SUN1 (Sad1/UNC-84 domain protein 1) is a widely expressed type II integral protein of the inner nuclear membrane and a core component of LINC (linker of nucleoskeleton and cytoskeleton) complexes. Its nucleoplasmic N-terminal region binds A-type lamins (preferentially prelamin A), emerin and short nesprin-2 isoforms; a single transmembrane segment is followed by luminal coiled coils that trimerize and a C-terminal SUN domain in the perinuclear space. SUN domain trimers bind the C-terminal KASH peptides of outer-nuclear-membrane nesprins (nesprin-1 to -4, KASH5 and JAW1/LRMP), with a conserved interchain disulfide, and trimers can pair into 6:6 or larger assemblies. The resulting nuclear-envelope-spanning bridges transmit forces between the cytoskeleton and the nuclear lamina, supporting nuclear positioning and movement, centrosome-nucleus coupling and nucleokinesis during neurogenesis and radial neuronal migration (redundantly with SUN2), nuclear mechanics and cell stiffness. In meiotic prophase, SUN1:KASH5 complexes attach telomeres to the nuclear envelope and couple them to dynein-driven chromosome movements required for homolog pairing and fertility. SUN1, unlike SUN2, is also associated with nuclear pore complexes and helps determine their distribution. SUN1 accumulation is implicated in the pathology of lamin A-related progeroid and dystrophic laminopathies.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000781 chromosome, telomeric region | IEA GO_REF:0000107 | ACCEPT | Summary: Chromosome, telomeric region (electronic ortholog projection from mouse Sun1). Reason: In meiotic prophase SUN1 concentrates at telomere attachment sites on the nuclear envelope, where SUN1:KASH5 complexes tether telomeres; mouse Sun1 loss disrupts telomere attachment. A meiosis-specific but well-established location. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC |
| GO:0001503 ossification | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ossification (electronic projection from rat). Reason: No evidence that SUN1 performs a function in bone formation; any skeletal phenotype would be an indirect consequence of general nuclear-envelope mechanics. |
| GO:0005515 protein binding | IPI PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: Protein binding with nesprin KASH domains (SYNE1/2/3); KASH domains of nesprins 1-3 bind the luminal domains of Sun1 and Sun2. Reason: Generic protein binding is uninformative. The partner is a KASH-domain protein, and binding of KASH peptides by the luminal SUN domain trimer is precisely how SUN1 bridges the inner nuclear membrane to cytoskeleton-coupled nesprins; GO:0140444 cytoskeleton-nuclear membrane anchor activity captures that function. (No KASH-domain-binding MF term exists in GO.) 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 |
| GO:0005515 protein binding | IPI PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: Protein binding with nesprin KASH domains (SYNE1/2/3); KASH domains of nesprins 1-3 bind the luminal domains of Sun1 and Sun2. Reason: Generic protein binding is uninformative. The partner is a KASH-domain protein, and binding of KASH peptides by the luminal SUN domain trimer is precisely how SUN1 bridges the inner nuclear membrane to cytoskeleton-coupled nesprins; GO:0140444 cytoskeleton-nuclear membrane anchor activity captures that function. (No KASH-domain-binding MF term exists in GO.) 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 |
| GO:0005515 protein binding | IPI PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: Protein binding with nesprin KASH domains (SYNE1/2/3); KASH domains of nesprins 1-3 bind the luminal domains of Sun1 and Sun2. Reason: Generic protein binding is uninformative. The partner is a KASH-domain protein, and binding of KASH peptides by the luminal SUN domain trimer is precisely how SUN1 bridges the inner nuclear membrane to cytoskeleton-coupled nesprins; GO:0140444 cytoskeleton-nuclear membrane anchor activity captures that function. (No KASH-domain-binding MF term exists in GO.) 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 |
| GO:0005515 protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | REMOVE | Summary: Protein binding with nesprin-1/-2 from the SUN2-KASH1/2 crystal structure paper. Reason: GO:0005515 protein binding is uninformative. The interaction is not disputed, but generic protein binding does not describe what SUN1 does; removal does not imply the interaction is false. In the cached full text the structures and binding experiments are of SUN2; SUN1 appears only in background. SUN1-KASH binding is captured by other rows (PMID:18396275, PMID:33393904). Supporting Evidence: PMID:22632968 We present crystal structures of the human SUN2-KASH1/2 complex PMID:22632968 LINC formation relies on direct binding of KASH and SUN in the perinuclear space |
| GO:0005515 protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | REMOVE | Summary: Protein binding with nesprin-1/-2 from the SUN2-KASH1/2 crystal structure paper. Reason: GO:0005515 protein binding is uninformative. The interaction is not disputed, but generic protein binding does not describe what SUN1 does; removal does not imply the interaction is false. In the cached full text the structures and binding experiments are of SUN2; SUN1 appears only in background. SUN1-KASH binding is captured by other rows (PMID:18396275, PMID:33393904). Supporting Evidence: PMID:22632968 We present crystal structures of the human SUN2-KASH1/2 complex PMID:22632968 LINC formation relies on direct binding of KASH and SUN in the perinuclear space |
| GO:0005515 protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | REMOVE | Summary: Protein binding with nesprin-1/-2 from the SUN2-KASH1/2 crystal structure paper. Reason: GO:0005515 protein binding is uninformative. The interaction is not disputed, but generic protein binding does not describe what SUN1 does; removal does not imply the interaction is false. In the cached full text the structures and binding experiments are of SUN2; SUN1 appears only in background. SUN1-KASH binding is captured by other rows (PMID:18396275, PMID:33393904). Supporting Evidence: PMID:22632968 We present crystal structures of the human SUN2-KASH1/2 complex PMID:22632968 LINC formation relies on direct binding of KASH and SUN in the perinuclear space |
| GO:0005515 protein binding | IPI PMID:24375709 Contribution of SUN1 mutations to the pathomechanism in musc... | MODIFY | Summary: Protein binding with lamin A/C; muscular-dystrophy SUN1 variants show reduced lamin A/C interaction. Reason: Generic protein binding is uninformative. The nucleoplasmic N-terminus of SUN1 binds A-type lamins, captured by GO:0005521 lamin binding. Proposed replacements: lamin binding Supporting Evidence: PMID:24375709 SUN1 of both patient fibroblasts exhibited reduced interaction with Lamin A/C PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 file:human/SUN1/SUN1-uniprot.txt complexes. Interacts with A-type lamin with a strong preference for |
| GO:0005515 protein binding | IPI PMID:28716842 Outer nuclear membrane protein Kuduk modulates the LINC comp... | REMOVE | Summary: Protein binding with TMEM258 (orthologue of Drosophila Kuduk), a LINC-associated outer nuclear membrane protein. Reason: GO:0005515 protein binding is uninformative. The interaction is not disputed, but generic protein binding does not describe what SUN1 does; removal does not imply the interaction is false. Supporting Evidence: PMID:28716842 We also found an association between TMEM258 and the SUN protein SUN1 |
| GO:0005515 protein binding | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | MODIFY | Summary: Protein binding with KASH proteins (nesprin-4, KASH5, nesprin-1) from crystal structures of SUN1-KASH 6:6 complexes. Reason: Generic protein binding is uninformative. The partner is a KASH-domain protein, and binding of KASH peptides by the luminal SUN domain trimer is precisely how SUN1 bridges the inner nuclear membrane to cytoskeleton-coupled nesprins; GO:0140444 cytoskeleton-nuclear membrane anchor activity captures that function. (No KASH-domain-binding MF term exists in GO.) Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33393904 SUN1-KASH4, SUN1-KASH5, and SUN1-KASH1 form 6:6 complexes in solution PMID:33393904 we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head |
| GO:0005515 protein binding | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | MODIFY | Summary: Protein binding with KASH proteins (nesprin-4, KASH5, nesprin-1) from crystal structures of SUN1-KASH 6:6 complexes. Reason: Generic protein binding is uninformative. The partner is a KASH-domain protein, and binding of KASH peptides by the luminal SUN domain trimer is precisely how SUN1 bridges the inner nuclear membrane to cytoskeleton-coupled nesprins; GO:0140444 cytoskeleton-nuclear membrane anchor activity captures that function. (No KASH-domain-binding MF term exists in GO.) Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33393904 SUN1-KASH4, SUN1-KASH5, and SUN1-KASH1 form 6:6 complexes in solution PMID:33393904 we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head |
| GO:0005515 protein binding | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | MODIFY | Summary: Protein binding with KASH proteins (nesprin-4, KASH5, nesprin-1) from crystal structures of SUN1-KASH 6:6 complexes. Reason: Generic protein binding is uninformative. The partner is a KASH-domain protein, and binding of KASH peptides by the luminal SUN domain trimer is precisely how SUN1 bridges the inner nuclear membrane to cytoskeleton-coupled nesprins; GO:0140444 cytoskeleton-nuclear membrane anchor activity captures that function. (No KASH-domain-binding MF term exists in GO.) Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:33393904 SUN1-KASH4, SUN1-KASH5, and SUN1-KASH1 form 6:6 complexes in solution PMID:33393904 we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding with lamin A from BioPlex high-throughput AP-MS. Reason: GO:0005515 protein binding is uninformative. The interaction is not disputed, but generic protein binding does not describe what SUN1 does; removal does not imply the interaction is false. The lamin interaction is captured by lamin binding rows. |
| GO:0005515 protein binding | IPI PMID:38291267 The crystal structure of SUN1-KASH6 reveals an asymmetric LI... | MODIFY | Summary: Protein binding with JAW1/LRMP (IRAG2, KASH6) from the SUN1-KASH6 crystal structure. Reason: Generic protein binding is uninformative. The partner is a KASH-domain protein, and binding of KASH peptides by the luminal SUN domain trimer is precisely how SUN1 bridges the inner nuclear membrane to cytoskeleton-coupled nesprins; GO:0140444 cytoskeleton-nuclear membrane anchor activity captures that function. (No KASH-domain-binding MF term exists in GO.) Proposed replacements: cytoskeleton-nuclear membrane anchor activity Supporting Evidence: PMID:38291267 we report the crystal structure of the SUN-KASH complex between SUN1 and JAW1/LRMP (KASH6) in an asymmetric 9:6 configuration |
| GO:0005521 lamin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Lamin binding (electronic ortholog projection). Reason: SUN1 binds A-type lamins, with preference for unprocessed prelamin A, via its nucleoplasmic N-terminus; this anchors the LINC complex to the nuclear lamina. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt complexes. Interacts with A-type lamin with a strong preference for PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 |
| GO:0005634 nucleus | IEA GO_REF:0000107 | ACCEPT | Summary: Nucleus (electronic). Reason: Correct but general; SUN1 is an inner nuclear membrane protein. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt Nucleus inner membrane |
| GO:0005635 nuclear envelope | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear envelope (IBA). Reason: SUN1 is a type II integral inner nuclear membrane protein of the nuclear envelope. Supporting Evidence: PMID:17724119 Topological analyses indicate that Sun1 is a type II integral protein of the INM file:human/SUN1/SUN1-uniprot.txt Nucleus inner membrane |
| GO:0005635 nuclear envelope | IDA PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | ACCEPT | Summary: Nuclear envelope (IDA). Reason: SUN1 is a type II integral inner nuclear membrane protein of the nuclear envelope. 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 | IEA GO_REF:0000107 | ACCEPT | Summary: Nuclear envelope (electronic). Reason: SUN1 is a type II integral inner nuclear membrane protein of the nuclear envelope. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt Nucleus inner membrane |
| GO:0005635 nuclear envelope | IMP PMID:21610090 Samp1 is functionally associated with the LINC complex and A... | ACCEPT | Summary: Colocalizes with nuclear envelope (IMP) in the Samp1 study. Reason: SUN1 is a type II integral inner nuclear membrane protein of the nuclear envelope. Samp1 partially colocalizes with SUN1 in the nuclear envelope. Supporting Evidence: PMID:21610090 it partially colocalizes with the LINC complex protein Sun1 |
| GO:0005637 nuclear inner membrane | EXP PMID:17132086 Characterization of the structures involved in localization ... | ACCEPT | Summary: Nuclear inner membrane (EXP). Reason: SUN1 is a type II integral protein of the inner nuclear membrane, with its SUN domain in the perinuclear space; this is its core location. Supporting Evidence: PMID:17132086 We found that a structurally related protein, SUN1, may be localized to the nuclear envelope through a different mechanism file:human/SUN1/SUN1-uniprot.txt Nucleus inner membrane |
| GO:0005637 nuclear inner membrane | EXP PMID:18845190 Sun1 forms immobile macromolecular assemblies at the nuclear... | ACCEPT | Summary: Nuclear inner membrane (EXP): Sun1 forms immobile oligomeric assemblies in the nuclear envelope. Reason: SUN1 is a type II integral protein of the inner nuclear membrane, with its SUN domain in the perinuclear space; this is its core location. Supporting Evidence: PMID:18845190 we provide evidence that within the nuclear envelope (NE) Sun1 proteins form highly immobile oligomeric complexes in interphase cells |
| GO:0005637 nuclear inner membrane | EXP PMID:19933576 Mammalian SUN protein interaction networks at the inner nucl... | ACCEPT | Summary: Nuclear inner membrane (EXP). Reason: SUN1 is a type II integral protein of the inner nuclear membrane, with its SUN domain in the perinuclear space; this is its core location. Supporting Evidence: PMID:19933576 SUN1 and SUN2 interact with lamin A, but lamin A is only required for NE localization of SUN2 PMID:17724119 Topological analyses indicate that Sun1 is a type II integral protein of the INM |
| GO:0005637 nuclear inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear inner membrane (UniProt subcellular location mapping). Reason: SUN1 is a type II integral protein of the inner nuclear membrane, with its SUN domain in the perinuclear space; this is its core location. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt Nucleus inner membrane |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasm (electronic ortholog projection from mouse). Reason: SUN1 is an inner nuclear membrane protein; a cytoplasmic pool is seen only in special states such as oocyte meiosis after nuclear envelope breakdown, where it is found around the spindle. Minor, stage-specific location. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt Note=At oocyte MI stage localized around the |
| GO:0009612 response to mechanical stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to mechanical stimulus (electronic projection from rat). Reason: LINC complexes containing SUN1 transmit mechanical forces across the nuclear envelope and disruption reduces cellular stiffness, so a mechanoresponsive role is plausible; broad, downstream term. Supporting Evidence: PMID:18396275 We demonstrate that the disruption of endogenous LINC complexes affect cellular mechanical stiffness file:human/SUN1/SUN1-uniprot.txt important role in the transmission of mechanical forces across the |
| GO:0016020 membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Membrane (electronic). Reason: SUN1 is an integral membrane protein; correct but general. Supporting Evidence: PMID:17724119 Topological analyses indicate that Sun1 is a type II integral protein of the INM |
| GO:0021817 nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration | IEA GO_REF:0000107 | ACCEPT | Summary: Nucleokinesis involved in cell motility in cerebral cortex radial glia guided migration (electronic ortholog projection from mouse). Reason: In mouse cortex, SUN1 and SUN2 redundantly form LINC complexes with Syne-2 that couple the nucleus to centrosome-anchored dynein/kinesin during radial neuronal migration and interkinetic nuclear migration. SUN1 does part of the work as the inner-nuclear-membrane anchor that transmits motor force to 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 file:human/SUN1/SUN1-uniprot.txt essential for nucleokinesis and centrosome-nucleus coupling during |
| GO:0031965 nuclear membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Nuclear membrane (HPA immunofluorescence). Reason: SUN1 is a type II integral inner nuclear membrane protein of the nuclear envelope. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt Nucleus inner membrane |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IBA GO_REF:0000033 | ACCEPT | Summary: Meiotic nuclear membrane microtubule tethering complex (IBA). Reason: SUN1 forms SUN1:KASH5 LINC complexes that tether meiotic telomeres to dynein-driven microtubule forces; the PAINT node placement across SUN-domain orthologs (including fission yeast Sad1) is sound. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC file:human/SUN1/SUN1-uniprot.txt Core component of the LINC complex which is composed of inner |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IDA PMID:18396275 Structural requirements for the assembly of LINC complexes a... | MODIFY | Summary: Meiotic LINC complex (IDA) from disruption of somatic nesprin-SUN LINC complexes in fibroblasts. Reason: SUN1 is a core LINC complex subunit. GO:0034993 is restricted to the meiotic LINC complex; this evidence concerns somatic nesprin (KASH1-4/KASH6) complexes, so the non-meiotic parent GO:0106094 nuclear membrane microtubule tethering complex is the appropriate term. 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 We demonstrate that the disruption of endogenous LINC complexes affect cellular mechanical stiffness |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IEA GO_REF:0000117 | ACCEPT | Summary: Meiotic nuclear membrane microtubule tethering complex (ARBA electronic). Reason: Consistent with SUN1's meiotic telomere-tethering role. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | MODIFY | Summary: Meiotic LINC complex (IPI) from the SUN2-KASH1/2 crystal structure paper. Reason: SUN1 is a core LINC complex subunit. GO:0034993 is restricted to the meiotic LINC complex; this evidence concerns somatic nesprin (KASH1-4/KASH6) complexes, so the non-meiotic parent GO:0106094 nuclear membrane microtubule tethering complex is the appropriate term. The cached full text reports SUN2 structures; SUN1 membership of LINC complexes is itself well established. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: PMID:22632968 LINC formation relies on direct binding of KASH and SUN in the perinuclear space |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IPI PMID:33058875 Structural Analysis of Different LINC Complexes Reveals Dist... | MODIFY | Summary: Meiotic LINC complex (IPI) from SUN2 structures with nesprin-3, nesprin-4 and KASH5 peptides. Reason: SUN1 is a core LINC complex subunit. GO:0034993 is restricted to the meiotic LINC complex; this evidence concerns somatic nesprin (KASH1-4/KASH6) complexes, so the non-meiotic parent GO:0106094 nuclear membrane microtubule tethering complex is the appropriate term. The structures are of SUN2; the paper infers that SUN1 is likewise promiscuous. 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... | ACCEPT | Summary: Meiotic LINC complex (IPI): SUN1 forms 6:6 complexes with KASH1, KASH4 and the meiotic KASH5. Reason: Direct structural and biophysical evidence that SUN1 assembles with KASH5 (meiotic) as well as somatic nesprins; the meiotic complex term is supported by the SUN1-KASH5 data. Supporting Evidence: PMID:33393904 SUN1-KASH4, SUN1-KASH5, and SUN1-KASH1 form 6:6 complexes in solution PMID:33393904 we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head |
| GO:0034993 meiotic nuclear membrane microtubule tethering complex | IPI PMID:38291267 The crystal structure of SUN1-KASH6 reveals an asymmetric LI... | MODIFY | Summary: Meiotic LINC complex (IPI) from the SUN1-KASH6 (JAW1/LRMP) crystal structure. Reason: SUN1 is a core LINC complex subunit. GO:0034993 is restricted to the meiotic LINC complex; this evidence concerns somatic nesprin (KASH1-4/KASH6) complexes, so the non-meiotic parent GO:0106094 nuclear membrane microtubule tethering complex is the appropriate term. KASH6/JAW1 is a non-meiotic (lymphocyte/taste-cell) KASH protein. Proposed replacements: nuclear membrane microtubule tethering complex Supporting Evidence: PMID:38291267 we report the crystal structure of the SUN-KASH complex between SUN1 and JAW1/LRMP (KASH6) in an asymmetric 9:6 configuration |
| GO:0042802 identical protein binding | IPI PMID:22632968 LINC complexes form by binding of three KASH peptides to dom... | ACCEPT | Summary: Identical protein binding (IPI). Reason: SUN1 self-associates into trimers via luminal coiled coils, a prerequisite for KASH binding, and forms higher-order oligomers in the nuclear envelope. Supporting Evidence: PMID:18845190 we provide evidence that within the nuclear envelope (NE) Sun1 proteins form highly immobile oligomeric complexes in interphase cells PMID:18845190 Our data in particular underline the self-association properties of the C-terminal coiled-coil Sun1 segment |
| GO:0042802 identical protein binding | IPI PMID:33393904 A molecular mechanism for LINC complex branching by structur... | ACCEPT | Summary: Identical protein binding (IPI): SUN1 trimers pair head-to-head in 6:6 SUN-KASH assemblies. Reason: Self-association is integral to LINC architecture. Supporting Evidence: PMID:33393904 we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 complex in which two constituent 3:3 complexes interact head-to-head |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-membrane adaptor activity (IBA). Reason: Correct but more general parent of GO:0140444 cytoskeleton-nuclear membrane anchor activity; SUN proteins anchor KASH proteins (and hence cytoskeletal networks) at the nuclear envelope. Retained as a sound PAINT inference. Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 file:human/SUN1/SUN1-uniprot.txt As a component of the LINC (LInker of Nucleoskeleton and |
| GO:0051642 centrosome localization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Centrosome localization (electronic ortholog projection from mouse). Reason: SUN1/SUN2-nesprin complexes mediate centrosome-nucleus coupling in migrating neurons and progenitors; SUN1 contributes to keeping the centrosome close to the nucleus rather than positioning it directly. Retained 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 PMID:17132086 we provide evidence indicating that SUN1 and SUN2 may form a physical interaction between the nuclear envelope and the centrosome |
| GO:0070197 meiotic attachment of telomere to nuclear envelope | IEA GO_REF:0000107 | ACCEPT | Summary: Meiotic attachment of telomere to nuclear envelope (electronic ortholog projection from mouse). Reason: SUN1 is the inner nuclear membrane component of the SUN1:KASH5 bridge that attaches meiotic telomeres to the envelope; mouse Sun1 loss causes telomere detachment and infertility. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC |
| GO:0090292 nuclear matrix anchoring at nuclear membrane | IDA PMID:18396275 Structural requirements for the assembly of LINC complexes a... | ACCEPT | Summary: Nuclear matrix anchoring at nuclear membrane (IDA). Reason: The nucleoplasmic domain of SUN1 binds A-type lamins while its luminal SUN domain binds KASH proteins, linking the lamina to the nuclear membrane and cytoskeleton. Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 file:human/SUN1/SUN1-uniprot.txt As a component of the LINC (LInker of Nucleoskeleton and |
| GO:0090292 nuclear matrix anchoring at nuclear membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Nuclear matrix anchoring at nuclear membrane (ARBA electronic). Reason: As above. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt As a component of the LINC (LInker of Nucleoskeleton and file:human/SUN1/SUN1-uniprot.txt complexes. Interacts with A-type lamin with a strong preference for |
| GO:0140444 cytoskeleton-nuclear membrane anchor activity | IDA PMID:18396275 Structural requirements for the assembly of LINC complexes a... | ACCEPT | Summary: Cytoskeleton-nuclear membrane anchor activity (IDA): KASH domains of nesprins 1-3 bind Sun1 luminal domains and disruption of LINC complexes reduces cellular stiffness. Reason: This is the defining molecular function of SUN1: the SUN domain trimer binds KASH peptides of outer-membrane nesprins, anchoring cytoskeleton-coupled nesprins at the nuclear envelope. Supporting Evidence: PMID:18396275 the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2 PMID:18396275 We demonstrate that the disruption of endogenous LINC complexes affect cellular mechanical stiffness file:human/SUN1/SUN1-uniprot.txt As a component of the LINC (LInker of Nucleoskeleton and |
| GO:0140444 cytoskeleton-nuclear membrane anchor activity | IEA GO_REF:0000117 | ACCEPT | Summary: Cytoskeleton-nuclear membrane anchor activity (ARBA electronic). Reason: Correct core function. Supporting Evidence: file:human/SUN1/SUN1-uniprot.txt As a component of the LINC (LInker of Nucleoskeleton and |
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Download this section (compressed HTML)Q: Should SUN1 carry an annotation for nuclear pore complex distribution (e.g. GO:0031081 nuclear pore distribution), given RNAi and dominant-negative evidence that SUN1 is a determinant of NPC spacing?
Suggested experts: nuclear envelope biologists, GO cellular component/process editors
Q: GOA places many non-meiotic SUN1-KASH interaction papers under GO:0034993 meiotic nuclear membrane microtubule tethering complex; should these be moved to the parent GO:0106094?
Suggested experts: GO editors, UniProt curators
Experiment: Sun1-specific versus Sun2-specific conditional knockout in migrating cortical neurons with live imaging of nucleus-centrosome distance and nuclear velocity.
Hypothesis: SUN1 and SUN2 are fully redundant for neuronal nucleokinesis, or one paralog dominates in specific neuron types.
Type: conditional genetics with live imaging
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