UniProt functional annotation for P18754

UniProt code: P18754.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Guanine-nucleotide releasing factor that promotes the exchange of Ran-bound GDP by GTP, and thereby plays an important role in RAN-mediated functions in nuclear import and mitosis (PubMed:1944575, PubMed:17435751, PubMed:20668449, PubMed:22215983, PubMed:11336674). Contributes to the generation of high levels of chromosome-associated, GTP-bound RAN, which is important for mitotic spindle assembly and normal progress through mitosis (PubMed:12194828, PubMed:17435751, PubMed:22215983). Via its role in maintaining high levels of GTP-bound RAN in the nucleus, contributes to the release of cargo proteins from importins after nuclear import (PubMed:22215983). Involved in the regulation of onset of chromosome condensation in the S phase (PubMed:3678831). Binds both to the nucleosomes and double- stranded DNA (PubMed:17435751, PubMed:18762580). {ECO:0000269|PubMed:11336674, ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:18762580, ECO:0000269|PubMed:1944575, ECO:0000269|PubMed:20668449, ECO:0000269|PubMed:22215983, ECO:0000269|PubMed:3678831}.
 
Subunit: Interacts with RAN (PubMed:17435751, PubMed:18762580, PubMed:29040603, PubMed:11336674). Interacts (via N-terminus and RCC1 repeats) with KPNA4 (PubMed:29042532). Interacts with ARRB2; the interaction is detected in the nucleus upon OR1D2 stimulation (PubMed:16820410). {ECO:0000269|PubMed:11336674, ECO:0000269|PubMed:16820410, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:18762580, ECO:0000269|PubMed:29040603, ECO:0000269|PubMed:29042532}.
Subcellular location: Nucleus {ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:16820410, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:2236072}. Chromosome {ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:18762580, ECO:0000269|PubMed:20668449}. Cytoplasm {ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:20668449}. Note=Predominantly nuclear in interphase cells (PubMed:12194828). Binds to mitotic chromosomes (PubMed:12194828, PubMed:17435751, PubMed:20668449). {ECO:0000269|PubMed:12194828, ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:20668449}.
Ptm: N-terminal methylation by METTL11A/NTM1 is required for binding double-stranded DNA and stable chromatin association. Di- and trimethylation produce a permanent positive charge on the amino group, which facilitates electrostatic binding to the phosphate groups on DNA, while inhibiting histone-binding. Methylated tail helps retain RCC1 on chromosomes during nucleotide exchange on Ran. {ECO:0000269|PubMed:17435751, ECO:0000269|PubMed:18762580, ECO:0000269|PubMed:20668449}.
Miscellaneous: Patients with Raynaud disease produce antibodies that bind to RCC1.

Annotations taken from UniProtKB at the EBI.