Alternative titles; symbols
HGNC Approved Gene Symbol: SURF4
Cytogenetic location: 9q34.2 Genomic coordinates (GRCh38): 9:133,361,464-133,377,949 (from NCBI)
SURF4 is a cargo receptor required for maintenance of the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and Golgi morphology (Mitrovic et al., 2008).
For background information on the surfeit genes, see SURF1 (185620).
Using PCR with primers based on the sequence of mouse Surf4 to screen a HeLa cell cDNA library, Reeves and Fried (1995) obtained a cDNA encoding human SURF4. The deduced 269-amino acid protein, which is 60% and 99% identical to the worm and mouse proteins, respectively, contains 7 transmembrane segments, a predicted luminal N terminus, multiple phosphorylation sites, and a double-lysine retrieval motif at the C terminus. Immunoblot analysis showed expression of a 30-kD membrane protein. Immunofluorescence microscopy demonstrated cytoplasmic expression.
Using Northern blot analysis, Garson et al. (1996) detected 3 variants of mouse Surf4 that were ubiquitously expressed, although the levels of each transcript varied between tissues.
Mitrovic et al. (2008) stated that SURF4 is a multispanning membrane protein with its C terminus predicted to face the cytosol. Immunofluorescence assays showed that SURF4 localized to the ERGIC in HeLa cells. Further analysis demonstrated that SURF4 was a cycling protein early in the secretory pathway that depended on a lysine signal.
Belden and Barlowe (2001) showed that Erv29, the yeast homolog of SURF4, is directly required for packaging glycosylated pro-alpha-factor (Gpaf) into COPII (see COPA; 601924) vesicles. Subcellular fractionation experiments indicated that Erv29 is equally distributed between ER and Golgi membranes. Increased expression of Erv29 in the ER alleviated the accumulation of Gpaf. Belden and Barlowe (2001) proposed that Erv29 binds to fully folded Gpaf and probably to other soluble secretory cargo in the ER, after which the Erv29-cargo complexes are packaged into COPII vesicles for transport to the Golgi complex. The authors noted that similar mechanisms have been postulated for ERGIC53 (LMAN1; 601567).
By fractionation and Western blot analyses in HepG2 cells, Mitrovic et al. (2008) showed that SURF4 interacted with p25 (TMED9; 620436) and ERGIC53 to form heterooligomeric complexes. Knockdown of SURF4 alone had no effect on ER, ERGIC, Golgi, and protein secretion in HeLa cells. However, knockdown of both SURF4 and ERGIC53 disrupted the Golgi apparatus. Likewise, knockdown of p25 disrupted Golgi structure in a manner indistinguishable from that following knockdown of SURF4 and ERGIC53. Morphologic, biochemical, and live-cell imaging analyses indicated that silencing of these cargo receptors destabilized ERGIC without initial impairment of ER exit sites or overall protein secretion. Moreover, the morphologic changes of the Golgi were unlikely to be due to impaired binding of matrix proteins to Golgi membranes, as Golgi matrix proteins remained associated with the dispersed Golgi in knockdown cells. Further analysis revealed that SURF4/ERGIC53 and p25 were required for coat protein I (COPI; see 601924) recruitment to membranes of the early secretory pathway, as silencing SURF4 and ERGIC53 or p25 led to partial dissociation of COPI.
Duhig et al. (1998) stated that the 5-prime end of each of the surfeit genes, including SURF4, is contained within a CpG island. Although the mouse Surf2 (185630) and Surf4 genes overlap at their 3-prime ends, human SURF2 and SURF4 are separated by 302 bp due to a much shorter 3-prime UTR in the human SURF2 gene.
By contig analysis, Duhig et al. (1998) mapped the SURF4 gene to the telomeric end of the surfeit locus on chromosome 9q34.
Belden, W. J., Barlowe, C. Role of Erv29p in collecting soluble secretory proteins into ER-derived transport vesicles. Science 294: 1528-1531, 2001. [PubMed: 11711675] [Full Text: https://doi.org/10.1126/science.1065224]
Duhig, T., Ruhrberg, C., Mor, O., Fried, M. The human surfeit locus. Genomics 52: 72-78, 1998. [PubMed: 9740673] [Full Text: https://doi.org/10.1006/geno.1998.5372]
Garson, K., Duhig, T., Fried, M. Tissue-specific processing of the Surf-5 and Surf-4 mRNAs. Gene Expr. 6: 209-218, 1996. [PubMed: 9196076]
Mitrovic, S., Ben-Tekaya, H., Koegler, E., Gruenberg, J., Hauri, H. P. The cargo receptors Surf4, endoplasmic reticulum-Golgi intermediate compartment (ERGIC)-53, and p25 are required to maintain the architecture of ERGIC and Golgi. Molec. Biol. Cell 19: 1976-1990, 2008. [PubMed: 18287528] [Full Text: https://doi.org/10.1091/mbc.e07-10-0989]
Reeves, J. E., Fried, M. The surf-4 gene encodes a novel 30 kDa integral membrane protein. Molec. Membr. Biol. 12: 201-208, 1995. [PubMed: 7540914] [Full Text: https://doi.org/10.3109/09687689509027508]