Q6ZWQ0 · SYNE2_MOUSE

  • Protein
    Nesprin-2
  • Gene
    Syne2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probable association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 seem to act redundantly in cerebellum, midbrain, brain stem, and other brain regions except cerebral cortex and hippocampus. During INM at G1 phase mediates respective LINC complex association with kinesin to push the nucleus away from the centrosome. Involved in nuclear migration in retinal photoreceptor progenitors. Required for centrosome migration to the apical cell surface during early ciliogenesis.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentfilopodium membrane
Cellular Componentfocal adhesion
Cellular Componentintermediate filament cytoskeleton
Cellular Componentlamellipodium membrane
Cellular Componentmeiotic nuclear membrane microtubule tethering complex
Cellular Componentmitochondrion
Cellular Componentmyofibril
Cellular Componentnuclear envelope
Cellular Componentnuclear membrane
Cellular Componentnuclear outer membrane
Cellular Componentnucleoplasm
Cellular Componentsarcoplasmic reticulum membrane
Cellular ComponentZ disc
Molecular Functionactin binding
Molecular Functioncytoskeleton-nuclear membrane anchor activity
Biological Processcentrosome localization
Biological Processnuclear migration along microfilament
Biological Processnucleokinesis involved in cell motility in cerebral cortex radial glia guided migration
Biological Processpositive regulation of cell migration
Biological Processregulation of cilium assembly

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Nesprin-2
  • Alternative names
    • KASH domain-containing protein 2 (KASH2)
    • Nuclear envelope spectrin repeat protein 2
    • Nucleus and actin connecting element protein (Protein NUANCE)
    • Synaptic nuclear envelope protein 2 (Syne-2)

Gene names

    • Name
      Syne2

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q6ZWQ0
  • Secondary accessions
    • Q640M5

Proteomes

Organism-specific databases

Subcellular Location

Nucleus outer membrane ; Single-pass type IV membrane protein
Sarcoplasmic reticulum membrane
; Single-pass type IV membrane protein
Cell membrane ; Single-pass membrane protein
Mitochondrion
Nucleus, nucleoplasm
Note: Different isoform patterns are found in the different compartments of the cell. The isoforms having the C-terminal transmembrane span can be found in several organellar membranes like the nuclear envelope, the sarcoplasmic reticulum of myoblasts, or the lamellipodia and focal adhesions at the cell membrane. The largest part of the outer nuclear membrane-associated protein is cytoplasmic, while its C-terminal part is associated with the nuclear envelope, most probably the outer nuclear membrane. Remains associated with the nuclear envelope during its breakdown in mitotic cells. Shorter soluble isoforms can be found in the cytoplasm and within the nucleus (By similarity).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-6823Cytoplasmic
Transmembrane6824-6844Helical; Anchor for type IV membrane protein
Topological domain6845-6874Perinuclear space

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis128Impairs interaction with F-actin; when assocoated with A-131.
Mutagenesis131Impairs interaction with F-actin; when assocoated with A-128.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 468 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue, disulfide bond.

TypeIDPosition(s)Description
ChainPRO_00003922101-6874Nesprin-2
Modified residue4096Phosphoserine
Modified residue5772Phosphoserine
Modified residue6348Phosphoserine
Modified residue6371Phosphoserine
Modified residue6400Phosphoserine
Modified residue6417Phosphoserine
Modified residue6418Phosphoserine
Modified residue6419Phosphoserine
Modified residue6448Phosphoserine
Disulfide bond6851Interchain (with C-577 in SUN2); alternate
Disulfide bond6851Interchain (with C-759 in SUN1); alternate

Post-translational modification

The disulfid bond with SUN2 is required for stability of the SUN2:SYNE2/KASH2 LINC complex under tensile forces though not required for the interaction.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

C-terminal isoforms are highly expressed in the brain, hert and skeletal muscle. Isoform 1 (Nesprin-2 Giant) is most prevalent in the brain, skin, kidney and skeletal muscle.

Gene expression databases

Interaction

Subunit

Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, some LINC complex constituents are tissue- or cell type-specific. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. The SUN2:SYNE2/KASH2 complex is a heterohexamer; the homotrimeric cloverleave-like conformation of the SUN domain is a prerequisite for LINC complex formation in which three separate SYNE2/KASH2 peptides bind at the interface of adjacent SUN domains. Interacts with EMD, LMNA, MKS3 and F-actin via its N-terminal domain. Interacts with DCTN1 and DYNC1I1/2; suggesting the association with the dynein-dynactin motor complex. Associates with kinesin motor complexes. Interacts with TMEM67. Interacts (via KASH domain) with TMEM258 (By similarity).
Interacts with BROX; this interaction promotes SYN2 ubiquitination and facilitates the relaxation of mechanical stress imposed by compressive actin fibers at the rupture site (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
XENO Q6ZWQ0-1FHOD1 Q9Y6132EBI-16108623, EBI-348433
BINARY Q6ZWQ0-1Sun2 Q8BJS4-32EBI-16108623, EBI-16189250

Protein-protein interaction databases

Miscellaneous

Structure

3D structure databases

Family & Domains

Features

Showing features for region, domain, repeat, coiled coil, compositional bias.

TypeIDPosition(s)Description
Region1-286Actin-binding
Domain31-136Calponin-homology (CH) 1
Domain183-288Calponin-homology (CH) 2
Repeat299-380Spectrin 1
Coiled coil299-6767
Repeat381-474Spectrin 2
Repeat475-577Spectrin 3
Repeat578-680Spectrin 4
Region675-723Disordered
Compositional bias679-693Polar residues
Compositional bias705-723Basic and acidic residues
Repeat727-834Spectrin 5
Repeat835-928Spectrin 6
Repeat929-1030Spectrin 7
Repeat1120-1211Spectrin 8
Repeat1262-1322Spectrin 9
Repeat1323-1409Spectrin 10
Repeat1410-1514Spectrin 11
Repeat1515-1626Spectrin 12
Repeat1627-1728Spectrin 13
Repeat1729-1820Spectrin 14
Repeat1821-1928Spectrin 15
Repeat1929-2026Spectrin 16
Repeat2027-2122Spectrin 17
Repeat2123-2233Spectrin 18
Repeat2234-2350Spectrin 19
Region2338-2397Disordered
Repeat2422-2503Spectrin 20
Repeat2504-2610Spectrin 21
Repeat2611-2707Spectrin 22
Repeat2708-2821Spectrin 23
Repeat2822-2923Spectrin 24
Repeat2924-3027Spectrin 25
Repeat3028-3133Spectrin 26
Repeat3134-3239Spectrin 27
Repeat3240-3343Spectrin 28
Repeat3344-3456Spectrin 29
Repeat3457-3563Spectrin 30
Repeat3564-3669Spectrin 31
Repeat3670-3767Spectrin 32
Repeat3768-3870Spectrin 33
Repeat3871-3976Spectrin 34
Repeat3977-4074Spectrin 35
Region4062-4152Disordered
Compositional bias4106-4122Basic and acidic residues
Region4171-4193Disordered
Repeat4218-4337Spectrin 36
Region4326-4348Disordered
Compositional bias4329-4343Basic and acidic residues
Region4401-4429Disordered
Repeat4507-4626Spectrin 37
Repeat4627-4714Spectrin 38
Repeat4715-4823Spectrin 39
Repeat4824-4929Spectrin 40
Repeat4930-5037Spectrin 41
Repeat5038-5150Spectrin 42
Repeat5151-5252Spectrin 43
Repeat5253-5377Spectrin 44
Repeat5378-5473Spectrin 45
Region5435-5459Disordered
Repeat5474-5576Spectrin 46
Repeat5577-5691Spectrin 47
Repeat5692-5786Spectrin 48
Repeat5787-5894Spectrin 49
Repeat5895-6004Spectrin 50
Repeat6005-6122Spectrin 51
Repeat6123-6230Spectrin 52
Repeat6231-6342Spectrin 53
Compositional bias6336-6375Basic and acidic residues
Region6336-6473Disordered
Compositional bias6414-6428Basic and acidic residues
Compositional bias6446-6465Basic and acidic residues
Repeat6450-6534Spectrin 54
Repeat6535-6650Spectrin 55
Repeat6651-6767Spectrin 56
Region6790-6812Disordered
Domain6815-6874KASH
Region6861-6874Sufficient for interaction with SUN2

Domain

The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.

Sequence similarities

Belongs to the nesprin family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

This entry describes 3 isoforms produced by Alternative splicing.

Q6ZWQ0-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Name
    1
  • Synonyms
    Nesprin-2 Giant, Nesp2G, NUANCE
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    6,874
  • Mass (Da)
    782,725
  • Last updated
    2010-03-23 v2
  • Checksum
    379792E42B95B7DB

Q6ZWQ0-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q6ZWQ0-3

Computationally mapped potential isoform sequences

There are 11 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q6ZWN0Q6ZWN0_MOUSESyne2528
D3YVK9D3YVK9_MOUSESyne2269
D3Z2J8D3Z2J8_MOUSESyne2112
D3Z2P5D3Z2P5_MOUSESyne282
D3Z412D3Z412_MOUSESyne2125
D6RH38D6RH38_MOUSESyne274
E9QP46E9QP46_MOUSESyne26870
F6W8R9F6W8R9_MOUSESyne21644
F7BX34F7BX34_MOUSESyne2733
F6VTU3F6VTU3_MOUSESyne2195
Q6DFZ2Q6DFZ2_MOUSESyne22152

Features

Showing features for alternative sequence, compositional bias.

TypeIDPosition(s)Description
Alternative sequenceVSP_0387991-4994in isoform 3
Alternative sequenceVSP_038800472-482in isoform 2
Alternative sequenceVSP_038801483-6874in isoform 2
Compositional bias679-693Polar residues
Compositional bias705-723Basic and acidic residues
Compositional bias4106-4122Basic and acidic residues
Compositional bias4329-4343Basic and acidic residues
Compositional bias6336-6375Basic and acidic residues
Compositional bias6414-6428Basic and acidic residues
Compositional bias6446-6465Basic and acidic residues
Alternative sequenceVSP_0388026781-6789in isoform 3

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK052521
EMBL· GenBank· DDBJ
BAC35023.1
EMBL· GenBank· DDBJ
mRNA
AC115714
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AC159897
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AC164121
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AC166991
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC082586
EMBL· GenBank· DDBJ
AAH82586.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp