Disease relevance of ARF4

• Based on this sequence, selective oligonucleotide probes were prepared and used to isolate clone psi ARF 4, a putative ARF pseudogene, from a human genomic library in lambda phage EMBL3 [1].
• Kinetic analysis of vesicular stomatitis virus G protein transport suggested that the hARF4 peptide inhibits a late vesicle fusion step [2].
• Rhodopsin C terminus, the site of mutations causing retinal disease, regulates trafficking by binding to ADP-ribosylation factor 4 (ARF4) [3].
• Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients with brain tumors [4].

High impact information on ARF4

• The effects of blocking ARF4 action were functionally equivalent to the effects of blocking the rhodopsin C-terminal sorting signal [3].
• Here, we report that this sorting motif binds specifically to the small GTPase ARF4, a member of the ARF family of membrane budding and protein sorting regulators [3].
• ARF4 was essential for the generation of post-Golgi carriers targeted to the rod outer segments of retinal photoreceptors [3].
• It appears that psi ARF 4 arose during human evolution by integration of processed ARF 4 mRNA into the genome [1].
• The GTP-bound form of ARF5 with amino acid residues in the N terminus mutated to those in ARF4 (another class II ARF) also bound to arfophilin, suggesting it is a target protein for GTP-bound forms of class II ARFs [5].

Biological context of ARF4

• They have recently been shown to play a role in vesicular trafficking and as activators of phospholipase D. The organization of the human ARF4 gene was determined from a genomic clone isolated from an arrayed PAC genomic library [6].
• The proximal 5'-flanking region of the human ARF4 gene lacks a TATA box, is highly GC rich, and contains multiple potential Spl-binding sites [6].
• Deduced amino acid sequences for rat ARFs 1, 2, 3, 5 and 6 were identical to those of the known cognate human and bovine ARFs; rat ARF4 was 96% identical to human ARF4 [7].
• Sequences of 3'-untranslated regions of rat and human ARF 4 mRNA were very similar with identical polyadenylation signals at similar positions [8].
• On Northern analysis of the developmental expression of rat ARF 4 mRNA, appearance of the shorter species was consistent with its involvement in a late stage of spermatogenesis [8].

Anatomical context of ARF4

• Two peptides corresponding to the NH2-terminal 16 amino acids of human ARF1 and ARF4 blocked GTP gamma S stimulation of fusion in dilute cytosol and reversed GTP gamma S inhibition of fusion in concentrated cytosol [9].
• A proposed cascade of molecular interactions, initiated by the rhodopsin C-terminal sequence VXPX-COOH during trafficking from the Golgi/TGN in retinal photoreceptors, is relayed by the small GTPase ARF4 to the downstream effectors [10].
• Of the ARF 4 mRNAs identified by RACE-PCR, with sizes of 1.1, 1.3, and 1.8 kb, the 1.1-kb mRNA was predominant in adult testis [8].

Associations of ARF4 with chemical compounds

• ADP-ribosylation factor 4 (ARF4) is a member of a family of approximately 20 kDa guanine nucleotide-binding proteins that were initially identified by their ability to stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro [6].

Other interactions of ARF4

• Both hARF1 and hARF4 encode GTP-binding proteins with predicted molecular masses of 20,000-21,000 Da [11].
• We observe that the NH2 termini of Group II ARFs (ARF4 and ARF5) are efficiently processed by removal of the initiating methionine [12].

References