Alternative titles; symbols
HGNC Approved Gene Symbol: GGA2
Cytogenetic location: 16p12.2 Genomic coordinates (GRCh38) : 16:23,463,542-23,524,359 (from NCBI)
For general information on the GGA family, see GGA1 (606004).
Hirst et al. (2000), Takatsu et al. (2000), and Dell'Angelica et al. (2000) independently cloned GGA1, GGA2, and GGA3 (606006). GGA2 shares 45% amino acid sequence identity with GGA1 and 35% with GGA3 (Hirst et al., 2000).
Poussu et al. (2000) independently cloned the GGA2 gene and called it VEAR for 'VHS domain and ear domain of gamma-adaptin' (603533). They found that it encodes a 613-amino acid protein that bears homology to several endocytosis-associated proteins in that it has a VHS domain in its N terminus. High levels of expression in kidney, muscle, and heart suggested a tissue-specific function of VEAR to Poussu et al. (2000).
Hirst et al. (2000) found that GGA1 and GGA2 do not associate with each other or with the AP-1 complex
Poussu et al. (2000) found that, in transfection experiments, hemagglutinin-tagged full-length VEAR and truncated VEAR lacking the VHS domain assembled on and caused compaction of the Golgi complex. Golgi association without compaction was seen with the ear domain of VEAR, whereas the VHS domain alone showed a diffuse membrane- and vesicle-associated distribution. The Golgi association and the bipartite structure, along with the differential targeting of its domains, suggest that VEAR is involved in heterotypic vesicle/suborganelle interactions associated with the Golgi complex.
Zhu et al. (2001) showed that the VHS domain of GGA2 binds the acidic cluster-dileucine motif in the cytoplasmic tail of the cation-independent mannose 6-phosphate receptor (CIMPR; 147280). Receptors with mutations in this motif were defective in lysosomal enzyme sorting. The hinge domain of GGA2 bound clathrin, suggesting that GGA2 could be a link between cargo molecules and clathrin-coated vesicle assembly. Thus, Zhu et al. (2001) concluded that GGA2 binding to the CIMPR is important for lysosomal enzyme targeting.
Hartz (2017) mapped the GGA2 gene to chromosome 16p12.2 based on an alignment of the GGA2 sequence (GenBank AB029003) with the genomic sequence (GRCh38).
Dell'Angelica, E. C., Puertollano, R., Mullins, C., Aguilar, R. C., Vargas, J. D., Hartnell, L. M., Bonifacino, J. S. GGAs: a family of ADP ribosylation factor-binding proteins related to adaptors and associated with the Golgi complex. J. Cell Biol. 149: 81-93, 2000. [PubMed: 10747089] [Full Text: https://doi.org/10.1083/jcb.149.1.81]
Hartz, P. A. Personal Communication. Baltimore, Md. 2/23/2017.
Hirst, J., Lui, W. W. Y., Bright, N. A., Totty, N., Seaman, M. N. J., Robinson, M. S. A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome. J. Cell Biol. 149: 67-69, 2000. [PubMed: 10747088] [Full Text: https://doi.org/10.1083/jcb.149.1.67]
Poussu, A., Lohi, O., Lehto, V.-P. Vear, a novel Golgi-associated protein with VHS and gamma-adaptin 'ear' domains. J. Biol. Chem. 275: 7176-7183, 2000. [PubMed: 10702286] [Full Text: https://doi.org/10.1074/jbc.275.10.7176]
Takatsu, H., Yoshino, K., Nakayama, K. Adaptor gamma-ear homology domain conserved in gamma-adaptin and GGA proteins that interact with gamma-synergin. Biochem. Biophys. Res. Commun. 271: 719-725, 2000. [PubMed: 10814529] [Full Text: https://doi.org/10.1006/bbrc.2000.2700]
Zhu, Y., Doray, B., Poussu, A., Lehto, V.-P., Kornfeld, S. Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor. Science 292: 1716-1718, 2001. [PubMed: 11387476] [Full Text: https://doi.org/10.1126/science.1060896]