SUN5 (SPAG4L, TSARG4) review notes

2026-09-27 — initial review (claude-code)

Sources: UniProt Q8TC36, GOA (17 rows), cached publications, Falcon deep research (arrived during review).

Identity / topology

• 379 aa single-pass SUN protein: nucleoplasmic N-terminus (1-105), TM 106-122, luminal coiled coil and SUN domain (205-364) [file:human/SUN5/SUN5-uniprot.txt].
• Stated INM location PMID:27640305 (by citation of prior work).

Localization dynamics (mouse)

• Golgi transit and glycosylation, then NE, then head-tail junction PMID:25775128. Excluded from acrosome-facing NE (contradicts earlier apical localization claim, PMID:21159740).
• Mature sperm: coupling apparatus in implantation fossa PMID:28945193.

Function

• Sun5-/- mice: acephalic sperm; HTCA assembles but detaches from implantation fossa; meiosis normal PMID:28945193.
• KASH partner = Nesprin-3 (SYNE3): co-IP + IF, Sun5 required to position Nesprin3 posteriorly PMID:34268309; human variant sperm + HEK293T co-IP SUN5-Nesprin3-ODF1 "triplet" [PMID:33848337, abstract only].
• Lamin B1 and Septin12/Septin2 partners (IP-MS; abstract only) PMID:38870534. Topology puzzle: septins are cytoplasmic, SUN domain luminal.
• DNAJB13 chaperone-like partner PMID:29298896.
• Claimed SPAG4L-Nesprin2 meiotic LINC complex [PMID:31144711, abstract only] — weak; not used for annotation.
• Human biallelic variants: acephalic spermatozoa syndrome (SPGF16) PMID:27640305.

Decisions

• GO:0034993 meiotic LINC IBA -> MODIFY to GO:0106094 (SUN5 forms a LINC complex with Nesprin3, but post-meiotically; meiosis normal in KO). propagation_review: TERM_SCOPING_PROBLEM / FUNCTIONAL_DIVERGENCE.
• Protein binding: LMNB1 -> MODIFY lamin binding; SEPTIN2/SEPTIN12 and SPAG4 (HuRI) -> REMOVE (uninformative; no septin-binding MF in GO).
• Golgi -> KEEP_AS_NON_CORE (transit compartment).
• Core: GO:0043495 protein-membrane adaptor activity; spermatid development; INM + sperm head-tail coupling apparatus; complex GO:0106094.

Deep research (Falcon)

• Consistent with the above; highlights Nesprin3/ODF1 and 2024 lamin B1/SEPTIN12 work [file:human/SUN5/SUN5-deep-research-falcon.md "Its core role is structural attachment of the sperm HTCA/neck to the nuclear envelope."]. DR-only (not verified here): ARRDC5/SEC22A trafficking of SUN5 (Liu 2023), SPAG4Lbeta isoform lacking TM.