Biology:RUFY2
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RUN and FYVE domain containing 2 (RUFY2) is a protein that in humans is encoded by the RUFY2 gene.[1] The RUFY2 gene is named for two of its domains, the RUN domain 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.[2]
Gene
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).[3] The gene produces a 2,080 base pair mRNA. There are 18 predicted exons in the human gene [4] with 13 alternative transcripts.[5]
Gene neighborhood
8,180 base pairs upstream of RUFY2 is the protein-coding gene for phenazine biosynthesis-like protein domain containing (PBLD).[6] While 6,770 base pairs downstream from RUFY2 is a DNA2 conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability.[7]
Protein
The protein of RUFY2 consists of 655[8] amino acid residues. RUFY2 protein contains a N-terminal RUN domain and a C-terminal FYVE domain with 2 coiled coil domains in between.[9] The molecular weight of the mature protein is 70.0 kdal[10] with an isoelectric point of 5.494.[11] 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[12] protein that localizes to the nucleus[13] and to membranes of early endosomes.[14] RUFY2 protein contains no signal peptide, no DNA/RNA binding sites, no mitochondrial targeting motifs and no peroxisomal targeting signal in the C-terminus.[13] There is no transmembrane domain in RUFY2.[15]
Domains
RUN domain
The RUN domain is between amino acids 45...168 and consists of the RPIP8, UNC-14, and NESCA proteins.[2] The RUN domain has been shown to have interacting functions with GTPases in the Rap and Rab signal transduction pathways[16] and endosomal membrane trafficking.[2]
DUF972
Domain of unknown function that is part of a family of hypothetical bacterial sequences pfam06156.[17] It make be linked to the YabA initiation control protein which functions as the chromosomal replication initiation control in bacteria.[18]
PspA/IM30
The PspA/IM30 family is a negative regulator of sigma54 transcription initiation factor in bacteria.[19]
FYVE domain
FYVE domain 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.[20]
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 (Etk) in signal transduction pathways.[14]
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.[21]
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: RUFY3, RUFY1, RUNDC3A, RUNDC3B.[22]
There are 60[23] orthologs of RUFY2 that have been identified including mammals, some birds, reptiles and fish.[24] 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)[25] | NCBI mRNA Accession | Sequence Similarity[26] | Protein Length | Common Gene Name |
---|---|---|---|---|---|---|
Homo sapiens[4] | Humans | -- | AF461266 | 100% | 606 | RUFY2 |
Pan troglodytes[27] | Common Chimp | 6.4 | XM_513483 | 99% | 641 | Predicted RUFY2 |
Pongo abelii[28] | Orangutan | 15.7 | NM_001133232 | 99% | 606 | Predicted RUFY2 |
Macaca mulatta[29] | Rhesus monkey | 29.2 | XM_001083568 | 100% | 606 | Predicted RUFY2 |
Sus scrofa[30] | Wild Boar | 94.2 | XM_001928184 | 99% | 640 | Predicted: Predicted RUFY2 |
Mus musculus[31] | Mouse | 942.4 | AF484555 | 95% | 606 | RUFY2 |
Gallus gallus[32] | Chicken | 301.7 | XM_421568 | 95% | 606 | Predicted RUFY2 |
Taeniopygia guttata[33] | Zebra Finch | 295.0 | XM_002190773 | 95% | 590 | RUFY2 transcript variant 2 |
Xenopus (Silurana) tropicalis[34] | Western Clawed Frog | 371.2 | NM_001016214 | 77% | 606 | RUFY2 |
Danio rerio[35] | Zebra Fish | 400.1 | NM_001105681 | 89% | 602 | RUFY2 transcript variant 2 |
Salmo salar[36] | Salmon | 427 | NM_001139888 | 91% | 427 | RUFY2 |
Anolis carolinensis[37] | Carolina anole | 301.7 | XM_003223694 | 91% | 649 | Predicted RUFY2 |
Drosophila melanogaster[38] | Fruit fly | 782.7 | NM_170324 | 63% | 729 | CG31064 |
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.[2]
Expression
RUFY2 protein has been shown to mainly be expressed in the brain, lung, and testes while microarray expression shows RUFY2 ubiquitous expression.[2][39][40]
References
- ↑ "Entrez Gene: RUFY2 RUN and FYVE domain containing 2". https://www.ncbi.nlm.nih.gov/gene?LinkName=nuccore_gene&from_uid=18266357.
- ↑ 2.0 2.1 2.2 2.3 2.4 Kitagishi, Yasuko; Matsuda, Satoru (2013). "RUFY, Rab and Rap Family Proteins Involved in a Regulation of Cell Polarity and Membrane Trafficking". International Journal of Molecular Sciences 14 (3): 6487–6498. doi:10.3390/ijms14036487. ISSN 1422-0067. PMID 23519112.
- ↑ National Center for Biotechnology Information, U.S. National Library of Medicine EntrezGene reference information for RUFY2 RUN and FYVE domain containing 2 (Homo sapiens)
- ↑ 4.0 4.1 NCBI Nucleotide: AF461266. 12 August 2002. https://www.ncbi.nlm.nih.gov/nuccore/AF461266.1.
- ↑ "GeneCards: RUFY2". https://www.genecards.org/cgi-bin/carddisp.pl?gene=RUFY2&search=RUFY2.
- ↑ "phenazine biosynthesis-like protein domain containing (PBLD)". http://genome.ucsc.edu/cgi-bin/hgGene?hgg_gene=uc001jns.1&hgg_prot=P30039&hgg_chrom=chr10&hgg_start=70042416&hgg_end=70092684&hgg_type=knownGene&db=hg19&hgsid=335785853.
- ↑ "DNA2 conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability". http://genome.ucsc.edu/cgi-bin/hgGene?hgg_gene=uc021prt.1&hgg_prot=P51530&hgg_chrom=chr10&hgg_start=70173820&hgg_end=70231879&hgg_type=knownGene&db=hg19&hgsid=335785853.
- ↑ "NCBI:Protein Q8WXA3.2". https://www.ncbi.nlm.nih.gov/protein/Q8WXA3.2.
- ↑ "Toward a confocal subcellular atlas of the human proteome". Mol. Cell. Proteomics 7 (3): 499–508. March 2008. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- ↑ "Methods and algorithms for statistical analysis of protein sequences". Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2002–6. March 1992. doi:10.1073/pnas.89.6.2002. PMID 1549558. Bibcode: 1992PNAS...89.2002B.
- ↑ "Gateway to Isoelectric Point Service". http://www.embl-heidelberg.de/cgi/pi-wrapper.pl.
- ↑ "SOSUI hydrophobicity". http://bp.nuap.nagoya-u.ac.jp/sosui/.
- ↑ 13.0 13.1 "iPSORT". http://ipsort.hgc.jp/.
- ↑ 14.0 14.1 "Interaction between tyrosine kinase Etk and a RUN domain- and FYVE domain-containing protein RUFY1. A possible role of ETK in regulation of vesicle trafficking". J. Biol. Chem. 277 (33): 30219–26. August 2002. doi:10.1074/jbc.M111933200. PMID 11877430.
- ↑ Glasgow, Ed; Littlejohn, T.; Major, F.; Lathrop, R.; Sankoff, R.; Sensen, C. (1998), A hidden Markov model for predicting transmembrane helices in protein sequences, Menlo Park, CA: AAAI Press, pp. 175–182, http://www.cbs.dtu.dk/services/TMHMM-2.0
- ↑ "RUN (IPR004012)". http://www.ebi.ac.uk/interpro/entry/IPR004012.
- ↑ "Family: DUF972 (PF06156)". http://pfam.sanger.ac.uk/family/PF06156.
- ↑ "YabA (IPR010377)". http://www.ebi.ac.uk/interpro/entry/IPR010377.
- ↑ "pfam04012: PspA_IM30". https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=112811.
- ↑ "cd00065:FYVE". https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=238022.
- ↑ Edouard de Castro, Christian J. A. Sigrist, Alexandre Gattiker, Virginie Bulliard, Petra S. Langendijk-Genevaux, Elisabeth Gasteiger, Amos Bairoch & Nicolas Hulo (July 2006). "ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins". Nucleic Acids Research 34 (Web Server issue): W362–W365. doi:10.1093/nar/gkl124. PMID 16845026.
- ↑ "Gene:RUFY2". https://www.ebi.ac.uk/s4/jump?from=aHR0cDovL3d3dy5lYmkuYWMudWsvczQvc3VtbWFyeS9tb2xlY3VsYXIvZ2VuZT90ZXJtPVJVRlkyJmNsYXNzaWZpY2F0aW9uPTk2MDYmdGlkPW5hbWVPcmdFTlNHMDAwMDAyMDQxMzA%3D&hash=2D884&url=http://www.ensembl.org/Homo_sapiens/Gene/Compara_Paralog?g%3DENSG00000204130%3Bdb%3Dcore.
- ↑ "EBI:RUFY2". https://www.ebi.ac.uk/s4/summary/molecular/gene?term=RUFY2&classification=9606&tid=nameOrgENSG00000204130.
- ↑ "Multiple sequence alignment with the Clustal series of programs". Nucleic Acids Res. 31 (13): 3497–500. July 2003. doi:10.1093/nar/gkg500. PMID 12824352.
- ↑ "Time Tree". http://www.timetree.org/.
- ↑ NCBI BLAST. http://blast.ncbi.nlm.nih.gov/Blast.cgi.
- ↑ NCBI Nucleotide: XM_003312585. 25 October 2012. https://www.ncbi.nlm.nih.gov/nuccore/XM_003312585.1.
- ↑ NCBI Nucleotide: NM_001133232. 26 March 2023. https://www.ncbi.nlm.nih.gov/nuccore/NM_001133232.1.
- ↑ NCBI Nucleotide: XM_001083568. June 2010. https://www.ncbi.nlm.nih.gov/nuccore/XM_001083568.2.
- ↑ NCBI Nucleotide: XM_003127928. 5 November 2010. https://www.ncbi.nlm.nih.gov/nuccore/XM_001928184.1.
- ↑ NCBI Nucleotide: AF484555. 24 April 2002. https://www.ncbi.nlm.nih.gov/nuccore/AF484555.1.
- ↑ NCBI Nucleotide: XM_421568. 16 December 2011. https://www.ncbi.nlm.nih.gov/nuccore/XM_421568.3.
- ↑ NCBI Nucleotide: XM_002190773. 12 February 2013. https://www.ncbi.nlm.nih.gov/nuccore/XM_002190773.2.
- ↑ NCBI Nucleotide: NM_001016214. 22 December 2019. https://www.ncbi.nlm.nih.gov/nuccore/NM_001016214.2.
- ↑ NCBI Nucleotide: NM_001105681. 6 August 2017. https://www.ncbi.nlm.nih.gov/nuccore/NM_001105681.2.
- ↑ NCBI Nucleotide: NM_001139888. 12 January 2022. https://www.ncbi.nlm.nih.gov/nuccore/NM_001139888.1.
- ↑ NCBI Nucleotide: XM_003223694. 30 March 2011. https://www.ncbi.nlm.nih.gov/nuccore/XM_003223694.1.
- ↑ NCBI Nucleotide: NM_170324. 16 January 2013. https://www.ncbi.nlm.nih.gov/nuccore/NM_170324.2.
- ↑ "LRRTM3 promotes processing of amyloid-precursor protein by BACE1 and is a positional candidate gene for late-onset Alzheimer's disease". Proc. Natl. Acad. Sci. U.S.A. 103 (47): 17967–72. November 2006. doi:10.1073/pnas.0605461103. PMID 17098871. Bibcode: 2006PNAS..10317967M.
- ↑ "RUFY2 Expression". http://biogps.org/#goto=genereport&id=55680.
![]() | Original source: https://en.wikipedia.org/wiki/RUFY2.
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