# Recent Advances in Proximity Labeling-Based Subcellular Proteomic Mapping

**Authors:** Gang Wang, Jiapeng Liu, Xuege Sun, Wei Qin, Shuo Han, Peng Zou

PMC · DOI: 10.1016/j.mcpro.2026.101520 · Molecular & Cellular Proteomics : MCP · 2026-01-29

## TL;DR

This paper reviews recent developments in proximity labeling techniques that help map proteins within cells with high precision.

## Contribution

The paper highlights novel PL strategies like optoPL and immunoPL that offer spatiotemporal control and non-genetic subcellular profiling.

## Key findings

- Proximity labeling methods now capture multidimensional protein features with subcellular precision.
- Photoactivatable and antibody-targeted PL techniques enable detailed proteome mapping without genetic manipulation.
- Integration with complementary techniques enhances understanding of protein interactions and trafficking.

## Abstract

The spatial organization of the cellular proteome is vital for cellular physiology, as protein localization is closely linked to post-translational modifications, subcellular trafficking, and protein-protein interactions. Systematic profiling of these spatial features can greatly enhance our understanding of protein functions. Recent advances in enzyme-mediated proximity labeling (PL) techniques, such as TurboID and APEX2, have improved our ability to map subcellular proteomes in living cells. This review discusses emerging trends in PL methods, which now offer subcellular precision with multi-dimensional protein features, including post-translational modifications, trafficking, turnover, and interaction with other biomolecules. Additionally, new techniques such as photoactivatable PL (optoPL) and antibody-targeted PL (immunoPL) provide enhanced spatiotemporal control and allow for detailed subcellular proteome mapping without genetic manipulation.

•Functional proximity labeling (PL) enables profiling protein features with subcellular precision.•PL provides valuable insights into protein interactomes with diverse biomolecules.•Photocatalytic PL allows enhanced spatiotemporal mapping of subcellular proteomes.•Antibody-targeted PL facilitates subcellular proteome profiling without genetic manipulation.

Functional proximity labeling (PL) enables profiling protein features with subcellular precision.

PL provides valuable insights into protein interactomes with diverse biomolecules.

Photocatalytic PL allows enhanced spatiotemporal mapping of subcellular proteomes.

Antibody-targeted PL facilitates subcellular proteome profiling without genetic manipulation.

This review highlights recent advances in proximity labeling (PL) technologies, including their integration with complementary techniques to probe multidimensional protein features at subcellular resolution as well as the development of photoactivatable and antibody-targeted PL strategies.

## Full-text entities

- **Genes:** GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, NEAT1 (nuclear paraspeckle assembly transcript 1) [NCBI Gene 283131] {aka LINC00084, NCRNA00084, TP53LC15, TncRNA, VINC}, CAPG (capping actin protein, gelsolin like) [NCBI Gene 822] {aka AFCP, HEL-S-66, MCP}, APEX2 (apurinic/apyrimidinic endodeoxyribonuclease 2) [NCBI Gene 27301] {aka APE2, APEXL2, XTH2, ZGRF2}, APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1) [NCBI Gene 328] {aka APE, APE1, APEN, APEX, APX, HAP1}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, SCRIB (scribble planar cell polarity protein) [NCBI Gene 23513] {aka CRIB1, SCRB1, SCRIB1, Vartul, oSCRIB}, Apex2 (apurinic/apyrimidinic endonuclease 2) [NCBI Gene 77622] {aka C430040P13Rik, ape2}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, BRD4 (bromodomain containing 4) [NCBI Gene 23476] {aka CAP, CDLS6, FSHRG4, HUNK1, HUNKI, MCAP}, OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [NCBI Gene 8473] {aka HINCUT-1, HRNT1, MRX106, O-GLCNAC, OGT1, XLID106}, Lgals4 (lectin, galactose binding, soluble 4) [NCBI Gene 16855] {aka gal-4}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, PHOT2 (phototropin 2) [NCBI Gene 835926] {aka AtPHOT2, K21L19.6, K21L19_6, NON PHOTOTROPIC HYPOCOTYL 1-LIKE, NPL1, phototropin 2}, SYNJ2BP (synaptojanin 2 binding protein) [NCBI Gene 55333] {aka ARIP2, OMP25}, XIST (X inactive specific transcript) [NCBI Gene 7503] {aka DXS1089, DXS399E, LINC00001, NCRNA00001, SXI1, swd66}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, LGALS1 (galectin 1) [NCBI Gene 3956] {aka GAL1, GBP}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, LMNA (lamin A/C) [NCBI Gene 4000] {aka CDCD1, CDDC, CMD1A, CMT2B1, EMD2, FPL}, Tyr (tyrosinase) [NCBI Gene 22173] {aka Oca1, albino, c, skc35}
- **Diseases:** toxicity (MESH:D064420), diabetic (MESH:D003920), cancer (MESH:D009369), neurodegenerative disorders (MESH:D019636), PL (MESH:D014897)
- **Chemicals:** amine (MESH:D000588), malachite green (MESH:C005095), arginine (MESH:D001120), glycan (MESH:D011134), phenoxyl radical (MESH:C042329), histidine (MESH:D006639), amino acid (MESH:D000596), QM (MESH:C068040), digoxigenin (MESH:D004076), Opto-Proximity (-), hydrogen peroxide (MESH:D006861), desthiobiotin (MESH:C004749), Singlet oxygen (MESH:D026082), Alkyne (MESH:D000480), aniline (MESH:C023650), reactive oxygen species (MESH:D017382), lysine (MESH:D008239), biotin (MESH:D001710), Eosin Y (MESH:D004801), flavin (MESH:C024132), guanosine (MESH:D006151), nitrene (MESH:C017621), hydrazide (MESH:D006834), carbene (MESH:C030011), diazirines (MESH:D003978), peptides (MESH:D010455), rhodamine 123 (MESH:D020112), cysteine (MESH:D003545), lipid (MESH:D008055), Ir (MESH:D007495), phenol (MESH:D019800), imidazole (MESH:C029899), osmium (MESH:D009992), tyrosine (MESH:D014443), methylene blue (MESH:D008751)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Danio rerio (leopard danio, species) [taxon 7955], Drosophila melanogaster (fruit fly, species) [taxon 7227], C. elegans [taxon 328850], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12969312/full.md

## References

145 references — full list in the complete paper: https://tomesphere.com/paper/PMC12969312/full.md

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Source: https://tomesphere.com/paper/PMC12969312