DYNLT1 (Tctex-1) — curation notes

Deep research status

• First run (--fallback perplexity-lite) stopped (falcon 600 s default timeout; perplexity-lite
  unavailable). Re-run with --timeout 2400: SUCCEEDED (falcon; DYNLT1-deep-research-falcon.md).
  It added Saito et al. 2017 (PMID:28607034), the 2024 DYNLT1-DYNLT2B heterodimer structure, OX1R
  and KIM-1 interactions, and a sperm/infertility association. These are integrated below where
  relevant.

Identity

• UniProt P63172, dynein light chain Tctex-type 1 (TCTEX1); DYNLT family with DYNLT3 (rp3) and the
  divergent DYNLT2B (TCTEX1D2, "Tctex-2"). Also identical to AGS2 (receptor-independent activator
  of G protein signaling) PMID:17491591.

Dynein light chain

• Recombinant human dynein-1 reconstitution includes DYNLT1
  PMID:24986880.
• Homo/heterodimers; homodimers bind all intermediate chains
  PMID:17965411;
  PMID:17965411;
  DYNLT associates exclusively with dynein PMID:17965411.
• Dynein-2: co-isolates with WDR34 PMID:25205765;
  in the dynein-2 structure as TCTEX-TCTEX1D2 dimer PMID:31451806.
• Cilium length: PMID:21700358;
  PMID:21700358.

Dynein-independent functions

• Gbetagamma effector, neurite outgrowth
  PMID:17491591;
  PMID:17491591.
• Rab3D binding in osteoclasts PMID:21262767.
• Viral Gag targeting (M-PMV) PMID:18647839.

Ciliary resorption (module role)

• PMID:21394082
• PMID:21394082
• Mechanism involves actin dynamics PMID:21394082.
• Upstream: IGF-1R -> AGS3-regulated Gbetagamma -> recruits pT94-Tctex-1 to the transition zone
  PMID:23954591.
• Note the apparent paradox: Tctex-1 depletion lengthens cilia PMID:21700358, consistent with
  both a dynein-2 role in length control and the resorption role. The two papers use different
  readouts (steady-state length vs. serum-induced resorption).
• Comparator check for NEW GO:0061523: NEDD9 (AURKA activator), AURKA and HDAC6 carry GO:0061523
  in human GOA. Phospho-Tctex-1 is a comparable signalling effector acting at the ciliary base, so
  the term fits the existing convention for regulators that execute part of the resorption
  programme. Evidence is the 2011 abstract (cached abstract-only) plus Yeh et al. 2013 (full text).

Mechanism of resorption (Saito et al. 2017; from deep research, verified in cached full text)

• PMID:28607034
• PMID:28607034
• PMID:28607034
• Deep research also reports the purified DYNLT1-DYNLT2B heterodimer (SEC-MALS 28.1 kDa, 2 Å
  crystal structure; Mukhopadhyay et al. 2024, not cached here), plus OX1R and KIM-1 interactions
  (not curated: no GOA rows, cell-model evidence).

Curation decisions summary

• ACCEPT core: cytoplasmic dynein complex, dynein complex, dynein intermediate chain binding,
  microtubule-based movement (as dynein subunit), intraciliary retrograde transport (dynein-2),
  cilium, cytoplasm/cytosol.
• MODIFY: identical protein binding -> protein homodimerization activity; protein binding with
  DYNLT3/DYNLT2B -> protein heterodimerization activity.
• REMOVE: other generic protein binding rows; host cell (a symbiont-side term mis-propagated to a
  host protein).
• MARK_AS_OVER_ANNOTATED: Reactome neutrophil-degranulation extracellular/granule lumen rows.
• UNDECIDED: male germ cell nucleus (NAS, basis not visible), positive regulation of SAC
  (NAS from an LIC1 paper; the sign looks inverted relative to dynein's role in checkpoint silencing).
• KEEP_AS_NON_CORE: spindle orientation, GPCR signaling regulation, negative regulation of
  neurogenesis, viral protein transport, Rab3D/secretory vesicle, Golgi, spindle, cytoplasmic
  microtubule, positive regulation of intracellular transport.
• NEW: GO:0061523 cilium disassembly (IMP, PMID:21394082; mechanism PMID:28607034) and
  GO:0035869 ciliary transition zone (IDA, PMID:21394082).

HPA cilium atlas vs module role

• HPA v25: no cilia/centrosome call; main locations Acrosome; Cytosol. No HPA-sourced GOA rows.
  The HPA atlas paper (PMID:41005307) is cached as metadata only.
• Module role (stage 7: "Tctex-1; resorption"). The primary literature supports this: phospho-T94
  Tctex-1 at the transition zone promotes ciliary resorption. The absence of a transition-zone call
  in HPA is not evidence against the role, because the active pool is a phospho-specific
  sub-population detected with a phospho-T94 antibody, while total Tctex-1 is mostly cytosolic.
• core_functions lists the dynein light chain role (dynein-1 and dynein-2) first, because it is the
  constitutive, best-supported function, and the resorption role second. The module should treat
  DYNLT1 as pleiotropic: the resorption function is a regulated, dynein-independent activity (PMID:28607034) of a
  phospho-pool, and dynein-2 membership also links it to retrograde IFT and length control.