Alternative titles; symbols
HGNC Approved Gene Symbol: UBQLN4
Cytogenetic location: 1q22 Genomic coordinates (GRCh38) : 1:156,031,247-156,053,798 (from NCBI)
By a yeast 2-hybrid screen of an adult human brain cDNA library, Davidson et al. (2000) isolated cDNA clones which they used to assemble a complete cDNA encoding the 601-amino acid ataxin-1 ubiquitin-like interacting protein (A1U). Sequence comparison revealed that A1U contains an N-terminal ubiquitin-like region, placing it within a large family of similar proteins. In addition, A1U shows substantial homology to human UBQLN2 (300264), a protein that binds the ATPase domain of the HSP70-like STCH protein (601100). Expression analyses demonstrated that A1U mRNA is widely expressed as a 4.0-kb transcript and is present in Purkinje cells, the primary site of spinocerebellar ataxia-1 (SCA1; 164400) cerebellar pathology. The A1U protein localized to the nucleus and cytoplasm of transfected COS-1 cells. Sequences important for the transport of A1U into the nucleus appeared to lie within the C terminus. In the nucleus, A1U colocalized with mutant ataxin-1 (ATX1; 601556), further demonstrating that A1U interacts with ataxin-1.
Using Northern and Western blot analyses, Su et al. (2010) detected variable Cip75 mRNA and protein expression in all mouse tissues examined.
Davidson et al. (2000) suggested that A1U may link ataxin-1 with the chaperone and ubiquitin/proteasome pathways and that ataxin-1 may function in the formation and regulation of multimeric protein complexes within the nucleus.
Monoubiquitination usually marks proteins for endocytosis, whereas lys48-linked tetraubiquitination typically marks proteins for proteasomal degradation. Su et al. (2010) showed that mouse Cip75 interacted with both synthetic monoubiquitinated and tetraubiquitinated proteins in vitro and with a host of endogenous ubiquitinated proteins in HeLa cell lysates. Cip75 also interacted with nonubiquitinated Cx43 (GJA1; 121014) in the endoplasmic reticulum. Even in the absence of Cx43 ubiquitination, Cip75 stimulated Cx43 proteasomal degradation.
Davidson et al. (2000) found that AIU (UBQLN4) is the same as C1orf6, which was mapped by FISH to chromosome 1q21 by Fogli et al. (1999).
Davidson, J. D., Riley, B., Burright, E.N., Duvick, L.A., Zoghbi, H.Y., Orr, H. T. Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein. Hum. Molec. Genet. 9: 2305-2312, 2000. [PubMed: 11001934] [Full Text: https://doi.org/10.1093/oxfordjournals.hmg.a018922]
Fogli, A., Giglio, S., Arrigo, G., Lo Nigro, C., Zollo, M., Viggiano, L., Rocchi, M., Archidiacono, N., Zuffardi, O., Carrozzo, R. Identification of two paralogous regions mapping to the short and long arms of human chromosome 2 comprising LIS1 pseudogenes. Cytogenet. Cell Genet. 86: 225-232, 1999. [PubMed: 10575211] [Full Text: https://doi.org/10.1159/000015344]
Su, V., Nakagawa, R., Koval, M., Lau, A. F. Ubiquitin-independent proteasomal degradation of endoplasmic reticulum-localized connexin43 mediated by CIP75. J. Biol. Chem. 285: 40979-40990, 2010. [PubMed: 20940304] [Full Text: https://doi.org/10.1074/jbc.M110.170753]