ADP-ribosylation factor 6 (ARF6)

The protein contains 175 amino acids for an estimated molecular weight of 20082 Da.

 

GTP-binding protein involved in protein trafficking that regulates endocytic recycling and cytoskeleton remodeling (PubMed:11266366, PubMed:21170023, PubMed:16737952, PubMed:7589240, PubMed:18400762). 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 (PubMed:14978216). 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).', '(Microbial infection) Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. (updated: Dec. 5, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 600464

Adp-ribosylation factor 6; arf6

GENE FAMILY

Intracellular membrane trafficking involves a series of membrane budding and fusion events. These are regulated by specific cytosolic and membrane-associated protein factors, among which are a group of Ras-like small guanosine triphosphatases (GTPases) called adenosine diphosphate (ADP)-ribosylation factors (ARFs). These factors were originally identified as cofactors required for the cholera toxin-catalyzed ADP-ribosylation of Gs, alpha subunit (GNAS1; 139320); see ADP-ribosylation factor-1 (ARF1; 103180). The ARF family consists of 15 structurally related gene products that include 6 ARF proteins and 11 ARF-like proteins. The ARF proteins are divided into 3 classes on the basis of size and amino acid identity. ARF1, ARF2, and ARF3 (103190) (181 amino acids) form class I; ARF4 and ARF5 (103188) (180 amino acids) form class II; ARF6 (175 amino acids) forms class III.

MAPPING

Gross (2015) mapped the ARF6 gene to chromosome 14q21.3 based on an alignment of the ARF6 sequence (GenBank GENBANK AF047432) with the genomic sequence (GRCh38).

GENE FUNCTION

D'Souza-Schorey et al. (1995) transiently expressed ARF6, ARF6 mutants, and ARF1 in Chinese hamster ovary cells and assessed the effects on receptor-mediated endocytosis. The authors demonstrated that ARF6, unlike ARF1 which is localized to the Golgi apparatus, has a central role in intra-Golgi transport, is localized to the cell periphery, and that overexpression of ARF6 causes dramatic alterations in endocytic traffic. Expression of a dominant-negative mutant of ARF6, thr27 to asn, resulted in an intracellular distribution of transferrin receptors and an inhibition of transferrin recycling to the cell surface. Cavenagh et al. (1996) examined the subcellular distribution of ARF proteins and demonstrated that ARF6 is uniquely localized to the plasma membranes in Chinese hamster ovary cells. This result suggests that ARF6 is unlikely to be involved in endocytic traffic. Studying rat hippocampal neurons in culture, Hernandez-Deviez et al. (2002) determined that dendritic arbor development is regulated by complex interactions of ARNO (CYTH2; 602488), ARF6, and RAC1 (602048). Activation of ARNO and ARF6 resulted in signaling through RAC1 that suppressed dendritic branching. By coimmunoprecipitation studies in COS-7 cells, Falace et al. (2010) found that TBC1D24 (613577) binds ARF6 and acts as a negative regulator of ARF6. The intensity of the coimmunoprecipitated band increased in the presence of inactive GDP-locked ARF6, indicating a GDP-dependent interaction. Zhu et al. (2012) showed that the direct, immediate, and disruptive effects of IL1-beta (IL1B; 147720) on endothelial stability in a human in vitro cell model are NF-kappa-B (see 164011)-independent and are instead the result of signaling through the small GTPase ARF6 and its activator ARNO. Moreover, Zhu et al. (2012) showed that ARNO binds directly to the adaptor protein MYD88 (602170), and thus proposed MYD88-ARNO-ARF6 as a proximal IL1-beta signaling pathway distinct from that mediated by NF-kappa-B. Finally, Zhu et al. (2012) showed that SecinH3 (182115), an inhibitor of ARF guanine nucleotide exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation. Using N1E-115 mouse neuroblastoma cells, Torii et al. (2014) found that Ccdc120 (300947) directed neurite localization of Cyth2 and was requi ... More on the omim web site

Subscribe to this protein entry history

Dec. 9, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600464 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed