Alternative titles; symbols
HGNC Approved Gene Symbol: NUBP1
Cytogenetic location: 16p13.13 Genomic coordinates (GRCh38): 16:10,743,842-10,769,351 (from NCBI)
NUBP1 is a member of the NUBP/MRP subfamily of ATP-binding proteins (Nakashima et al., 1999).
By screening a human neuroblastoma library, Shahrestanifar et al. (1994) cloned NUBP1, which they called NBP. The deduced 320-amino acid protein has a molecular mass of 34.5 kD. NBP displays sequence similarity with the product of the MinD gene from Escherichia coli. MinD is involved in the proper placement of the division septum and has ATPase activity. Both NBP and MinD contain consensus nucleotide-binding domains. The NBP mRNA is approximately 1,500 nucleotides long and was expressed in several human cell lines and in all rat tissues examined, with the highest levels in lung and testis. Shahrestanifar et al. (1994) indicated that the yeast homolog of the NBP gene had been isolated and found to exhibit 40% identity with human NBP. Furthermore, mutation of the gene was found to be lethal in yeast, indicating that NBP plays a vital role in cell function.
Nakashima et al. (1999) showed that NUBP1 contains a conserved ATP/GTP binding motif A (P-loop), an ATP/GTP binding motif A-prime, and NUBP/MRP alpha and beta motifs. NUBP1 has an additional N-terminal sequence with 4 cysteine residues that is not present in NUBP2 (610779).
Stehling et al. (2008) noted that the N and C termini of human NBP35 have several conserved cysteines that may form iron-binding sites. Using ultraviolet and visible spectroscopy and low-temperature electron paramagnetic resonance, they showed that NBP35 likely coordinated a 4Fe-4S cluster. Both fluorescence-tagged and endogenous HeLa cell NBP35 localized to the cytosol, which was verified by cell fractionation.
Stehling et al. (2008) found that depletion of NBP35 in HeLa cells via RNA interference impaired maturation of the cytosolic Fe-S proteins GPAT (PPAT; 172450) and IRP1 (ACO1; 100880). IRP1 is a bifunctional protein; in the presence of a 4Fe-4S cluster, it functions as a cytosolic aconitase, and in the absence of a 4Fe-4S cluster, it regulates cellular iron homeostasis by binding iron regulatory elements (IREs) in target mRNAs, influencing mRNA translation. Depletion of NBP35 in HeLa cells resulted in a time-dependent decrease in IRP1 cytosolic aconitase activity and a concomitant increase in IRP1 binding to IREs. Binding of IRP1 to a 5-prime IRE in ferritin heavy chain (FTH1; 134770) mRNA inhibits translation and thereby reduces cytosolic iron storage capacity, whereas binding of IRP1 to 3-prime IREs in transferrin receptor (TFRC; 190010) mRNA stabilizes the mRNA, leading to increased translation and increased uptake of transferrin (190000). Increased IRE binding by IRP1 in NBP35-depleted cells led to decreased levels of ferritin heavy chain, increased levels of transferrin receptor, and increased transferrin uptake. NBP35 also interacted with coexpressed CFD1 (NUBP2; 610779) in transfected HeLa cells, suggesting that the 2 proteins may function in a complex for regulation of cellular iron homeostasis and cytosolic Fe-S protein assembly.
Hartz (2012) mapped the NUBP1 gene to chromosome 16p13.13 based on an alignment of the NUBP1 sequence (GenBank AK223204) with the genomic sequence (GRCh37).
Nakashima et al. (1999) mapped the mouse Nubp1 gene to the t-complex region of mouse chromosome 16, which shows homology of synteny with human chromosome 16p13.1.
Hartz, P. A. Personal Communication. Baltimore, Md. 9/11/2012.
Nakashima, H., Grahovac, M. J., Mazzarella, R., Fujiwara, H., Kitchen, J. R., Threat, T. A., Ko, M. S. H. Two novel mouse genes--Nubp2, mapped to the t-complex on chromosome 17, and Nubp1, mapped to the chromosome 16--establish a new gene family of nucleotide-binding proteins in eukaryotes. Genomics 60: 152-160, 1999. [PubMed: 10486206] [Full Text: https://doi.org/10.1006/geno.1999.5898]
Shahrestanifar, M., Saha, D. P., Scala, L. A., Basu, A., Howells, R. D. Cloning of a human cDNA encoding a putative nucleotide-binding protein related to Escherichia coli MinD. Gene 147: 281-285, 1994. [PubMed: 7926816] [Full Text: https://doi.org/10.1016/0378-1119(94)90082-5]
Stehling, O., Netz, D. J. A., Niggemeyer, B., Rosser, R., Eisenstein, R. S., Puccio, H., Pierik, A. J., Lill, R. Human Nbp35 is essential for both cytosolic iron-sulfur protein assembly and iron homeostasis. Molec. Cell. Biol. 28: 5517-5528, 2008. [PubMed: 18573874] [Full Text: https://doi.org/10.1128/MCB.00545-08]