RuvB-like 2 (RUVBL2)
The protein contains 463 amino acids for an estimated molecular weight of 51157 Da.
Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (5' to 3') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity (PubMed:10428817, PubMed:17157868). Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). This modification may both alter nucleosome -DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (PubMed:14966270). This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair (PubMed:14966270). The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400 (PubMed:14966270). NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage (PubMed:14966270). Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (PubMed:24463511). Proposed core component of the chromatin remodeling INO80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome slidi (updated: Nov. 13, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
Biological Process
Box C/D snoRNP assembly
Cellular response to estradiol stimulus
Cellular response to UV
Chromatin organization
Chromatin remodeling
DNA duplex unwinding
DNA recombination
DNA repair
Establishment of protein localization to chromatin
Histone acetylation
Histone H2A acetylation
Histone H4 acetylation
Negative regulation of canonical Wnt signaling pathway
Obsolete negative regulation of estrogen receptor binding
Positive regulation of histone acetylation
Positive regulation of telomerase RNA localization to Cajal body
Positive regulation of transcription by RNA polymerase II
Protein folding
Regulation of growth
Regulation of transcription by RNA polymerase II
Transcription, DNA-templated
Transcriptional activation by promoter-enhancer looping
Cellular Component
Centrosome
Cytoplasm
Cytosol
Dynein axonemal particle
Euchromatin
Extracellular exosome
Ino80 complex
Intracellular anatomical structure
Intracellular ribonucleoprotein complex
Membrane
MLL1 complex
NuA4 histone acetyltransferase complex
Nuclear euchromatin
Nuclear matrix
Nucleoplasm
Nucleus
R2TP complex
Ribonucleoprotein complex
Swr1 complex
Molecular Function
5'-3' DNA helicase activity
ADP binding
ATP binding
ATP-dependent 5'-3' DNA helicase activity
ATP-dependent DNA helicase activity
ATPase binding
Beta-catenin binding
Chromatin DNA binding
Damaged DNA binding
DNA helicase activity
Identical protein binding
Promoter-enhancer loop anchoring activity
Protein homodimerization activity
RNA polymerase II cis-regulatory region sequence-specific DNA binding
RNA polymerase II core promoter sequence-specific DNA binding
RNA polymerase II distal enhancer sequence-specific DNA binding
TBP-class protein binding
TFIID-class transcription factor complex binding
Transcription corepressor activity
Unfolded protein binding
The reference OMIM entry for this protein is 604788
Ruvb, e. coli, homolog-like 2; ruvbl2
Tata box-binding protein-interacting protein, 48-kd; tip48
Tbp-interacting protein, 48-kd
Tip49b
Reptin
Erythrocyte cytosolic protein, 51-kd; ecp51
CLONING
Most organisms contain multiple DNA helicases that catalyze the unwinding of double-stranded DNA to single-stranded DNA in an ATP-dependent manner, an essential process in replication, repair, and transcription. RuvB is a bacterial DNA helicase involved in homologous recombination and double-strand break repair. By amplifying sequences related to 2 EST clones, Kanemaki et al. (1999) obtained a cDNA encoding RuvB-like-2 (RUVBL2), which they termed TIP49B. The deduced 463-amino acid protein contains Walker A and B motifs and is highly similar structurally to other TIP49 family proteins, including TIP49A (RUVBL1; 603449). Western blot analysis revealed that, similar to RUVBL1, RUVBL2 is ubiquitously expressed, with highest levels in testis and thymus. Using affinity chromatography of erythrocyte cytosol, followed by micropeptide sequence analysis, EST database searching, PCR, and RACE, Salzer et al. (1999) isolated cDNAs encoding RUVBL1 and RUVBL2, which they termed ECP54 and ECP51, respectively. Northern blot analysis revealed wide expression of a 1.5-kb RUVBL2 transcript that was most abundant in heart, skeletal muscle, and testis. Wood et al. (2000) identified human homologs of the RuvB protein. By use of the MYC (190080) transactivation domain to affinity purify tightly associated nuclear proteins, they identified RUVBL1 and RUVBL2, which they called TIP48. RUVBL1 and RUVBL2 are both highly conserved in evolution and contain ATPase/helicase motifs. The RUVBL2 protein contains 463 amino acids and shares 45% amino acid identity with RUVBL1. By RT-PCR, Parfait et al. (2000) found that RUVBL2, like RUVBL1, is ubiquitously expressed in human tissues, with highest expression in testis.GENE FUNCTION
Functional analysis by Kanemaki et al. (1999) showed that RUVBL2 has both ATPase and DNA helicase (preferentially moving in the 5-prime to 3-prime direction) activity and that RUVBL2 binds to RUVBL1. Coimmunoprecipitation assays determined that RUVBL1 and RUVBL2 are included in an approximately 700-kD complex in the cell nucleus. Gene disruption analysis showed that like RUVBL1, RUVBL2 is an essential gene for growth in yeast. Wood et al. (2000) found that RUVBL1 and RUVBL2 are complexed with MYC in vivo, and binding is dependent on a MYC domain essential for oncogenic activity. The NuA4 histone acetyltransferase (HAT) complex is responsible for acetylation of the N-terminal tails of histone H4 (see 602822) and H2A (see 613499) in yeast. Its catalytic subunit, Esa1, is homologous to human TIP60 (HTATIP; 601409). Using affinity purification, Western blot analysis, cell fractionation, immunoprecipitation, and mass spectrometry, Doyon et al. (2004) found that TIP60 and its splice variant, TIP60B/PLIP, were part of a multisubunit NuA4 complex with HAT activity in several human cell lines. They identified RUVBL2 as 1 of 3 subunits specific to the human NuA4 HAT complex. Using RNA interference in mouse embryonic stem (ES) cells, Fazzio et al. (2008) found that depletion of any of 7 components of the Tip60-p400 (EP400; 606265) HAT and nucleosome remodeling complex, including Ruvbl2, caused the same phenotype. Unlike normal ES cells, which grow in spherical 3-dimensional colonies, ES cells depleted of any the 7 Tip60-p400 HAT components showed a flattened and elongated morphology, with monolayer growth and reduced cell-cell contacts. These knockdown cells continued to cycle, with reduced cells in S phase and increased cells ... More on the omim web site
Dec. 2, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604788 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed