RUFY2

Last updated
RUFY2
Identifiers
Aliases RUFY2 , RABIP4R, ZFYVE13, RUN and FYVE domain containing 2
External IDs OMIM: 610328 MGI: 1917682 HomoloGene: 23064 GeneCards: RUFY2
Orthologs
SpeciesHumanMouse
Entrez

55680

70432

Ensembl

ENSG00000204130

ENSMUSG00000020070

UniProt

Q8WXA3

Q8R4C2

RefSeq (mRNA)

NM_001042417
NM_001278225
NM_017987
NM_001330103

NM_027425

RefSeq (protein)

NP_001035882
NP_001265154
NP_001317032
NP_060457

NP_081701

Location (UCSC) Chr 10: 68.34 – 68.41 Mb Chr 10: 62.82 – 62.85 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

RUN and FYVE domain containing 2 (RUFY2) is a protein that in humans is encoded by the RUFY2 gene. [5] 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. [6]

Contents

Gene

Homo sapiens Chromosome 10 with RUFY2 gene highlighted in red RUFY2 gene.png
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]

Gene neighborhood

8,180 base pairs upstream of RUFY2 is the protein-coding gene for phenazine biosynthesis-like protein domain containing (PBLD). [10] While 6,770 base pairs downstream from RUFY2 is a DNA2 conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability. [11]

Protein

Features of the RUFY2 protein depicting the RUN, DUF972, PspA_IM30 and FYVE domains. Homo sapiens RUFY2 protein domains.pdf
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]

Domains

RUN domain

The RUN domain is between amino acids 45...168 and consists of the RPIP8, UNC-14, and NESCA proteins. [6] The RUN domain has been shown to have interacting functions with GTPases in the Rap and Rab signal transduction pathways [20] and endosomal membrane trafficking. [6]

DUF972

Domain of unknown function that is part of a family of hypothetical bacterial sequences pfam06156. [21] It make be linked to the YabA initiation control protein which functions as the chromosomal replication initiation control in bacteria. [22]

PspA/IM30

The PspA/IM30 family is a negative regulator of sigma54 transcription initiation factor in bacteria. [23]

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. [24]

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. [18]

Post-translational modifications

Modification sites on RUFY2 protein Modification sites on RUFY2 protein.png
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]

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. [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 NameDivergence from Humans (MYA) [29] NCBI mRNA AccessionSequence Similarity [30] Protein LengthCommon Gene Name
Homo sapiens [8] Humans--AF461266100%606RUFY2
Pan troglodytes [31] Common Chimp6.4XM_51348399%641Predicted RUFY2
Pongo abelii [32] Orangutan15.7NM_00113323299%606Predicted RUFY2
Macaca mulatta [33] Rhesus monkey29.2XM_001083568100%606Predicted RUFY2
Sus scrofa [34] Wild Boar94.2XM_00192818499%640Predicted: Predicted RUFY2
Mus musculus [35] Mouse942.4AF48455595%606RUFY2
Gallus gallus [36] Chicken301.7XM_42156895%606Predicted RUFY2
Taeniopygia guttata [37] Zebra Finch295.0XM_00219077395%590RUFY2 transcript variant 2
Xenopus (Silurana) tropicalis [38] Western Clawed Frog371.2NM_00101621477%606RUFY2
Danio rerio [39] Zebra Fish400.1NM_00110568189%602RUFY2 transcript variant 2
Salmo salar [40] Salmon427NM_00113988891%427RUFY2
Anolis carolinensis [41] Carolina anole301.7XM_00322369491%649Predicted RUFY2
Drosophila melanogaster [42] Fruit fly782.7NM_17032463%729CG31064
Unrooted phylogenetic tree of RUFY2 protein Unrooted phylogenetic tree of RUFY2.jpg
Unrooted phylogenetic tree of RUFY2 protein

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. [6]

Expression

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]

Related Research Articles

<span class="mw-page-title-main">EEA1</span> Protein-coding gene in humans

The gene EEA1 encodes for the 1400 amino acid protein, Early Endosome Antigen 1.

<span class="mw-page-title-main">FGD1</span> Protein-coding gene in the species Homo sapiens

FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. Orthologs of the FGD1 gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and C. elegans. It is a member of the FYVE, RhoGEF and PH domain containing family.

<span class="mw-page-title-main">BMX (gene)</span> Type of enzyme

Cytoplasmic tyrosine-protein kinase BMX is an enzyme that in humans is encoded by the BMX gene.

<span class="mw-page-title-main">ZFYVE16</span> Protein-coding gene in the species Homo sapiens

Zinc finger FYVE domain-containing protein 16 is a protein that in humans is encoded by the ZFYVE16 gene.

<span class="mw-page-title-main">YIF1A</span> Protein-coding gene in the species Homo sapiens

Protein YIF1A is a Yip1 domain family proteins that in humans is encoded by the YIF1A gene.

<span class="mw-page-title-main">FGD4</span> Protein-coding gene in humans

FYVE, RhoGEF and PH domain-containing protein 4 is a protein encoded in humans by the FGD4 gene.

<span class="mw-page-title-main">RUFY1</span> Protein-coding gene in humans

RUN and FYVE domain-containing protein 1 is a protein that in humans is encoded by the RUFY1 gene. It is named after the RUN and FYVE domains it contains.

<span class="mw-page-title-main">LRRC40</span> Protein-coding gene in the species Homo sapiens

Leucine rich repeat containing 40 (LRRC40) is a protein that in humans is encoded by the LRRC40 gene.

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-like GTPase signalling pathways.

<span class="mw-page-title-main">Interferon-inducible GTPase 5</span> Protein-coding gene in the species Homo sapiens

Interferon-inducible GTPase 5 also known as immunity-related GTPase cinema 1 (IRGC1) is an enzyme that in humans is coded by the IRGC gene. It is predicted to behave like other proteins in the p47-GTPase-like and IRG families. It is most expressed in the testis.

<span class="mw-page-title-main">TMEM131</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 131 (TMEM131) is a protein that is encoded by the TMEM131 gene in humans. The TMEM131 protein contains three domains of unknown function 3651 (DUF3651) and two transmembrane domains. This protein has been implicated as having a role in T cell function and development. TMEM131 also resides in a locus (2q11.1) that is associated with Nievergelt's Syndrome when deleted.

<span class="mw-page-title-main">Transmembrane Protein 205</span> Protein-coding gene in the species Homo sapiens

Transmembrane Protein 205 (TMEM205) is a protein encoded on chromosome 19 by the TMEM205 gene.

<span class="mw-page-title-main">ZFYVE27</span> Protein-coding gene in the species Homo sapiens

Zinc finger, FYVE domain containing 27 is a protein that in humans is encoded by the ZFYVE27 gene.

<span class="mw-page-title-main">SLC46A3</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 46 member 3 (SLC46A3) is a protein that in humans is encoded by the SLC46A3 gene. Also referred to as FKSG16, the protein belongs to the major facilitator superfamily (MFS) and SLC46A family. Most commonly found in the plasma membrane and endoplasmic reticulum (ER), SLC46A3 is a multi-pass membrane protein with 11 α-helical transmembrane domains. It is mainly involved in the transport of small molecules across the membrane through the substrate translocation pores featured in the MFS domain. The protein is associated with breast and prostate cancer, hepatocellular carcinoma (HCC), papilloma, glioma, obesity, and SARS-CoV. Based on the differential expression of SLC46A3 in antibody-drug conjugate (ADC)-resistant cells and certain cancer cells, current research is focused on the potential of SLC46A3 as a prognostic biomarker and therapeutic target for cancer. While protein abundance is relatively low in humans, high expression has been detected particularly in the liver, small intestine, and kidney.

<span class="mw-page-title-main">EVI5L</span> Protein-coding gene in the species Homo sapiens

EVI5L is a protein that in humans is encoded by the EVI5L gene. EVI5L is a member of the Ras superfamily of monomeric guanine nucleotide-binding (G) proteins, and functions as a GTPase-activating protein (GAP) with a broad specificity. Measurement of in vitro Rab-GAP activity has shown that EVI5L has significant Rab2A- and Rab10-GAP activity.

<span class="mw-page-title-main">SSMEM1</span> Protein-coding gene in the species Homo sapiens

Serine-rich single pass membrane protein 1 is a protein that in humans is encoded by the SSMEM1 gene.

<span class="mw-page-title-main">TMCO6</span> Protein-coding gene in the species Homo sapiens

Transmembrane and coiled-coil domain 6, TMCO6, is a protein that in humans is encoded by the TMCO6 gene with aliases of PRO1580, HQ1580 or FLJ39769.1.

<span class="mw-page-title-main">Zinc finger protein 684</span> Protein found in humans

Zinc finger protein 684 is a protein that in humans is encoded by the ZNF684 gene.

Eps15 homology domain-containing protein 3, abbreviated as EHD3 and also known as PAST3, is a protein encoded by the EHD3 gene. It has been observed in humans, mice and rats. It belongs to the EHD protein family, a group of four membrane remodeling proteins related to the Dynamin superfamily of large GTPases. Although the four of them are 70-80% amino acid identical, they all have different locations. Its main function is related to endocytic transport.

<span class="mw-page-title-main">CLIP4</span> Protein

CAP-Gly Domain Containing Linker Protein Family Member 4 is a protein that in humans is encoded by the CLIP4 gene. In terms of conserved domains, the CLIP4 gene contains primarily ankyrin repeats and the eponymous CAP-Gly domains. The structure of the CLIP4 protein is largely made up of coil, with alpha helices dominating the rest of the protein. CLIP4 mRNA expression occurs largely in the adrenal cortex and atrioventricular node. The literature encompassing CLIP4's conserved domains and paralogs points toward microtubule regulation as a possible function of CLIP4.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000204130 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020070 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: RUFY2 RUN and FYVE domain containing 2".
  6. 1 2 3 4 5 Kitagishi Y, Matsuda S (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. PMC   3634510 . PMID   23519112.
  7. ↑ National Center for Biotechnology Information, U.S. National Library of Medicine EntrezGene reference information for RUFY2 RUN and FYVE domain containing 2 (Homo sapiens)
  8. 1 2 "NCBI Nucleotide: AF461266". 12 August 2002.{{cite journal}}: Cite journal requires |journal= (help)
  9. ↑ "GeneCards: RUFY2".
  10. ↑ "phenazine biosynthesis-like protein domain containing (PBLD)".
  11. ↑ "DNA2 conserved helicase/nuclease involved in the maintenance of mitochondrial and nuclear DNA stability".
  12. ↑ "NCBI:Protein Q8WXA3.2".
  13. ↑ Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H (March 2008). "Toward a confocal subcellular atlas of the human proteome". Mol. Cell. Proteomics. 7 (3): 499–508. doi: 10.1074/mcp.M700325-MCP200 . PMID   18029348.
  14. ↑ Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2002–6. Bibcode:1992PNAS...89.2002B. doi: 10.1073/pnas.89.6.2002 . PMC   48584 . PMID   1549558.
  15. ↑ "Gateway to Isoelectric Point Service". Archived from the original on 2008-10-26.
  16. ↑ "SOSUI hydrophobicity". Archived from the original on 2004-03-18. Retrieved 2013-05-09.
  17. 1 2 "iPSORT".
  18. 1 2 Yang J, Kim O, Wu J, Qiu Y (August 2002). "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. doi: 10.1074/jbc.M111933200 . PMID   11877430.
  19. ↑ Glasgow E, 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
  20. ↑ "RUN (IPR004012)".
  21. ↑ "Family: DUF972 (PF06156)".
  22. ↑ "YabA (IPR010377)".
  23. ↑ "pfam04012: PspA_IM30".
  24. ↑ "cd00065:FYVE".
  25. ↑ 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. PMC   1538847 . PMID   16845026.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ↑ "Gene:RUFY2".
  27. ↑ "EBI:RUFY2".
  28. ↑ Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG, Thompson JD (July 2003). "Multiple sequence alignment with the Clustal series of programs". Nucleic Acids Res. 31 (13): 3497–500. doi:10.1093/nar/gkg500. PMC   168907 . PMID   12824352.
  29. ↑ "Time Tree".
  30. ↑ "NCBI BLAST".{{cite journal}}: Cite journal requires |journal= (help)
  31. ↑ "NCBI Nucleotide: XM_003312585". 25 October 2012.{{cite journal}}: Cite journal requires |journal= (help)
  32. ↑ "NCBI Nucleotide: NM_001133232". 26 March 2023.{{cite journal}}: Cite journal requires |journal= (help)
  33. ↑ "NCBI Nucleotide: XM_001083568". June 2010.{{cite journal}}: Cite journal requires |journal= (help)
  34. ↑ "NCBI Nucleotide: XM_003127928". 5 November 2010.{{cite journal}}: Cite journal requires |journal= (help)
  35. ↑ "NCBI Nucleotide: AF484555". 24 April 2002.{{cite journal}}: Cite journal requires |journal= (help)
  36. ↑ "NCBI Nucleotide: XM_421568". 16 December 2011.{{cite journal}}: Cite journal requires |journal= (help)
  37. ↑ "NCBI Nucleotide: XM_002190773". 12 February 2013.{{cite journal}}: Cite journal requires |journal= (help)
  38. ↑ "NCBI Nucleotide: NM_001016214". 22 December 2019.{{cite journal}}: Cite journal requires |journal= (help)
  39. ↑ "NCBI Nucleotide: NM_001105681". 6 August 2017.{{cite journal}}: Cite journal requires |journal= (help)
  40. ↑ "NCBI Nucleotide: NM_001139888". 12 January 2022.{{cite journal}}: Cite journal requires |journal= (help)
  41. ↑ "NCBI Nucleotide: XM_003223694". 30 March 2011.{{cite journal}}: Cite journal requires |journal= (help)
  42. ↑ "NCBI Nucleotide: NM_170324". 16 January 2013.{{cite journal}}: Cite journal requires |journal= (help)
  43. ↑ Majercak J, Ray WJ, Espeseth A, Simon A, Shi XP, Wolffe C, Getty K, Marine S, Stec E, Ferrer M, Strulovici B, Bartz S, Gates A, Xu M, Huang Q, Ma L, Shughrue P, Burchard J, Colussi D, Pietrak B, Kahana J, Beher D, Rosahl T, Shearman M, Hazuda D, Sachs AB, Koblan KS, Seabrook GR, Stone DJ (November 2006). "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. Bibcode:2006PNAS..10317967M. doi: 10.1073/pnas.0605461103 . PMC   1635650 . PMID   17098871.
  44. ↑ "RUFY2 Expression".
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