Protein: ADP-ribosylation factor 6 (EC 3.6.5.2) (P62330)
Organism: Homo sapiens (Human)
Function: GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling. Required for normal completion of mitotic cytokinesis (By similarity). Plays a role in the reorganization of the actin cytoskeleton and the formation of stress fibers (By similarity). Involved in the regulation of dendritic spine development, contributing to the regulation of dendritic branching and filopodia extension. Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization. Regulates surface levels of adherens junction proteins such as CDH1 (By similarity). Required for NTRK1 sorting to the recycling pathway from early endosomes (By similarity).
Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:23603394, ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:36017701, ECO:0000269|PubMed:7589240}. Cell membrane {ECO:0000269|PubMed:16737952, ECO:0000269|PubMed:17398095, ECO:0000269|PubMed:17555535, ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:36017701, ECO:0000269|PubMed:37417384}; Lipid-anchor {ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:7589240}. Endosome membrane {ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:20682791, ECO:0000269|PubMed:21951725}; Lipid-anchor {ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:7589240}. Recycling endosome membrane {ECO:0000269|PubMed:21951725}; Lipid-anchor {ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:7589240}. Cell projection, filopodium membrane {ECO:0000269|PubMed:14978216}; Lipid-anchor {ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:7589240}. Cell projection, ruffle {ECO:0000269|PubMed:16737952}. Cleavage furrow {ECO:0000269|PubMed:23603394}. Midbody, Midbody ring {ECO:0000269|PubMed:23603394}. Early endosome membrane {ECO:0000250|UniProtKB:P62331}; Lipid-anchor {ECO:0000250|UniProtKB:P62331}. Golgi apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:P62331}; Lipid-anchor {ECO:0000250|UniProtKB:P62331}. Note=Distributed uniformly on the plasma membrane, as well as throughout the cytoplasm during metaphase. Subsequently concentrated at patches in the equatorial region at the onset of cytokinesis, and becomes distributed in the equatorial region concurrent with cleavage furrow ingression. In late stages of cytokinesis, concentrates at the midbody ring/Flemming body (PubMed:23603394). Recruitment to the midbody ring requires both activation by PSD/EFA6A and interaction with KIF23/MKLP1 (PubMed:23603394). After abscission of the intercellular bridge, incorporated into one of the daughter cells as a midbody remnant and localizes to punctate structures beneath the plasma membrane (PubMed:23603394). Recruited to the cell membrane in association with CYTH2 and ARL4C (PubMed:17398095). Colocalizes with DAB2IP at the plasma membrane and endocytic vesicles (PubMed:19948740). Myristoylation is required for proper localization to membranes: myristoylation on Lys-3 allows ARF6 to remain on membranes during the GTPase cycle (PubMed:32103017, PubMed:7589240). {ECO:0000269|PubMed:17398095, ECO:0000269|PubMed:19948740, ECO:0000269|PubMed:23603394, ECO:0000269|PubMed:32103017, ECO:0000269|PubMed:7589240}.
Interaction partners:
- Cytohesin-3
- Cytohesin-2
- C-Jun-amino-terminal kinase-interacting protein 4
- Cytohesin-1
- Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1
- Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3
- Rab11 family-interacting protein 3
- ADP-ribosylation factor-binding protein GGA3
- Phospholipase D2
- Cytohesin-4
Sequence:
MGKVLSKIFGNKEMRILMLGLDAAGKTTILYKLKLGQSVTTIPTVGFNVETVTYKNVKFNVWDVGGQDKIRPLWRHYYTGTQGLIFVVDCADRDRIDEARQELHRIINDREMRDAIILIFANKQDLPDAMKPHEIQEKLGLTRIRDRNWYVQPSCATSGDGLYEGLTWLTSNYKS