SEC23A is a subunit of the inner layer of the coat protein complex II (COPII), which forms transport vesicles and tubular carriers at endoplasmic reticulum exit sites to export secretory and membrane cargo to the Golgi. As a SEC23-SEC24 heterodimer recruited from the cytosol by GTP-bound SAR1 to the cytoplasmic face of the ER membrane, SEC23 is the GTPase-activating protein for SAR1, inserting an arginine into the SAR1 active site; the SEC23/24 complex binds cargo such as the SNARE SEC22B, and SEC23 recruits the SEC13-SEC31 outer coat that polymerises the coat and drives vesicle fission. SEC23A contains a zinc finger, trunk, beta-sandwich, helical and gelsolin-like domain; the gelsolin-like domain binds PPP motifs in the large-cargo receptors MIA3 (TANGO1) and MIA2 (cTAGE5) and in SEC31. Loss of SEC23A function in human causes cranio-lenticulo-sutural dysplasia with ER distension and a collagen secretion defect. The donkey entry A0A9L0IQB9 is one of several alternative transcript products of the SEC23A gene; it lacks a 26-residue segment (human 554-579) through an in-frame exon skip but retains all domains and characterised functional residues.
Summary: GTPase activator activity, transferred by TreeGrafter from a PANTHER PTHR11141 ancestral node. SEC23 is the GTPase-activating protein (GAP) for the small GTPase SAR1 in the COPII coat; this was shown biochemically for yeast Sec23p, structurally (arginine finger into the Sar1 active site), and human SEC23A (same PANTHER subfamily PTHR11141:SF7 as the donkey gene) complements a yeast sec23 mutant. The same term is propagated by PAINT to human SEC23A from the SEC23 node PTN000124617, with yeast Sec23 among the experimental donors.
Reason: The SAR1 GAP activity is the defining activity of the SEC23 subfamily and arose deep in the eukaryotic SEC23 lineage (yeast experimental data); donkey SEC23A sits in the vertebrate SEC23A subfamily PTHR11141:SF7 together with human Q15436 and mouse Q01405, and no lineage-specific loss is indicated. The benchmark product is an exon-skipping transcript model that retains all domains of the canonical protein (file:EQUAS/SEC23A/SEC23A-bioinformatics/RESULTS-rereview.md), so the activity is transferred to the gene product with the caveat that the 26-residue deletion has not been tested. Core molecular function.
hSec23Ap is a functional homologue of the yeast Sec23p as the hSec23A isoform complemented the temperature sensitivity of the Saccharomyces cerevisiae sec23-1 mutation
The outer coat stimulates the GTPase-activating protein Sec23 which activates Sar1 GTP hydrolysis allowing depolymerisation of the coat and recycling of its components.
Summary: ER membrane (peripheral, cytoplasmic side), from the UniProt subcellular-location mapping. Human SEC23A is experimentally localized to the transitional ER, and the SEC23/24 inner coat is recruited to the ER membrane by SAR1-GTP.
Reason: Correct location of the membrane-bound pool of the inner coat; supported by immuno-EM of human SEC23A and by the mechanism of SAR1-dependent recruitment. The more specific ER exit site term is also accepted.
By immunoelectron microscopy, hSec23Ap was found essentially in the ribosome-free transitional face of the endoplasmic reticulum (ER) and associated vesicles.
Summary: Cytosol, from the UniProt subcellular-location mapping. COPII components are recruited from a soluble cytosolic pool; cytosolic human SEC23A behaves as part of a ~350 kDa complex.
Reason: Correct; the soluble pool of the coat is in the cytosol and is replenished after SAR1 GTP hydrolysis releases the coat.
Summary: Intracellular protein transport, from InterPro2GO mappings of the Sec23/Sec24 domains. COPII carriers move secretory and membrane proteins from the ER to the Golgi.
Reason: True, because the cargo COPII carries is protein, but broad. It is not an is_a ancestor of the accepted ER to Golgi vesicle-mediated transport (GO:0006888), COPII-coated vesicle cargo loading or COPII-coated vesicle budding terms (checked in OLS), so no more specific descendant of this term is available to substitute; it is kept as a correct, non-core process.
SEC23A is an essential component of the COPII-coated vesicles that transport secretory proteins from the endoplasmic reticulum to the Golgi complex.
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport
IEA GO_REF:0000002
ACCEPT
Summary: ER to Golgi vesicle-mediated transport, from InterPro2GO. This is the process the COPII coat executes; a SEC23A missense variant (F382L) abolishes SEC23A budding activity in vitro and causes ER distension in patient fibroblasts.
Reason: Core process. SEC23A does work in this process as a structural coat subunit and SAR1 GAP; human functional evidence (complementation, cell-free budding with the CLSD variant) is transferable within PTHR11141:SF7. F382 is conserved in the donkey product.
Our data demonstrate that hSec23Ap is the functional human counterpart of the yeast COPII component Sec23p and suggest that it plays a similar role in mammalian protein export from the ER.
Summary: Zinc ion binding, from InterPro2GO for the Sec23/Sec24 zinc finger. Human SEC23A crystal and NMR structures contain bound zinc, and the four zinc-coordinating cysteines are conserved in the donkey product.
Reason: The zinc site is a structural feature of the zinc-finger domain, not the functional activity of the protein; it is correct and as specific as the evidence allows, but peripheral to the GAP and coat functions.
Summary: ER to Golgi transport vesicle membrane (COPII-coated vesicle membrane, cytoplasmic side), from the UniProt subcellular-location mapping. Human SEC23A is found on transitional ER and associated vesicles.
Reason: SEC23A is an inner-coat subunit on the cytoplasmic face of COPII-coated vesicles.
By immunoelectron microscopy, hSec23Ap was found essentially in the ribosome-free transitional face of the endoplasmic reticulum (ER) and associated vesicles.
Summary: COPII vesicle coat, from the combined IEA pipeline (InterPro plus PANTHER node). SEC23 forms the inner coat with SEC24 and SAR1, onto which SEC13-SEC31 assembles; the same term reaches human SEC23A by PAINT from the SEC23 node and by experiment.
Reason: Defining complex membership, conserved across the SEC23 family.
Summary: ER exit site, from TreeGrafter. Human SEC23A is concentrated at the ribosome-free transitional ER (ER exit sites); PAINT propagates this location from the SEC23 node with donors from plant, fly, worm and trypanosome.
Reason: Experimentally supported for human SEC23A in the same subfamily and the site of COPII assembly.
By immunoelectron microscopy, hSec23Ap was found essentially in the ribosome-free transitional face of the endoplasmic reticulum (ER) and associated vesicles.
Summary: COPII-coated vesicle cargo loading, from TreeGrafter. The SEC23/24 complex binds cargo; the SNARE SEC22B binds at the SEC23/SEC24 interface, and the SEC23A gelsolin-like domain binds PPP motifs of the procollagen-export receptors TANGO1 (MIA3) and cTAGE5 (MIA2).
Reason: SEC23A contributes binding surfaces for cargo (SEC22B, with SEC24) and for large-cargo receptors, so it does part of the work of cargo loading rather than merely being required for it. The PPP-binding residues are conserved in the donkey product.
These data indicate that TANGO1 binds to the gelsolin-like domain of Sec23a via a PPP motif that repeats through the TANGO1 and cTAGE5 cytosolic regions.
Summary: COPII-coated vesicle budding, from InterPro2GO (Sec23 C-terminal domain). SEC23A recruits the SEC13-SEC31 outer coat; the CLSD variant of SEC23A recruits SEC13-SEC31 poorly and inhibits vesicle formation.
Reason: SEC23A is a structural inner-coat subunit, SAR1 GAP and outer-coat recruiter that directly participates in vesicle budding; shown for human SEC23A in reconstituted budding assays.
Experiments revealed that an interaction between Sar1p and the Sec23p subunit of an oligomeric protein is also required for vesicle budding.
Core Functions
Inner-coat COPII subunit and SAR1 GTPase-activating protein that, at ER exit sites, binds cargo and cargo receptors with SEC24, recruits the SEC13-SEC31 outer coat and drives COPII carrier budding for ER-to-Golgi transport.
Q: Is the donkey SEC23A transcript ENSEAST00005045719, which skips a 78-nt exon and so lacks the segment equivalent to human 554-579, expressed in donkey tissues, and does the deletion affect SEC31 or TANGO1-family binding or SAR1 GAP stimulation?
Suggested Experiments
Experiment: RT-PCR across the skipped exon in donkey fibroblast and chondrocyte RNA to detect the exon-skipped SEC23A transcript, then test the encoded protein for SAR1 GAP activity, SEC13-SEC31 recruitment and COPII budding in a reconstituted assay, alongside the full-length canonical product.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Assessment of 1 ProtNLM2 GO prediction for donkey SEC23A (A0A9L0IQB9), judged against the donkey GOA record (GTPase activator activity, COPII vesicle coat, ER to Golgi vesicle-mediated transport, COPII-coated vesicle budding and cargo loading, ER membrane, ER exit site, cytosol), the re-reviewed donkey gene review, the human ortholog Q15436, budding assays on human SEC23A (PMID:17981132) and yeast Sec23p (PMID:8451644), a donkey-human alignment (99% identity) and a comparison with the canonical donkey product A0A9L0JMP6. This accession is an exon-skipping transcript product whose 26-residue deletion falls inside the Sec23/Sec24 helical domain, so COPII-coated vesicle budding, a correct and already-annotated process for the gene, is uncertain for this product (UNC). Non-GO ProtNLM2 output, not scored: subcellular location 'Membrane', which is true but much less informative than the curated peripheral ER-membrane and COPII-vesicle-membrane locations. No function text was emitted for this accession.
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
Review rationale: COPII-coated vesicle budding is a core process of the SEC23A gene, whose canonical product is an inner-coat COPII subunit and the SAR1 GTPase-activating protein; Sec23p-Sar1p interaction is required for budding in yeast, and a disease variant of human SEC23A that poorly recruits Sec13-Sec31 inhibits vesicle formation in vitro. The term is already in donkey GOA for this gene (InterPro2GO mapping of the Sec23 C-terminal domain), so it is not novel. The scored sequence, A0A9L0IQB9, is an in-frame exon-skipping transcript product that lacks the 26 residues equivalent to human 554-579. It keeps the zinc finger and its four Cys ligands, the trunk domain with F382, the beta-sandwich domain and the gelsolin-like PPP-motif-binding residues, but the deletion falls inside the Sec23/Sec24 helical domain. That domain spans residues 518-616 in the canonical donkey product A0A9L0JMP6, while its Pfam match on A0A9L0IQB9 covers only 553-590. Whether a Sec23 with a truncated helical domain still folds, binds SEC24 and SEC31 and supports vesicle budding has not been tested, and there is no expression evidence for this transcript. Because the required feature, an intact Sec23 fold, cannot be confirmed for this product, the prediction is uncertain at product level.