RUN and FYVE domain containing 2 (RUFY2) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''RUFY2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The RUFY2 gene is named for two of its domains, the

RUN domain The RUN domain is an evolutionary conserved protein–protein binding protein domain. They often interact with GTPases and could play a role in multiple Ras superfamily, Ras-like GTPase Cell signaling, signalling pathways. This domain is pres ...

and FYVE domains. RUFY2 is a member of the RUFY family of proteins that include RUFY1, RUFY2, RUFY3, and RUFY4. RUFY2 protein has a dynamic role in endosomal membrane trafficking.

Gene

The human ''RUFY2'' gene is located on the long (q) arm of

chromosome 10 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tota ...

at region 21 band 3, from

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

70,100,864 to base pair 70,167,051 on the reverse strand (Build GRCh37/hg19
(map)
The gene produces a 2,080

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

. There are 18 predicted

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

in the human gene with 13 alternative transcripts.

Gene neighborhood

8,180 base pairs upstream of RUFY2 is the protein-coding gene for phenazine biosynthesis-like protein domain containing (PBLD). While 6,770 base pairs downstream from RUFY2 is a DNA2 conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability.

Protein

The protein of RUFY2 consists of 655 amino acid residues. RUFY2 protein contains a N-terminal RUN domain and a C-terminal FYVE domain with 2 coiled coil domains in between. The molecular weight of the mature protein is 70.0 kdal with an isoelectric point of 5.494. 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 protein that localizes to the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

and to membranes of early endosomes. RUFY2 protein contains no signal peptide, no DNA/RNA binding sites, no mitochondrial targeting motifs and no

peroxisomal A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen per ...

targeting signal in the C-terminus. There is no transmembrane domain in RUFY2.

Domains

RUN domain

The RUN domain is between amino acids 45...168 and consists of the RPIP8, UNC-14, and NESCA proteins. The RUN domain has been shown to have interacting functions with

GTPases GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a pro ...

in the Rap and Rab

signal transduction pathways Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

and

endosomal Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...

membrane trafficking.

DUF972

Domain of unknown function that is part of a family of hypothetical bacterial sequences pfam06156. It make be linked to the YabA initiation control protein which functions as the chromosomal replication initiation control in bacteria.

PspA/IM30

The PspA/IM30 family is a negative regulator of sigma54

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

initiation factor in bacteria.

FYVE domain

FYVE domain In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidylin ...

consists of Fab-1, YGL023, Vps27, and EEA1 proteins. Within the FYVE domain there are Zinc finger binding sites that interact with phosphatidylinositol-3-phosphate, to bring target proteins to membrane lipids.

Protein interactions

The proline rich motif in the FYVE domain of RUFY2 has been shown to have binding activity with the SH3 domain of

EPHA3 EPH receptor A3 (ephrin type-A receptor 3) is a protein that in humans is encoded by the ''EPHA3'' gene. Function This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been ...

(Etk) in signal transduction pathways.

Post-translational modifications

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.

Other notable modification sites within the protein

*4 Lysine acetylation sites *4 N-myristolation sites *3 N-glycosylation sites

Homology and evolution

RUFY2 has 4

paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

: RUFY3, RUFY1, RUNDC3A, RUNDC3B. There are 60

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

of RUFY2 that have been identified including mammals, some birds, reptiles and fish. RUFY2 is highly conserved among its orthologs but is not present in plants,

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

archea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaeb ...

protist A protist () is any eukaryotic organism (that is, an organism whose cells contain a cell nucleus) that is not an animal, plant, or fungus. While it is likely that protists share a common ancestor (the last eukaryotic common ancestor), the exc ...

Species distribution

The following table lists the homologs of RUFY2. Unrooted phylogenetic tree of RUFY2

Clinical significance

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.

Expression

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

References

{{Reflist, 35em Protein domains