Sources: UniProt Q8WXH0, cached GOA publications, PMID:19874786, PMID:32619477,
PMID:39115447 (newly cached; PubMed-verified via eutils), SYNE2-deep-research-falcon.md.
Key biology:
- Giant isoform: CH-domain actin binding PMID:12118075.
- KASH binds SUN1/SUN2 promiscuously PMID:18396275.
- TAN lines with SUN2 couple nucleus to retrograde actin flow PMID:20724637.
- Motor coupling for neuronal nuclear migration: BICD2-dynein PMID:32619477; 2024 work
PMID:39115447
and "Both motor binding sites are required to rescue nuclear migration defects caused by the loss of function of Nesprin-2."
Decisions of note:
- Meiotic LINC complex (GO:0034993) rows MODIFIED to non-meiotic parent GO:0106094.
- Protein binding: LMNA row MODIFIED to lamin binding; the rest REMOVED (SUN binding is captured
by GO:0140444 and LINC complex membership).
- NEW GO:0021817 nucleokinesis (ISS from rat/mouse data, PMID:32619477, PMID:19874786, PMID:39115447).
- HPA intermediate filament cytoskeleton row UNDECIDED (image not evaluable; no mechanism).
Points for the nucleokinesis module:
- Module says BICD2 binds the nesprin-2 LEWD motif. PMID:32619477 interpreted the LEWD (LEAA)
mutation as mainly affecting dynein recruitment, but PMID:39115447 shows LEWD is the
kinesin-1 (KLC) site and dynein-dynactin-BicD2 binds independently via Spindly/CC1-like motifs.
- Module says kinesin-1 restrains nuclear movement (inhibition accelerates migration; cortex,
PMID:32619477). In cerebellar granule neurons PMID:39115447 finds both motor-binding sites are
required and kinesin contributes productively; the relationship appears cell-type dependent.