Functional Annotation of the Human **COPG2** Gene (Coatomer Subunit Gamma-2) OpenAI o3-deep-research-2025-06-26 76 citations 2025-11-04T03:14:37.935187

Functional Annotation of the Human COPG2 Gene (Coatomer Subunit Gamma-2)

Overview and Gene Context

COPG2 encodes the γ2-COP protein, one of the gamma subunits of the COPI (coat protein complex I) vesicle coat in human cells (pmc.ncbi.nlm.nih.gov). COPI is a heptameric protein complex (coatomer) composed of seven subunits (α-, β-, β′-, γ-, δ-, ε-, ζ-COP) that assemble on Golgi membranes to form vesicle coats (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). In mammals, two isoforms exist for the γ subunit: γ1-COP (encoded by COPG1) and γ2-COP (encoded by COPG2), which share ~80% sequence identity (pmc.ncbi.nlm.nih.gov). These arose from gene duplication and are highly conserved across eukaryotes (yeast has a single γ-COP homolog, Sec21p, essential for viability). COPG2 was initially identified as “gamma2-COP” on human chromosome 7q32 in an imprinted gene cluster (pmc.ncbi.nlm.nih.gov). Notably, COPG2 lies near the imprinted MEST/Peg1 gene, and early studies suggested allele-specific expression; however, expression of COPG2 is generally biallelic with some tissue-specific regulatory effects from the MEST locus (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). This places COPG2 in a unique genomic context, though its primary role is structural in vesicle trafficking rather than epigenetic regulation.

Molecular Function of γ2-COP Protein

The γ2-COP protein is a structural component of the COPI coat complex and is not an enzyme or transporter. Its primary function is to help form the lattice of the COPI coat on budding vesicles and to organize interactions with other coatomer subunits, cargo proteins, and regulatory factors (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). COPI-coated vesicles mediate retrograde transport from the Golgi back to the endoplasmic reticulum (ER) as well as intra-Golgi transport between Golgi cisternae (pubmed.ncbi.nlm.nih.gov). During vesicle formation, the small GTPase ARF1 in its GTP-bound form recruits coatomer to the Golgi membrane (pmc.ncbi.nlm.nih.gov). The coatomer then binds to sorting signals on the cytosolic tails of cargo proteins – notably, dilysine motifs (KKXX or KXKXX at the C-terminus of membrane proteins) which serve as ER retrieval signals (pubmed.ncbi.nlm.nih.gov). These interactions ensure that ER-resident proteins (e.g. those captured by KDEL receptors) and other cargo are selectively packaged into the budding COPI vesicle for transport back to the ER (pubmed.ncbi.nlm.nih.gov). While binding of the dilysine motifs is mediated largely by the α- and β′-COP subunits of coatomer (pubmed.ncbi.nlm.nih.gov), the γ-COP subunits (γ1/γ2) contribute to the overall coat architecture and recruitment of regulatory factors.

Importantly, the γ2-COP protein contains a C-terminal appendage (ear) domain structurally similar to the appendages of clathrin adaptins (pubmed.ncbi.nlm.nih.gov). The crystal structure of the γ-COP appendage revealed a platform subdomain that provides a protein–protein interaction site (pubmed.ncbi.nlm.nih.gov). In yeast, this site on γ-COP binds the ARF GTPase-activating protein Glo3p, and in mammals γ-COP similarly binds ARFGAP2 (a Glo3p ortholog) (pubmed.ncbi.nlm.nih.gov). This interaction links the coatomer to ARF regulatory machinery: ARFGAP proteins trigger ARF1 GTP hydrolysis, promoting uncoating once the vesicle buds. Thus, γ2-COP is thought to help time the vesicle uncoating and perhaps also contribute to cargo selection through ARFGAP-dependent mechanisms (pubmed.ncbi.nlm.nih.gov). Additionally, mutational analysis in yeast (Sec21p) suggests the γ-COP appendage may have a second interface that contacts the coatomer’s α/β′/ε subcomplex, helping bridge the two halves of the complex (pubmed.ncbi.nlm.nih.gov). Overall, γ2-COP serves as a scaffolding molecule in the COPI coat, coordinating coat assembly and disassembly by binding other coat subunits, ARF1, ARF-GAPs, and possibly accessory proteins. It does not catalyze a chemical reaction nor transport a substrate in the classical sense; rather, its “substrate” is the nascent vesicle membrane/cargo complex, which it helps to deform and pinch off in concert with the rest of coatomer.

Biological Processes and Pathways

As part of the COPI coat, COPG2/γ2-COP is critically involved in the early secretory pathway – especially retrograde Golgi–ER transport. COPI-coated vesicles retrieve escaped ER proteins and recycling membrane proteins from the Golgi, maintaining protein localization and organelle homeostasis (pubmed.ncbi.nlm.nih.gov). For example, membrane proteins bearing a KKXX retrieval signal (such as the KDEL receptor loaded with ER chaperones) are captured by coatomer and sent back to the ER (pubmed.ncbi.nlm.nih.gov). COPI vesicles also mediate intra-Golgi traffic, carrying enzymes and other cargo between Golgi cisternae (pubmed.ncbi.nlm.nih.gov). This is crucial for the Golgi’s function as a processing and sorting station. Indeed, one model of Golgi transport (the cisternal maturation model) assigns COPI vesicles the role of recycling Golgi-resident enzymes backwards within the stack, thereby preserving the polarized distribution of enzymes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In any case, COPI (and thus γ2-COP) is essential for retrograde transport and for the fidelity of protein sorting in the secretory pathway.

In addition to transport, COPI coat function contributes to Golgi structural maintenance and dynamics. Experimental disruption of coatomer subunits leads to Golgi disorganization. Notably, knockout of the γ2-COP gene in cells (or its paralog γ1-COP) causes fragmentation of the Golgi: electron microscopy of cells lacking γ2-COP showed an increased number of smaller Golgi stacks relative to wild-type (pmc.ncbi.nlm.nih.gov), and similarly shortened Golgi cisternae length (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In γ1-COP–deficient cells, an abnormal accumulation of vesicles at Golgi remnants was observed, indicating pronounced Golgi fragmentation when the coat is compromised (pmc.ncbi.nlm.nih.gov). These phenotypes underscore that a functional COPI coat (with either γ1 or γ2) is required to maintain normal Golgi architecture (pmc.ncbi.nlm.nih.gov), likely by continuously retrieving membrane and proteins to counterbalance the anterograde flow. Consistent with these findings, coatomer also influences processing and turnover of certain membrane proteins; for example, coatomer-mediated retrieval has been implicated in the proper recycling of LDL receptors and in processing of the amyloid precursor protein (www.proteinatlas.org) (pmc.ncbi.nlm.nih.gov). Thus, COPG2’s role in COPI impacts not only vesicle trafficking but also downstream cellular processes such as lipid uptake (via LDLR) and protein cleavage pathways, through its effect on protein localization.

At the cellular pathway level, COPG2/γ2-COP functions in concert with ARF1 and ARF-GAP in the vesicle budding/uncoating cycle. ARF1-GTP recruits coatomer to initiate a bud, and after vesicle scission, ARF1 is inactivated by ARFGAP (which, as noted, binds γ-COP) to trigger coat disassembly (pubmed.ncbi.nlm.nih.gov). This ensures COPI vesicles shed their coat and can fuse with target membranes (ER or Golgi). The COPI pathway also intersects with other trafficking routes; for instance, COPI-coated intermediates form at the ER-Golgi intermediate compartment (ERGIC) as well, and recent 3D electron microscopy showed COPI coats on vesicles carrying SARS-CoV-2 virions from the ERGIC to Golgi during infection (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Depleting coatomer components (e.g. COPB2) in infected cells causes nascent virions to be trapped in the ERGIC, blocking their export (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). This exemplifies how fundamental COPI vesicle function, with γ2-COP as a part, is even hijacked in pathological contexts. In summary, COPG2 is integral to the COPI-mediated transport pathway, which is vital for recycling membrane proteins, maintaining organelle identity, and supporting various cellular processes that rely on correct protein localization.

Subcellular Localization and Expression

The γ2-COP protein is predominantly intracellular and cytosolic, with a dynamic association to Golgi membranes. Like all coatomer subunits, γ2-COP resides in the cytosol when not active, and upon ARF1 activation it localizes to the cytosolic face of the Golgi and ERGIC membranes to drive vesicle budding (pmc.ncbi.nlm.nih.gov). Immunolocalization studies have shown coatomer concentrated at the Golgi region as punctate perinuclear staining, corresponding to coatomer-coated vesicles and buds. The Human Protein Atlas reports that COPG2 shows ubiquitous cytoplasmic expression in most human tissues (www.proteinatlas.org), consistent with its housekeeping role in secretory trafficking. mRNA profiling indicates low tissue specificity – COPG2 is expressed in virtually all cell types at baseline (www.proteinatlas.org). Nonetheless, there are subtle variations: for example, single-cell RNA data show enhanced expression of COPG2 in certain neuron populations and germ cells (www.proteinatlas.org), and during mouse neuronal differentiation Copg2 expression tends to be down-regulated in mature neurons (relative to its paralog, see below) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Overall, the evidence suggests γ2-COP is broadly expressed and available in all cells, reflecting its fundamental role in general cell physiology.

At the subcellular level, γ2-COP (within coatomer) shuttles between the cytosol and Golgi/ERGIC membranes. Recruitment to membranes is transient – the coat assembles to form a vesicle and then disassembles after budding, returning coatomer subunits (including γ2-COP) to the cytoplasm (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). This cyclical localization is regulated by ARF1’s GTP/GDP state. Notably, studies of coatomer isoforms revealed that distinct coatomer complexes can localize differently in cells: coatomer containing γ2-COP (paired with ζ1-COP) showed somewhat different steady-state distribution compared to complexes with γ1-COP (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In rat liver cells, three coatomer isoform pools – γ1/ζ1, γ1/ζ2, and γ2/ζ1 – were identified in roughly a 2:1:2 ratio (pmc.ncbi.nlm.nih.gov). Intriguingly, the γ2/ζ1 coatomer isoform was found to concentrate on a specific subset of COPI vesicles (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), implying that γ2-COP–containing coatomers might preferentially cycle on certain routes (for instance, specific retrograde carriers). These findings still await full mechanistic explanation, but they reinforce that γ2-COP localizes to COPI vesicles in vivo, potentially with a bias toward particular trafficking pathways (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In summary, γ2-COP is an intracellular protein cycling between cytosol and Golgi membranes, present in essentially all cells to support vesicle transport.

Pathway Integration and Functional Insights from Research

For many years, γ1-COP and γ2-COP were assumed to be functionally redundant components of COPI. Indeed, core COPI functions (Golgi–ER transport, vesicle formation) can be carried out by coatomer containing either γ1 or γ2 subunits. Gene knockout experiments in mice and cell lines show that neither COPG1 (γ1) nor COPG2 (γ2) is individually essential for cell viability – loss of one paralog can be compensated by up-regulation of the other, allowing coatomer levels to be maintained (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In pluripotent mouse cells, knocking out Copg2 alone still permits cell survival and basic secretory transport (γ1-COP levels increase in compensation), and vice versa (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This indicates considerable redundancy: both γ-COP isoforms can fulfill the “essential functions” of the COPI coat (pmc.ncbi.nlm.nih.gov). However, emerging research has highlighted context-specific roles that distinguish the paralogs. A 2020 study by Goyal et al. found that during neuronal differentiation, the two isoforms are differentially expressed and have unique contributions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In mouse embryonic stem cells induced to form neurons, Copg1 (γ1) expression was strongly upregulated at the stage of mature neuron formation, whereas Copg2 was not (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Functionally, loss of γ1-COP impaired neuronal outgrowth: Copg1 knockout cells formed fewer and shorter neurites upon differentiation (pmc.ncbi.nlm.nih.gov). In contrast, Copg2 knockout did not hinder neurite outgrowth or neuron formation in this model (pmc.ncbi.nlm.nih.gov). Even when γ2-COP was overexpressed or knocked into the Copg1 locus, it could not fully rescue the neurite extension phenotype, indicating that γ1-COP has a paralog-specific role in supporting neurite/polarization processes that γ2-COP cannot completely substitute (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This was the first clear evidence of a functional divergence: COPG1/γ1 appears specialized for certain aspects of neuronal cell biology, whereas COPG2/γ2 plays a more general or supportive role (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The mechanistic basis is still under investigation, but one hypothesis is that γ1-COP–containing coatomer might interact with specific cargo or adaptor proteins critical for neurite extension (or conversely, γ2-COP might direct vesicle traffic to slightly different destinations) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Aside from developmental contexts, coatomer subunits including γ-COP have been linked to human disease and cellular stress pathways. Mutations or dysregulation of COPI subunits can lead to tissue-specific disorders despite their housekeeping roles. For example, certain inherited mutations in other COPI subunits (β- or δ-COP) cause neurological and developmental syndromes, underscoring the importance of COPI in the nervous system (pmc.ncbi.nlm.nih.gov). Genome studies have occasionally flagged the COPG2 locus in disorders – it resides in a region implicated in Silver–Russell syndrome (a growth retardation condition involving imprinting abnormalities) (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov), and it was once examined as a candidate gene in autism due to its location on chromosome 7q32 (though no causative mutations were confirmed). In cancer biology, COPI components are being explored for their role in sustaining the heightened secretory demands of tumor cells. While γ2-COP itself has not been singled out as a frequent mutation target, the coatomer complex as a whole is required for rapidly proliferating cells; recent work showed certain cancer cells rely on the COPI zeta1 subunit (COPZ1) for survival, a concept termed “non-oncogene addiction” (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). It is conceivable that redundancy between γ1 and γ2 has so far masked any unique dependency on γ2 in such contexts. Nevertheless, COPG2’s contribution is indispensable in a general sense – at least one γ-COP isoform must be present for any cell to survive, given the essential nature of COPI trafficking (pmc.ncbi.nlm.nih.gov). In summary, contemporary research paints COPG2 as a broadly acting coat protein with some emerging specialized roles. Its primary function is structural: enabling COPI vesicle formation for retrograde transport. Through this activity, it indirectly influences numerous pathways (protein sorting, organelle homeostasis, signaling protein localization), but it does not appear to have a direct signaling or enzymatic role beyond vesicle coat dynamics. The ongoing dissection of γ1 vs γ2 functions – for instance in neurons – is shedding light on why two paralogs exist. It suggests that COPG2/γ2-COP may be optimized for routine housekeeping trafficking, whereas COPG1/γ1-COP might support trafficking demands in specialized cells or conditions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This nuanced understanding is still evolving, and future precise studies (e.g. proteomic cargo profiles of γ1- vs γ2-coatomers and knockout animal models) will further clarify COPG2’s specific role within the essential COPI machinery.

References: (Key references are provided for each claim in the text above, with publication year and source indicated where available.)

Citations

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  39. AnnotationURLCitation(end_index=13615, start_index=13461, title='COPG2 protein expression summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000158623-COPG2#:~:text=TISSUE%20RNA%20EXPRESSION%20Tissue%20specificity,Single%20cell%20type')
  40. AnnotationURLCitation(end_index=13937, start_index=13774, title='COPG2 protein expression summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000158623-COPG2#:~:text=Single%20cell%20type%20specificity,immune%20cell%20specificity%20Immune%20cell')
  41. AnnotationURLCitation(end_index=14240, start_index=14082, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=COPI%20pathway%20lead%20to%20specific,did%20not%20affect%20retinoic%20acid')
  42. AnnotationURLCitation(end_index=14366, start_index=14241, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=This%20is%20in%20contrast%20to,Altogether')
  43. AnnotationURLCitation(end_index=14943, start_index=14809, title='Coatomer complex I is required for the transport of SARS-CoV-2 progeny virions from the endoplasmic reticulum-Golgi intermediate compartment - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39611845/#:~:text=as%20array%20tomography%20and%20electron,Hence%2C%20our')
  44. AnnotationURLCitation(end_index=15044, start_index=14944, title='Coatomer complex I is required for the transport of SARS-CoV-2 progeny virions from the endoplasmic reticulum-Golgi intermediate compartment - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39611845/#:~:text=virus%20replication,2')
  45. AnnotationURLCitation(end_index=15464, start_index=15360, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=%CE%B31%2F%CE%B61,COP')
  46. AnnotationURLCitation(end_index=15593, start_index=15465, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=In%20Fig,coatomer%20and%20thus%20resides%20in')
  47. AnnotationURLCitation(end_index=15837, start_index=15713, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=match%20at%20L122%20%CE%B31%2F%CE%B61,COP')
  48. AnnotationURLCitation(end_index=16112, start_index=15943, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=the%20complex%20defined%20by%20the,isotype%20is%20preferentially%20incorporated%20into')
  49. AnnotationURLCitation(end_index=16217, start_index=16113, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=%CE%B31%2F%CE%B61,COP')
  50. AnnotationURLCitation(end_index=16712, start_index=16543, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=the%20complex%20defined%20by%20the,isotype%20is%20preferentially%20incorporated%20into')
  51. AnnotationURLCitation(end_index=16817, start_index=16713, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=%CE%B31%2F%CE%B61,COP')
  52. AnnotationURLCitation(end_index=17715, start_index=17530, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=strongly%20affect%20the%20global%20expression,%E2%88%92%2F%E2%88%92%7D%20cells%20compared%20with%20WT')
  53. AnnotationURLCitation(end_index=17866, start_index=17716, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=regulated,antibody%2C%20which%20specifically%20recognizes%20native')
  54. AnnotationURLCitation(end_index=18208, start_index=18038, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=expression%20of%20several%20COP%20subunits,To%20verify%20whether%20coatomer%20subunits')
  55. AnnotationURLCitation(end_index=18359, start_index=18209, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=regulated,antibody%2C%20which%20specifically%20recognizes%20native')
  56. AnnotationURLCitation(end_index=18624, start_index=18480, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=As%20a%20functional%20COPI%20pathway,COP%20paralog%20is%20up')
  57. AnnotationURLCitation(end_index=19048, start_index=18878, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=paralogous%20subunits%20of%20the%20protein,for%20distinct%20functions%20for%20coatomer')
  58. AnnotationURLCitation(end_index=19207, start_index=19049, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=COPI%20pathway%20lead%20to%20specific,did%20not%20affect%20retinoic%20acid')
  59. AnnotationURLCitation(end_index=19534, start_index=19378, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=Moreover%2C%20binding%20of%20%CE%B1,both%20gene%20disruptions%20led%20to')
  60. AnnotationURLCitation(end_index=19660, start_index=19535, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=This%20is%20in%20contrast%20to,Altogether')
  61. AnnotationURLCitation(end_index=19948, start_index=19798, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=Copg1%20or%20Copg2%20in%20P19,role%20of%20COPI%20vesicles%20during')
  62. AnnotationURLCitation(end_index=20201, start_index=20051, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=Copg1%20or%20Copg2%20in%20P19,role%20of%20COPI%20vesicles%20during')
  63. AnnotationURLCitation(end_index=20603, start_index=20473, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=viability,role%20of%20COPI%20vesicles%20during')
  64. AnnotationURLCitation(end_index=20776, start_index=20604, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=formation%20of%20loose%20embryoid%20bodies,required%20to%20promote%20neurite%20outgrowth')
  65. AnnotationURLCitation(end_index=21152, start_index=20976, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=the%20paralogous%20coatomer%20subunits%20%CE%B31,paralogous%20subunits%20in%20this%20process')
  66. AnnotationURLCitation(end_index=21303, start_index=21153, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=Copg1%20or%20Copg2%20in%20P19,role%20of%20COPI%20vesicles%20during')
  67. AnnotationURLCitation(end_index=21752, start_index=21585, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=through%20a%20combination%20of%20genome,paralogous%20subunits%20in%20this%20process')
  68. AnnotationURLCitation(end_index=21857, start_index=21753, title='Novel Isotypic γ/ζ Subunits Reveal Three Coatomer Complexes in Mammals - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC321441/#:~:text=%CE%B31%2F%CE%B61,COP')
  69. AnnotationURLCitation(end_index=22474, start_index=22298, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=Several%20lines%20of%20evidence%2C%20however%2C,mRNA%20expression%20profiling%20data%2C%20we')
  70. AnnotationURLCitation(end_index=22821, start_index=22679, title='Tissue-specific alternative polyadenylation at the imprinted gene Mest regulates allelic usage at Copg2 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/22053079/#:~:text=The%20gene%20Mest%20,into%20the%20downstream%20antisense%20gene')
  71. AnnotationURLCitation(end_index=22983, start_index=22822, title='Tissue-specific alternative polyadenylation at the imprinted gene Mest regulates allelic usage at Copg2 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/22053079/#:~:text=mouse%20and%20only%20the%20paternal,produced%20exclusively%20in%20the%20developing')
  72. AnnotationURLCitation(end_index=23651, start_index=23547, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=article%20%5D%20,DOI')
  73. AnnotationURLCitation(end_index=23741, start_index=23652, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=5,DOI')
  74. AnnotationURLCitation(end_index=24195, start_index=24051, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=As%20a%20functional%20COPI%20pathway,COP%20paralog%20is%20up')
  75. AnnotationURLCitation(end_index=25124, start_index=24948, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=the%20paralogous%20coatomer%20subunits%20%CE%B31,paralogous%20subunits%20in%20this%20process')
  76. AnnotationURLCitation(end_index=25275, start_index=25125, title='A paralog-specific role of COPI vesicles in the neuronal differentiation of mouse pluripotent cells - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7368096/#:~:text=Copg1%20or%20Copg2%20in%20P19,role%20of%20COPI%20vesicles%20during')