SUN-1 (matefin, MTF-1) is a C. elegans SUN-domain protein of the inner nuclear membrane, a type II membrane protein with a nucleoplasmic N-terminus and a luminal C-terminal region that contains the SUN domain. SUN-1 binds the divergent short KASH domain of the Hook-family protein ZYG-12 in the perinuclear space (through a luminal region outside the canonical SUN domain) and retains ZYG-12 in the outer nuclear membrane. In early embryos the SUN-1/ZYG-12 bridge, with dynein, attaches centrosomes to the nuclear envelope, which is essential for normal spindles and embryonic viability; SUN-1 also anchors telomeres at the nuclear periphery in embryos together with the shelterin protein POT-1. In the germline, SUN-1/ZYG-12 complexes gather into mobile patches at the nuclear envelope where the chromosomal pairing centers attach, and connect them to cytoplasmic microtubules and dynein. The resulting chromosome movements drive homolog pairing and prevent nonhomologous synapsis. CHK-2-dependent phosphorylation of the SUN-1 nucleoplasmic domain in leptotene/zygotene regulates this program. SUN-1 is also reported to bind the apoptosis protein CED-4 and to be required for its translocation to the nuclear envelope during apoptosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:16938876 Matefin/SUN-1 is a nuclear envelope receptor for CED-4 durin... | MODIFY | Summary: SUN-1 binds the apoptosis regulator CED-4 and is required to retain it at the nuclear envelope. Reason: Generic protein binding is uninformative. The paper describes SUN-1 as the nuclear-envelope receptor for CED-4, i.e. a membrane protein that recruits a soluble protein to the nuclear membrane, which is the definition of GO:0043495 protein-membrane adaptor activity (already assigned to SUN-1 by IBA). This is a single-study, non-core function. Proposed replacements: protein-membrane adaptor activity Supporting Evidence: PMID:16938876 Our data demonstrate that matefin/SUN-1 binds CED-4 and is specifically required for CED-4 translocation and maintenance at the NE. |
| GO:0005515 protein binding | IPI PMID:19759181 SUN-1 and ZYG-12, mediators of centrosome-nucleus attachment... | MODIFY | Summary: SUN-1 binds the ZYG-12 mini-KASH domain in the perinuclear space. Reason: This is the SUN-KASH interaction that holds ZYG-12 in the outer nuclear membrane; replace generic protein binding with GO:0140444 cytoskeleton-nuclear membrane anchor activity, as for the human SUN reviews. Notably the ZYG-12-binding region of SUN-1 lies outside the SUN domain. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:19759181 The proteins interact in the luminal space of the nuclear envelope via the ZYG-12 mini KASH domain and a region of SUN-1 that does not include the SUN domain. |
| GO:0005635 nuclear envelope | EXP PMID:24297748 The shelterin protein POT-1 anchors Caenorhabditis elegans t... | ACCEPT | Summary: SUN-1 at the nuclear envelope in embryos. Reason: Consistent with all SUN-1 localization data. Supporting Evidence: PMID:24297748 Telomere position in early embryos required the NE protein SUN-1 |
| GO:0005635 nuclear envelope | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear envelope, PAINT inference for SUN proteins. Reason: Correct; experimentally confirmed. |
| GO:0005635 nuclear envelope | IDA PMID:17543861 The nuclear envelope protein Matefin/SUN-1 is required for h... | ACCEPT | Summary: SUN-1 at the nuclear envelope of germline nuclei. Reason: Correct. Supporting Evidence: PMID:17543861 Caenorhabditis elegans nuclear envelope protein matefin MTF-1/SUN-1 |
| GO:0005635 nuclear envelope | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear envelope from UniProt subcellular location. Reason: Correct. |
| GO:0005635 nuclear envelope | ISS PMID:14697201 The C. elegans hook protein, ZYG-12, mediates the essential ... | ACCEPT | Summary: Nuclear envelope, by similarity to UNC-84. Reason: Correct and experimentally confirmed by later work. Supporting Evidence: PMID:19759181 SUN-1 is a type II inner nuclear membrane protein |
| GO:0008104 intracellular protein localization | IMP PMID:14697201 The C. elegans hook protein, ZYG-12, mediates the essential ... | MODIFY | Summary: SUN-1 is required for ZYG-12 localization to the nuclear envelope. Reason: The general term is accurate but uninformative. SUN-1 localizes ZYG-12 specifically to the nuclear envelope (and is sufficient to do so in cells), which GO:0090435 protein localization to nuclear envelope captures. Proposed replacements: protein localization to nuclear envelope Supporting Evidence: PMID:14697201 localizes to both the nuclear envelope (via SUN-1) and centrosomes PMID:19759181 show that SUN-1 is sufficient to localize ZYG-12 in cells |
| GO:0009792 embryo development ending in birth or egg hatching | IMP PMID:14697201 The C. elegans hook protein, ZYG-12, mediates the essential ... | KEEP AS NON CORE | Summary: Embryonic lethality after loss of SUN-1. Reason: Lethality follows from centrosome detachment and spindle defects; the annotation records a consequence of the centrosome-nucleus attachment function. Supporting Evidence: PMID:14697201 Mutations in the zyg-12 gene of Caenorhabditis elegans perturb the attachment of the centrosome to the nucleus, giving rise to aberrant spindles and ultimately, DNA segregation defects and lethality. |
| GO:0010824 regulation of centrosome duplication | IGI PMID:17446307 Suppressors of zyg-1 define regulators of centrosome duplica... | KEEP AS NON CORE | Summary: sun-1 mutations suppress zyg-1, restoring centrosome duplication. Reason: Genetic suppressor evidence that SUN-1 influences centrosome duplication, separable from its attachment role. The mechanism is unknown and may be indirect, so it is retained as non-core. Supporting Evidence: PMID:17446307 We further show that the role of SUN-1 in centrosome duplication is distinct from its role in attachment. |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear membrane from UniProt subcellular location. Reason: Correct; inner nuclear membrane is more specific. |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IBA GO_REF:0000033 | ACCEPT | Summary: Meiotic nuclear membrane microtubule tethering complex, PAINT inference. Reason: Unlike UNC-84, SUN-1 is the C. elegans meiotic SUN protein: SUN-1/ZYG-12 complexes connect meiotic pairing centers to cytoplasmic microtubules and dynein. The PAINT placement is correct for this gene. Supporting Evidence: PMID:19913287 These connections through the intact nuclear envelope require the SUN/KASH domain protein pair SUN-1 and ZYG-12. |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-membrane adaptor activity, PAINT inference. Reason: SUN-1 retains ZYG-12 (and CED-4) at the nuclear envelope; a sound general parent of GO:0140444. Supporting Evidence: PMID:19759181 show that SUN-1 is sufficient to localize ZYG-12 in cells |
| GO:0051642 centrosome localization | IMP PMID:14697201 The C. elegans hook protein, ZYG-12, mediates the essential ... | ACCEPT | Summary: SUN-1 is required for attachment of centrosomes to the nucleus in embryos. Reason: Core embryonic function, via retention of ZYG-12 at the nuclear envelope. Supporting Evidence: PMID:14697201 We propose that dynein and ZYG-12 move the centrosomes toward the nucleus, followed by a ZYG-12/SUN-1-dependent anchorage. |
| GO:0007129 homologous chromosome pairing at meiosis | IMP PMID:17543861 The nuclear envelope protein Matefin/SUN-1 is required for h... | NEW | Summary: sun-1(jf18) abolishes presynaptic homolog alignment; SUN-1/ZYG-12 transmit microtubule forces to pairing centers. Reason: SUN-1 does part of the work of pairing: it is the inner-membrane half of the bridge that physically connects pairing centers to microtubules and dynein, and it aggregates at the chromosome attachment sites (structural participation, not only necessity). Comparator: the human KASH5 review and SUN1 review carry the equivalent meiotic chromosome movement/pairing terms, and GO:0007129 is annotated in C. elegans to structural pairing/synapsis proteins (HTP-3, SYP proteins). No GOA row currently records the defining meiotic function of SUN-1. Supporting Evidence: PMID:17543861 The reorganization of chromatin in early meiosis is disrupted in mtf-1/sun-1(jf18) gonads, concomitant with the absence of presynaptic homolog alignment. PMID:19913287 These connections through the intact nuclear envelope require the SUN/KASH domain protein pair SUN-1 and ZYG-12. PMID:19913286 They bridge the nuclear envelope, connecting the cytoplasm and the nucleoplasm to transmit forces that allow chromosome movement and homolog pairing and prevent nonhomologous synapsis. |
| GO:0005637 nuclear inner membrane | IDA PMID:19759181 SUN-1 and ZYG-12, mediators of centrosome-nucleus attachment... | NEW | Summary: Topology mapping shows SUN-1 is a type II inner nuclear membrane protein. Reason: Direct evidence for the defining location of SUN proteins; only broader nuclear envelope/membrane terms are currently annotated. Supporting Evidence: PMID:19759181 SUN-1 is a type II inner nuclear membrane protein |
| GO:0034398 telomere tethering at nuclear periphery | IMP PMID:24297748 The shelterin protein POT-1 anchors Caenorhabditis elegans t... | NEW | Summary: SUN-1 is required for perinuclear telomere position in early embryos, and targeted POT-1 anchors chromatin to the NE in a SUN-1-dependent manner. Reason: SUN-1 is the nuclear-envelope anchor to which POT-1-bound telomeres are tethered (structural participation). Limited to early embryos; postmitotic cells use other mechanisms. Supporting Evidence: PMID:24297748 Telomere position in early embryos required the NE protein SUN-1, the single-strand binding protein POT-1, and the small ubiquitin-like modifier (SUMO) ligase GEI-17. PMID:24297748 targeted POT-1 was sufficient to anchor chromatin to the NE in a SUN-1-dependent manner |
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Download this section (compressed HTML)Q: C. elegans meiosis attaches subtelomeric pairing centers rather than telomeres to the nuclear envelope. Is there a GO process term for meiotic pairing-center attachment to the nuclear envelope, analogous to GO:0070197 meiotic attachment of telomere to nuclear envelope, or should GO:0070197 be interpreted to include it?
Suggested experts: GO biological process editors, meiosis biologists
Q: Should SUN-1's reported role as the nuclear-envelope receptor for CED-4 during apoptosis (PMID:16938876) be captured by a process annotation, given that it rests on a single study?
Suggested experts: WormBase curators
Experiment: Structural analysis of the SUN-1-ZYG-12 luminal complex, which uses a SUN-1 region outside the canonical SUN domain and a mini-KASH peptide.
Hypothesis: The SUN-1-ZYG-12 interface differs from the canonical SUN2-KASH groove, explaining binding outside the SUN domain.
Type: structural biology
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