TRAPPC13/C5orf44 is a Trs65-related large TRAPP subunit curated in human TRAPPII and TRAPPIII complex contexts. Its main role is contribution to TRAPP complex RAB1/Rab GEF trafficking and ER-to-Golgi vesicle-mediated transport, rather than independent GEF activity, COPII coat assembly, generic protein binding, or a direct TRAPPC13-specific autophagy function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:1990072
TRAPPIII protein complex
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: TRAPPC13 is supportable as a mammalian TRAPPIII-associated TRAPP subunit, while its exact TRAPPII/TRAPPIII partition remains source-dependent. Cryo-EM of metazoan TRAPPIII positions TRAPPC13, with TRAPPC12, at the vertex where the TRAPPC8 and TRAPPC11 arms meet, consistent with bona fide TRAPPIII membership.
Reason: Accept as PN-relevant complex membership. GO Central, UniProt, and the TRAPP review place human TRAPPC13 in TRAPP complex context, and the review specifically notes mammalian TRAPP III contains core TRAPP plus TrappC8, 11-13. The falcon deep research summarizes Galindo et al. (2021) cryo-EM placing TRAPPC13 as a metazoan TRAPPIII-specific subunit at the arm vertex, providing structural corroboration of TRAPPIII membership.
Supporting Evidence:
PMID:27066478
TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP III, which contains core TRAPP plus TrappC8, 11-13
PMID:27066478
The inclusion of TrappC13, the homolog of Trs65, in the mammalian TRAPP III differs from its inclusion in the yeast TRAPP II complex
file:human/TRAPPC13/TRAPPC13-uniprot.txt
GO; GO:1990072; C:TRAPPIII protein complex; IBA:GO_Central.
Reactome:R-HSA-8877475
RAB1 and the TRAPPCIII complex play a role in the formation of the pre-autophagosomal structure (PAS)
file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
High-resolution cryo-EM analysis from Galindo et al. (2021) definitively positioned TRAPPC13, together with TRAPPC12, at the vertex where the TRAPPC8 and TRAPPC11 arms meet
|
|
GO:0005515
protein binding
|
IPI
PMID:21453443 Organization and assembly of the TRAPPII complex. |
MARK AS OVER ANNOTATED |
Summary: Generic protein binding is not informative for TRAPPC13 function. The interactions captured are with other TRAPP subunits, consistent with TRAPPC13's role as a structural/accessory subunit positioned at the vertex of the TRAPPIII arms rather than an independent binding partner.
Reason: Mark as over-annotated. The PMID:21453443/IntAct evidence reflects interactions with TRAPP components and is better captured as TRAPP complex membership and complex-level trafficking function. The falcon deep research reinforces that TRAPPC13 is best understood as a structural/accessory subunit contributing to complex organization, not via a generic protein-binding function.
Supporting Evidence:
PMID:21453443
proteins related to Trs85, Trs65 and Tca17 are part of the same TRAPP complex in
file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
TRAPPC13 is therefore best understood as a **structural/accessory subunit** rather than the catalytic GEF center.
file:human/TRAPPC13/TRAPPC13-uniprot.txt
A5PLN9; Q9UL33: TRAPPC2L; NbExp=3
file:human/TRAPPC13/TRAPPC13-uniprot.txt
A5PLN9; O43617: TRAPPC3; NbExp=2
file:human/TRAPPC13/TRAPPC13-uniprot.txt
A5PLN9; Q9Y2L5: TRAPPC8; NbExp=2
|
|
GO:0005515
protein binding
|
IPI
PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... |
MARK AS OVER ANNOTATED |
Summary: Generic protein binding from a proteome-scale AP-MS map is not an informative TRAPPC13 molecular-function annotation.
Reason: Mark as over-annotated. The BioPlex-style interactome evidence can support interaction context, but the more informative representation for TRAPPC13 is TRAPP complex membership and complex-level trafficking.
Supporting Evidence:
PMID:33961781
These networks model the interactome whose structure encodes protein function, localization, and complex membership
file:human/TRAPPC13/TRAPPC13-uniprot.txt
A5PLN9; Q9UL33: TRAPPC2L; NbExp=3
|
|
GO:0005737
cytoplasm
|
NAS
PMID:27066478 TRAPP Complexes in Secretion and Autophagy. |
ACCEPT |
Summary: Cytoplasm is a broad but reasonable location for TRAPPC13-containing TRAPP biology.
Reason: Accept as broad supported cellular location/context. UniProt/ComplexPortal includes the cytoplasm row, and TRAPPC13 participates in cytosolic/peripheral TRAPP trafficking complexes.
Supporting Evidence:
file:human/TRAPPC13/TRAPPC13-uniprot.txt
GO; GO:0005737; C:cytoplasm; NAS:ComplexPortal.
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
|
|
GO:0006888
endoplasmic reticulum to Golgi vesicle-mediated transport
|
NAS
PMID:27066478 TRAPP Complexes in Secretion and Autophagy. |
ACCEPT |
Summary: TRAPPC13-containing TRAPP complex context supports ER-to-Golgi vesicle-mediated transport.
Reason: Accept as the best supported process-level annotation. Reactome models TRAPPC complexes II and III as RAB1 GEFs in COPII-mediated ER-to-ERGIC/Golgi traffic, and UniProt/ComplexPortal carries the ER-to-Golgi transport row. The falcon deep research reinforces that TRAPPC13, via its TRAPPIII context, supports Rab1 activation in ER-to-Golgi vesicular transport (a complex-level role, not a TRAPPC13-autonomous activity).
Supporting Evidence:
Reactome:R-HSA-8877475
RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
PMID:27066478
The mammalian Golgi TRAPP II (see above) was shown to act in vitro as a Rab1, but not Rab11, GEF
file:human/TRAPPC13/TRAPPC13-uniprot.txt
GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; NAS:ComplexPortal.
file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
TRAPPC13, through its role in TRAPPIII, is essential for ER-to-Golgi vesicular transport
|
|
GO:0006901
vesicle coat assembly
|
NAS
PMID:27066478 TRAPP Complexes in Secretion and Autophagy. |
MODIFY |
Summary: The coat-assembly annotation captures COPII-associated transport context but overstates TRAPPC13 as a coat assembly factor.
Reason: Modify to ER-to-Golgi vesicle-mediated transport. The accessible evidence supports TRAPP complex recruitment/RAB1 exchange in COPII-associated early secretory traffic, not direct assembly of a vesicle coat by TRAPPC13.
Proposed replacements:
endoplasmic reticulum to Golgi vesicle-mediated transport
Supporting Evidence:
Reactome:R-HSA-8877475
RAB1 is involved in COPII-mediated anterograde traffic from the endoplasmic reticulum to the ERGIC
Reactome:R-HSA-8877475
TRAPPCII is recruited to ER-derived vesicles by virtue of an interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein SEC23
PMID:27066478
These findings provide information of TRAPP interactions with one membrane
|
|
GO:0099022
obsolete vesicle tethering
|
NAS
PMID:27066478 TRAPP Complexes in Secretion and Autophagy. |
MODIFY |
Summary: The obsolete vesicle-tethering annotation should not be retained as-is.
Reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported TRAPPC13 TRAPP process. The term is obsolete and the review literature cautions that direct TRAPP membrane-tethering evidence remains inconclusive.
Proposed replacements:
endoplasmic reticulum to Golgi vesicle-mediated transport
Supporting Evidence:
PMID:27066478
evidence that any TRAPP complex acts as a membrane tether is currently inconclusive
PMID:27066478
evidence for a direct role for TRAPP complexes in membrane tethering is lacking
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
|
|
GO:1990071
TRAPPII protein complex
|
NAS
PMID:27066478 TRAPP Complexes in Secretion and Autophagy. |
ACCEPT |
Summary: TRAPPC13 is supportable as part of human TRAPPII complex context, especially from UniProt/ComplexPortal and Trs65/TRAPPII literature.
Reason: Accept as supported complex membership/context. UniProt lists TRAPPII ComplexPortal membership for TRAPPC13, and TRAPPC13 is the human Trs65 homolog, a TRAPP II-specific subunit in yeast; mammalian assignments differ between TRAPPII and TRAPPIII sources, so both complex rows should be retained with this caveat.
Supporting Evidence:
file:human/TRAPPC13/TRAPPC13-uniprot.txt
GO; GO:1990071; C:TRAPPII protein complex; NAS:ComplexPortal.
file:human/TRAPPC13/TRAPPC13-uniprot.txt
ComplexPortal; CPX-4749; TRAPP II complex, TRAPPC2 variant.
file:human/TRAPPC13/TRAPPC13-uniprot.txt
ComplexPortal; CPX-6902; TRAPP II complex, TRAPPC2B variant.
PMID:27066478
Trs65 (560)TrappC13 (C5orf44) (417)Yeast TRAPP II assembly, dimer formation
PMID:21453443
Trs65 and Tca17 interact with distinct domains of Trs130
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-8877475 |
ACCEPT |
Summary: Cytosol is consistent with TRAPPC13-containing TRAPP trafficking reactions.
Reason: Accept as supported location/context for soluble/peripheral TRAPP complex biology.
Supporting Evidence:
file:human/TRAPPC13/TRAPPC13-uniprot.txt
GO; GO:0005829; C:cytosol; TAS:Reactome.
Reactome:R-HSA-8877475
RAB1 nucleotide exchange is stimulated in these pathways by the GEF activity of the multisubunit TRAPPC complexes II and III
|
Q: Should human TRAPPC13 be curated as TRAPPII, TRAPPIII, or both, given the difference between yeast Trs65/TRAPPII assignment, mammalian genetic-interaction TRAPPIII models, and ComplexPortal TRAPPII entries?
Suggested experts: ComplexPortal curators, Reactome TRAPP curators, GO transport editors
Q: Should TRAPPC13 generic protein-binding annotations be replaced by more informative TRAPP complex membership and complex-level Rab/RAB GEF annotations?
Suggested experts: GO molecular function editors, IntAct curators
Q: Is there direct experimental evidence for a TRAPPC13-specific autophagy or ATG9-trafficking annotation, or should PN autophagy context remain limited to TRAPPIII/TRAPP complex membership?
Suggested experts: GO autophagy editors, Reactome TRAPP curators
Experiment: Reconstitute human TRAPPC13-containing TRAPPII and TRAPPIII assemblies and measure RAB1 nucleotide exchange with and without TRAPPC13.
Hypothesis: TRAPPC13 contributes to complex-level RAB1 GEF activity through TRAPP complex assembly or stability rather than acting as an independent enzyme.
Type: complex reconstitution and RAB GEF assay
Experiment: Deplete and rescue TRAPPC13 in mammalian cells and compare ER-to-Golgi cargo transport, Golgi morphology, RAB1 activation, and TRAPP subunit integrity.
Hypothesis: TRAPPC13 supports early secretory trafficking by maintaining functional TRAPP complex architecture.
Type: trafficking rescue assay
Experiment: Test TRAPPC13 perturbation in ATG9 cycling, LC3/WIPI2 puncta formation, and starvation-induced autophagy alongside TRAPPC8-positive controls.
Hypothesis: If TRAPPC13 has a specific PN autophagy role, it should affect TRAPPIII-dependent ATG9/autophagosome initiation readouts beyond generic secretory pathway disruption.
Type: autophagy trafficking assay
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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
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TRAPPC13 (also known as C5orf44) encodes trafficking protein particle complex subunit 13 in humans, a component of the TRAPPIII complex involved in membrane trafficking and autophagy (hall2024trappopathiesseveremultisystem pages 1-2, galindo2021cryo‐emstructureof pages 1-2). This gene identity is consistent across recent scientific literature, confirming that the protein described in UniProt as belonging to the TRAPPC13 family is indeed the metazoan-specific TRAPPIII subunit characterized in structural and functional studies (galindo2023thetrappcomplexes pages 2-3, hall2024trappopathiesseveremultisystem pages 4-5).
TRAPPC13 functions as a structural component of the TRAPPIII complex, one of two major TRAPP (Transport Protein Particle) complexes in metazoans (galindo2023thetrappcomplexes pages 1-2, galindo2023thetrappcomplexes pages 2-3). The TRAPPIII complex comprises a shared TRAPP core (TRAPPC1-7 subunits, with TRAPPC3 present twice) plus four metazoan-specific subunits: TRAPPC8, TRAPPC11, TRAPPC12, and TRAPPC13 (hall2024trappopathiesseveremultisystem pages 4-5, galindo2021cryo‐emstructureof pages 1-2). Recent cryo-electron microscopy structures at ~4-6 Å resolution have revealed that TRAPPIII adopts a distinctive triangular architecture with an elongated central core flanked by two large arms (galindo2021cryo‐emstructureof pages 1-2, galindo2021cryo‐emstructureof pages 3-4).
High-resolution cryo-EM analysis from Galindo et al. (2021) definitively positioned TRAPPC13, together with TRAPPC12, at the vertex where the TRAPPC8 and TRAPPC11 arms meet (galindo2021cryo‐emstructureof pages 1-2, galindo2021cryo‐emstructureof pages 3-4, galindo2021cryo‐emstructureof pages 7-9). This vertex represents the joint between the two large arms that extend from opposite ends of the core complex. TRAPPC8 and TRAPPC11 bind to the core through TRAPPC2 and TRAPPC2L, respectively, and their C-terminal regions extend to form the vertex where TRAPPC12 and TRAPPC13 are positioned (galindo2023thetrappcomplexes pages 5-7, galindo2021cryo‐emstructureof pages 5-7). This strategic location suggests TRAPPC13 contributes to the overall stability and organization of the triangular TRAPPIII architecture rather than directly participating in catalysis.
TRAPPC13 does not itself catalyze nucleotide exchange but rather supports the guanine nucleotide exchange factor (GEF) activity of the TRAPPIII complex toward Rab1 GTPase (galindo2023thetrappcomplexes pages 1-2, galindo2021cryo‐emstructureof pages 1-2). The catalytic site for Rab1 activation resides in the TRAPP core, specifically in TRAPPC1 and TRAPPC4, which form the active site for GDP-to-GTP exchange (galindo2023thetrappcomplexes pages 2-3, bagde2023thetrappcomplexes pages 1-3). Biochemical studies demonstrate that a "miniTRAPPIII" complex lacking TRAPPC12 and TRAPPC13 retains Rab1 GEF activity in vitro, indicating these subunits are dispensable for basal catalytic function (galindo2021cryo‐emstructureof pages 1-2, galindo2021cryo‐emstructureof pages 3-4). However, the larger TRAPPC8 and TRAPPC11 arms are essential for proper Rab1 activation in vivo, with TRAPPC8 positioned such that it contacts Rab1 bound to the core, thereby enhancing specificity and activity (galindo2021cryo‐emstructureof pages 1-2, galindo2021cryo‐emstructureof pages 7-9, galindo2021cryo‐emstructureof pages 9-10).
TRAPPC13, as an integral component of TRAPPIII, localizes to multiple compartments within the early secretory pathway (galindo2023thetrappcomplexes pages 1-2, maeda2025disease‐associatedfactorsat pages 8-9). The TRAPPIII complex functions at the endoplasmic reticulum (ER)-Golgi interface and the ER-Golgi intermediate compartment (ERGIC), where it regulates anterograde transport of cargo from the ER to the Golgi apparatus (maeda2025disease‐associatedfactorsat pages 1-2, hall2024trappopathiesseveremultisystem pages 4-5). Additionally, TRAPPIII localizes to the Golgi apparatus itself, where Rab1 activation is critical for maintaining Golgi structure and function (papaioannou2023biochemicalstructureand pages 1-2, maeda2025disease‐associatedfactorsat pages 8-9). Beyond the classical secretory pathway, TRAPPIII also functions at autophagosome formation sites, where it activates Rab1 during the initiation of macroautophagy (hall2024trappopathiesseveremultisystem pages 1-2, galindo2023thetrappcomplexes pages 1-2, galindo2021cryo‐emstructureof pages 9-10).
The TRAPPIII complex acts on membrane surfaces rather than in the cytosol, consistent with its role in activating prenylated Rab GTPases that are anchored to lipid bilayers (galindo2021cryo‐emstructureof pages 10-12, galindo2021cryo‐emstructureof pages 9-10). Biochemical reconstitution experiments demonstrate that TRAPPIII exhibits enhanced GEF activity toward membrane-bound Rab1 compared to soluble Rab1, emphasizing the importance of membrane association for physiological function (galindo2021cryo‐emstructureof pages 10-12, galindo2021cryo‐emstructureof pages 9-10).
TRAPPC13, through its role in TRAPPIII, is essential for ER-to-Golgi vesicular transport (hall2024trappopathiesseveremultisystem pages 1-2, galindo2023thetrappcomplexes pages 1-2). TRAPPIII activates Rab1, which serves as a master regulator of the early secretory pathway (galindo2023thetrappcomplexes pages 1-2, galindo2021cryo‐emstructureof pages 1-2). Once activated (GTP-bound), Rab1 recruits multiple effector proteins including tethering factors such as p115, GM130, and Golgin-84, which facilitate the tethering and fusion of COPII-coated vesicles with Golgi membranes (galindo2023thetrappcomplexes pages 2-3, bagde2023thetrappcomplexes pages 1-3). This Rab1-mediated tethering is crucial for the directional flow of newly synthesized proteins through the secretory pathway.
TRAPPIII plays a critical role in autophagosome formation, with TRAPPC13 contributing as a structural component of this function (hall2024trappopathiesseveremultisystem pages 1-2, galindo2023thetrappcomplexes pages 1-2, bagde2023thetrappcomplexes pages 1-3). During autophagy initiation, TRAPPIII activates Rab1 at pre-autophagosomal structures, which is essential for the recruitment of Atg1 kinase and the Atg11 tethering factor (galindo2023thetrappcomplexes pages 2-3, maeda2025disease‐associatedfactorsat pages 8-9). This Rab1 activation step is required for the first stage of macroautophagy—the formation of the isolation membrane that eventually forms the double-membrane autophagosome (galindo2023thetrappcomplexes pages 1-2, galindo2021cryo‐emstructureof pages 9-10). The involvement of TRAPPIII in autophagy highlights the dual role of this complex in both biosynthetic (secretory) and catabolic (autophagic) membrane trafficking pathways.
Rab1 activation by TRAPPIII is necessary for maintaining the structural integrity of the Golgi apparatus (maeda2025disease‐associatedfactorsat pages 8-9). Studies have shown that depletion or inhibition of TRAPPC13 or other TRAPPIII components can lead to Golgi fragmentation and disruption of ER-Golgi transport, underscoring the importance of this complex in Golgi homeostasis (maeda2025disease‐associatedfactorsat pages 9-11, maeda2025disease‐associatedfactorsat pages 8-9).
The TRAPPIII complex, including TRAPPC13, is highly specific for Rab1 as its physiological GTPase substrate (galindo2023thetrappcomplexes pages 1-2, galindo2023thetrappcomplexes pages 2-3, galindo2021cryo‐emstructureof pages 1-2). This specificity is remarkable because TRAPPIII and TRAPPII share an identical catalytic core yet activate different Rab GTPases—Rab1 and Rab11, respectively (galindo2023thetrappcomplexes pages 1-2, galindo2023thetrappcomplexes pages 2-3, bagde2023thetrappcomplexes pages 1-3). Recent structural and biochemical studies have revealed that substrate specificity is determined by the large accessory subunits rather than the core (galindo2021cryo‐emstructureof pages 1-2, bagde2023thetrappcomplexes pages 1-3). The TRAPPC8 arm of TRAPPIII is positioned to contact Rab1 when it is bound to the catalytic core, thereby enhancing both the affinity and specificity of the interaction (galindo2021cryo‐emstructureof pages 7-9, galindo2021cryo‐emstructureof pages 9-10). The C-terminal hypervariable domain (HVD) of Rab1, which connects the GTPase domain to the membrane via prenyl anchors, also plays a role in substrate discrimination, with yeast studies showing that the length of the HVD is critical for preventing promiscuous activation by the wrong TRAPP complex (bagde2023thetrappcomplexes pages 3-5, bagde2023thetrappcomplexes pages 1-3).
Biochemical assays have confirmed that TRAPPIII has robust GEF activity toward Rab1 and can also activate Rab43 (a Rab1 family member), but shows no detectable activity toward Rab11 or most other Rab GTPases tested (galindo2021cryo‐emstructureof pages 1-2, bagde2023thetrappcomplexes pages 1-3). This stringent specificity ensures that Rab1 is activated only at appropriate membrane compartments where TRAPPIII is localized.
TRAPPC13 is relatively ubiquitously expressed across human tissues, consistent with the fundamental importance of membrane trafficking in all cell types (hall2024trappopathiesseveremultisystem pages 1-2). Despite this broad expression pattern, TRAPPC13 is reported to be non-essential for viability in human cell lines, in contrast to TRAPPC8 and TRAPPC11, which are essential for Rab1 recruitment and cell viability (hall2024trappopathiesseveremultisystem pages 4-5, galindo2023thetrappcomplexes pages 3-5, galindo2021cryo‐emstructureof pages 1-2). This differential essentiality suggests that while TRAPPC12 and TRAPPC13 contribute to the structural organization and potentially the regulation of TRAPPIII, they are not absolutely required for the minimal GEF activity necessary to sustain cellular function under standard culture conditions. However, they may play important regulatory or modulatory roles in vivo under physiological stress or in specific developmental contexts that have not yet been fully characterized.
To date, no monogenic human diseases have been specifically attributed to mutations in TRAPPC13 (hall2024trappopathiesseveremultisystem pages 1-2, hall2024trappopathiesseveremultisystem pages 2-4). This contrasts with several other TRAPP subunits, where pathogenic variants cause a spectrum of disorders collectively termed "TRAPPopathies," including neurodevelopmental disorders, muscular dystrophies, and skeletal dysplasias (hall2024trappopathiesseveremultisystem pages 1-2, hall2024trappopathiesseveremultisystem pages 2-4, hall2024trappopathiesseveremultisystem pages 4-5). For example, mutations in TRAPPC2 cause spondyloepiphyseal dysplasia tarda (SEDT), mutations in TRAPPC11 cause limb-girdle muscular dystrophy type 18 (LGMD18), and mutations in TRAPPC4 and TRAPPC6B cause severe neurodevelopmental disorders (hall2024trappopathiesseveremultisystem pages 2-4, hall2024trappopathiesseveremultisystem pages 4-5, maeda2025disease‐associatedfactorsat pages 9-11, maeda2025disease‐associatedfactorsat pages 8-9). The absence of reported disease associations for TRAPPC13 may reflect: (1) genuine functional redundancy or dispensability in humans, consistent with its non-essential status in cell lines; (2) the possibility that TRAPPC13 mutations are embryonic lethal and thus not observed in clinical populations; or (3) insufficient clinical genetic data, as TRAPPC13-related disorders may be extremely rare or yet to be identified.
Recent authoritative reviews have synthesized the growing understanding of TRAPP complex biology. Hall et al. (2024) provided a comprehensive review of TRAPPopathies, explicitly noting that TRAPPC13 has no reported disease associations despite being relatively ubiquitously expressed (hall2024trappopathiesseveremultisystem pages 1-2). Galindo and Munro (2023) published a detailed review in FEBS Letters summarizing the structural mechanisms by which TRAPP complexes discriminate between Rab substrates, integrating cryo-EM structures with functional data (galindo2023thetrappcomplexes pages 1-2, galindo2023thetrappcomplexes pages 2-3). Maeda et al. (2025) reviewed disease-associated factors at the ER-Golgi interface, discussing TRAPPC13 in the context of TRAPPIII's role in maintaining ER and Golgi homeostasis (maeda2025disease‐associatedfactorsat pages 1-2, maeda2025disease‐associatedfactorsat pages 8-9). These recent works emphasize that while structural details of TRAPPC13 are now well-defined, functional characterization—particularly regarding its regulatory roles in vivo—remains an area for future investigation.
While the structural position and general function of TRAPPC13 within TRAPPIII are now well-established, several important questions remain. First, the precise regulatory role of TRAPPC13 and TRAPPC12 at the vertex of TRAPPIII is unclear. Although they are dispensable for in vitro GEF activity, they may modulate GEF activity, membrane recruitment, or complex stability in response to cellular signals. Second, the lack of disease associations for TRAPPC13 mutations requires further investigation to determine whether this reflects true dispensability or whether mutations remain undiscovered. Third, the evolutionary origin and conservation of TRAPPC13 across species (present in metazoans but absent in budding yeast, which lacks TRAPPC11, TRAPPC12, and TRAPPC13) suggests that these subunits confer additional regulatory complexity in higher eukaryotes, but the nature of this regulation is poorly understood.
| Property | Description | Evidence/Citations |
|---|---|---|
| Gene name/synonyms | Human TRAPPC13 encodes trafficking protein particle complex subunit 13; the target identity is consistent with the human TRAPPIII-specific subunit discussed in structural and review literature. The user-provided synonym is C5orf44. | (hall2024trappopathiesseveremultisystem pages 1-2, galindo2021cryo‐emstructureof pages 1-2) |
| Protein complex membership | TRAPPC13 is a metazoan TRAPPIII-specific subunit. TRAPPIII in humans/metazoans comprises the shared TRAPP core plus TRAPPC8, TRAPPC11, TRAPPC12, and TRAPPC13. | (galindo2023thetrappcomplexes pages 2-3, hall2024trappopathiesseveremultisystem pages 4-5, maeda2025disease‐associatedfactorsat pages 8-9, galindo2021cryo‐emstructureof pages 1-2) |
| Structural role in complex | Cryo-EM places TRAPPC13, together with TRAPPC12, at the vertex/joint where the TRAPPC8 and TRAPPC11 arms meet, helping organize the triangular TRAPPIII architecture. TRAPPC13 is therefore best understood as a structural/accessory subunit rather than the catalytic GEF center. | (galindo2023thetrappcomplexes pages 5-7, galindo2021cryo‐emstructureof pages 1-2, galindo2021cryo‐emstructureof pages 10-12) |
| Subcellular localization | TRAPPC13 acts as part of TRAPPIII on membrane trafficking compartments of the early secretory pathway, especially the ER-Golgi interface / ERGIC / Golgi-associated membranes, and in autophagy-related membranes where Rab1 is activated. The exact localization evidence is mainly at the complex level rather than TRAPPC13 alone. | (galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 4-5, maeda2025disease‐associatedfactorsat pages 8-9, galindo2021cryo‐emstructureof pages 9-10) |
| Primary molecular function | TRAPPC13 does not itself catalyze nucleotide exchange; instead it contributes to the assembly/stability/organization of the TRAPPIII Rab1 GEF complex. Through TRAPPIII, it supports activation of Rab1 by promoting the complex architecture needed for membrane trafficking and autophagy in vivo. | (galindo2023thetrappcomplexes pages 1-2, galindo2021cryo‐emstructureof pages 1-2, galindo2021cryo‐emstructureof pages 9-10, bagde2023thetrappcomplexes pages 1-3) |
| Biological processes | By virtue of its role in TRAPPIII, TRAPPC13 is implicated in ER-to-Golgi transport, early secretory pathway organization, Golgi homeostasis, and autophagosome formation/autophagy. | (hall2024trappopathiesseveremultisystem pages 1-2, galindo2023thetrappcomplexes pages 1-2, hall2024trappopathiesseveremultisystem pages 4-5, maeda2025disease‐associatedfactorsat pages 8-9, bagde2023thetrappcomplexes pages 1-3) |
| Substrate specificity | TRAPPC13 has no independent substrate specificity known. At the complex level, TRAPPIII is the physiological GEF for Rab1 in metazoans; Rab1 is the relevant small GTPase substrate for the TRAPPC13-containing complex. | (galindo2023thetrappcomplexes pages 1-2, galindo2023thetrappcomplexes pages 2-3, galindo2021cryo‐emstructureof pages 1-2, bagde2023thetrappcomplexes pages 1-3) |
| Essential for viability | Recent reviews summarize TRAPPC13 as non-essential for viability in human cell lines, in contrast to TRAPPC8 and TRAPPC11, which are reported as essential for Rab1 recruitment/activity in vivo. Consistent with this, TRAPPIII lacking TRAPPC12/TRAPPC13 retained Rab1 GEF activity in vitro in a recombinant “miniTRAPPIII” preparation. | (galindo2023thetrappcomplexes pages 3-5, galindo2021cryo‐emstructureof pages 1-2) |
| Disease associations | As of recent reviews, there are no specific monogenic human disease associations reported for TRAPPC13, unlike several other TRAPP subunits. Reviews of TRAPPopathies explicitly note no reported disease associations for TRAPPC13. | (hall2024trappopathiesseveremultisystem pages 2-4, hall2024trappopathiesseveremultisystem pages 1-2) |
| Tissue expression pattern | TRAPPC13 is reported to be relatively ubiquitously expressed across human tissues, with some tissues showing higher expression than others; however, recent reviews emphasize that detailed functional and disease data remain limited. | (hall2024trappopathiesseveremultisystem pages 1-2) |
Table: This table summarizes the best-supported structural and functional features of human TRAPPC13 based on recent TRAPP-complex literature. It highlights what is established directly from cryo-EM and biochemical studies, while distinguishing areas where evidence is still limited or inferential.
TRAPPC13 (C5orf44, UniProt A5PLN9) is a structural component of the metazoan TRAPPIII complex that functions at the ER-Golgi interface and during autophagy to support Rab1 activation. Together with TRAPPC12, TRAPPC13 occupies a vertex position at the junction between the TRAPPC8 and TRAPPC11 arms of the triangular TRAPPIII architecture, contributing to complex organization and stability. While not directly involved in catalysis and non-essential for basal GEF activity in vitro, TRAPPC13 is part of a sophisticated molecular machine that ensures precise spatiotemporal activation of Rab1, a master regulator of ER-to-Golgi transport, Golgi homeostasis, and autophagosome formation. The absence of reported disease associations for TRAPPC13, in contrast to other TRAPP subunits, suggests either functional redundancy or yet-to-be-discovered clinical relevance. Ongoing research, particularly utilizing recent high-resolution structural insights from cryo-EM studies (2021-2023) and comprehensive reviews (2023-2025), continues to refine our understanding of how TRAPPC13 and the TRAPPIII complex orchestrate membrane trafficking in human cells.
References
(hall2024trappopathiesseveremultisystem pages 1-2): Riley Hall, Vallari Sawant, Jinchao Gu, Tim Sikora, Ben Rollo, Silvia Velasco, Jinkuk Kim, Nava Segev, John Christodoulou, and Nicole J. Van Bergen. Trappopathies: severe multisystem disorders caused by variants in genes of the transport protein particle (trapp) complexes. International Journal of Molecular Sciences, 25:13329, Dec 2024. URL: https://doi.org/10.3390/ijms252413329, doi:10.3390/ijms252413329. This article has 8 citations.
(galindo2021cryo‐emstructureof pages 1-2): Antonio Galindo, Vicente J Planelles‐Herrero, Gianluca Degliesposti, and Sean Munro. Cryo‐em structure of metazoan trappiii, the multi‐subunit complex that activates the gtpase rab1. The EMBO Journal, May 2021. URL: https://doi.org/10.15252/embj.2020107608, doi:10.15252/embj.2020107608. This article has 49 citations.
(galindo2023thetrappcomplexes pages 2-3): Antonio Galindo and Sean Munro. The
(hall2024trappopathiesseveremultisystem pages 4-5): Riley Hall, Vallari Sawant, Jinchao Gu, Tim Sikora, Ben Rollo, Silvia Velasco, Jinkuk Kim, Nava Segev, John Christodoulou, and Nicole J. Van Bergen. Trappopathies: severe multisystem disorders caused by variants in genes of the transport protein particle (trapp) complexes. International Journal of Molecular Sciences, 25:13329, Dec 2024. URL: https://doi.org/10.3390/ijms252413329, doi:10.3390/ijms252413329. This article has 8 citations.
(galindo2023thetrappcomplexes pages 1-2): Antonio Galindo and Sean Munro. The
(galindo2021cryo‐emstructureof pages 3-4): Antonio Galindo, Vicente J Planelles‐Herrero, Gianluca Degliesposti, and Sean Munro. Cryo‐em structure of metazoan trappiii, the multi‐subunit complex that activates the gtpase rab1. The EMBO Journal, May 2021. URL: https://doi.org/10.15252/embj.2020107608, doi:10.15252/embj.2020107608. This article has 49 citations.
(galindo2021cryo‐emstructureof pages 7-9): Antonio Galindo, Vicente J Planelles‐Herrero, Gianluca Degliesposti, and Sean Munro. Cryo‐em structure of metazoan trappiii, the multi‐subunit complex that activates the gtpase rab1. The EMBO Journal, May 2021. URL: https://doi.org/10.15252/embj.2020107608, doi:10.15252/embj.2020107608. This article has 49 citations.
(galindo2023thetrappcomplexes pages 5-7): Antonio Galindo and Sean Munro. The
(galindo2021cryo‐emstructureof pages 5-7): Antonio Galindo, Vicente J Planelles‐Herrero, Gianluca Degliesposti, and Sean Munro. Cryo‐em structure of metazoan trappiii, the multi‐subunit complex that activates the gtpase rab1. The EMBO Journal, May 2021. URL: https://doi.org/10.15252/embj.2020107608, doi:10.15252/embj.2020107608. This article has 49 citations.
(bagde2023thetrappcomplexes pages 1-3): Saket R. Bagde and J. Christopher Fromme. The
(galindo2021cryo‐emstructureof pages 9-10): Antonio Galindo, Vicente J Planelles‐Herrero, Gianluca Degliesposti, and Sean Munro. Cryo‐em structure of metazoan trappiii, the multi‐subunit complex that activates the gtpase rab1. The EMBO Journal, May 2021. URL: https://doi.org/10.15252/embj.2020107608, doi:10.15252/embj.2020107608. This article has 49 citations.
(maeda2025disease‐associatedfactorsat pages 8-9): Miharu Maeda, Masashi Arakawa, and Kota Saito. Disease‐associated factors at the endoplasmic reticulum–golgi interface. Traffic (Copenhagen, Denmark), Jan 2025. URL: https://doi.org/10.1111/tra.70001, doi:10.1111/tra.70001. This article has 2 citations.
(maeda2025disease‐associatedfactorsat pages 1-2): Miharu Maeda, Masashi Arakawa, and Kota Saito. Disease‐associated factors at the endoplasmic reticulum–golgi interface. Traffic (Copenhagen, Denmark), Jan 2025. URL: https://doi.org/10.1111/tra.70001, doi:10.1111/tra.70001. This article has 2 citations.
(papaioannou2023biochemicalstructureand pages 1-2): Peter Papaioannou, Michael J. Wallace, Nipun Malhotra, Peter J. Mohler, and Mona El Refaey. Biochemical structure and function of trapp complexes in the cardiac system. Dec 2023. URL: https://doi.org/10.1016/j.jacbts.2023.03.011, doi:10.1016/j.jacbts.2023.03.011. This article has 11 citations.
(galindo2021cryo‐emstructureof pages 10-12): Antonio Galindo, Vicente J Planelles‐Herrero, Gianluca Degliesposti, and Sean Munro. Cryo‐em structure of metazoan trappiii, the multi‐subunit complex that activates the gtpase rab1. The EMBO Journal, May 2021. URL: https://doi.org/10.15252/embj.2020107608, doi:10.15252/embj.2020107608. This article has 49 citations.
(maeda2025disease‐associatedfactorsat pages 9-11): Miharu Maeda, Masashi Arakawa, and Kota Saito. Disease‐associated factors at the endoplasmic reticulum–golgi interface. Traffic (Copenhagen, Denmark), Jan 2025. URL: https://doi.org/10.1111/tra.70001, doi:10.1111/tra.70001. This article has 2 citations.
(bagde2023thetrappcomplexes pages 3-5): Saket R. Bagde and J. Christopher Fromme. The
(galindo2023thetrappcomplexes pages 3-5): Antonio Galindo and Sean Munro. The
(hall2024trappopathiesseveremultisystem pages 2-4): Riley Hall, Vallari Sawant, Jinchao Gu, Tim Sikora, Ben Rollo, Silvia Velasco, Jinkuk Kim, Nava Segev, John Christodoulou, and Nicole J. Van Bergen. Trappopathies: severe multisystem disorders caused by variants in genes of the transport protein particle (trapp) complexes. International Journal of Molecular Sciences, 25:13329, Dec 2024. URL: https://doi.org/10.3390/ijms252413329, doi:10.3390/ijms252413329. This article has 8 citations.
Review started from just fetch-gene human TRAPPC13. The proteostasis network places TRAPPC13 under Autophagy-Lysosome Pathway > Autophagophore initiation and elongation > Autophagy component recruitment to autophagophore > TRAPP complex component.
Falcon deep research was requested with just deep-research-falcon human TRAPPC13, but the provider timed out after 600 seconds and no TRAPPC13-deep-research-falcon.md file was produced. I am completing the review using the cached primary literature, UniProt record, GOA seed, and Reactome context described below.
TRAPPC13/C5orf44 is a Trs65-related TRAPP subunit. UniProt describes it as "Part of the multisubunit TRAPP (transport protein particle) complex" and lists ComplexPortal TRAPPII entries [file:human/TRAPPC13/TRAPPC13-uniprot.txt]. The TRAPP review maps yeast Trs65 to human TrappC13/C5orf44 and says the mammalian genetic-interaction model includes TRAPP II with core TRAPP plus TrappC9-10 and TRAPP III with core TRAPP plus TrappC8, 11-13 PMID:27066478. Accept TRAPPII and TRAPPIII complex context, while noting that the precise human complex assignment differs across sources.
TRAPPC13 should be modeled as contributing to complex-level RAB GEF/trafficking rather than independently enabling a catalytic molecular function. Reactome states that RAB1 nucleotide exchange is stimulated by "the GEF activity of the multisubunit TRAPPC complexes II and III" [Reactome:R-HSA-8877475 "TRAPPC complexes exchange GTP for GDP on RAB1"]. The TRAPP review says TRAPP acts as a Ypt/Rab GEF and specifically notes that mammalian Golgi TRAPP II acts in vitro as a Rab1, but not Rab11, GEF PMID:27066478. Accept ER-to-Golgi vesicle-mediated transport as the supported process for the PN TRAPP component context.
The PN autophagy context should not be converted into a TRAPPC13-specific autophagy process annotation without direct evidence. Reactome links TRAPPCIII/RAB1 to pre-autophagosomal structure biology, but the review cautions that the mammalian TRAPP III-autophagy connection was not clear in 2016 PMID:27066478. For this draft, represent the PN context through TRAPPIII/TRAPP complex membership and RAB1/TRAPP trafficking rather than adding a direct autophagy row.
The vesicle coat assembly and obsolete vesicle tethering rows are over-specific. Reactome supports COPII-associated ER-to-ERGIC traffic and TRAPP complex RAB1 exchange, but TRAPPC13 is not shown to assemble vesicle coats. The TRAPP review says "evidence that any TRAPP complex acts as a membrane tether is currently inconclusive" PMID:27066478. Modify both rows to ER-to-Golgi vesicle-mediated transport.
Generic protein binding rows from TRAPP and proteome-scale interactome sources are not informative molecular-function annotations. The PMID:21453443/UniProt interactions with TRAPPC2L, TRAPPC3, and TRAPPC8 support TRAPP complex context, while PMID:33961781 is a proteome-scale AP-MS interaction map. Mark these rows as over-annotated rather than treating generic binding as a core function.
Annotation stance:
- Core: TRAPPII/TRAPPIII complex context, contributes-to TRAPP complex RAB1 GEF activity, ER-to-Golgi vesicle-mediated transport, cytoplasm and cytosol.
- Modify: vesicle coat assembly and obsolete vesicle tethering to ER-to-Golgi vesicle-mediated transport.
- Mark over-annotated: generic protein binding rows.
- No new direct autophagy annotation unless Falcon or later primary literature provides TRAPPC13-specific support.
The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.
*-deep-research*.md file found in this gene directory.Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|TRAPP complex component ; PN-node mapping: type-leaf mapped, scope=ok_for_propagation_to_go, GO:0030008 TRAPP complex (entailed_by_goa_closure)This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.
id: A5PLN9
gene_symbol: TRAPPC13
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >-
TRAPPC13/C5orf44 is a Trs65-related large TRAPP subunit curated in human TRAPPII and TRAPPIII
complex contexts. Its main role is contribution to TRAPP complex RAB1/Rab GEF trafficking and
ER-to-Golgi vesicle-mediated transport, rather than independent GEF activity, COPII coat assembly,
generic protein binding, or a direct TRAPPC13-specific autophagy function.
alternative_products:
- name: '1'
id: A5PLN9-1
- name: '2'
id: A5PLN9-2
sequence_note: VSP_038356
- name: '3'
id: A5PLN9-4
sequence_note: VSP_038356, VSP_038359
- name: '4'
id: A5PLN9-5
sequence_note: VSP_038359
- name: '5'
id: A5PLN9-7
sequence_note: VSP_038356, VSP_038357, VSP_038358
existing_annotations:
- term:
id: GO:1990072
label: TRAPPIII protein complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: part_of
review:
summary: TRAPPC13 is supportable as a mammalian TRAPPIII-associated TRAPP subunit,
while its exact TRAPPII/TRAPPIII partition remains source-dependent. Cryo-EM of
metazoan TRAPPIII positions TRAPPC13, with TRAPPC12, at the vertex where the
TRAPPC8 and TRAPPC11 arms meet, consistent with bona fide TRAPPIII membership.
action: ACCEPT
reason: Accept as PN-relevant complex membership. GO Central, UniProt, and the
TRAPP review place human TRAPPC13 in TRAPP complex context, and the review
specifically notes mammalian TRAPP III contains core TRAPP plus TrappC8, 11-13.
The falcon deep research summarizes Galindo et al. (2021) cryo-EM placing
TRAPPC13 as a metazoan TRAPPIII-specific subunit at the arm vertex, providing
structural corroboration of TRAPPIII membership.
additional_reference_ids:
- PMID:27066478
- file:human/TRAPPC13/TRAPPC13-uniprot.txt
- Reactome:R-HSA-8877475
- file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supported_by:
- reference_id: PMID:27066478
supporting_text: TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP
III, which contains core TRAPP plus TrappC8, 11-13
- reference_id: PMID:27066478
supporting_text: The inclusion of TrappC13, the homolog of Trs65, in the
mammalian TRAPP III differs from its inclusion in the yeast TRAPP II complex
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: GO; GO:1990072; C:TRAPPIII protein complex; IBA:GO_Central.
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 and the TRAPPCIII complex play a role in the formation of
the pre-autophagosomal structure (PAS)
- reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supporting_text: High-resolution cryo-EM analysis from Galindo et al. (2021)
definitively positioned TRAPPC13, together with TRAPPC12, at the vertex where
the TRAPPC8 and TRAPPC11 arms meet
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21453443
qualifier: enables
review:
summary: Generic protein binding is not informative for TRAPPC13 function. The
interactions captured are with other TRAPP subunits, consistent with TRAPPC13's
role as a structural/accessory subunit positioned at the vertex of the TRAPPIII
arms rather than an independent binding partner.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The PMID:21453443/IntAct evidence reflects
interactions with TRAPP components and is better captured as TRAPP complex
membership and complex-level trafficking function. The falcon deep research
reinforces that TRAPPC13 is best understood as a structural/accessory subunit
contributing to complex organization, not via a generic protein-binding function.
additional_reference_ids:
- PMID:21453443
- file:human/TRAPPC13/TRAPPC13-uniprot.txt
- file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supported_by:
- reference_id: PMID:21453443
supporting_text: proteins related to Trs85, Trs65 and Tca17 are part of the same
TRAPP complex in
- reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supporting_text: TRAPPC13 is therefore best understood as a **structural/accessory
subunit** rather than the catalytic GEF center.
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: "A5PLN9; Q9UL33: TRAPPC2L; NbExp=3"
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: "A5PLN9; O43617: TRAPPC3; NbExp=2"
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: "A5PLN9; Q9Y2L5: TRAPPC8; NbExp=2"
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33961781
qualifier: enables
review:
summary: Generic protein binding from a proteome-scale AP-MS map is not an
informative TRAPPC13 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The BioPlex-style interactome evidence can support
interaction context, but the more informative representation for TRAPPC13 is
TRAPP complex membership and complex-level trafficking.
additional_reference_ids:
- PMID:33961781
- file:human/TRAPPC13/TRAPPC13-uniprot.txt
supported_by:
- reference_id: PMID:33961781
supporting_text: These networks model the interactome whose structure encodes
protein function, localization, and complex membership
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: "A5PLN9; Q9UL33: TRAPPC2L; NbExp=3"
- term:
id: GO:0005737
label: cytoplasm
evidence_type: NAS
original_reference_id: PMID:27066478
qualifier: located_in
review:
summary: Cytoplasm is a broad but reasonable location for TRAPPC13-containing TRAPP
biology.
action: ACCEPT
reason: Accept as broad supported cellular location/context. UniProt/ComplexPortal
includes the cytoplasm row, and TRAPPC13 participates in cytosolic/peripheral
TRAPP trafficking complexes.
additional_reference_ids:
- file:human/TRAPPC13/TRAPPC13-uniprot.txt
- Reactome:R-HSA-8877475
supported_by:
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: GO; GO:0005737; C:cytoplasm; NAS:ComplexPortal.
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 nucleotide exchange is stimulated in these pathways by the
GEF activity of the multisubunit TRAPPC complexes II and III
- term:
id: GO:0006888
label: endoplasmic reticulum to Golgi vesicle-mediated transport
evidence_type: NAS
original_reference_id: PMID:27066478
qualifier: involved_in
review:
summary: TRAPPC13-containing TRAPP complex context supports ER-to-Golgi
vesicle-mediated transport.
action: ACCEPT
reason: Accept as the best supported process-level annotation. Reactome models
TRAPPC complexes II and III as RAB1 GEFs in COPII-mediated ER-to-ERGIC/Golgi
traffic, and UniProt/ComplexPortal carries the ER-to-Golgi transport row. The
falcon deep research reinforces that TRAPPC13, via its TRAPPIII context, supports
Rab1 activation in ER-to-Golgi vesicular transport (a complex-level role, not a
TRAPPC13-autonomous activity).
additional_reference_ids:
- Reactome:R-HSA-8877475
- PMID:27066478
- file:human/TRAPPC13/TRAPPC13-uniprot.txt
- file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supported_by:
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 is involved in COPII-mediated anterograde traffic from the
endoplasmic reticulum to the ERGIC
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 nucleotide exchange is stimulated in these pathways by the
GEF activity of the multisubunit TRAPPC complexes II and III
- reference_id: PMID:27066478
supporting_text: The mammalian Golgi TRAPP II (see above) was shown to act in
vitro as a Rab1, but not Rab11, GEF
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: GO; GO:0006888; P:endoplasmic reticulum to Golgi
vesicle-mediated transport; NAS:ComplexPortal.
- reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supporting_text: TRAPPC13, through its role in TRAPPIII, is essential for
ER-to-Golgi vesicular transport
- term:
id: GO:0006901
label: vesicle coat assembly
evidence_type: NAS
original_reference_id: PMID:27066478
qualifier: involved_in
review:
summary: The coat-assembly annotation captures COPII-associated transport context
but overstates TRAPPC13 as a coat assembly factor.
action: MODIFY
reason: Modify to ER-to-Golgi vesicle-mediated transport. The accessible evidence
supports TRAPP complex recruitment/RAB1 exchange in COPII-associated early
secretory traffic, not direct assembly of a vesicle coat by TRAPPC13.
proposed_replacement_terms:
- id: GO:0006888
label: endoplasmic reticulum to Golgi vesicle-mediated transport
additional_reference_ids:
- Reactome:R-HSA-8877475
- PMID:27066478
supported_by:
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 is involved in COPII-mediated anterograde traffic from the
endoplasmic reticulum to the ERGIC
- reference_id: Reactome:R-HSA-8877475
supporting_text: TRAPPCII is recruited to ER-derived vesicles by virtue of an
interaction between the TRAPPCII component TRAPPC3 and the COPII coat protein
SEC23
- reference_id: PMID:27066478
supporting_text: These findings provide information of TRAPP interactions with
one membrane
- term:
id: GO:0099022
label: obsolete vesicle tethering
evidence_type: NAS
original_reference_id: PMID:27066478
qualifier: involved_in
review:
summary: The obsolete vesicle-tethering annotation should not be retained as-is.
action: MODIFY
reason: Modify to ER-to-Golgi vesicle-mediated transport, the supported TRAPPC13
TRAPP process. The term is obsolete and the review literature cautions that
direct TRAPP membrane-tethering evidence remains inconclusive.
proposed_replacement_terms:
- id: GO:0006888
label: endoplasmic reticulum to Golgi vesicle-mediated transport
additional_reference_ids:
- PMID:27066478
- Reactome:R-HSA-8877475
supported_by:
- reference_id: PMID:27066478
supporting_text: evidence that any TRAPP complex acts as a membrane tether is
currently inconclusive
- reference_id: PMID:27066478
supporting_text: evidence for a direct role for TRAPP complexes in membrane
tethering is lacking
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 nucleotide exchange is stimulated in these pathways by the
GEF activity of the multisubunit TRAPPC complexes II and III
- term:
id: GO:1990071
label: TRAPPII protein complex
evidence_type: NAS
original_reference_id: PMID:27066478
qualifier: part_of
review:
summary: TRAPPC13 is supportable as part of human TRAPPII complex context,
especially from UniProt/ComplexPortal and Trs65/TRAPPII literature.
action: ACCEPT
reason: Accept as supported complex membership/context. UniProt lists TRAPPII
ComplexPortal membership for TRAPPC13, and TRAPPC13 is the human Trs65 homolog,
a TRAPP II-specific subunit in yeast; mammalian assignments differ between
TRAPPII and TRAPPIII sources, so both complex rows should be retained with this
caveat.
additional_reference_ids:
- PMID:21453443
- PMID:27066478
- file:human/TRAPPC13/TRAPPC13-uniprot.txt
supported_by:
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: GO; GO:1990071; C:TRAPPII protein complex; NAS:ComplexPortal.
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: ComplexPortal; CPX-4749; TRAPP II complex, TRAPPC2 variant.
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: ComplexPortal; CPX-6902; TRAPP II complex, TRAPPC2B variant.
- reference_id: PMID:27066478
supporting_text: Trs65 (560)TrappC13 (C5orf44) (417)Yeast TRAPP II assembly,
dimer formation
- reference_id: PMID:21453443
supporting_text: Trs65 and Tca17 interact with distinct domains of Trs130
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8877475
qualifier: located_in
review:
summary: Cytosol is consistent with TRAPPC13-containing TRAPP trafficking
reactions.
action: ACCEPT
reason: Accept as supported location/context for soluble/peripheral TRAPP complex
biology.
additional_reference_ids:
- Reactome:R-HSA-8877475
- file:human/TRAPPC13/TRAPPC13-uniprot.txt
supported_by:
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: GO; GO:0005829; C:cytosol; TAS:Reactome.
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 nucleotide exchange is stimulated in these pathways by the
GEF activity of the multisubunit TRAPPC complexes II and III
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: PMID:21453443
title: Organization and assembly of the TRAPPII complex.
findings: []
- id: PMID:27066478
title: TRAPP Complexes in Secretion and Autophagy.
findings: []
- id: PMID:33961781
title: Dual proteome-scale networks reveal cell-specific remodeling of the human
interactome.
findings: []
- id: Reactome:R-HSA-8877475
title: TRAPPC complexes exchange GTP for GDP on RAB1
findings: []
- id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
title: UniProtKB record for TRAPPC13
findings: []
- id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
title: Falcon deep research report for TRAPPC13
findings: []
reference_review:
relevance: HIGH
correctness: UNVERIFIED
review_notes: >-
LLM-synthesized (Edison/Falcon) literature report. It is internally careful to
distinguish TRAPPC13 subunit-specific evidence from holo-complex inference: it
correctly states TRAPPC13 does NOT itself catalyze nucleotide exchange and that a
recombinant "miniTRAPPIII" lacking TRAPPC12/TRAPPC13 still retains Rab1 GEF activity
in vitro (subunit-specific, structural/accessory role at the TRAPPC8/TRAPPC11 arm
vertex), while attributing Rab1 GEF activity, ER-to-Golgi transport, Golgi
homeostasis, and autophagosome formation to the TRAPPIII complex as a whole. Those
complex-level claims should be read as holo-complex inference, not TRAPPC13-specific
function. The report frames TRAPPC13 primarily as a TRAPPIII subunit (metazoan
TRAPPC8/11/12/13), whereas the existing GOA/ComplexPortal annotations also place it
in TRAPPII; this TRAPPII/TRAPPIII partition remains source-dependent and unresolved.
Underlying primary sources (Galindo 2021 EMBO J cryo-EM; Galindo & Munro 2023 and
Bagde & Fromme 2023 FEBS Lett reviews; Hall 2024 TRAPPopathies; Maeda 2025) are not
in the publications/ cache and have not been independently verified here, so
correctness is left UNVERIFIED.
core_functions:
- contributes_to_molecular_function:
id: GO:0005085
label: guanyl-nucleotide exchange factor activity
in_complex:
id: GO:1990071
label: TRAPPII protein complex
description: TRAPPC13 contributes to human TRAPPII/TRAPP complex trafficking, where
Reactome and review literature model mammalian TRAPP complexes as Rab/RAB1 GEFs
in early secretory traffic. This is a complex-level contribution, not independent
GEF activity or generic protein binding.
directly_involved_in:
- id: GO:0006888
label: endoplasmic reticulum to Golgi vesicle-mediated transport
locations:
- id: GO:0005829
label: cytosol
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 nucleotide exchange is stimulated in these pathways by the
GEF activity of the multisubunit TRAPPC complexes II and III
- reference_id: PMID:27066478
supporting_text: The mammalian Golgi TRAPP II (see above) was shown to act in
vitro as a Rab1, but not Rab11, GEF
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: GO; GO:1990071; C:TRAPPII protein complex; NAS:ComplexPortal.
- reference_id: file:human/TRAPPC13/TRAPPC13-uniprot.txt
supporting_text: Part of the multisubunit TRAPP (transport protein particle)
- contributes_to_molecular_function:
id: GO:0005085
label: guanyl-nucleotide exchange factor activity
in_complex:
id: GO:1990072
label: TRAPPIII protein complex
description: TRAPPC13 is also curated in mammalian TRAPPIII context, which explains
its PN placement under TRAPP complex components. Cryo-EM places TRAPPC13 (with
TRAPPC12) at the vertex joining the TRAPPC8 and TRAPPC11 arms, so it is best
understood as a structural/accessory subunit that contributes to TRAPPIII assembly
and organization rather than to catalysis, since a recombinant miniTRAPPIII lacking
TRAPPC12/TRAPPC13 still retains Rab1 GEF activity in vitro. Current evidence supports
TRAPPIII/RAB1 complex context and shared TRAPP trafficking semantics, but not a
direct TRAPPC13-specific autophagy process annotation.
directly_involved_in:
- id: GO:0006888
label: endoplasmic reticulum to Golgi vesicle-mediated transport
locations:
- id: GO:0005829
label: cytosol
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: PMID:27066478
supporting_text: TRAPP II, which contains core TRAPP plus TrappC9-10, and TRAPP
III, which contains core TRAPP plus TrappC8, 11-13
- reference_id: PMID:27066478
supporting_text: The inclusion of TrappC13, the homolog of Trs65, in the mammalian
TRAPP III differs from its inclusion in the yeast TRAPP II complex
- reference_id: Reactome:R-HSA-8877475
supporting_text: RAB1 and the TRAPPCIII complex play a role in the formation of the
pre-autophagosomal structure (PAS)
- reference_id: PMID:27066478
supporting_text: the connection of the mammalian TRAPP III complex to autophagy is
currently not clear
- reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supporting_text: TRAPPC13 does not itself catalyze nucleotide exchange but rather
supports the guanine nucleotide exchange factor (GEF) activity of the TRAPPIII
complex toward Rab1 GTPase
- reference_id: file:human/TRAPPC13/TRAPPC13-deep-research-falcon.md
supporting_text: 'a "miniTRAPPIII" complex lacking TRAPPC12 and TRAPPC13 retains
Rab1 GEF activity in vitro, indicating these subunits are dispensable for basal
catalytic function'
proposed_new_terms: []
suggested_questions:
- question: Should human TRAPPC13 be curated as TRAPPII, TRAPPIII, or both, given the
difference between yeast Trs65/TRAPPII assignment, mammalian genetic-interaction
TRAPPIII models, and ComplexPortal TRAPPII entries?
experts:
- ComplexPortal curators
- Reactome TRAPP curators
- GO transport editors
- question: Should TRAPPC13 generic protein-binding annotations be replaced by more
informative TRAPP complex membership and complex-level Rab/RAB GEF annotations?
experts:
- GO molecular function editors
- IntAct curators
- question: Is there direct experimental evidence for a TRAPPC13-specific autophagy or
ATG9-trafficking annotation, or should PN autophagy context remain limited to
TRAPPIII/TRAPP complex membership?
experts:
- GO autophagy editors
- Reactome TRAPP curators
suggested_experiments:
- description: Reconstitute human TRAPPC13-containing TRAPPII and TRAPPIII assemblies
and measure RAB1 nucleotide exchange with and without TRAPPC13.
experiment_type: complex reconstitution and RAB GEF assay
hypothesis: TRAPPC13 contributes to complex-level RAB1 GEF activity through TRAPP
complex assembly or stability rather than acting as an independent enzyme.
- description: Deplete and rescue TRAPPC13 in mammalian cells and compare ER-to-Golgi
cargo transport, Golgi morphology, RAB1 activation, and TRAPP subunit integrity.
experiment_type: trafficking rescue assay
hypothesis: TRAPPC13 supports early secretory trafficking by maintaining functional
TRAPP complex architecture.
- description: Test TRAPPC13 perturbation in ATG9 cycling, LC3/WIPI2 puncta formation,
and starvation-induced autophagy alongside TRAPPC8-positive controls.
experiment_type: autophagy trafficking assay
hypothesis: If TRAPPC13 has a specific PN autophagy role, it should affect
TRAPPIII-dependent ATG9/autophagosome initiation readouts beyond generic
secretory pathway disruption.