| Domain/Region | Residues | Function | Key Modifications |
|---|---:|---|---|
| RRM domain | aa 1-89 | Canonical RNA-recognition motif that provides the main RNA-binding interface; binds target mRNAs, especially in UTRs, through conserved ribonucleoprotein elements and supports post-transcriptional control of mRNA stability and translation (pqac-00000001, pqac-00000003, pqac-00000019) | No principal PTM hotspot emphasized in the recent reviews; activity is functionally coupled to PTMs in C-terminal regions that alter localization and access to RNA targets (pqac-00000019, pqac-00000023) |
| RGG domain | aa 90-137 | Arginine/glycine-rich regulatory region involved in RNA/protein interactions, phase separation behavior, stress-granule recruitment, and nuclear import via TNPO1; contributes to translational repression in stress granules and broader control of localization/function (pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000022) | PRMT1-dependent arginine methylation promotes nuclear-to-cytoplasmic translocation and stress-granule targeting under stress; SRPK1 phosphorylation on the RGG region impairs liquid-liquid phase separation and stress-granule recruitment; CK2/GSK3β phosphorylation in response to UV stress promotes cytoplasmic translocation and alters RNA-target interactions/activity (pqac-00000018, pqac-00000020, pqac-00000023) |
| RSY-NLS domain | C-terminal RSY motif; core motif reported as Y-R-x-S-Y-D-S-Y around aa 160-167 | Non-canonical nuclear localization signal recognized by TNPO3; mediates phosphorylation-independent nuclear import and helps maintain nuclear localization under basal conditions (pqac-00000016, pqac-00000044, pqac-00000047, pqac-00000050) | Serine/tyrosine phosphorylation within the RSY-NLS inhibits TNPO3 binding and reduces/abolishes nuclear import, in contrast to classical phospho-dependent TNPO3 cargos (pqac-00000044, pqac-00000046, pqac-00000047, pqac-00000051) |
| Intrinsically disordered region | aa 90-172 | Disordered C-terminal region encompassing the RGG region and RSY-NLS; supports multivalent interactions, condensation/phase behavior, transportin binding, and stress-responsive switching between nuclear, cytoplasmic, stress-granule, and extracellular states (pqac-00000017, pqac-00000019, pqac-00000020) | PTMs are concentrated in this region: PRMT1-mediated methylation and kinase-driven phosphorylation (SRPK1, CK2, GSK3β) regulate nucleocytoplasmic shuttling, phase separation, stress-granule recruitment, and target access; phosphorylation can antagonize importin interactions and LLPS (pqac-00000018, pqac-00000020, pqac-00000023, pqac-00000051) |


*Table: This table summarizes the major structural regions of human CIRBP and links each region to its best-supported functions and regulatory post-translational modifications. It is useful for connecting domain architecture to stress-responsive localization, RNA binding, and phase behavior.*