SUN2 (SUN domain-containing protein 2, UNC-84B) is a type II integral membrane protein of the inner nuclear membrane and a core component of the LINC (linker of nucleoskeleton and cytoskeleton) complex. Its N-terminal nucleoplasmic domain binds A-type lamins, while its coiled-coil region trimerizes the C-terminal SUN domain in the perinuclear space, where each SUN2 trimer binds three KASH peptides of outer-nuclear-membrane nesprins (SYNE1-4, KASH5), with a conserved SUN-KASH disulfide stabilizing the complex under tension. By tethering nesprins, SUN2 transmits mechanical force between the cytoskeleton and the nuclear lamina, contributing to nuclear positioning, nuclear migration along actin (TAN lines) and microtubules, centrosome-nucleus coupling, and cellular mechanical stiffness. Acting redundantly with SUN1, it is required for interkinetic nuclear migration and nucleokinesis during cortical neurogenesis and neuronal migration, and it contributes to telomere attachment to the nuclear envelope in meiosis. SUN2 is widely expressed, with high levels in heart, lung and muscle.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Telomeric chromosome region, transferred from mouse Sun2 via Ensembl Compara; reflects the meiotic SUN-KASH5 attachment sites of telomeres at the nuclear envelope. Reason: SUN2 contributes (partially redundantly with SUN1) to attaching meiotic telomeres to the nuclear envelope, where it concentrates at telomere attachment sites. SUN2 itself is an inner nuclear membrane protein rather than a chromatin component, so this is a meiosis-specific, non-core location. Supporting Evidence: file:human/SUN2/SUN2-uniprot.txt Required for telomere attachment to nuclear envelope and gametogenesis. |
| GO:0000794 condensed nuclear chromosome | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Condensed nuclear chromosome, transferred from mouse by Ensembl Compara. Reason: SUN2 is an integral inner nuclear membrane protein. Its meiotic role is at telomere attachment sites on the nuclear envelope; describing it as a component of condensed chromosomes over-extends that association. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. file:human/SUN2/SUN2-uniprot.txt Required for telomere attachment to nuclear envelope and gametogenesis. |
| GO:0005515 protein binding | IPI PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: SUN2 luminal domain binds the KASH domains of nesprin-1, -2 and -3 (SYNE1/2/3), the defining LINC-complex interaction. Reason: The partner rows (SYNE1, SYNE2, SYNE3) represent SUN-KASH binding across the perinuclear space, which is the mechanism of SUN2's cytoskeleton-nuclear membrane anchor activity. GO has no KASH-domain-binding term; the informative MF is GO:0140444, which this same paper also supports by IDA. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 PMID:18396275 the disruption of endogenous LINC complexes affect cellular mechanical stiffness |
| GO:0005515 protein binding | IPI PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: SUN2 luminal domain binds the KASH domains of nesprin-1, -2 and -3 (SYNE1/2/3), the defining LINC-complex interaction. Reason: The partner rows (SYNE1, SYNE2, SYNE3) represent SUN-KASH binding across the perinuclear space, which is the mechanism of SUN2's cytoskeleton-nuclear membrane anchor activity. GO has no KASH-domain-binding term; the informative MF is GO:0140444, which this same paper also supports by IDA. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 PMID:18396275 the disruption of endogenous LINC complexes affect cellular mechanical stiffness |
| GO:0005515 protein binding | IPI PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: SUN2 luminal domain binds the KASH domains of nesprin-1, -2 and -3 (SYNE1/2/3), the defining LINC-complex interaction. Reason: The partner rows (SYNE1, SYNE2, SYNE3) represent SUN-KASH binding across the perinuclear space, which is the mechanism of SUN2's cytoskeleton-nuclear membrane anchor activity. GO has no KASH-domain-binding term; the informative MF is GO:0140444, which this same paper also supports by IDA. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 PMID:18396275 the disruption of endogenous LINC complexes affect cellular mechanical stiffness |
| GO:0005515 protein binding | IPI PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | MODIFY | Summary: SUN2 nucleoplasmic domain interactions with lamin A, emerin and short nesprin-2 isoforms at the inner nuclear membrane. Reason: The informative, well-supported activity in this paper is binding to A-type lamin, which is already captured by the lamin binding IDA from the same paper; emerin and nucleoplasmic nesprin-2 isoform binding have no informative MF term and are best represented through lamin binding and the LINC anchor function. Proposed replacements: lamin binding Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 PMID:19933576 we identify emerin and short nesprin-2 isoforms as novel nucleoplasmic binding partners of SUN1/2 |
| GO:0005515 protein binding | IPI PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | MODIFY | Summary: SUN2 nucleoplasmic domain interactions with lamin A, emerin and short nesprin-2 isoforms at the inner nuclear membrane. Reason: The informative, well-supported activity in this paper is binding to A-type lamin, which is already captured by the lamin binding IDA from the same paper; emerin and nucleoplasmic nesprin-2 isoform binding have no informative MF term and are best represented through lamin binding and the LINC anchor function. Proposed replacements: lamin binding Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 PMID:19933576 we identify emerin and short nesprin-2 isoforms as novel nucleoplasmic binding partners of SUN1/2 |
| GO:0005515 protein binding | IPI PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | MODIFY | Summary: SUN2 nucleoplasmic domain interactions with lamin A, emerin and short nesprin-2 isoforms at the inner nuclear membrane. Reason: The informative, well-supported activity in this paper is binding to A-type lamin, which is already captured by the lamin binding IDA from the same paper; emerin and nucleoplasmic nesprin-2 isoform binding have no informative MF term and are best represented through lamin binding and the LINC anchor function. Proposed replacements: lamin binding Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 PMID:19933576 we identify emerin and short nesprin-2 isoforms as novel nucleoplasmic binding partners of SUN1/2 |
| GO:0005515 protein binding | IPI PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | MODIFY | Summary: SUN2 nucleoplasmic domain interactions with lamin A, emerin and short nesprin-2 isoforms at the inner nuclear membrane. Reason: The informative, well-supported activity in this paper is binding to A-type lamin, which is already captured by the lamin binding IDA from the same paper; emerin and nucleoplasmic nesprin-2 isoform binding have no informative MF term and are best represented through lamin binding and the LINC anchor function. Proposed replacements: lamin binding Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 PMID:19933576 we identify emerin and short nesprin-2 isoforms as novel nucleoplasmic binding partners of SUN1/2 |
| GO:0005515 protein binding | IPI PMID:20551905 A classical NLS and the SUN domain contribute to the targeti... | REMOVE | Summary: Interactions of SUN2 with importin alpha (KPNA2) and coatomer (COPB1) that mediate its own targeting to the inner nuclear membrane. Reason: These partners are targeting machinery acting on SUN2 as cargo (a classical NLS read by importin, and an arginine motif for COPI retrieval). The interactions are real but GO:0005515 is uninformative and SUN2 performs no molecular function for these partners; the relevant biology is captured by the inner nuclear membrane localization annotations. Supporting Evidence: PMID:20551905 One such targeting element is a classical nuclear localization signal (cNLS) present in the N-terminal, nucleoplasmic domain of SUN2 PMID:20551905 a cluster of arginines that serves coatomer-mediated retrieval of SUN2 from the Golgi |
| GO:0005515 protein binding | IPI PMID:20551905 A classical NLS and the SUN domain contribute to the targeti... | REMOVE | Summary: Interactions of SUN2 with importin alpha (KPNA2) and coatomer (COPB1) that mediate its own targeting to the inner nuclear membrane. Reason: These partners are targeting machinery acting on SUN2 as cargo (a classical NLS read by importin, and an arginine motif for COPI retrieval). The interactions are real but GO:0005515 is uninformative and SUN2 performs no molecular function for these partners; the relevant biology is captured by the inner nuclear membrane localization annotations. Supporting Evidence: PMID:20551905 One such targeting element is a classical nuclear localization signal (cNLS) present in the N-terminal, nucleoplasmic domain of SUN2 PMID:20551905 a cluster of arginines that serves coatomer-mediated retrieval of SUN2 from the Golgi |
| GO:0005515 protein binding | IPI PMID:21391237 TMEM43 mutations in Emery-Dreifuss muscular dystrophy-relate... | REMOVE | Summary: SUN2 interacts with the nuclear membrane protein LUMA/TMEM43. Reason: Generic protein binding; the interaction with TMEM43 is reported but GO:0005515 is uninformative and no specific SUN2 activity towards TMEM43 is defined. Supporting Evidence: PMID:21391237 we demonstrated for the first time that LUMA can interact with another nuclear membrane protein, SUN2, in addition to emerin |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: High-throughput yeast two-hybrid interaction of SUN2 with RAB5A from a liver interactome screen. Reason: Generic protein binding from a high-throughput liver interactome screen. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (RAB5A) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. |
| GO:0005515 protein binding | IPI PMID:22555292 LINC complex alterations in DMD and EDMD/CMT fibroblasts. | REMOVE | Summary: Interactions of SUN2 with lamin A/C, COPB1 and nesprin-2 reported in a study of LINC complex alterations in patient fibroblasts (abstract only in cache). Reason: GO:0005515 is uninformative. The informative activities implied (SUN-nesprin anchoring and lamin binding) are already captured by GO:0140444 and GO:0005521 with direct evidence; removal does not dispute the reported interactions. Supporting Evidence: PMID:22555292 SUN proteins together with the Nesprins form the core of the LINC complex which connects the nucleus with the cytoskeleton |
| GO:0005515 protein binding | IPI PMID:22555292 LINC complex alterations in DMD and EDMD/CMT fibroblasts. | REMOVE | Summary: Interactions of SUN2 with lamin A/C, COPB1 and nesprin-2 reported in a study of LINC complex alterations in patient fibroblasts (abstract only in cache). Reason: GO:0005515 is uninformative. The informative activities implied (SUN-nesprin anchoring and lamin binding) are already captured by GO:0140444 and GO:0005521 with direct evidence; removal does not dispute the reported interactions. Supporting Evidence: PMID:22555292 SUN proteins together with the Nesprins form the core of the LINC complex which connects the nucleus with the cytoskeleton |
| GO:0005515 protein binding | IPI PMID:22555292 LINC complex alterations in DMD and EDMD/CMT fibroblasts. | REMOVE | Summary: Interactions of SUN2 with lamin A/C, COPB1 and nesprin-2 reported in a study of LINC complex alterations in patient fibroblasts (abstract only in cache). Reason: GO:0005515 is uninformative. The informative activities implied (SUN-nesprin anchoring and lamin binding) are already captured by GO:0140444 and GO:0005521 with direct evidence; removal does not dispute the reported interactions. Supporting Evidence: PMID:22555292 SUN proteins together with the Nesprins form the core of the LINC complex which connects the nucleus with the cytoskeleton |
| GO:0005515 protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | MODIFY | Summary: Crystal structures of the SUN2-KASH1/KASH2 complex: three KASH peptides bind grooves between adjacent SUN domains of a SUN2 trimer. Reason: The SYNE1/SYNE2 KASH binding shown structurally is the mechanism of SUN2's cytoskeleton-nuclear membrane anchor activity; replace uninformative protein binding with GO:0140444. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:22632968 The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. PMID:22632968 a disulfide between conserved cysteines on SUN and KASH covalently links both proteins |
| GO:0005515 protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | MODIFY | Summary: Crystal structures of the SUN2-KASH1/KASH2 complex: three KASH peptides bind grooves between adjacent SUN domains of a SUN2 trimer. Reason: The SYNE1/SYNE2 KASH binding shown structurally is the mechanism of SUN2's cytoskeleton-nuclear membrane anchor activity; replace uninformative protein binding with GO:0140444. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:22632968 The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. PMID:22632968 a disulfide between conserved cysteines on SUN and KASH covalently links both proteins |
| GO:0005515 protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | MODIFY | Summary: Crystal structures of the SUN2-KASH1/KASH2 complex: three KASH peptides bind grooves between adjacent SUN domains of a SUN2 trimer. Reason: The SYNE1/SYNE2 KASH binding shown structurally is the mechanism of SUN2's cytoskeleton-nuclear membrane anchor activity; replace uninformative protein binding with GO:0140444. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:22632968 The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. PMID:22632968 a disulfide between conserved cysteines on SUN and KASH covalently links both proteins |
| GO:0005515 protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | MODIFY | Summary: Crystal structures of the SUN2-KASH1/KASH2 complex: three KASH peptides bind grooves between adjacent SUN domains of a SUN2 trimer. Reason: The SYNE1/SYNE2 KASH binding shown structurally is the mechanism of SUN2's cytoskeleton-nuclear membrane anchor activity; replace uninformative protein binding with GO:0140444. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:22632968 The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. PMID:22632968 a disulfide between conserved cysteines on SUN and KASH covalently links both proteins |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput interaction of SUN2 with NRM. Reason: Generic protein binding from a proteome-scale yeast two-hybrid screen. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (NRM) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: High-throughput interaction of SUN2 with RAB5A. Reason: Generic protein binding from a high-throughput quantitative interactome (AP-MS). The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (RAB5A) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: High-throughput interaction of SUN2 with RAB5A. Reason: Generic protein binding from a high-throughput AP-MS interactome (BioPlex). The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (RAB5A) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | REMOVE | Summary: High-throughput interaction of SUN2 with EMD, SYNE2. Reason: Generic protein binding from a high-throughput interaction screen of interferon-stimulated genes. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (EMD, SYNE2) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | REMOVE | Summary: High-throughput interaction of SUN2 with EMD, SYNE2. Reason: Generic protein binding from a high-throughput interaction screen of interferon-stimulated genes. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (EMD, SYNE2) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: High-throughput interaction of SUN2 with RAB5A. Reason: Generic protein binding from a high-throughput proteomics study of EGFR network rewiring. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (RAB5A) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:32353859 A SARS-CoV-2 protein interaction map reveals targets for dru... | REMOVE | Summary: High-throughput interaction of SUN2 with the SARS-CoV-2 ORF3a protein. Reason: Generic protein binding from a SARS-CoV-2 protein interaction map. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (SARS-CoV-2 ORF3a) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. A viral-host contact does not inform on SUN2's normal function. |
| GO:0005515 protein binding | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | MODIFY | Summary: Crystal structures of human SUN2 bound to KASH peptides of nesprin-3, nesprin-4 and KASH5 (plus nesprin-1/2 partners). Reason: Structural SUN-KASH binding is the mechanism of the LINC anchor function; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33058875 we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5 |
| GO:0005515 protein binding | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | MODIFY | Summary: Crystal structures of human SUN2 bound to KASH peptides of nesprin-3, nesprin-4 and KASH5 (plus nesprin-1/2 partners). Reason: Structural SUN-KASH binding is the mechanism of the LINC anchor function; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33058875 we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5 |
| GO:0005515 protein binding | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | MODIFY | Summary: Crystal structures of human SUN2 bound to KASH peptides of nesprin-3, nesprin-4 and KASH5 (plus nesprin-1/2 partners). Reason: Structural SUN-KASH binding is the mechanism of the LINC anchor function; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33058875 we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5 |
| GO:0005515 protein binding | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | MODIFY | Summary: Crystal structures of human SUN2 bound to KASH peptides of nesprin-3, nesprin-4 and KASH5 (plus nesprin-1/2 partners). Reason: Structural SUN-KASH binding is the mechanism of the LINC anchor function; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33058875 we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5 |
| GO:0005515 protein binding | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | MODIFY | Summary: Crystal structures of human SUN2 bound to KASH peptides of nesprin-3, nesprin-4 and KASH5 (plus nesprin-1/2 partners). Reason: Structural SUN-KASH binding is the mechanism of the LINC anchor function; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33058875 we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5 |
| GO:0005515 protein binding | IPI PMID:33060197 Comparative host-coronavirus protein interaction networks re... | REMOVE | Summary: High-throughput interaction of SUN2 with the SARS-CoV-2 ORF3a protein. Reason: Generic protein binding from a comparative coronavirus-host interactome. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (SARS-CoV-2 ORF3a) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. A viral-host contact does not inform on SUN2's normal function. |
| GO:0005515 protein binding | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | MODIFY | Summary: SUN2-KASH 6:6 assemblies with nesprin-1, nesprin-4 and KASH5 established crystallographically and biophysically. Reason: SUN-KASH binding underlies the load-bearing nucleus-cytoskeleton linkage; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33393904 SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head PMID:33393904 enabling the coordinated transduction of large forces across the nuclear envelope |
| GO:0005515 protein binding | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | MODIFY | Summary: SUN2-KASH 6:6 assemblies with nesprin-1, nesprin-4 and KASH5 established crystallographically and biophysically. Reason: SUN-KASH binding underlies the load-bearing nucleus-cytoskeleton linkage; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33393904 SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head PMID:33393904 enabling the coordinated transduction of large forces across the nuclear envelope |
| GO:0005515 protein binding | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | MODIFY | Summary: SUN2-KASH 6:6 assemblies with nesprin-1, nesprin-4 and KASH5 established crystallographically and biophysically. Reason: SUN-KASH binding underlies the load-bearing nucleus-cytoskeleton linkage; GO:0140444 is the informative replacement for generic protein binding. Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33393904 SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head PMID:33393904 enabling the coordinated transduction of large forces across the nuclear envelope |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interaction of SUN2 with LMNA, RAB5A. Reason: Generic protein binding from a high-throughput dual proteome-scale interactome. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (LMNA, RAB5A) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: High-throughput interaction of SUN2 with LMNA, RAB5A. Reason: Generic protein binding from a high-throughput dual proteome-scale interactome. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (LMNA, RAB5A) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:35311970 Inner nuclear membrane protein TMEM201 maintains endothelial... | REMOVE | Summary: SUN2 co-immunoprecipitates with the inner nuclear membrane protein TMEM201 in endothelial cells. Reason: Generic protein binding; TMEM201 associates with the LINC complex but no specific SUN2 molecular function towards TMEM201 is defined. Uninformative for GO MF. Supporting Evidence: PMID:35311970 the N-terminal of TMEM201 interacted with the linker of nucleoskeleton and cytoskeleton complex |
| GO:0005515 protein binding | IPI PMID:36217030 A comprehensive SARS-CoV-2-human protein-protein interactome... | REMOVE | Summary: High-throughput interaction of SUN2 with the SARS-CoV-2 ORF3a protein. Reason: Generic protein binding from a SARS-CoV-2-human interactome. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (SARS-CoV-2 ORF3a) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. A viral-host contact does not inform on SUN2's normal function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interaction of SUN2 with RAB5A, SYNE2. Reason: Generic protein binding from a high-throughput multimodal cell map. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (RAB5A, SYNE2) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: High-throughput interaction of SUN2 with RAB5A, SYNE2. Reason: Generic protein binding from a high-throughput multimodal cell map. The reported interaction is not disputed, but GO:0005515 conveys no functional information and the partner (RAB5A, SYNE2) is not part of a characterized SUN2 activity that would justify a more specific molecular function term. Where the partner is a nesprin or lamin, the informative activity is already captured by GO:0140444 or GO:0005521 from low-throughput studies. |
| GO:0005521 lamin binding | IDA PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | ACCEPT | Summary: SUN2 binds lamin A through its nucleoplasmic domain, and lamin A is required for SUN2 nuclear envelope localization. Reason: Direct binding assays show SUN2-lamin A interaction; this links the LINC complex to the nuclear lamina and is the nucleoplasmic half of SUN2's bridging function. Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 |
| GO:0005635 nuclear envelope | EXP PMID:15082709 Sun2 is a novel mammalian inner nuclear membrane protein. | ACCEPT | Summary: SUN2 nuclear envelope localization shown with anti-Sun2 antibodies, tagged constructs and electron microscopy. Reason: Well established; SUN2 is a resident nuclear envelope (inner nuclear membrane) protein. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. PMID:15082709 In HeLa cells, Sun2 displays a nuclear rim-like pattern typical for a nuclear envelope protein. |
| GO:0005635 nuclear envelope | EXP PMID:17132086 Characterization of the structures involved in localization ... | ACCEPT | Summary: SUN2 nuclear envelope localization and mapping of a localization substructure. Reason: Consistent with extensive evidence that SUN2 resides in the nuclear envelope. Supporting Evidence: PMID:17132086 we characterized a nuclear envelope protein SUN2 and identified a substructure involved in its localization to the nuclear envelope |
| GO:0005635 nuclear envelope | EXP PMID:17724119 Functional association of Sun1 with nuclear pore complexes. | ACCEPT | Summary: SUN2 localizes to the nuclear envelope (distinct from SUN1 in not associating with nuclear pore complexes). Reason: Immunofluorescence and immuno-EM place SUN2 in the nuclear envelope. Supporting Evidence: PMID:17724119 Sun1 but not Sun2 is intimately associated with nuclear pore complexes PMID:17724119 Sun1 and 2 are A-type lamin-binding proteins that, in association with nesprins, form a link between the inner nuclear membranes (INMs) and outer nuclear membranes |
| GO:0005635 nuclear envelope | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear envelope, phylogenetically inferred for the SUN-domain family. Reason: SUN-domain proteins are nuclear envelope residents from yeast to human; SUN2 localization is experimentally confirmed. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. PMID:15082709 In HeLa cells, Sun2 displays a nuclear rim-like pattern typical for a nuclear envelope protein. |
| GO:0005635 nuclear envelope | IDA PMID:16380439 Coupling of the nucleus and cytoplasm: role of the LINC comp... | ACCEPT | Summary: SUN2 at the nuclear envelope where, with SUN1, it retains nesprin-2 Giant at the outer nuclear membrane. Reason: Direct localization evidence and functional role of SUN2 at the nuclear envelope. Supporting Evidence: PMID:16380439 both Sun1 and Sun2 contribute to nesp2G localization PMID:16380439 support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS |
| GO:0005635 nuclear envelope | IDA PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | ACCEPT | Summary: SUN2 nuclear envelope localization, dependent on lamin A. Reason: Direct localization evidence. Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 |
| GO:0005635 nuclear envelope | IDA PMID:21610090 Samp1 is functionally associated with the LINC complex and A... | ACCEPT | Summary: SUN2 colocalizes with Samp1 at the nuclear envelope; unlike SUN1, its organization is not disrupted by Samp1 mutants. Reason: A colocalizes_with nuclear envelope annotation is consistent with SUN2's established nuclear envelope residence. Supporting Evidence: PMID:21610090 but not lamin B, Sun2 or nucleoporins |
| GO:0005635 nuclear envelope | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear envelope from combined automated methods. Reason: Correct and consistent with experimental data. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. PMID:15082709 In HeLa cells, Sun2 displays a nuclear rim-like pattern typical for a nuclear envelope protein. |
| GO:0005635 nuclear envelope | TAS PMID:10375507 UNC-84 localizes to the nuclear envelope and is required for... | ACCEPT | Summary: Nuclear envelope, traceable author statement from the C. elegans UNC-84 paper. Reason: The cited paper characterizes the worm SUN ortholog UNC-84 at the nuclear envelope; the statement is correct for human SUN2 and is supported directly by later experiments. Supporting Evidence: PMID:10375507 UNC-84 is widely expressed and localized to the nuclear envelope PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. |
| GO:0005637 nuclear inner membrane | EXP PMID:15082709 Sun2 is a novel mammalian inner nuclear membrane protein. | ACCEPT | Summary: SUN2 is an inner nuclear membrane protein with its SUN domain in the perinuclear space. Reason: Primary experimental definition of SUN2 as a type II inner nuclear membrane protein; this is its core location. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. PMID:15082709 we show that the SUN domain of Sun2 is localized to the periplasmic space between the inner and the outer nuclear membranes |
| GO:0005637 nuclear inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Inner nuclear membrane from automated methods. Reason: Correct; matches experimental data. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. |
| GO:0007052 mitotic spindle organization | TAS PMID:10375507 UNC-84 localizes to the nuclear envelope and is required for... | REMOVE | Summary: Mitotic spindle organization, author statement from the C. elegans UNC-84 paper. Reason: The cited paper concerns worm UNC-84 in nuclear migration and anchorage and notes similarity to the fission yeast spindle pole body protein Sad1; it provides no evidence that SUN2 organizes the mitotic spindle. No direct evidence for SUN2 in spindle organization was identified. Supporting Evidence: PMID:10375507 a C-terminal region with similarity to the S. pombe spindle pole body protein Sad1 |
| GO:0007097 nuclear migration | TAS PMID:10508607 The missing (L) UNC? | ACCEPT | Summary: Nuclear migration, author statement from a review of UNC-84 function. Reason: SUN2 (redundantly with SUN1) couples the nucleus to the centrosome and motors for nuclear migration, as shown in mouse neurogenesis and neuronal migration. Supporting Evidence: PMID:10508607 the recently characterised UNC84 protein appears to be involved PMID:19874786 We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. PMID:19874786 These results indicate that SUN1, SUN2 and Syne-2 play essential roles in nucleokinesis, likely through coupling the centrosome to the nucleus and transducing the pulling force from the microtubule network to the nucleus. |
| GO:0008017 microtubule binding | TAS PMID:10375507 UNC-84 localizes to the nuclear envelope and is required for... | REMOVE | Summary: Microtubule binding, author statement from the C. elegans UNC-84 paper. Reason: SUN2 does not bind microtubules directly: its SUN domain is in the perinuclear space and its N-terminus in the nucleoplasm. Coupling to microtubules is indirect, through KASH nesprins and their dynein/kinesin adaptors. The cited worm paper does not show microtubule binding. Supporting Evidence: PMID:15082709 we show that the SUN domain of Sun2 is localized to the periplasmic space between the inner and the outer nuclear membranes PMID:19874786 Syne-2 is connected to the centrosome through interactions with both dynein/dynactin and kinesin complexes. |
| GO:0010008 endosome membrane | EXP PMID:10818110 A novel membrane-anchored Rab5 interacting protein required ... | MARK AS OVER ANNOTATED | Summary: Endosome membrane localization of overexpressed rab5ip/SUN2. Reason: The endosomal localization derives from overexpressed rab5ip (SUN2) in the original rab5-interactor study. Endogenous SUN2 detected with specific antibodies is a nuclear envelope/inner nuclear membrane protein, and the endosomal role has not been substantiated since. Not removed because the full text is unavailable, but this is not a meaningful representation of SUN2 location. Supporting Evidence: PMID:10818110 localized extensively with GFP-rab5(wt) in punctate endosome-like structures PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Endosome membrane from the UniProt subcellular location mapping. Reason: The endosomal localization derives from overexpressed rab5ip (SUN2) in the original rab5-interactor study. Endogenous SUN2 detected with specific antibodies is a nuclear envelope/inner nuclear membrane protein, and the endosomal role has not been substantiated since. Not removed because the full text is unavailable, but this is not a meaningful representation of SUN2 location. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. |
| GO:0021817 nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration | IEA GO_REF:0000107 | ACCEPT | Summary: Nucleokinesis in radial glia-guided cortical migration, transferred from mouse Sun2. Reason: Mouse Sun1/Sun2 double knockouts show that SUN proteins are required, redundantly, for nucleokinesis and centrosome-nucleus coupling in radially migrating cortical neurons. SUN2 participates structurally by anchoring the nesprin-motor complex that pulls the nucleus. Supporting Evidence: PMID:19874786 We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. PMID:19874786 These results indicate that SUN1, SUN2 and Syne-2 play essential roles in nucleokinesis, likely through coupling the centrosome to the nucleus and transducing the pulling force from the microtubule network to the nucleus. PMID:19874786 These results indicate that SUN1 and SUN2 are essential and mutually redundant for the normal radial neuronal migration in the cerebral cortex. |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell migration, transferred from mouse. Reason: SUN2 participates in cell migration by physically coupling the nucleus to the cytoskeleton (captured by the nuclear migration and nucleokinesis terms); it is not a regulator that modulates migration rate. Positive regulation of cell migration is an indirect phenotype-based over-reach. Supporting Evidence: PMID:19874786 We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. |
| GO:0030335 positive regulation of cell migration | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell migration by sequence similarity to mouse Sun2. Reason: SUN2 participates in cell migration by physically coupling the nucleus to the cytoskeleton (captured by the nuclear migration and nucleokinesis terms); it is not a regulator that modulates migration rate. Positive regulation of cell migration is an indirect phenotype-based over-reach. Supporting Evidence: PMID:19874786 We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. |
| GO:0031022 nuclear migration along microfilament | IEA GO_REF:0000107 | ACCEPT | Summary: Nuclear migration along microfilaments via TAN lines, transferred from mouse. Reason: In migrating fibroblasts SUN2 and nesprin-2G assemble into transmembrane actin-associated nuclear (TAN) lines that couple the nucleus to retrograde actin flow, moving the nucleus rearward. Supporting Evidence: file:human/SUN2/SUN2-uniprot.txt in arrays of transmembrane actin-associated nuclear (TAN) lines which file:human/SUN2/SUN2-uniprot.txt flow during actin-dependent nuclear movement. |
| GO:0031022 nuclear migration along microfilament | ISS GO_REF:0000024 | ACCEPT | Summary: Nuclear migration along microfilaments by similarity to mouse Sun2 (TAN lines). Reason: SUN2 is a TAN-line component coupling the nucleus to moving actin cables. Supporting Evidence: file:human/SUN2/SUN2-uniprot.txt in arrays of transmembrane actin-associated nuclear (TAN) lines which file:human/SUN2/SUN2-uniprot.txt flow during actin-dependent nuclear movement. |
| GO:0031965 nuclear membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Nuclear membrane localization from Human Protein Atlas immunofluorescence. Reason: Consistent with SUN2 as an inner nuclear membrane protein. Supporting Evidence: PMID:15082709 From our data, we conclude that Sun2 is a new mammalian inner nuclear membrane protein. |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IBA GO_REF:0000033 | MODIFY | Summary: Meiotic LINC complex, phylogenetically inferred for SUN-domain proteins. Reason: SUN2 forms LINC complexes with KASH5 in meiocytes and contributes, partially redundantly with SUN1, to telomere attachment to the nuclear envelope. However most SUN2 function is in somatic LINC complexes, which GO represents by the non-meiotic parent GO:0106094. The IBA is correct for the meiotic role, but the non-meiotic parent GO:0106094 covers both somatic and meiotic SUN2 LINC complexes and better represents SUN2. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000308197 SUPPORTS TRANSFER Ancestral SUN node carrying the meiotic LINC complex IBD; seeded by meiotic SUN/KASH evidence (e.g. fission yeast Sad1, mouse Sun1). SUN2 is inside the clade and does form meiotic KASH5 complexes, so the transfer is sound; the issue is only that the meiotic child term under-represents SUN2's predominantly somatic LINC function. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: file:human/SUN2/SUN2-uniprot.txt Required for telomere attachment to nuclear envelope and gametogenesis. PMID:33058875 we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5 |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IDA PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: SUN2-nesprin (KASH) complexes in somatic cultured cells. Reason: The experiment characterizes somatic LINC complexes (nesprin-1/2/3 with SUN1/SUN2) that underlie cellular mechanical stiffness, not meiotic complexes. The appropriate complex term is the non-meiotic parent GO:0106094 nuclear membrane microtubule tethering complex. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 PMID:18396275 the disruption of endogenous LINC complexes affect cellular mechanical stiffness |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IEA GO_REF:0000117 | MODIFY | Summary: Meiotic LINC complex from ARBA. Reason: SUN2 forms LINC complexes with KASH5 in meiocytes and contributes, partially redundantly with SUN1, to telomere attachment to the nuclear envelope. However most SUN2 function is in somatic LINC complexes, which GO represents by the non-meiotic parent GO:0106094. Replace with GO:0106094, which covers both contexts. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: file:human/SUN2/SUN2-uniprot.txt Required for telomere attachment to nuclear envelope and gametogenesis. |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | MODIFY | Summary: Crystal structure of SUN2 with nesprin-1/2 KASH peptides. Reason: SUN2-KASH1/2 is the core of the somatic LINC complex; there is nothing meiosis-specific in the evidence. Use GO:0106094. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: PMID:22632968 The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | MODIFY | Summary: Crystal structures of SUN2 with KASH peptides including KASH5, the meiotic KASH protein. Reason: The SUN2-KASH5 structure supports a meiotic-type LINC complex, but the same study covers somatic nesprin-3/4 partners; the non-meiotic parent GO:0106094 represents all of these SUN2 LINC complexes. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: PMID:33058875 we solved high resolution crystal structures of human SUN2 in complex with the KASH-peptides of Nesprin3, Nesprin4, and KASH5 |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | MODIFY | Summary: SUN2-KASH 6:6 assemblies including KASH5. Reason: The assemblies include somatic nesprin-1/4 as well as meiotic KASH5 partners; the non-meiotic parent GO:0106094 represents all of these SUN2 LINC complexes. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: PMID:33393904 SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head |
| GO:0042802 identical protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | KEEP AS NON CORE | Summary: SUN2 self-association into a trimer, prerequisite for KASH binding. Reason: SUN2 homotrimerization via its coiled coil is structurally required for LINC complex formation; identical protein binding is correct but describes a structural prerequisite rather than the core activity. Supporting Evidence: PMID:22632968 The SUN2 domain is rigidly attached to a trimeric coiled coil that prepositions it to bind three KASH peptides. |
| GO:0042802 identical protein binding | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | KEEP AS NON CORE | Summary: SUN2 self-association (trimeric SUN domain; possible self-locked state). Reason: Correct but a structural prerequisite for the anchor activity rather than the core function. Supporting Evidence: PMID:33058875 a possible self-locked state for unbound SUN |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-membrane adaptor activity, phylogenetically inferred for the SUN-domain family. Reason: SUN proteins retain KASH proteins in the outer nuclear membrane and link them to the lamina; GO:0043495 is the direct parent of the more specific GO:0140444 cytoskeleton-nuclear membrane anchor activity, which SUN2 also carries by IDA. The IBA is correct at the family level. Supporting Evidence: PMID:16380439 support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 |
| GO:0051642 centrosome localization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Centrosome localization, transferred from mouse Sun2. Reason: SUN1/SUN2 double-mutant mouse brains show centrosome-nucleus uncoupling, so SUN2 contributes to keeping the centrosome close to the nucleus. This is a consequence of its LINC anchor function rather than a dedicated centrosome-positioning activity, so kept as non-core. Supporting Evidence: PMID:19874786 We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. |
| GO:0051642 centrosome localization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Centrosome localization by similarity to mouse Sun2. Reason: SUN1/SUN2 double-mutant mouse brains show centrosome-nucleus uncoupling, so SUN2 contributes to keeping the centrosome close to the nucleus. This is a consequence of its LINC anchor function rather than a dedicated centrosome-positioning activity, so kept as non-core. Supporting Evidence: PMID:19874786 We show that SUN1 and SUN2 redundantly form complexes with Syne-2 to mediate the centrosome-nucleus coupling during both INM and radial neuronal migration in the cerebral cortex. |
| GO:0090292 nuclear matrix anchoring at nuclear membrane | IDA PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | ACCEPT | Summary: SUN2 links the nuclear lamina to the inner nuclear membrane through lamin A binding. Reason: SUN2 binds lamin A and depends on it for nuclear envelope retention, forming the lamina-anchoring half of the LINC bridge. Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 |
| GO:0090292 nuclear matrix anchoring at nuclear membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Nuclear matrix anchoring at nuclear membrane from ARBA. Reason: Consistent with experimental lamin A binding. Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 |
| GO:0140444 cytoskeleton-nuclear membrane anchor activity | IDA PMID:18396275 Structural requirements for the assembly of LINC complexes a... | ACCEPT | Summary: SUN2 luminal domains bind nesprin KASH domains to hold nesprins, and thereby cytoskeletal attachments, at the nuclear envelope. Reason: Core molecular function. Dominant-negative SUN/KASH constructs displace endogenous nesprins and reduce cellular mechanical stiffness, showing that SUN-KASH binding anchors cytoskeleton-linked nesprins to the nuclear membrane. Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 PMID:18396275 These constructs disrupt endogenous LINC complexes as indicated by the displacement of endogenous Nesprins from the nuclear envelope. PMID:18396275 the disruption of endogenous LINC complexes affect cellular mechanical stiffness |
| GO:0140444 cytoskeleton-nuclear membrane anchor activity | IEA GO_REF:0000117 | ACCEPT | Summary: Cytoskeleton-nuclear membrane anchor activity from ARBA. Reason: Matches the experimentally supported core function. Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 PMID:16380439 support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS |
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Download this section (compressed HTML)Q: Should the SUN2-KASH structural IPI/IDA rows currently annotated to the meiotic LINC complex term (GO:0034993) be moved to the non-meiotic parent GO:0106094, given that the evidence concerns somatic nesprin-1/2/3 complexes?
Suggested experts: GO cellular component editors, LINC complex structural biologists
Q: Is there any evidence for endogenous SUN2 on endosomes, or is the rab5ip endosomal localization an overexpression artifact?
Suggested experts: nuclear envelope cell biologists
Experiment: Neuron-specific SUN2 single knockout (on a SUN1-null background with inducible rescue) combined with live imaging of nucleokinesis, to separate SUN2-specific contributions from SUN1 redundancy in migrating cortical and cerebellar neurons.
Type: genetic perturbation with live imaging
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