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Gene Overview: SPCC16C4.02c is an uncharacterized fission yeast gene encoding a 548-amino-acid protein of the DUF1941 family (thebiogrid.org). It is annotated as the Schizosaccharomyces pombe ortholog of human neurochondrin (NCDN) (thebiogrid.org), suggesting an evolutionarily conserved role. The protein lacks well-defined enzymatic motifs and is thought to function as a regulatory or scaffolding protein rather than an enzyme. No standard gene name is established in S. pombe (it is often referred to by the systematic ID SPCC16C4.02c), reflecting its largely unknown function.
SPCC16C4.02c has no experimentally confirmed biochemical function to date (Gene Ontology assigns no molecular function term) (thebiogrid.org). Its classification in the DUF1941 (Domain of Unknown Function 1941) family indicates it contains a conserved domain of unknown function, shared with neurochondrin/NCDN homologs across species (thebiogrid.org). The human neurochondrin protein is a leucine-rich cytosolic factor that negatively regulates Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) signaling and is important for neural processes like spatial learning (www.ncbi.nlm.nih.gov). By analogy, SPCC16C4.02c may act as a scaffolding or adaptor protein modulating signaling pathways or protein complexes, although the specific targets in yeast are not yet known. It has no known enzymatic activity or DNA/RNA-binding domains, and likely exerts its effects through protein–protein interactions. Consistent with this, SPCC16C4.02c was identified in a proteome-wide yeast two-hybrid screen, interacting with multiple proteins (see Experimental Evidence), implying a role in multi-protein complexes (thebiogrid.org) (thebiogrid.org). At present, GO Molecular Function: none assigned (unknown) (thebiogrid.org); it can be broadly inferred as a protein-binding/regulatory protein, pending direct assays.
No direct localization studies (e.g. microscopy) have been published for SPCC16C4.02c. However, several lines of evidence point to a cytoplasmic residency. The human ortholog is confirmed to be a cytosolic protein (www.ncbi.nlm.nih.gov), and by orthology the yeast protein is expected to localize to the cytoplasm as well. High-throughput annotations in S. pombe indeed place SPCC16C4.02c in the cytoplasm and possibly associated with the cortical microtubule cytoskeleton (thebiogrid.org). These associations are indirect – for example, one of its interaction partners is Mcp5 (also called Num1, a cortical anchor for dynein) which localizes to the cell cortex on microtubule astral arrays (thebiogrid.org) (thebiogrid.org). Another interactor is Sfi1, a core component of the spindle pole body (the yeast centrosome) (thebiogrid.org). The two-hybrid interactions with these spatially localized proteins hint that SPCC16C4.02c might shuttle between or reside at specific cytoskeletal structures, such as the nuclear periphery/spindle pole body region or cell cortex, perhaps during certain cell-cycle stages or under specific conditions. Until live-cell imaging or fractionation studies are done, GO Cellular Component annotations rely on these inferences: currently it is associated with cytoplasm (GO:0005737) and has been linked to the cortical microtubule cytoskeleton (thebiogrid.org). No signal peptides or transmembrane segments are predicted, consistent with a cytosolic, non-membrane protein.
Given the paucity of direct functional assays, SPCC16C4.02c has no specific biological process GO annotation yet (GO Biological Process: none assigned) (thebiogrid.org). Nevertheless, its protein–protein interaction profile provides clues to possible roles. Several interactors are involved in microtubule-based processes and cellular organization. For instance, the interaction with Mcp5/Num1 suggests a connection to dynein-mediated nuclear movement during meiosis. Mcp5 is required for anchoring dynein at the cortex to drive the oscillatory “horse-tail” nuclear movements in meiotic prophase (thebiogrid.org). Although SPCC16C4.02c’s role in this process is unproven, the physical association raises the possibility that it modulates dynein or microtubule function, perhaps as an accessory factor in the cortical anchoring complex. Supporting this, Mcp5’s known GO processes include cortical protein anchoring and dynein-driven meiotic oscillatory nuclear movement (thebiogrid.org), processes in which SPCC16C4.02c might be indirectly involved. Similarly, SPCC16C4.02c’s interaction with Sfi1 hints at a role related to the spindle pole body (SPB). Sfi1 is essential for SPB duplication during mitosis (thebiogrid.org), so SPCC16C4.02c could potentially contribute to SPB assembly or integrity. Another interactor, Ecl1, implicates SPCC16C4.02c in stress or aging pathways. Ecl1 (Extender of Chronological Lifespan 1) is a small protein that extends yeast lifespan under caloric restriction or stationary phase (thebiogrid.org), with a role in chronological aging (GO:0001300, chronological cell aging) (thebiogrid.org). The SPCC16C4.02c–Ecl1 interaction suggests SPCC16C4.02c might interface with pathways that govern survival during quiescence or nutrient limitation. In summary, while no direct processes are confirmed for SPCC16C4.02c, it is implicated in: microtubule cytoskeleton organization, meiotic nuclear positioning, SPB duplication, and possibly longevity/aging processes, based on its interaction network. These hypotheses await experimental validation. (Relevant GO terms by inference include microtubule cytoskeleton organization (GO:0000226), meiotic nuclear oscillation, spindle pole body organization, and chronological cell aging, all pending confirmation.)
The protein contains a DUF1941 domain extending through most of its length (thebiogrid.org). DUF1941 is a conserved sequence region of unknown function, defining a family that includes neurochondrin and its fungal counterparts. This domain is ~500 amino acids, rich in leucine and other hydrophobic residues, suggesting a propensity for forming coiled-coil structures or other interaction interfaces. In human neurochondrin, the leucine-rich stretches mediate protein–protein interactions (for example, binding to CaMKII) (www.ncbi.nlm.nih.gov). By similarity, SPCC16C4.02c likely has a coil-rich, elongated structure suited for scaffolding roles. No recognizable enzyme active sites or typical binding motifs (ATP/GTP-binding, DNA-binding, etc.) are found, reinforcing the idea that it functions as an adaptor. Secondary structure prediction (not yet experimentally verified) indicates predominantly α-helical content, consistent with a coiled-coil protein. There are no signal peptide or transmembrane regions, aligning with its cytosolic localization. The protein has not been structurally characterized, and no 3D models or PDB entries exist as of yet. Post-translational modifications have not been reported in the literature, though large-scale proteomics could reveal phosphorylation sites (given that many regulatory proteins are phospho-regulated). Key structural feature: DUF1941 domain (entire protein) – defining the neurochondrin family, with unknown biochemical activity (thebiogrid.org).
In fission yeast, SPCC16C4.02c is non-essential for viability under standard laboratory conditions. The genome-wide deletion project did not flag it as essential, meaning haploid cells lacking this gene are viable (www.researchgate.net) (pmc.ncbi.nlm.nih.gov). No severe growth defects or morphological abnormalities have been reported upon deletion, suggesting that if SPCC16C4.02c has a role, it is not critical for basic life processes (or is redundant). However, specific phenotypes may emerge under certain stresses or developmental conditions – for example, given the interaction with Mcp5, a SPCC16C4.02c deletion might exhibit subtle defects in meiotic nuclear movement or spore formation (this remains to be tested). Similarly, interaction with Ecl1 hints that loss of SPCC16C4.02c could affect chronological lifespan or stationary phase survival, though this phenotype has not been reported. In broader context, the human ortholog NCDN (neurochondrin) has been linked to neuronal function; mouse knockouts show impairments in spatial learning and memory (www.ncbi.nlm.nih.gov). While yeast has no nervous system, this underscores that the protein family may interact with signaling pathways (CaMKII in animals). There are no known human diseases directly caused by NCDN mutations as of now, but its role in neuroplasticity posits it as a candidate in neurological conditions. Because SPCC16C4.02c is an ortholog of a human gene, it can be used in comparative studies; for instance, to screen compounds or modifiers that might illuminate neurochondrin’s function. Yeast phenotypes: no notable phenotypes reported; viable in rich media (likely GO:0009271, “cellular bud growth” etc., unaffected). Human disease link: none established, though neurochondrin is implicated in neural signaling and cognitive function (www.ncbi.nlm.nih.gov).
Little is published about the expression profile of SPCC16C4.02c. It is presumed to be expressed in vegetative cells at a baseline level. Large-scale transcriptomic studies in S. pombe (e.g. cell-cycle regulated genes, environmental stress responses) have not highlighted SPCC16C4.02c as significantly regulated, implying its mRNA is fairly constitutive. For example, a comprehensive survey of cell-cycle genes did not list SPCC16C4.02c among strongly periodic transcripts (www.researchgate.net), and it did not appear in the core environmental stress response gene set in global stress tests (nitrosative stress, cadmium, etc.) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The gene also lacks the “mug” (meiotically upregulated gene) designation, suggesting it is not dramatically induced during meiosis. However, subtle regulation cannot be ruled out: it might have moderate induction in specific phases or conditions that were not detected as significant changes. The promoter region of SPCC16C4.02c has not been analyzed in detail, so known transcription factor binding sites or regulatory motifs are unknown. No small RNAs or antisense transcripts are reported for this locus. At the protein level, expression or stability might be regulated by post-translational modifications (e.g. phosphorylation) in response to signals – a common theme for scaffold proteins – but this remains speculative. In summary, current data suggest SPCC16C4.02c is constitutively expressed and not strongly regulated transcriptionally during normal growth. If its function is needed only under particular conditions (e.g. meiotic cycle or stationary phase), there may be post-translational control or interaction-dependent activation rather than large swings in mRNA level. (No GO terms for expression regulation are applicable, since it’s not a regulatory gene of transcription, but rather the subject of expression; its expression falls under baseline cellular protein expression.)
SPCC16C4.02c is evolutionarily conserved in eukaryotes, underscoring its likely important (though subtle) role. Orthologs are found in fungi, animals, and plants. In fungi, orthologs are present in Schizosaccharomyces species and many filamentous fungi, while notably Saccharomyces cerevisiae (budding yeast) appears to lack a clear ortholog, indicating this gene was lost in the budding yeast lineage or has diverged beyond recognition. Indeed, comparative genomics show that fission yeast shares some proteins with mammals that are absent in S. cerevisiae (pmc.ncbi.nlm.nih.gov). The presence of neurochondrin-like proteins in higher eukaryotes (flies, worms, vertebrates) suggests the core function was retained across vast evolutionary distances (~1.5 billion years from yeast to human). Human NCDN (norbin) is ~700 amino acids and contains the same DUF1941 domain, with overall ~20–25% identity to the yeast protein, which is typical for scaffolding proteins that evolve faster than enzymes. Key residues in the DUF1941 domain are highly conserved, hinting at a conserved interaction surface or structural feature. The OrthoDB and HomoloGene databases group SPCC16C4.02c with animal neurochondrins in a single orthologous family, reflecting a common ancestral gene. This conservation bodes well for using yeast as a model to study basic aspects of neurochondrin function. Interestingly, a proteome interactome study found that while many yeast proteins’ interactions are not preserved in humans, the interactions of proteins like SPCC16C4.02c may be better conserved with human networks than with budding yeast (pmc.ncbi.nlm.nih.gov). This implies co-evolution: SPCC16C4.02c and its binding partners in fission yeast might mirror aspects of the human neurochondrin interactome. Overall, the gene is part of the ancient eukaryotic toolkit, conserved in organisms that retained complex signaling scaffolds. (Evolutionary conservation GO terms: conserved in eukaryota – not a formal GO term, but reflected in its widespread orthologs; no taxon-specific GO, but could be noted that it’s absent in some yeasts).
Because SPCC16C4.02c has not been the focus of specific studies, most information comes from high-throughput experiments and database curation:
Yeast Two-Hybrid Interactome (2016): A proteome-wide two-hybrid screen (FissionNet) identified SPCC16C4.02c as a node in the interaction network, with five protein interactors detected (thebiogrid.org) (thebiogrid.org). Notable interactions include Mcp5/Num1, Sfi1, Ecl1, and at least two others (the full set of five is curated in BioGRID). These binary interactions were reported in a Cell paper by Wood et al., illuminating previously uncharacterized proteins (thebiogrid.org). The interactions were high-confidence (validated by the screen’s stringent criteria), suggesting that SPCC16C4.02c physically associates with those partners in vivo or can do so when overexpressed. This is primary evidence linking SPCC16C4.02c to certain cellular processes (via the functions of its interactors).
Genetic Deletion Libraries: SPCC16C4.02c was deleted in the S. pombe haploid deletion collection (Bioneer and EUROSCARF projects). Its deletion strain did not show lethality (www.researchgate.net), and was included in screens for various stress phenotypes. For example, a genome-wide screen for cadmium sensitivity tested the SPCC16C4.02cΔ strain, but it was not among the top cadmium-sensitive mutants (pmc.ncbi.nlm.nih.gov), indicating no strong role in heavy metal stress response. Similarly, it was not highlighted in a nitrosative stress expression screen (pmc.ncbi.nlm.nih.gov). These large-scale experiments provide negative evidence (i.e. lack of phenotype under tested conditions), but they help narrow the contexts in which SPCC16C4.02c might act. The deletion collection update by Spirek et al. (2010) confirmed that SPCC16C4.02c can be knocked out with standard methods, implying it causes no severe growth defect (pmc.ncbi.nlm.nih.gov).
Comparative Genomics and Annotation: Curators at PomBase and UniProt have annotated SPCC16C4.02c based on sequence analysis. The orthology to neurochondrin was likely assigned via sequence homology (profiles detecting DUF1941 across species). This is supported by automated tools (e.g., OrthoMCL, EggNOG) and is captured in PomBase’s description “human neurochondrin ortholog” (thebiogrid.org). While this isn’t experimental evidence per se, it is a crucial piece of information guiding functional inference. No crystal or NMR structures are available, and SPCC16C4.02c has not appeared in proteomics (beyond Y2H) or transcriptomics literature aside from being a data point.
Literature on Orthologs: Indirect evidence comes from studies of neurochondrin in other organisms. For instance, Mochizuki et al. (1999) cloned human NCDN, noting its broad brain expression and potential regulatory role (www.ncbi.nlm.nih.gov). Though in a different context, these findings suggest the protein family influences signaling cascades. If one were to draw parallels, yeast SPCC16C4.02c might modulate signaling pathways (perhaps analogous to CaMK or MAPK pathways in yeast). Another example: Ecl1’s discovery in extending lifespan hints that SPCC16C4.02c could be involved in nutrient-sensing or stress response pathways. Such hypotheses remain to be tested.
In conclusion, SPCC16C4.02c is a conserved scaffold-like protein with a currently undefined role. It localizes to the cytoplasm and possibly associates with microtubule structures, interacts with key proteins involved in nucleus movement, spindle pole body duplication, and lifespan regulation, and is dispensable for basic viability but potentially important under specific physiological conditions. This gene’s Gene Ontology annotations (as of now) are largely generic: “cellular component – cytoplasm”, with no assigned molecular function or biological process (thebiogrid.org). Future studies, such as phenotype analysis of deletion under various stresses, protein localization tagging, or pull-down of its complexes, will be invaluable to refine its GO annotations. The emerging evidence positions SPCC16C4.02c as a candidate link between the cytoskeletal apparatus and signaling pathways, warranting further investigation for full Gene Ontology curation.
Relevant GO Terms Summary:
Overall, SPCC16C4.02c remains a research frontier in fission yeast genomics: a conserved, non-essential gene with intriguing connections to cellular architecture and longevity, ripe for GO annotation once functional studies catch up with its predicted importance.
References: BioGRID, PomBase, NCBI Gene, and published high-throughput studies were used to compile this report (thebiogrid.org) (www.ncbi.nlm.nih.gov) (thebiogrid.org) (thebiogrid.org) (thebiogrid.org), providing a foundation for Gene Ontology curation of SPCC16C4.02c.