalysisof pages 31-36).

Pathway-level context and signaling/trafficking links
• ARF6–recycling axis: SCAMP family actions in recycling endosomes intersect with ARF6-dependent pathways that control endosome-to-surface traffic and receptor/cargo recycling. Demonstrated mechanistically for SCAMP2 and NHE5 trafficking, this likely delineates the trafficking context for SCAMP1-containing carriers given their co-compartmentalization and shared NPF/EH machinery (URL: https://doi.org/10.14288/1.0071692; Jan 2011) (diering2011exploringthephysiological pages 130-134).
• EGFR and endocytic signaling context: SCAMPs modulate receptor fate by shaping recycling compartments. Family literature indicates that SCAMP-dependent recycling influences signaling outputs (e.g., EGFR), aligning with broader models where endocytosis/recycling define spatial signaling gradients (URL: https://doi.org/10.1016/j.molonc.2009.05.008; Aug 2009; foundational SCAMP family/topology work, Sep 2000) (hubbard2000thesecretorycarrier pages 1-2, diering2011exploringthephysiological pages 130-134).

Current applications, disease associations, and real-world implementations
• Viral infection—HBV restriction factor: Multi‑omics profiling of endocytosis upon HBV infection identified SCAMP1 as differentially regulated at transcriptome, proteome, and ubiquitylome levels. Gain- and loss-of-function experiments showed SCAMP1 overexpression suppresses HBV RNAs/pgRNA and secreted HBsAg/HBeAg, whereas SCAMP1 knockdown increases viral production. Mechanistically, SCAMP1 inhibits HBV EnhI/Xp, SP1, and SP2 promoter activities and can interact with viral proteins (L and X) in co‑IP assays, suggesting transcriptional suppression and/or trafficking-associated antiviral mechanisms (URL: https://doi.org/10.3390/ijms23042211; Feb 2022) (yousaf2022multiomicsanalysisof pages 1-2, yousaf2022multiomicsanalysisof pages 10-14, yousaf2022multiomicsanalysisof pages 19-20). These findings propose SCAMP1 as a host restriction factor and a potential target/modulator in HBV research contexts.
• Cancer—pancreatic adenocarcinoma (PAAD): Transcriptomic and clinical analyses show SCAMP1 upregulated in PAAD versus normal tissue, with higher SCAMP1 expression associated with worse overall survival; SCAMP1 emerged as an independent prognostic factor in multivariate analyses in that cohort study (URL: https://doi.org/10.18632/aging.202377; Jan 2021) (mao2021expressionandprognostic pages 6-10, mao2021expressionandprognostic pages 14-15). Related literature points to SCAMP1’s involvement in invasion/migration phenotypes across cancers, consistent with its trafficking role (mao2021expressionandprognostic pages 14-15).

Relevant statistics and data
• HBV multi-omics study (HepG2/HepG2.2.15): quantified 273 endocytosis-associated genes (RNA-seq), 190 proteins (proteomics), and 221 ubiquitinated lysines across 77 proteins (ubiquitylome); SCAMP1 was differentially expressed across all three layers. Functional assays reported reductions in HBV secreted proteins upon SCAMP1 overexpression and increases upon knockdown; promoter luciferase assays showed significant inhibition of EnhI/Xp, SP1, SP2 by SCAMP1 (URL: https://doi.org/10.3390/ijms23042211; Feb 2022) (yousaf2022multiomicsanalysisof pages 1-2, yousaf2022multiomicsanalysisof pages 10-14, yousaf2022multiomicsanalysisof pages 19-20).
• PAAD clinical association: SCAMP1 overexpression in tumor vs. normal and association with poorer overall survival are reported; SCAMP1 and SCAMP5 were independent prognostic factors in multivariate analyses (URL: https://doi.org/10.18632/aging.202377; Jan 2021) (mao2021expressionandprognostic pages 6-10).

Expert opinions and analysis (authoritative sources)
• Structural/topological consensus: The 2000 MBoC study provides definitive topology and domain organization for SCAMPs, establishing cytosolic orientation of termini, four TM core, and membrane-active amphipathic elements—features foundational to SCAMP1 mechanism in trafficking and exo–endocytic coupling (URL: https://doi.org/10.1091/mbc.11.9.2933; Sep 2000) (hubbard2000thesecretorycarrier pages 1-2).
• Mechanistic consensus: Family synopses emphasize NPF–EH interactions (Eps15/intersectin) as a recurrent mechanism coupling SCAMPs to endocytic/recycling scaffolds and identify the E peptide as a functional regulator of exocytosis and fusion pore dynamics; SCAMP1 knockout phenotypes point to pore stabilization and compensatory endocytosis coupling (URL: n/a; 2012 synopsis) (stevens2012geneticanalysisof pages 31-36). Together these support a model in which SCAMP1 acts as trafficking machinery rather than itinerant cargo.

Recent developments (2023–2024) and limitations
• In the evidence retrieved here, SCAMP1-specific primary articles from 2023–2024 were limited. Broad 2024 reviews of lipid modifications and contemporary organelle proteomics support the importance of membrane-embedded adaptors in trafficking but do not provide SCAMP1-specific new mechanisms in this corpus. As such, the most recent SCAMP1-focused functional advances we can cite from the present evidence are the 2022 HBV restriction study and 2021 oncology analyses (yousaf2022multiomicsanalysisof pages 1-2, yousaf2022multiomicsanalysisof pages 10-14, mao2021expressionandprognostic pages 6-10). Additional targeted searching may uncover 2023–2024 SCAMP1-focused mechanistic studies beyond this dataset.

Synthesis—functional annotation for SCAMP1 (human)
• Molecular role: SCAMP1 is a membrane-embedded trafficking factor concentrated in recycling endosomes, trans‑Golgi–derived carriers, and secretory granules. It helps coordinate exocytosis with compensatory endocytosis and supports endosome-to-plasma-membrane recycling. Mechanistically, its N‑terminal NPF motifs recruit EH‑domain scaffolds (Eps15/intersectin), and its conserved amphipathic segments interact with phospholipids (likely PI(4,5)P2‑enriched membranes), aligning SCAMP1 with ARF6‑regulated recycling pathways. Functionally, SCAMP1 contributes to fusion pore stabilization and vesicle cycling, with disease-relevant consequences for receptor signaling and pathogen interactions (URLs: https://doi.org/10.1091/mbc.11.9.2933; Sep 2000; https://doi.org/10.14288/1.0071692; Jan 2011) (hubbard2000thesecretorycarrier pages 1-2, diering2011exploringthephysiological pages 130-134, stevens2012geneticanalysisof pages 31-36).
• Pathways: SCAMP1 operates in endocytosis/recycling circuits that control plasma-membrane composition and signaling outputs (e.g., EGFR context) and participates in ARF6‑linked recycling from early/recycling endosomes to surface (URLs: https://doi.org/10.1091/mbc.11.9.2933; Sep 2000; https://doi.org/10.14288/1.0071692; Jan 2011) (hubbard2000thesecretorycarrier pages 1-2, diering2011exploringthephysiological pages 130-134).
• Disease/applications: SCAMP1 acts as an HBV host restriction factor by suppressing viral promoter activity and reducing virion components; it is also upregulated in pancreatic adenocarcinoma and associates with worse survival, nominating SCAMP1 as a candidate prognostic biomarker and a trafficking node influencing tumor biology (URLs: https://doi.org/10.3390/ijms23042211; Feb 2022; https://doi.org/10.18632/aging.202377; Jan 2021) (yousaf2022multiomicsanalysisof pages 1-2, yousaf2022multiomicsanalysisof pages 10-14, mao2021expressionandprognostic pages 6-10, mao2021expressionandprognostic pages 14-15).

Mandatory verification check
• Gene/protein match: SCAMP1 gene symbol and description match UniProt O15126 (Secretory carrier-associated membrane protein 1). The organism is Homo sapiens. Family/domain features (SCAMP family; four TMs; cytosolic termini; N‑terminal NPF motifs; amphipathic E peptide) are consistent across cited literature (hubbard2000thesecretorycarrier pages 1-2, stevens2012geneticanalysisof pages 31-36).

References (URLs, publication dates)
• Hubbard CH et al. The secretory carrier membrane protein family: structure and membrane topology. Mol Biol Cell. Published Sep 2000. URL: https://doi.org/10.1091/mbc.11.9.2933 (hubbard2000thesecretorycarrier pages 1-2).
• Stevens RJ. Genetic analysis of synaptogyrin function in the synaptic vesicle cycle (family-level SCAMP synopsis embedded). 2012. URL: n/a (stevens2012geneticanalysisof pages 31-36).
• Diering GH. Exploring the physiological function of the brain-enriched Na+/H+ exchanger NHE5 (SCAMP family mechanisms; ARF6/recycling context). Published Jan 2011. URL: https://doi.org/10.14288/1.0071692 (diering2011exploringthephysiological pages 130-134).
• Yousaf T et al. Multiomics Analysis… and Identification of SCAMP1 as a Novel Host Restriction Factor against HBV Replication. Int J Mol Sci. Published Feb 2022. URL: https://doi.org/10.3390/ijms23042211 (yousaf2022multiomicsanalysisof pages 1-2, yousaf2022multiomicsanalysisof pages 10-14, yousaf2022multiomicsanalysisof pages 19-20).
• Mao F et al. Expression and prognostic analyses of SCAMPs in pancreatic adenocarcinoma. Aging (Albany NY). Published Jan 2021. URL: https://doi.org/10.18632/aging.202377 (mao2021expressionandprognostic pages 6-10, mao2021expressionandprognostic pages 14-15).

Limitations and next steps
The present evidence corpus contained limited SCAMP1-specific 2023–2024 primary studies. For a forward-looking update, targeted searches of proteomics interactomes, receptor trafficking datasets, and disease-focused cohorts from 2023–2024 may reveal additional mechanistic or translational insights not covered here. Nonetheless, the structural/functional foundation and the 2021–2022 disease studies provide a robust, well-supported functional annotation for human SCAMP1.

References

(hubbard2000thesecretorycarrier pages 1-2): Charles H. Hubbard, David R. Singleton, Michelle Rauch, Sajith Jayasinghe, D. Cafiso, and David Castle. The secretory carrier membrane protein family: structure and membrane topology. Molecular biology of the cell, 11 9:2933-47, Sep 2000. URL: https://doi.org/10.1091/mbc.11.9.2933, doi:10.1091/mbc.11.9.2933. This article has 69 citations and is from a domain leading peer-reviewed journal.
(stevens2012geneticanalysisof pages 31-36): RJ Stevens. Genetic analysis of synaptogyrin function in the synaptic vesicle cycle. Unknown journal, 2012.
(diering2011exploringthephysiological pages 130-134): Graham Hugh Diering. Exploring the physiological function of the brain-enriched na+/h+ exchanger nhe5. ArXiv, Jan 2011. URL: https://doi.org/10.14288/1.0071692, doi:10.14288/1.0071692. This article has 0 citations.
(mao2021expressionandprognostic pages 6-10): Feiyu Mao, Heng Duan, Aly Allamyradov, Zechang Xin, Yan Du, Xiaodong Wang, Peng Xu, Zhennan Li, Jianjun Qian, and Jie Yao. Expression and prognostic analyses of scamps in pancreatic adenocarcinoma. Aging (Albany NY), 13:4096-4114, Jan 2021. URL: https://doi.org/10.18632/aging.202377, doi:10.18632/aging.202377. This article has 17 citations.
(yousaf2022multiomicsanalysisof pages 1-2): Tanzeel Yousaf, Yuting Sun, Wajeeha Naz, Yang Liu, Jiaqi Xu, Sen Yuan, Kangwei Wu, Min Wang, Jun Wang, Mingxiong Guo, and Guihong Sun. Multiomics analysis of endocytosis upon hbv infection and identification of scamp1 as a novel host restriction factor against hbv replication. International Journal of Molecular Sciences, 23:2211, Feb 2022. URL: https://doi.org/10.3390/ijms23042211, doi:10.3390/ijms23042211. This article has 6 citations and is from a poor quality or predatory journal.
(yousaf2022multiomicsanalysisof pages 10-14): Tanzeel Yousaf, Yuting Sun, Wajeeha Naz, Yang Liu, Jiaqi Xu, Sen Yuan, Kangwei Wu, Min Wang, Jun Wang, Mingxiong Guo, and Guihong Sun. Multiomics analysis of endocytosis upon hbv infection and identification of scamp1 as a novel host restriction factor against hbv replication. International Journal of Molecular Sciences, 23:2211, Feb 2022. URL: https://doi.org/10.3390/ijms23042211, doi:10.3390/ijms23042211. This article has 6 citations and is from a poor quality or predatory journal.
(yousaf2022multiomicsanalysisof pages 19-20): Tanzeel Yousaf, Yuting Sun, Wajeeha Naz, Yang Liu, Jiaqi Xu, Sen Yuan, Kangwei Wu, Min Wang, Jun Wang, Mingxiong Guo, and Guihong Sun. Multiomics analysis of endocytosis upon hbv infection and identification of scamp1 as a novel host restriction factor against hbv replication. International Journal of Molecular Sciences, 23:2211, Feb 2022. URL: https://doi.org/10.3390/ijms23042211, doi:10.3390/ijms23042211. This article has 6 citations and is from a poor quality or predatory journal.
(mao2021expressionandprognostic pages 14-15): Feiyu Mao, Heng Duan, Aly Allamyradov, Zechang Xin, Yan Du, Xiaodong Wang, Peng Xu, Zhennan Li, Jianjun Qian, and Jie Yao. Expression and prognostic analyses of scamps in pancreatic adenocarcinoma. Aging (Albany NY), 13:4096-4114, Jan 2021. URL: https://doi.org/10.18632/aging.202377, doi:10.18632/aging.202377. This article has 17 citations.

Citations

hubbard2000thesecretorycarrier pages 1-2
stevens2012geneticanalysisof pages 31-36
diering2011exploringthephysiological pages 130-134
mao2021expressionandprognostic pages 14-15
mao2021expressionandprognostic pages 6-10
yousaf2022multiomicsanalysisof pages 1-2
yousaf2022multiomicsanalysisof pages 10-14
yousaf2022multiomicsanalysisof pages 19-20
https://doi.org/10.1091/mbc.11.9.2933;
https://doi.org/10.1242/jcs.02503;
https://doi.org/10.14288/1.0071692;
https://doi.org/10.1016/j.molonc.2009.05.008;
https://doi.org/10.3390/ijms23042211;
https://doi.org/10.18632/aging.202377;
https://doi.org/10.1091/mbc.11.9.2933
https://doi.org/10.14288/1.0071692
https://doi.org/10.3390/ijms23042211
https://doi.org/10.18632/aging.202377
https://doi.org/10.1091/mbc.11.9.2933,
https://doi.org/10.14288/1.0071692,
https://doi.org/10.18632/aging.202377,
https://doi.org/10.3390/ijms23042211,

📄 View Raw YAML

id: O15126
gene_symbol: SCAMP1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: SCAMP1 (Secretory carrier-associated membrane protein 1) is a tetraspanning integral membrane
  protein that functions as a trafficking factor in post-Golgi recycling pathways. The protein contains
  four transmembrane domains with both N- and C-termini exposed to the cytoplasm, N-terminal NPF motifs
  that bind EH-domain proteins (such as Eps15 and intersectin), and a conserved amphipathic E peptide
  between TM2-TM3 that interacts with membranes. SCAMP1 localizes primarily to the trans-Golgi network
  and recycling endosomes, where it participates in shuttling cargo proteins (such as the Na+/H+ exchanger
  NHE7) between these compartments and the plasma membrane. SCAMP1 is involved in coupling exocytosis
  with compensatory endocytosis and may contribute to fusion pore stabilization during regulated secretion.
  The protein interacts with multiple trafficking-associated proteins and has been implicated in neutrophil
  degranulation pathways.
existing_annotations:
- term:
    id: GO:0006887
    label: exocytosis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation for exocytosis is well-supported by the role of SCAMPs in regulated secretion
      pathways. Studies have shown that SCAMP proteins, including SCAMP1, participate in dense-core granule
      release and fusion pore dynamics. SCAMP1 localizes to secretory granules and participates in post-Golgi
      vesicle-mediated transport, contributing to exocytotic processes. Deep research (SCAMP1-deep-research-falcon.md)
      cites family-level evidence for SCAMP involvement in exocytosis and fusion pore regulation.
    action: ACCEPT
    reason: The IBA annotation is consistent with experimental evidence showing SCAMP family involvement
      in exocytosis. The phylogenetic inference is supported by the conserved role of SCAMPs in vesicular
      transport and the conservation of the E peptide domain implicated in fusion pore dynamics. This
      represents a core function of the SCAMP family.
    supported_by:
    - reference_id: GO_REF:0000033
      supporting_text: Phylogenetic annotation from IBA pipeline based on PANTHER family
    - reference_id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
      supporting_text: Overexpression of the SCAMP E peptide inhibits dense-core granule release, and SCAMP1 knockout studies indicate altered fusion dynamics with increased transient fusion events
- term:
    id: GO:0032588
    label: trans-Golgi network membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation for trans-Golgi network membrane is strongly supported by direct experimental
      evidence. PMID:15840657 demonstrated that SCAMP1 localizes to the trans-Golgi network where it interacts
      with the Na+/H+ exchanger NHE7.
    action: ACCEPT
    reason: The IBA annotation is supported by IDA evidence from PMID:15840657 showing SCAMP1 co-immunolocalization
      with TGN markers and co-sedimentation with TGN fractions. This represents a primary localization
      site for SCAMP1.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: The majority of the NHE7-SCAMP complexes accumulated at the TGN
- term:
    id: GO:0055038
    label: recycling endosome membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation for recycling endosome membrane is well-supported. PMID:15840657 showed that
      SCAMP1 localizes to recycling vesicles.
    action: ACCEPT
    reason: This annotation is supported by IDA evidence showing SCAMP1 in recycling vesicles. The recycling
      endosome is a key site for SCAMP1 function in cargo shuttling between TGN and plasma membrane.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: a minor fraction also resided in recycling vesicles
- term:
    id: GO:0005794
    label: Golgi apparatus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: IEA annotation for Golgi apparatus is correct but less specific than the IDA annotation for
      trans-Golgi network. This is a parent term that encompasses the more specific TGN localization.
    action: ACCEPT
    reason: The annotation is accurate as the TGN is part of the Golgi apparatus, and this IEA annotation
      serves as an appropriate broader annotation consistent with the experimental data.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: The majority of the NHE7-SCAMP complexes accumulated at the TGN
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation for protein transport is supported by the IDA evidence from PMID:15840657
      showing that SCAMP1 regulates trafficking of NHE7 between recycling vesicles and the TGN.
    action: ACCEPT
    reason: SCAMP1 participates in protein transport by regulating shuttling of cargo proteins like NHE7
      between organellar compartments. This is a core function of the protein.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: IEA annotation for membrane is accurate but very general. SCAMP1 is an integral membrane
      protein with four transmembrane domains.
    action: ACCEPT
    reason: The annotation is correct; SCAMP1 is a multi-pass membrane protein. More specific membrane
      localizations (TGN membrane, recycling endosome membrane) are also annotated.
    supported_by:
    - reference_id: UniProt:O15126
      supporting_text: Multi-pass membrane protein
- term:
    id: GO:0055038
    label: recycling endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Duplicate IEA annotation for recycling endosome membrane, paralleling the IBA annotation.
      This is consistent with experimental evidence.
    action: ACCEPT
    reason: The annotation is supported by experimental evidence from PMID:15840657 showing SCAMP1 in
      recycling vesicles.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: a minor fraction also resided in recycling vesicles
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  review:
    summary: High-throughput interactome study (HI-II-14) identifying protein-protein interactions. The
      term 'protein binding' is uninformative for a protein whose function depends on protein-protein
      interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: While SCAMP1 clearly binds proteins as part of its trafficking function, the generic 'protein
      binding' term does not capture the specific nature of these interactions. More informative terms
      describing the functional context of interactions would be preferred.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: Another high-throughput interactome study identifying SCAMP1 interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: Same rationale as above; 'protein binding' is too generic for meaningful annotation.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: Reference map of human binary protein interactome detecting SCAMP1 interactions.
    action: MARK_AS_OVER_ANNOTATED
    reason: Same rationale; 'protein binding' lacks specificity about the functional context.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: we refer to HI-III-20 as a reference map of the human binary protein interactome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    summary: Interactome mapping in neurodegenerative disease context.
    action: MARK_AS_OVER_ANNOTATED
    reason: '''Protein binding'' is uninformative; SCAMP1 interactions should be annotated with more specific
      functional terms where evidence supports.'
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: Cell-specific interactome remodeling study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Same rationale regarding uninformative nature of 'protein binding'.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: we have created two proteome-scale, cell-line-specific interaction networks
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35156780
  review:
    summary: CFTR interactome study identifying SCAMP1-CFTR interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: While the SCAMP1-CFTR interaction is interesting given both are involved in membrane trafficking,
      'protein binding' is too generic to capture this relationship meaningfully.
    supported_by:
    - reference_id: PMID:35156780
      supporting_text: CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  review:
    summary: CFTR proximity labeling study identifying enrichment of SLC transporters.
    action: MARK_AS_OVER_ANNOTATED
    reason: '''Protein binding'' is uninformative; the CFTR-SCAMP1 proximity relationship may be biologically
      relevant for CFTR trafficking but requires more specific annotation.'
    supported_by:
    - reference_id: PMID:36012204
      supporting_text: The two proximity labeling approaches identified both known and additional CFTR protein partners, including multiple SLC transporters
- term:
    id: GO:0006897
    label: endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA annotation for endocytosis based on ortholog inference. SCAMP1 is involved in recycling
      pathways that are coupled to endocytosis, particularly compensatory endocytosis after exocytosis.
    action: ACCEPT
    reason: SCAMP1 participates in recycling pathways that intersect with endocytic machinery. The NPF
      motifs recruit EH-domain proteins like Eps15 and intersectin, which are endocytic scaffolds. While
      SCAMP1 may not directly drive initial clathrin-coated vesicle formation, it functions in endocytic
      recycling.
    supported_by:
    - reference_id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
      supporting_text: SCAMP1/2 localize to recycling endosomes, where NPF motifs recruit EH-domain proteins (Eps15/intersectin)
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA annotation for protein domain specific binding. SCAMP1 contains NPF motifs that specifically
      bind EH domains in proteins like Eps15 and intersectin.
    action: ACCEPT
    reason: The NPF-EH domain interaction is well-established for SCAMP proteins, representing a specific
      domain-based interaction mechanism for coupling to endocytic machinery.
    supported_by:
    - reference_id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
      supporting_text: SCAMP1 contains multiple NPF motifs in its N-terminus that bind EH-domain proteins (Eps15, intersectin)
- term:
    id: GO:0030136
    label: clathrin-coated vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA annotation for clathrin-coated vesicle localization based on ortholog inference.
    action: ACCEPT
    reason: SCAMP1 interacts with EH-domain proteins that are components of clathrin-associated endocytic
      machinery, supporting transient localization to clathrin-coated vesicles.
    supported_by:
    - reference_id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
      supporting_text: NPF motifs recruit EH-domain proteins (Eps15/intersectin), linking SCAMP1 to clathrin-associated endocytic scaffolds
- term:
    id: GO:0030659
    label: cytoplasmic vesicle membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA annotation for cytoplasmic vesicle membrane is accurate but less specific than annotations
      for recycling endosome membrane or TGN membrane.
    action: ACCEPT
    reason: SCAMP1 localizes to various cytoplasmic vesicle membranes including recycling endosomes and
      post-Golgi vesicles. This is a valid parent term.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: a minor fraction also resided in recycling vesicles
- term:
    id: GO:0030672
    label: synaptic vesicle membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation for synaptic vesicle membrane based on ortholog inference. SCAMP1 is expressed
      in brain and has been found in synaptic vesicle preparations.
    action: KEEP_AS_NON_CORE
    reason: While SCAMP1 is highly expressed in brain and localizes to synaptic vesicles in neurons, this
      is not its primary or core localization. SCAMP1 is widely expressed and its core function is in
      general post-Golgi recycling pathways.
    supported_by:
    - reference_id: UniProt:O15126
      supporting_text: Widely expressed, with highest expression in brain
- term:
    id: GO:0042589
    label: zymogen granule membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA annotation for zymogen granule membrane based on ortholog inference. Zymogen granules
      are specialized secretory granules in pancreatic acinar cells.
    action: KEEP_AS_NON_CORE
    reason: SCAMPs have been detected in secretory granules including zymogen granules, consistent with
      their role in regulated secretion. However, this represents tissue-specific localization rather
      than a core function.
    supported_by:
    - reference_id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
      supporting_text: SCAMPs concentrate in endomembrane systems that recycle between plasma membrane and internal compartments (early/recycling endosomes, trans-Golgi network, secretory granules)
- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: IEA annotation for synapse localization based on ortholog inference.
    action: KEEP_AS_NON_CORE
    reason: SCAMP1 localizes to synapses in neurons due to its presence on synaptic vesicles and recycling
      compartments. This is tissue-specific and not a core localization.
    supported_by:
    - reference_id: UniProt:O15126
      supporting_text: Widely expressed, with highest expression in brain
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799350
  review:
    summary: TAS annotation for plasma membrane from Reactome neutrophil degranulation pathway. SCAMP1
      cycles between intracellular compartments and the plasma membrane.
    action: ACCEPT
    reason: SCAMP1 functions in recycling pathways that deliver cargo to the plasma membrane, and a fraction
      of SCAMP1 transiently localizes to the surface during this cycling.
    supported_by:
    - reference_id: Reactome:R-HSA-6799350
      supporting_text: Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances
    - reference_id: UniProt:O15126
      supporting_text: Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.
- term:
    id: GO:0035579
    label: specific granule membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6799350
  review:
    summary: TAS annotation for specific granule membrane from Reactome. Specific granules are secondary
      granules in neutrophils containing antimicrobial substances.
    action: KEEP_AS_NON_CORE
    reason: This is a neutrophil-specific localization related to degranulation. While SCAMP1 is involved,
      this represents cell-type-specific function rather than core function.
    supported_by:
    - reference_id: Reactome:R-HSA-6799350
      supporting_text: Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances
- term:
    id: GO:0030136
    label: clathrin-coated vesicle
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ISS annotation for clathrin-coated vesicle localization based on sequence similarity.
    action: ACCEPT
    reason: Consistent with the IEA annotation; SCAMP1 interacts with clathrin-associated machinery through
      NPF-EH domain interactions.
    supported_by:
    - reference_id: GO_REF:0000024
      supporting_text: Manual transfer of experimentally-verified manual GO annotation data to orthologs
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15840657
  review:
    summary: IPI annotation for protein binding based on interaction with NHE7 (SLC9A7). This is from
      a focused study showing functional interaction between SCAMP1 and NHE7.
    action: MODIFY
    reason: While the SCAMP1-NHE7 interaction is experimentally validated, 'protein binding' is uninformative.
      A more specific term describing the functional relationship would be preferred. SCAMP1 interacts
      with NHE7 through a conserved cytoplasmic loop to regulate NHE7 trafficking.
    proposed_replacement_terms:
    - id: GO:0019904
      label: protein domain specific binding
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: the C-terminal cytoplasmic tail of NHE7 bound preferentially to a highly conserved cytoplasmic loop between the second and the third transmembrane segments (TM2-TM3 loop) of SCAMP2
- term:
    id: GO:0005802
    label: trans-Golgi network
  evidence_type: IDA
  original_reference_id: PMID:15840657
  review:
    summary: IDA annotation for trans-Golgi network localization based on direct experimental evidence
      from Lin et al. 2005.
    action: ACCEPT
    reason: Strong experimental evidence from co-immunolocalization and sucrose gradient fractionation
      demonstrating SCAMP1 accumulation at the TGN. This is a core localization site.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: The majority of the NHE7-SCAMP complexes accumulated at the TGN, but a minor fraction also resided in recycling vesicles
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IDA
  original_reference_id: PMID:15840657
  review:
    summary: IDA annotation for protein transport based on functional studies showing SCAMP1 regulates
      NHE7 trafficking between TGN and recycling vesicles.
    action: ACCEPT
    reason: The experimental evidence demonstrates that SCAMP1 participates in shuttling cargo proteins
      between compartments, representing a core function.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:15840657
  review:
    summary: IDA annotation for membrane localization from the same study.
    action: ACCEPT
    reason: SCAMP1 is an integral membrane protein demonstrated by fractionation studies.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: co-sedimentation in membrane fractions resolved on sucrose density gradients
- term:
    id: GO:0055038
    label: recycling endosome membrane
  evidence_type: IDA
  original_reference_id: PMID:15840657
  review:
    summary: IDA annotation for recycling endosome membrane based on localization studies.
    action: ACCEPT
    reason: Experimental evidence shows SCAMP1 in recycling vesicles, representing a core localization
      for its function in cargo recycling.
    supported_by:
    - reference_id: PMID:15840657
      supporting_text: a minor fraction also resided in recycling vesicles
- term:
    id: GO:0006892
    label: post-Golgi vesicle-mediated transport
  evidence_type: TAS
  original_reference_id: PMID:9378760
  review:
    summary: TAS annotation for post-Golgi vesicle-mediated transport based on the original characterization
      of mammalian SCAMPs.
    action: ACCEPT
    reason: This term accurately captures the core function of SCAMP1 in mediating transport from the
      Golgi to other cellular destinations via carrier vesicles.
    supported_by:
    - reference_id: PMID:9378760
      supporting_text: SCAMPs may largely function at the same sites during vesicular transport rather than in separate post-Golgi recycling pathways
- term:
    id: GO:0032456
    label: endocytic recycling
  evidence_type: TAS
  original_reference_id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
  review:
    summary: Annotation for endocytic recycling based on deep research review of SCAMP1 literature showing
      SCAMP1 participates in recycling pathways that return cargo from endosomes to plasma membrane.
    action: NEW
    reason: SCAMP1 localizes to recycling endosomes and contains NPF motifs that recruit EH-domain endocytic
      scaffolds (Eps15, intersectin), coupling SCAMP1-containing carriers to the endocytic machinery.
    supported_by:
    - reference_id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
      supporting_text: SCAMP1 participates in recycling pathways rather than initial clathrin-coated vesicle formation
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator
    judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
    Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15840657
  title: Secretory carrier membrane proteins interact and regulate trafficking of the organellar (Na+,K+)/H+
    exchanger NHE7.
  findings:
  - statement: SCAMP1 interacts with NHE7 at the TGN and recycling vesicles
    supporting_text: The majority of the NHE7-SCAMP complexes accumulated at the TGN, but a minor fraction also resided in recycling vesicles
  - statement: SCAMP1 regulates shuttling of NHE7 between compartments
    supporting_text: We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN
  - statement: Interaction is mediated by the conserved TM2-TM3 cytoplasmic loop
    supporting_text: the C-terminal cytoplasmic tail of NHE7 bound preferentially to a highly conserved cytoplasmic loop between the second and the third transmembrane segments (TM2-TM3 loop) of SCAMP2
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings:
  - statement: High-throughput binary protein-protein interaction mapping
    supporting_text: Here, we describe a systematic map of ?14,000 high-quality human binary protein-protein interactions
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease networks.
  findings:
  - statement: Interactome mapping study
    supporting_text: BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings:
  - statement: Systematic binary interactome mapping
    supporting_text: we refer to HI-III-20 as a reference map of the human binary protein interactome
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread
    Protein Aggregation in Affected Brains.
  findings:
  - statement: Neurodegenerative disease protein interaction network
    supporting_text: an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings:
  - statement: Cell-type-specific interactome analysis
    supporting_text: we have created two proteome-scale, cell-line-specific interaction networks
- id: PMID:35156780
  title: CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.
  findings:
  - statement: SCAMP1 identified as CFTR interactor
    supporting_text: CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system
- id: PMID:36012204
  title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC
    Transporters.
  findings:
  - statement: CFTR proximity labeling identifies trafficking factors
    supporting_text: The two proximity labeling approaches identified both known and additional CFTR protein partners, including multiple SLC transporters
- id: PMID:9378760
  title: Three mammalian SCAMPs (secretory carrier membrane proteins) are highly related products of distinct
    genes having similar subcellular distributions.
  findings:
  - statement: SCAMP1-3 are products of distinct genes
    supporting_text: The structures indicated that SCAMPs are highly related products of distinct genes
  - statement: SCAMPs have similar subcellular distributions in post-Golgi compartments
    supporting_text: Examination of the codistribution of the three forms within individual cells using double label immunofluorescence indicates extensive colocalization
  - statement: SCAMPs function together at same sites during vesicular transport
    supporting_text: SCAMPs may largely function at the same sites during vesicular transport rather than in separate post-Golgi recycling pathways
- id: Reactome:R-HSA-6799350
  title: Exocytosis of specific granule membrane proteins
  findings:
  - statement: SCAMP1 involved in neutrophil specific granule exocytosis
    supporting_text: Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances
- id: file:human/SCAMP1/SCAMP1-deep-research-falcon.md
  title: Deep research review of SCAMP1 literature
  findings:
  - statement: SCAMP family structural and functional analysis from multiple studies
    supporting_text: NPF motifs recruit EH-domain proteins (Eps15/intersectin), and E peptide is conserved and membrane-active
core_functions:
- description: SCAMP1 functions as a trafficking factor that mediates transport of cargo proteins from
    the trans-Golgi network to other cellular destinations including the plasma membrane and recycling
    endosomes. The protein contains NPF motifs that specifically bind EH domains in endocytic scaffold
    proteins, and interacts with cargo proteins like NHE7 through its conserved TM2-TM3 cytoplasmic loop.
    This is supported by experimental evidence showing SCAMP1 regulates trafficking of NHE7 between TGN
    and recycling vesicles (PMID:15840657) and the original characterization of SCAMPs as secretory
    carrier-associated membrane proteins involved in post-Golgi recycling pathways (PMID:9378760).
  molecular_function:
    id: GO:0019904
    label: protein domain specific binding
  directly_involved_in:
    - id: GO:0006892
      label: post-Golgi vesicle-mediated transport
    - id: GO:0032456
      label: endocytic recycling
  locations:
    - id: GO:0032588
      label: trans-Golgi network membrane
    - id: GO:0055038
      label: recycling endosome membrane
  supported_by:
    - reference_id: PMID:15840657
      supporting_text: We propose a model wherein SCAMPs participate in the shuttling of NHE7 between recycling vesicles and the TGN
    - reference_id: PMID:9378760
      supporting_text: SCAMPs may largely function at the same sites during vesicular transport rather than in separate post-Golgi recycling pathways
proposed_new_terms: []
suggested_questions:
- question: What is the precise mechanism by which SCAMP1 stabilizes fusion pores during exocytosis, and
    does this involve its amphipathic E peptide?
- question: Does SCAMP1 have cargo specificity, or does it function as a general trafficking factor for
    post-Golgi recycling?
suggested_experiments:
- description: Live-cell imaging of SCAMP1 dynamics during regulated secretion in neuroendocrine cells
    to characterize its role in exocytosis and compensatory endocytosis. Would clarify the temporal relationship
    between SCAMP1 localization and fusion pore dynamics.
- description: Proximity labeling (BioID/APEX) of SCAMP1 to comprehensively identify cargo proteins and
    trafficking machinery that co-localize with SCAMP1 carriers. Would expand understanding of SCAMP1
    cargo specificity and interaction partners beyond NHE7 and CFTR.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Citations

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