RUFY2

Homo sapiens Chromosome 10 with RUFY2 gene highlighted in red

The human RUFY2 gene is located on the long (q) arm of chromosome 10 at region 21 band 3, from base pair 70,100,864 to base pair 70,167,051 on the reverse strand (Build GRCh37/hg19) (map).[7] The gene produces a 2,080 base pair mRNA. There are 18 predicted exons in the human gene [8] with 13 alternative transcripts.[9]

Features of the RUFY2 protein depicting the RUN, DUF972, PspA_IM30 and FYVE domains.

The protein of RUFY2 consists of 655[12] amino acid residues. RUFY2 protein contains a N-terminal RUN domain and a C-terminal FYVE domain with 2 coiled coil domains in between.[13] The molecular weight of the mature protein is 70.0 kdal[14] with an isoelectric point of 5.494.[15] PHYRE2 protein tertiary structure tool suggests that RUFY2 has 15 alpha helices and the longest helix spanning amino acids 199...512 as seen in the figure to the right. RUFY2 is a soluble[16] protein that localizes to the nucleus[17] and to membranes of early endosomes.[18] RUFY2 protein contains no signal peptide, no DNA/RNA binding sites, no mitochondrial targeting motifs and no peroxisomal targeting signal in the C-terminus.[17] There is no transmembrane domain in RUFY2.[19]

Post-translational modifications

Modification sites on RUFY2 protein

RUFY2 possibly has 6 phosphorylation sites and are located mainly in the DUF972 region. RUFY2 also has 6 protein kinase C phosphorylation sites that are located mainly within the FYVE domain.[25]

RUFY2 has 4 paralogs: RUFY3, RUFY1, RUNDC3A, RUNDC3B.[26]

There are 60[27] orthologs of RUFY2 that have been identified including mammals, some birds, reptiles and fish.[28] RUFY2 is highly conserved among its orthologs but is not present in plants, bacteria, archea or protist.

Species distribution

The following table lists the homologs of RUFY2.

Genus Species	Organism Common Name	Divergence from Humans (MYA)[29]	NCBI mRNA Accession	Sequence Similarity[30]	Protein Length	Common Gene Name
Homo sapiens[8]	Humans	--	AF461266	100%	606	RUFY2
Pan troglodytes[31]	Common Chimp	6.4	XM_513483	99%	641	Predicted RUFY2
Pongo abelii[32]	Orangutan	15.7	NM_001133232	99%	606	Predicted RUFY2
Macaca mulatta[33]	Rhesus monkey	29.2	XM_001083568	100%	606	Predicted RUFY2
Sus scrofa[34]	Wild Boar	94.2	XM_001928184	99%	640	Predicted: Predicted RUFY2
Mus musculus[35]	Mouse	942.4	AF484555	95%	606	RUFY2
Gallus gallus[36]	Chicken	301.7	XM_421568	95%	606	Predicted RUFY2
Taeniopygia guttata[37]	Zebra Finch	295.0	XM_002190773	95%	590	RUFY2 transcript variant 2
Xenopus (Silurana) tropicalis[38]	Western Clawed Frog	371.2	NM_001016214	77%	606	RUFY2
Danio rerio[39]	Zebra Fish	400.1	NM_001105681	89%	602	RUFY2 transcript variant 2
Salmo salar[40]	Salmon	427	NM_001139888	91%	427	RUFY2
Anolis carolinensis[41]	Carolina anole	301.7	XM_003223694	91%	649	Predicted RUFY2
Drosophila melanogaster[42]	Fruit fly	782.7	NM_170324	63%	729	CG31064

Unrooted phylogenetic tree of RUFY2 protein

Certain neurodegenerative diseases such as Alzheimer's have been found to have defective endosomal trafficking. Therefore, the involvement of RUFY2 protein domains, RUN and FYVE, may possibly play a role in neurodegenerative diseases such as Alzheimer's.[6]

RUFY2 protein has been shown to mainly be expressed in the brain, lung, and testes while microarray expression shows RUFY2 ubiquitous expression.[6][43][44]