GBF1

This gene encodes a member of the Sec7 domain family. The encoded protein is a guanine nucleotide exchange factor that regulates the recruitment of proteins to membranes by mediating GDP to GTP exchange. The encoded protein is localized to the Golgiapparatus and plays a role in vesicular trafficking by activating ADP ribosylation factor 1. The encoded protein has also been identified as an important host factor for viral replication. Multiple transcript variants have been observed for this gene.

Full Name

golgi-specific brefeldin A resistant guanine nucleotide exchange factor 1

Function

Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP with GTP. Recruitment to cis-Golgi membranes requires membrane association of Arf-GDP and can be regulated by ARF1, ARF3, ARF4 and ARF5. Involved in the recruitment of the COPI coat complex to the endoplasmic reticulum exit sites (ERES), and the endoplasmic reticulum-Golgi intermediate (ERGIC) and cis-Golgi compartments which implicates ARF1 activation. Involved in COPI vesicle-dependent retrograde transport from the ERGIC and cis-Golgi compartments to the endoplasmic reticulum (ER) (PubMed:16926190, PubMed:17956946, PubMed:18003980, PubMed:12047556, PubMed:12808027, PubMed:19039328, PubMed:24213530).

Involved in the trans-Golgi network recruitment of GGA1, GGA2, GGA3, BIG1, BIG2, and the AP-1 adapter protein complex related to chlathrin-dependent transport; the function requires its GEF activity (probably at least in part on ARF4 and ARF5) (PubMed:23386609).

Has GEF activity towards ARF1 (PubMed:15616190).

Has in vitro GEF activity towards ARF5 (By similarity).

Involved in the processing of PSAP (PubMed:17666033).

Required for the assembly of the Golgi apparatus (PubMed:12808027, PubMed:18003980).

The AMPK-phosphorylated form is involved in Golgi disassembly during mitotis and under stress conditions (PubMed:18063581, PubMed:23418352).

May be involved in the COPI vesicle-dependent recruitment of PNPLA2 to lipid droplets; however, this function is under debate (PubMed:19461073, PubMed:22185782).

In neutrophils, involved in G protein-coupled receptor (GPCR)-mediated chemotaxis und superoxide production. Proposed to be recruited by phosphatidylinositol-phosphates generated upon GPCR stimulation to the leading edge where it recruits and activates ARF1, and is involved in recruitment of GIT2 and the NADPH oxidase complex (PubMed:22573891).

Plays a role in maintaining mitochondrial morphology (PubMed:25190516).

Biological Process

Cell activation involved in immune response Source: UniProtKB
Cellular response to virus Source: UniProtKB
Cilium assembly Source: Reactome
COPI coating of Golgi vesicle Source: UniProtKB
Endoplasmic reticulum-Golgi intermediate compartment organization Source: UniProtKB
Endoplasmic reticulum to Golgi vesicle-mediated transport Source: Reactome
Establishment of monopolar cell polarity Source: UniProtKB
Golgi disassembly Source: UniProtKB
Golgi organization Source: UniProtKB
Golgi to endosome transport Source: UniProtKB
Neutrophil chemotaxis Source: UniProtKB
Post-Golgi vesicle-mediated transport Source: Reactome
Protein localization to endoplasmic reticulum exit site Source: UniProtKB
Protein localization to endoplasmic reticulum tubular network Source: UniProtKB
Protein localization to Golgi apparatus Source: UniProtKB
Protein transport Source: UniProtKB-KW
Reactive oxygen species biosynthetic process Source: UniProtKB
Regulation of ARF protein signal transduction Source: InterPro
Regulation of mitotic cell cycle Source: UniProtKB
Regulation of protein localization to cell surface Source: UniProtKB
Retrograde transport, endosome to Golgi Source: UniProtKB
Retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum Source: UniProtKB

Cellular Location

Cytoplasm; Cis-Golgi network; Trans-Golgi network; Golgi apparatus; Endoplasmic reticulum-Golgi intermediate compartment; Lipid droplet; Membrane. Cycles rapidly on and off early Golgi membranes (PubMed:15616190). Stabilized on membranes when complexed with ARF1-GDP and is released from both ARF1 and membranes after it catalyzes GDP displacement and ARF1 binds GTP. Continuous cycles of recruitment and dissociation of GBF1 to membranes are required for sustained ARF activation and COP I recruitment (PubMed:15813748). In neutrophils is translocated from the Golgi to the leading edge upon GPCR stimulation (PubMed:22573891). Localization to lipid droplets is questionable (PubMed:22185782).

PTM

AMPK-mediated phosphorylation at Thr-1337 is induced by 2-deoxyglucose (2-DG) and AICA ribonucleotide, and occurs during mitosis leading to membrane disassociation and inactivation of ARF1 during mitosis.