RCC1type

RCC1-type refers to a family of eukaryotic proteins defined by a conserved RCC1-like domain that functions as a guanine nucleotide exchange factor (GEF) for the Ran GTPase. Members of this family are involved in regulating nucleocytoplasmic transport, chromosome condensation, and mitotic spindle assembly. The best-characterized member is RCC1, or Regulator of Chromosome Condensation 1, but the term also encompasses RCC1-like proteins (RLPs) found in many organisms.

Structure and localization: A typical RCC1-type protein contains an N-terminal region that mediates localization and protein interactions, and a C-terminal RCC1-like catalytic domain. The catalytic domain often folds into a seven-bladed beta-propeller that supports efficient GDP-to-GTP exchange on Ran. Some variants include additional targeting motifs or regulatory segments that modulate activity or localization.

Function: Through its RanGEF activity, RCC1-type proteins generate a high RanGTP concentration near chromatin. This gradient drives cargo release from import receptors and is essential for directional nuclear transport. During mitosis, RanGTP promotes spindle assembly and nuclear envelope reformation; in interphase, it contributes to chromatin organization and gene regulation via the Ran network.

Distribution and evolution: RCC1 itself is chromatin-associated, particularly during mitosis. RCC1-like proteins exhibit diverse subcellular localization, from nucleus to cytoplasm, and sometimes organelle-associated. The RCC1-like domain is conserved across eukaryotes, with lineage-specific expansions giving rise to tissue- or cell-type–specific variants.

Clinical relevance and research: Altered expression or mutation of RCC1-type proteins can perturb nucleocytoplasmic transport and cell cycle control. Abnormal RCC1-family activity has been observed in some cancers and developmental disorders, making RCC1-type proteins important subjects for studies of Ran-dependent transport and mitosis.