The reference OMIM entry for this protein is 610089

Rad50-interacting protein 1; rint1

CLONING

Using a C-terminal fragment of RAD50 (604040) as bait in a yeast 2-hybrid screen of a human B-cell cDNA library, Xiao et al. (2001) cloned RINT1. The deduced 792-amino acid protein has several leucine heptad repeats that form an N-terminal coiled-coil region. Western blot analysis of human cell lines detected an 87-kD RINT1 doublet. Further experiments suggested that the higher molecular mass protein may be translated from an upstream non-AUG start codon. By immunohistochemical analysis, Lin et al. (2007) found that RINT1 was expressed in endoplasmic reticulum (ER), Golgi apparatus, and centrosomes of human HeLa and U2OS cells.

MAPPING

By genomic sequence analysis, Xiao et al. (2001) mapped the RINT1 gene to chromosome 7q22.1.

GENE FUNCTION

Using truncated proteins, Xiao et al. (2001) found that the second leucine heptad repeat of RAD50 and amino acids 257 to 792 of RINT1 were required for RAD50-RINT1 interaction. RINT1 bound RAD50 only during late S and G2/M phases, and human breast cancer cells expressing an N-terminally truncated RINT1 protein displayed defective radiation-induced G2/M checkpoint. Xiao et al. (2001) concluded that RINT1 may play a role in cell cycle control after DNA damage. Kong et al. (2006) found that RBL2 (180203) and RINT1 were essential for telomere length control in human fibroblasts, with loss of either protein leading to longer telomeres. They proposed that RBL2 forms a complex with RAD50 through RINT1 to block telomerase-independent telomere lengthening. Using RNA interference, Lin et al. (2007) found that depletion of RINT1 in HeLa cells led to loss of pericentriolar positioning and dispersal of the Golgi apparatus, concurrent with centrosome amplification in interphase. In synchronized cells, RINT1 deficiency led to multiple abnormalities upon mitotic entry, including aberrant Golgi dynamics during early mitosis and defective reassembly at telophase, formation of multiple spindle poles, and missegregation of chromosomes. Mitotic cells underwent cell death due to overwhelming cellular defects. Lin et al. (2007) concluded that RINT1 is essential to maintain the dynamic integrity of the Golgi apparatus and the centrosome. Docking and fusion of transport vesicles with target membranes requires membrane tethering factors and membrane fusion factors, or SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors). Arasaki et al. (2013) stated that RINT1 functions as a component of an ER tethering complex that interacts with SNAREs at the ER. This tethering complex also includes ZW10 (603954) and NAG (NBAS; 608025). Using immunoprecipitation and binding studies, Arasaki et al. (2013) found that RINT1 also interacted with the octameric COG complex (see COG1, 606973) at the trans-Golgi network (TGN), and that the COG complex bound SNAREs at the TGN. At the TGN, RINT1 interacted directly with the COG component COG1 and with the SNARE component syntaxin-16 (STX16; 603666). The same N-terminal domain of RINT1 was required for interaction with ZW10 at the ER and with COG1 at the TGN, suggesting a switching mechanism. Knockdown of RINT1 in human cell lines inhibited endosome-to-trans-Golgi vesicle trafficking and caused redistribution of TGN marker proteins to endosomes.

ANIMAL MODEL

Lin et al. (2007) found that homozygous deletion of Rint1 was lethal at embryonic day 5 to 6 in mouse and caused failure of blastocyst outgrowth ex vivo. Approximately ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 610089 was added.

Feb. 23, 2019: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).