Disease relevance of Surf1

• The PCR products (VH and VL) were ligated (with a G-rich spacer) into the lambda Surf-Zap (Stratagene) vector and expressed as a surface fusion protein on the M13 phage [1].
• Nevertheless, the acute toxicity and lethality of ferrochloroquine seemed to be dependent on gastric surfeit [2].
• Conversely, Pi surfeit may have an anabolic effect on bone and may antagonize bone resorption [3].

High impact information on Surf1

• The organization of the mouse surfeit locus is unusual in that it contains six housekeeping genes (Surf-1-Surf-6), which are unrelated by sequence homology, in the tightest mammalian gene cluster thus far described [4].
• The tight clustering and juxtaposition of at least five of the surfeit genes (Surf-1-Surf-5) and their associated CpG-rich islands have been found to be conserved over the 600 million years of divergent evolution that separates birds and mammals [4].
• This strongly suggests that the surfeit locus represents a different form of gene cluster in which gene organization may play both a positive and negative regulatory role in gene expression possibly via cis-interactions between the closely spaced genes [4].
• All four surfeit genes, which are unrelated by sequence similarity, were found to have the properties of "housekeeping" genes, being expressed in a variety of differentiated mouse cell lines and containing unmethylated CpG-rich islands in the vicinity of their 5' ends [5].
• The frequency of -/-, +/+ and +/- genotypes in newborn mice followed a mendelian distribution, indicating that the ablation of Surf1 is compatible with postnatal survival [6].

Biological context of Surf1

• The mouse surfeit locus contains a cluster of six genes associated with four CpG-rich islands in 32 kilobases of genomic DNA [7].
• The mouse Surfeit locus, which contains a cluster of at least four genes (Surf-1 to Surf-4), is unusual in that adjacent genes are separated by no more than 73 base pairs (bp) [8].
• Surfeit locus gene homologs are widely distributed in invertebrate genomes [9].
• The five Surfeit genes (Surf-1 to -5) that have been previously isolated and characterized do not share any DNA or amino acid sequence homology [10].
• One of the tightly clustered genes of the mouse surfeit locus is a highly expressed member of a multigene family whose other members are predominantly processed pseudogenes [11].

Anatomical context of Surf1

• These Surfeit genes appear to be housekeeping genes, with the Surf-3 gene encoding the 1.7a ribosomal protein and the Surf-4 gene encoding an integral membrane protein most likely associated with the endoplasmic reticulum [10].
• The mitochondrial membrane potential was unchanged in KO versus wild-type neurons, suggesting that the effects of the ablation of Surf1 on Ca(2+) homeostasis, and possibly on longevity, may be independent, at least in part, from those on COX assembly and mitochondrial bioenergetics [6].

Other interactions of Surf1

• Ribosomal protein L7a is encoded by a gene (Surf-3) within the tightly clustered mouse surfeit locus [8].
• The Surf-6 gene of the mouse surfeit locus encodes a novel nucleolar protein [10].
• The bidirectional promoter of the divergently transcribed mouse Surf-1 and Surf-2 genes [12].
• The mouse surfeit locus is unusual in that it contains a number of closely clustered genes (Surf-1, -2, and -4) that alternate in their direction of transcription (T. Williams, J. Yon, C. Huxley, and M. Fried, Proc. Natl. Acad. Sci. USA 85:3527-3530, 1988) [11].

Analytical, diagnostic and therapeutic context of Surf1

• The genomic region around the Surf-3/rpL7a gene was analyzed by low-stringency hybridization with murine Surfeit gene probes, by partial sequence analysis, and by hybridization of fragments to Northern (RNA) blots [13].

References