TINCR (A0A2R8Y7D0) review notes

2026-10-08 — MICROPROTEINS Tier 2 review (claude-code)

Identity

• HGNC TINCR (HGNC:14607), formerly LINC00036 / PLAC2; long annotated as the lncRNA
  "terminal differentiation-induced ncRNA". UniProt A0A2R8Y7D0 (Swiss-Prot, PE1), 87 aa,
  a single ubiquitin-like (beta-grasp) domain (PS50053, 14-83) with a C-terminal
  SUMO-interacting motif (79-83). MANE Select NM_001396408.1 now carries the CDS, so the
  ORF is the main ORF of the TINCR transcript (not an alt-ORF of another host gene); the
  folder name follows the HGNC symbol.
• Crystal structure PDB 7MRJ (res 2-87) from PMID:36899004.
• Names in the literature: TUBL (Nita 2021), pTINCR (Boix 2022), TINCR microprotein
  (Morgado-Palacin 2023).

Existence

• Stratum corneum proteomics PMID:32012357.
• Endogenous FLAG knock-in mice and targeted proteomics PMID:34351912.

Function evidence

• Proliferation (Nita 2021, PMID:34351912): overexpression in NHEKs increased S phase; ORF
  frameshift (1-bp del, RNA structure preserved) abolishes the effect in mouse primary
  keratinocytes PMID:34351912. Human NHEK siRNA knockdown decreased S phase.
  Frameshift mice: delayed wound closure PMID:34351912. Nita found that
  two of three siRNAs did not affect involucrin induction, i.e. no differentiation effect.
• Differentiation (Boix 2022, PMID:36369429): start-codon KO HaCaT/MCF7 cells fail to
  differentiate; pTINCR binds SUMO1/2/3 non-covalently via its SIM (GST pull-down) and
  co-IPs with CDC42, increases CDC42 SUMOylation and GTP-CDC42; SIM mutant inactive
  PMID:36369429. In tumour /
  epithelial lines pTINCR decreases proliferation PMID:36369429.
• Tumour suppressor in SCC (Morgado-Palacin 2023, PMID:36899004): TP53/UV-induced; Tincr KO
  mice get more UVB SCC.
• So the direction of the proliferation effect differs between normal keratinocytes (Nita,
  pro-proliferative) and transformed epithelial cells (Boix, Morgado-Palacin, anti-
  proliferative). Neither group explains the discrepancy; mechanism of the Nita effect is
  unknown.

Localization

• Endogenous: nucleus and cell-cell junctions in HaCaT/MCF7 PMID:36369429. Overexpressed FLAG-TUBL: cytoplasm in HeLa PMID:34351912. IHC in SCC is cytoplasmic.

Decisions

• Locations: all accepted (nucleus, cytoplasm, anchoring junction).
• Keratinocyte proliferation IMP: kept as non-core (context-dependent; opposite direction in
  transformed cells; molecular route unknown).
• Wound healing ISS (from mouse A0A1B0GRQ3 frameshift mice): non-core.
• NEW: SUMO binding GO:0032183 (direct, SIM-dependent, PMID:36369429); positive regulation of
  epithelial cell differentiation GO:0030858 (start-codon KO + rescue; it is the pTINCR
  protein that acts, via CDC42). Did not propose small GTPase binding as an MF (co-IP only;
  direct binding not shown) nor protein sumoylation regulation (mechanism unknown: TINCR is
  not an E3; it may act as a SUMO-loaded adaptor).