Summary: Ribonuclease HII
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Ribonuclease H Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
|retroviral ribonuclease H|
|PDB structures||RCSB PDB PDBe PDBsum|
Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from bacteria to archaea to eukaryotes.
The family is divided into evolutionarily related groups with slightly different substrate preferences, broadly designated ribonuclease H1 and H2. The human genome encodes both H1 and H2. Human ribonuclease H2 is a heterotrimeric complex composed of three subunits, mutations in any of which are among the genetic causes of a rare disease known as Aicardiâ€“GoutiÃ¨res syndrome. A third type, closely related to H2, is found only in a few prokaryotes, whereas H1 and H2 occur in all domains of life. Additionally, RNase H1-like retroviral ribonuclease H domains occur in multidomain reverse transcriptase proteins, which are encoded by retroviruses such as HIV and are required for viral replication.
Classification and nomenclature
Ribonuclease H is a family of endonuclease enzymes with a shared substrate specificity for the RNA strand of RNA-DNA duplexes. By definition, RNases H cleave RNA backbone phosphodiester bonds to leave a 3' hydroxyl and a 5' phosphate group. RNases H have been proposed as members of an evolutionarily related superfamily encompassing other nucleases and nucleic acid processing enzymes such as retroviral integrases, DNA transposases, Holliday junction resolvases, Piwi and Argonaute proteins, various exonucleases, and the spliceosomal protein Prp8.
RNases H can be broadly divided into two subtypes, H1 and H2, which for historical reasons are given Arabic numeral designations in eukaryotes and Roman numeral designations in prokaryotes. Thus the Escherichia coli RNase HI is a homolog of the Homo sapiens RNase H1. In E. coli and many other prokaryotes, the rnhA gene encodes HI and the rnhB gene encodes HII. A third related class, called HIII, occurs in a few bacteria and archaea; it is closely related to prokaryotic HII enzymes.
The structure of RNase H commonly consists of a 5-stranded Î²-sheet surrounded by a distribution of Î±-helices. All RNases H have an active site centered on a conserved sequence motif composed of aspartate and glutamate residues, often referred to as the DEDD motif. These residues interact with catalytically required magnesium ions.
RNases H2 are larger than H1 and usually have additional helices. The domain organization of the enzymes varies; some prokaryotic and most eukaryotic members of the H1 group have an additional small domain at the N-terminus known as the "hybrid binding domain", which facilitates binding to RNA:DNA hybrid duplexes and sometimes confers increased processivity. While all members of the H1 group and the prokaryotic members of the H2 group function as monomers, eukaryotic H2 enzymes are obligate heterotrimers. Prokaryotic HIII enzymes are members of the broader H2 group and share most structural features with H2, with the addition of an N-terminal TATA box binding domain. Retroviral RNase H domains occurring in multidomain reverse transcriptase proteins have structures closely resembling the H1 group.
RNases H1 have been extensively studied to explore the relationships between structure and enzymatic activity. They are also used, especially the E. coli homolog, as model systems to study protein folding. Within the H1 group, a relationship has been identified between higher substrate-binding affinity and the presence of structural elements consisting of a helix and flexible loop providing a larger and more basic substrate-binding surface. The C-helix has a scattered taxonomic distribution; it is present in the E. coli and human RNase H1 homologs and absent in the HIV RNase H domain, but examples of retroviral domains with C-helices do exist.
Ribonuclease H enzymes cleave the phosphodiester bonds of RNA in a double-stranded RNA:DNA hybrid, leaving a 3' hydroxyl and a 5' phosphate group on either end of the cut site with a two-metal-ion catalysis mechanism, in which two divalent cations, such as Mg2+ and Mn2+, directly participate in the catalytic function. Depending on the differences in their amino acid sequences, these RNases H are classified into type 1 and type 2 RNases H. Type 1 RNases H have prokaryotic and eukaryotic RNases H1 and retroviral RNase H. Type 2 RNases H have prokaryotic and eukaryotic RNases H2 and bacterial RNase H3. These RNases H exist in a monomeric form, except for eukaryotic RNases H2, which exist in a heterotrimeric form. RNase H1 and H2 have distinct substrate preferences and distinct but overlapping functions in the cell. In prokaryotes and lower eukaryotes, neither enzyme is essential, whereas both are believed to be essential in higher eukaryotes. The combined activity of both H1 and H2 enzymes is associated with maintenance of genome stability due to the enzymes' degradation of the RNA component of R-loops.
Ribonuclease H1 enzymes require at least four ribonucleotide-containing base pairs in a substrate and cannot remove a single ribonucleotide from a strand that is otherwise composed of deoxyribonucleotides. For this reason, it is considered unlikely that RNase H1 enzymes are involved in the processing of RNA primers from Okazaki fragments during DNA replication. RNase H1 is not essential in unicellular organisms where it has been investigated; in E. coli, RNase H1 knockouts confer a temperature-sensitive phenotype, and in S. cerevisiae, they produce defects in stress response.
In many eukaryotes, including mammals, RNase H1 genes include a mitochondrial targeting sequence, leading to expression of isoforms with and without the MTS present. As a result, RNase H1 is localized to both mitochondria and the nucleus. In knockout mouse models, RNase H1-null mutants are lethal during embryogenesis due to defects in replicating mitochondrial DNA. The defects in mitochondrial DNA replication induced by loss of RNase H1 are likely due to defects in R-loop processing.
In prokaryotes, RNase H2 is enzymatically active as a monomeric protein. In eukaryotes, it is an obligate heterotrimer composed of a catalytic subunit A and structural subunits B and C. While the A subunit is closely homologous to the prokaryotic RNase H2, the B and C subunits have no apparent homologs in prokaryotes and are poorly conserved at the sequence level even among eukaryotes. The B subunit mediates protein-protein interactions between the H2 complex and PCNA, which localizes H2 to replication foci.
Both prokaryotic and eukaryotic H2 enzymes can cleave single ribonucleotides in a strand. however, they have slightly different cleavage patterns and substrate preferences: prokaryotic enzymes have lower processivity and hydrolyze successive ribonucleotides more efficiently than ribonucleotides with a 5' deoxyribonucleotide, while eukaryotic enzymes are more processive and hydrolyze both types of substrate with similar efficiency. The substrate specificity of RNase H2 gives it a role in ribonucleotide excision repair, removing misincorporated ribonucleotides from DNA, in addition to R-loop processing. Although both H1 and H2 are present in the mammalian cell nucleus, H2 is the dominant source of RNase H activity there and is important for maintaining genome stability.
Some prokaryotes possess an additional H2-type gene designated RNase HIII in the Roman-numeral nomenclature used for the prokaryotic genes. HIII proteins are more closely related to the H2 group by sequence identity and structural similarity, but have substrate preferences that more closely resemble H1. Unlike HI and HII, which are both widely distributed among prokaryotes, HIII is found in only a few organisms with a scattered taxonomic distribution; it is somewhat more common in archaea and is rarely or never found in the same prokaryotic genome as HI.
The charged residues bind two metal ions that are required for catalysis; under physiological conditions these are magnesium ions, but manganese also usually supports enzymatic activity, while calcium or high concentration of Mg2+ inhibits activity.
Based on experimental evidence and computer simulations the enzyme activates a water molecule bound to one of the metal ions with the conserved histidine. The transition state is associative in nature  and forms an intermediate with protonated phosphate and deprotonated alkoxide leaving group. The leaving group is protonated via the glutamate which has an elevated pKa and is likely to be protonated. The mechanism is similar to RNase T and the RuvC subunit in the Cas9 enzyme which both also use a histidine and a two-metal ion mechanism.
The mechanism of the release of the cleaved product is still unresolved. Experimental evidence from time-resolved crystallography and similar nucleases points to a role of a third ion in the reaction recruited to the active site. 
In human biology
The human genome contains four genes encoding RNase H:
- RNASEH1, an example of the H1 (monomeric) subtype
- RNASEH2A, the catalytic subunit of the trimeric H2 complex
- RNASEH2B, a structural subunit of the trimeric H2 complex
- RNASEH2C, a structural subunit of the trimeric H2 complex
In addition, genetic material of retroviral origin appears frequently in the genome, reflecting integration of the genomes of human endogenous retroviruses. Such integration events result in the presence of genes encoding retroviral reverse transcriptase, which includes an RNase H domain. An example is ERVK6. Long terminal repeat (LTR) and non-long terminal repeat (non-LTR) retrotransposons are also common in the genome and often include their own RNase H domains, with a complex evolutionary history.
Role in disease
Mutations in any of the three RNase H2 subunits are well-established as causes of a rare genetic disorder known as Aicardiâ€“GoutiÃ¨res syndrome (AGS), which manifests as neurological and dermatological symptoms at an early age. The symptoms of AGS closely resemble those of congenital viral infection and are associated with inappropriate upregulation of type I interferon. AGS can also be caused by mutations in other genes: TREX1, SAMHD1, ADAR, and MDA5/IFIH1, all of which are involved in nucleic acid processing. Characterization of mutational distribution in an AGS patient population found 5% of all AGS mutations in RNASEH2A, 36% in 2B, and 12% in 2C. Mutations in 2B have been associated with somewhat milder neurological impairment and with an absence of interferon-induced gene upregulation that can be detected in patients with other AGS-associated genotypes.
Two groups of viruses use reverse transcription as part of their life cycles: retroviruses, which encode their genomes in single-stranded RNA and replicate through a double-stranded DNA intermediate; and dsDNA-RT viruses, which replicate their double-stranded DNA genomes through an RNA "pregenome" intermediate. Pathogenic examples include human immunodeficiency virus and hepatitis B virus, respectively. Both encode large multifunctional reverse transcriptase (RT) proteins containing RNase H domains.
Retroviral RT proteins from HIV-1 and murine leukemia virus are the best-studied members of the family. Retroviral RT is responsible for converting the virus' single-stranded RNA genome into double-stranded DNA. This process requires three steps: first, RNA-dependent DNA polymerase activity produces minus-strand DNA from the plus-strand RNA template, generating an RNA:DNA hybrid intermediate; second, the RNA strand is destroyed; and third, DNA-dependent DNA polymerase activity synthesizes plus-strand DNA, generating double-stranded DNA as the final product. The second step of this process is carried out by an RNase H domain located at the C-terminus of the RT protein.
RNase H performs three types of cleaving actions: non-specific degradation of the plus-strand RNA genome, specific removal of the minus-strand tRNA primer, and removal of the plus-strand purine-rich polypurine tract (PPT) primer. RNase H plays a role in the priming of the plus-strand, but not in the conventional method of synthesizing a new primer sequence. Rather RNase H creates a "primer" from the PPT that is resistant to RNase H cleavage. By removing all bases but the PPT, the PPT is used as a marker for the end of the U3 region of its long terminal repeat.
Because RNase H activity is required for viral proliferation, this domain has been considered a drug target for the development of antiretroviral drugs used in the treatment of HIV/AIDS and other conditions caused by retroviruses. Inhibitors of retroviral RNase H of several different chemotypes have been identified, many of which have a mechanism of action based on chelation of the active-site cations. Reverse-transcriptase inhibitors that specifically inhibit the polymerase function of RT are in widespread clinical use, but not inhibitors of the RNase H function; it is the only enzymatic function encoded by HIV that is not yet targeted by drugs in clinical use.
RNases H are widely distributed and occur in all domains of life. The family belongs to a larger superfamily of nuclease enzymes and is considered to be evolutionarily ancient. In prokaryotic genomes, multiple RNase H genes are often present, but there is little correlation between occurrence of HI, HII, and HIII genes and overall phylogenetic relationships, suggesting that horizontal gene transfer may have played a role in establishing the distribution of these enzymes. RNase HI and HIII rarely or never appear in the same prokaryotic genome. When an organism's genome contains more than one RNase H gene, they sometimes have significant differences in activity level. These observations have been suggested to reflect an evolutionary pattern that minimizes functional redundancy among RNase H genes. RNase HIII, which is unique to prokaryotes, has a scattered taxonomic distribution and is found in both bacteria and archaea; it is believed to have diverged from HII fairly early.
The evolutionary trajectory of RNase H2 in eukaryotes, especially the mechanism by which eukaryotic homologs became obligate heterotrimers, is unclear; the B and C subunits have no apparent homologs in prokaryotes.
Because RNase H specifically degrades only the RNA in double-stranded RNA:DNA hybrids, it is commonly used as a laboratory reagent in molecular biology. Purified preparations of E. coli RNase HI and HII are commercially available. RNase HI is often used to destroy the RNA template after first-strand complementary DNA (cDNA) synthesis by reverse transcription. It can also be used to cleave specific RNA sequences in the presence of short complementary segments of DNA. Highly sensitive techniques such as surface plasmon resonance can be used for detection. RNase HII can be used to degrade the RNA primer component of an Okazaki fragment or to introduce single-stranded nicks at positions containing a ribonucleotide. A variant of hot start PCR, known as RNase H-dependent PCR or rhPCR, has been described using a thermostable RNase HII from the hyperthermophilic archaeon Pyrococcus abyssi. Of note, the ribonuclease inhibitor protein commonly used as a reagent is not effective at inhibiting the activity of either HI or HII.
Ribonucleases H were first discovered in the laboratory of Peter Hausen when researchers found RNA:DNA hybrid endonuclease activity in calf thymus in 1969 and gave it the name "ribonuclease H" to designate its hybrid specificity. RNase H activity was subsequently discovered in E. coli and in a sample of oncoviruses with RNA genomes during early studies of viral reverse transcription. It later became clear that calf thymus extract contained more than one protein with RNase H activity and that E. coli contained two RNase H genes. Originally, the enzyme now known as RNase H2 in eukaryotes was designated H1 and vice versa, but the names of the eukaryotic enzymes were switched to match those in E. coli to facilitate comparative analysis, yielding the modern nomenclature in which the prokaryotic enzymes are designated with Roman numerals and the eukaryotic enzymes with Arabic numerals. The prokaryotic RNase HIII, reported in 1999, was the last RNase H subtype to be identified.
Characterizing eukaryotic RNase H2 was historically a challenge, in part due to its low abundance. Careful efforts at purification of the enzyme suggested that, unlike the E. coli RNase H2, the eukaryotic enzyme had multiple subunits. The S. cerevisiae homolog of the E. coli protein (that is, the H2A subunit) was easily identifiable by bioinformatics when the yeast genome was sequenced, but the corresponding protein was found not to have enzymatic activity in isolation. Eventually, the yeast B and C subunits were isolated by co-purification and found to be required for enzymatic activity. However, the yeast B and C subunits have very low sequence identity to their homologs in other organisms, and the corresponding human proteins were conclusively identified only after mutations in all three were found to cause Aicardiâ€“GoutiÃ¨res syndrome.
- doi:10.1006/jmbi.2001.5184. PMIDÂ 11734003. â€‹; Goedken ER, Marqusee S (December 2001). "Native-state energetics of a thermostabilized variant of ribonuclease HI". Journal of Molecular Biology. 314 (4): 863â€“71.
- Cerritelli SM, Crouch RJ (March 2009). "Ribonuclease H: the enzymes in eukaryotes". The FEBS Journal. 276 (6): 1494â€“505. doi:10.1111/j.1742-4658.2009.06908.x. PMCÂ 2746905. PMIDÂ 19228196.
- Crow YJ, Leitch A, Hayward BE, Garner A, Parmar R, Griffith E, etÂ al. (August 2006). "Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-GoutiÃ¨res syndrome and mimic congenital viral brain infection". Nature Genetics. 38 (8): 910â€“6. doi:10.1038/ng1842. PMIDÂ 16845400. S2CIDÂ 8076225.
- Figiel M, Nowotny M (August 2014). "Crystal structure of RNase H3-substrate complex reveals parallel evolution of RNA/DNA hybrid recognition". Nucleic Acids Research. 42 (14): 9285â€“94. doi:10.1093/nar/gku615. PMCÂ 4132731. PMIDÂ 25016521.
- Davies JF, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA (April 1991). "Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase". Science. 252 (5002): 88â€“95. Bibcode:1991Sci...252...88D. doi:10.1126/science.1707186. PMIDÂ 1707186.
- Hansen J, Schulze T, Mellert W, Moelling K (January 1988). "Identification and characterization of HIV-specific RNase H by monoclonal antibody". The EMBO Journal. 7 (1): 239â€“43. doi:10.1002/j.1460-2075.1988.tb02805.x. PMCÂ 454263. PMIDÂ 2452083.
- Tadokoro T, Kanaya S (March 2009). "Ribonuclease H: molecular diversities, substrate binding domains, and catalytic mechanism of the prokaryotic enzymes". The FEBS Journal. 276 (6): 1482â€“93. doi:10.1111/j.1742-4658.2009.06907.x. PMIDÂ 19228197. S2CIDÂ 29008571.
- Majorek KA, Dunin-Horkawicz S, Steczkiewicz K, Muszewska A, Nowotny M, Ginalski K, Bujnicki JM (April 2014). "The RNase H-like superfamily: new members, comparative structural analysis and evolutionary classification". Nucleic Acids Research. 42 (7): 4160â€“79. doi:10.1093/nar/gkt1414. PMCÂ 3985635. PMIDÂ 24464998.
- Rice P, Craigie R, Davies DR (February 1996). "Retroviral integrases and their cousins". Current Opinion in Structural Biology. 6 (1): 76â€“83. doi:10.1016/s0959-440x(96)80098-4. PMIDÂ 8696976.
- Schmitt TJ, Clark JE, Knotts TA (December 2009). "Thermal and mechanical multistate folding of ribonuclease H". The Journal of Chemical Physics. 131 (23): 235101. Bibcode:2009JChPh.131w5101S. doi:10.1063/1.3270167. PMIDÂ 20025349.
- Nowotny M, Cerritelli SM, Ghirlando R, Gaidamakov SA, Crouch RJ, Yang W (April 2008). "Specific recognition of RNA/DNA hybrid and enhancement of human RNase H1 activity by HBD". The EMBO Journal. 27 (7): 1172â€“81. doi:10.1038/emboj.2008.44. PMCÂ 2323259. PMIDÂ 18337749.
- Cecconi C, Shank EA, Bustamante C, Marqusee S (September 2005). "Direct observation of the three-state folding of a single protein molecule". Science. 309 (5743): 2057â€“60. Bibcode:2005Sci...309.2057C. doi:10.1126/science.1116702. PMIDÂ 16179479. S2CIDÂ 43823877.
- Hollien J, Marqusee S (March 1999). "A thermodynamic comparison of mesophilic and thermophilic ribonucleases H". Biochemistry. 38 (12): 3831â€“6. doi:10.1021/bi982684h. PMIDÂ 10090773.
- Raschke TM, Marqusee S (April 1997). "The kinetic folding intermediate of ribonuclease H resembles the acid molten globule and partially unfolded molecules detected under native conditions". Nature Structural Biology. 4 (4): 298â€“304. doi:10.1038/nsb0497-298. PMIDÂ 9095198. S2CIDÂ 33673059.
- Schultz SJ, Champoux JJ (June 2008). "RNase H activity: structure, specificity, and function in reverse transcription". Virus Research. 134 (1â€“2): 86â€“103. doi:10.1016/j.virusres.2007.12.007. PMCÂ 2464458. PMIDÂ 18261820.
- Champoux JJ, Schultz SJ (March 2009). "Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription". The FEBS Journal. 276 (6): 1506â€“16. doi:10.1111/j.1742-4658.2009.06909.x. PMCÂ 2742777. PMIDÂ 19228195.
- Yang W, Lee JY, Nowotny M (April 2006). "Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate specificity". Molecular Cell. 22 (1): 5â€“13. doi:10.1016/j.molcel.2006.03.013. PMIDÂ 16600865.
- Ohtani N, Haruki M, Morikawa M, Kanaya S (January 1999). "Molecular diversities of RNases H". Journal of Bioscience and Bioengineering. 88 (1): 12â€“9. doi:10.1016/s1389-1723(99)80168-6. PMIDÂ 16232566.
- Bubeck D, Reijns MA, Graham SC, Astell KR, Jones EY, Jackson AP (May 2011). "PCNA directs type 2 RNase H activity on DNA replication and repair substrates". Nucleic Acids Research. 39 (9): 3652â€“66. doi:10.1093/nar/gkq980. PMCÂ 3089482. PMIDÂ 21245041.
- Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M (March 2011). "The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-GoutiÃ¨res syndrome defects". The Journal of Biological Chemistry. 286 (12): 10540â€“50. doi:10.1074/jbc.M110.181974. PMCÂ 3060507. PMIDÂ 21177858.
- Amon JD, Koshland D (December 2016). "RNase H enables efficient repair of R-loop induced DNA damage". eLife. 5: e20533. doi:10.7554/eLife.20533. PMCÂ 5215079. PMIDÂ 27938663.
- Lima WF, Murray HM, Damle SS, Hart CE, Hung G, De Hoyos CL, etÂ al. (June 2016). "Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function". Nucleic Acids Research. 44 (11): 5299â€“312. doi:10.1093/nar/gkw350. PMCÂ 4914116. PMIDÂ 27131367.
- Arudchandran A, Cerritelli S, Narimatsu S, Itaya M, Shin DY, Shimada Y, Crouch RJ (October 2000). "The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair". Genes to Cells. 5 (10): 789â€“802. doi:10.1046/j.1365-2443.2000.00373.x. PMIDÂ 11029655.
- Cerritelli SM, Frolova EG, Feng C, Grinberg A, Love PE, Crouch RJ (March 2003). "Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice". Molecular Cell. 11 (3): 807â€“15. doi:10.1016/s1097-2765(03)00088-1. PMIDÂ 12667461.
- Reyes A, Melchionda L, Nasca A, Carrara F, Lamantea E, Zanolini A, etÂ al. (July 2015). "RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy". American Journal of Human Genetics. 97 (1): 186â€“93. doi:10.1016/j.ajhg.2015.05.013. PMCÂ 4572567. PMIDÂ 26094573.
- Hollis T, Shaban NM (2011-01-01). Nicholson AW (ed.). Ribonucleases. Nucleic Acids and Molecular Biology. Springer Berlin Heidelberg. pp.Â 299â€“317. doi:10.1007/978-3-642-21078-5_12. ISBNÂ 978-3-642-21077-8.
- Chon H, Vassilev A, DePamphilis ML, Zhao Y, Zhang J, Burgers PM, etÂ al. (January 2009). "Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex". Nucleic Acids Research. 37 (1): 96â€“110. doi:10.1093/nar/gkn913. PMCÂ 2615623. PMIDÂ 19015152.
- Reijns MA, Jackson AP (August 2014). "Ribonuclease H2 in health and disease". Biochemical Society Transactions. 42 (4): 717â€“25. doi:10.1042/BST20140079. PMIDÂ 25109948.
- Wahba L, Amon JD, Koshland D, Vuica-Ross M (December 2011). "RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability". Molecular Cell. 44 (6): 978â€“88. doi:10.1016/j.molcel.2011.10.017. PMCÂ 3271842. PMIDÂ 22195970.
- Kim N, Huang SN, Williams JS, Li YC, Clark AB, Cho JE, etÂ al. (June 2011). "Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I". Science. 332 (6037): 1561â€“4. Bibcode:2011Sci...332.1561K. doi:10.1126/science.1205016. PMCÂ 3380281. PMIDÂ 21700875.
- Ohtani N, Haruki M, Morikawa M, Crouch RJ, Itaya M, Kanaya S (January 1999). "Identification of the genes encoding Mn2+-dependent RNase HII and Mg2+-dependent RNase HIII from Bacillus subtilis: classification of RNases H into three families". Biochemistry. 38 (2): 605â€“18. doi:10.1021/bi982207z. PMIDÂ 9888800.
- Kochiwa H, Tomita M, Kanai A (July 2007). "Evolution of ribonuclease H genes in prokaryotes to avoid inheritance of redundant genes". BMC Evolutionary Biology. 7: 128. doi:10.1186/1471-2148-7-128. PMCÂ 1950709. PMIDÂ 17663799.
- Alla NR, Nicholson AW (December 2012). "Evidence for a dual functional role of a conserved histidine in RNAÂ·DNA heteroduplex cleavage by human RNase H1". FEBS Journal. 279 (24): 4492â€“500. doi:10.1111/febs.12035. PMCÂ 3515698. PMIDÂ 23078533.
- Rosta E, Yang W, Hummer G (February 2014). "Calcium inhibition of ribonuclease H1 two-metal ion catalysis". Journal of the American Chemical Society. 136 (8): 3137â€“44. doi:10.1021/ja411408x. PMCÂ 3985467. PMIDÂ 24499076.
- DÃ¼rr S, Bohusewicz O, Berta D, Suardiaz R, Peter C, Jambrina PG, Peter C, Shao Y, Rosta E (16 June 2021). "The Role of Conserved Residues in the DEDDh Motif: the Proton-Transfer Mechanism of HIV-1 RNase H". ACS Catalysis. 11 (13): 7915â€“7927. doi:10.1021/acscatal.1c01493. S2CIDÂ 236285134.
- Gan J, Shaw G, Tropea JE, Waugh DS, Court DL, Ji X (January 2008). "A stepwise model for double-stranded RNA processing by ribonuclease III". Mol Microbiol. 67 (1): 143â€“54. doi:10.1111/j.1365-2958.2007.06032.x. PMIDÂ 18047582.
- Samara NL, Yang W (August 2019). "Cation trafficking propels RNA hydrolysis". Nature Structural & Molecular Biology. 25 (8): 715â€“721. doi:10.1038/s41594-018-0099-4. PMCÂ 6110950. PMIDÂ 30076410.
- Reus K, Mayer J, Sauter M, Scherer D, MÃ¼ller-Lantzsch N, Meese E (March 2001). "Genomic organization of the human endogenous retrovirus HERV-K(HML-2.HOM) (ERVK6) on chromosome 7". Genomics. 72 (3): 314â€“20. doi:10.1006/geno.2000.6488. PMIDÂ 11401447.
- Ustyantsev K, Blinov A, Smyshlyaev G (14 March 2017). "Convergence of retrotransposons in oomycetes and plants". Mobile DNA. 8 (1): 4. doi:10.1186/s13100-017-0087-y. PMCÂ 5348765. PMIDÂ 28293305.
- Ustyantsev K, Novikova O, Blinov A, Smyshlyaev G (May 2015). "Convergent evolution of ribonuclease h in LTR retrotransposons and retroviruses". Molecular Biology and Evolution. 32 (5): 1197â€“207. doi:10.1093/molbev/msv008. PMCÂ 4408406. PMIDÂ 25605791.
- Malik HS (2005). "Ribonuclease H evolution in retrotransposable elements". Cytogenetic and Genome Research. 110 (1â€“4): 392â€“401. doi:10.1159/000084971. PMIDÂ 16093691. S2CIDÂ 7481781.
- Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M (March 2011). "The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-GoutiÃ¨res syndrome defects". The Journal of Biological Chemistry. 286 (12): 10540â€“50. doi:10.1074/jbc.M110.181974. PMCÂ 3060507. PMIDÂ 21177858.
- Orcesi S, La Piana R, Fazzi E (2009). "Aicardi-Goutieres syndrome". British Medical Bulletin. 89: 183â€“201. doi:10.1093/bmb/ldn049. PMIDÂ 19129251.
- Crow YJ, Manel N (July 2015). "Aicardi-GoutiÃ¨res syndrome and the type I interferonopathies". Nature Reviews. Immunology. 15 (7): 429â€“40. doi:10.1038/nri3850. PMIDÂ 26052098. S2CIDÂ 34259643.
- Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, etÂ al. (February 2015). "Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1". American Journal of Medical Genetics. Part A. 167A (2): 296â€“312. doi:10.1002/ajmg.a.36887. PMCÂ 4382202. PMIDÂ 25604658.
- Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, etÂ al. (October 2007). "Clinical and molecular phenotype of Aicardi-Goutieres syndrome". American Journal of Human Genetics. 81 (4): 713â€“25. doi:10.1086/521373. PMCÂ 2227922. PMIDÂ 17846997.
- Sarafianos SG, Das K, Tantillo C, Clark AD, Ding J, Whitcomb JM, etÂ al. (March 2001). "Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA". The EMBO Journal. 20 (6): 1449â€“61. doi:10.1093/emboj/20.6.1449. PMCÂ 145536. PMIDÂ 11250910.
- Seeger C, Mason WS (May 2015). "Molecular biology of hepatitis B virus infection". Virology. 479â€“480: 672â€“86. doi:10.1016/j.virol.2015.02.031. PMCÂ 4424072. PMIDÂ 25759099.
- Moelling K, Broecker F, Kerrigan JE (2014-01-01). "RNase H: specificity, mechanisms of action, and antiviral target". In Vicenzi E, Poli G (eds.). Human Retroviruses. Methods in Molecular Biology. 1087. Humana Press. pp.Â 71â€“84. doi:10.1007/978-1-62703-670-2_7. ISBNÂ 978-1-62703-669-6. PMIDÂ 24158815.
- Mizuno M, Yasukawa K, Inouye K (February 2010). "Insight into the mechanism of the stabilization of moloney murine leukaemia virus reverse transcriptase by eliminating RNase H activity". Bioscience, Biotechnology, and Biochemistry. 74 (2): 440â€“2. doi:10.1271/bbb.90777. PMIDÂ 20139597. S2CIDÂ 28110533.
- CotÃ© ML, Roth MJ (June 2008). "Murine leukemia virus reverse transcriptase: structural comparison with HIV-1 reverse transcriptase". Virus Research. 134 (1â€“2): 186â€“202. doi:10.1016/j.virusres.2008.01.001. PMCÂ 2443788. PMIDÂ 18294720.
- Nowotny M, Figiel M (2013-01-01). LeGrice S, Gotte M (eds.). Human Immunodeficiency Virus Reverse Transcriptase. Springer New York. pp.Â 53â€“75. doi:10.1007/978-1-4614-7291-9_3. ISBNÂ 978-1-4614-7290-2.
- Beilhartz GL, GÃ¶tte M (April 2010). "HIV-1 Ribonuclease H: Structure, Catalytic Mechanism and Inhibitors". Viruses. 2 (4): 900â€“26. doi:10.3390/v2040900. PMCÂ 3185654. PMIDÂ 21994660.
- Klarmann GJ, Hawkins ME, Le Grice SF (2002). "Uncovering the complexities of retroviral ribonuclease H reveals its potential as a therapeutic target". AIDS Reviews. 4 (4): 183â€“94. PMIDÂ 12555693.
- Tramontano E, Di Santo R (2010). "HIV-1 RT-associated RNase H function inhibitors: Recent advances in drug development". Current Medicinal Chemistry. 17 (26): 2837â€“53. doi:10.2174/092986710792065045. PMIDÂ 20858167.
- Cao L, Song W, De Clercq E, Zhan P, Liu X (June 2014). "Recent progress in the research of small molecule HIV-1 RNase H inhibitors". Current Medicinal Chemistry. 21 (17): 1956â€“67. doi:10.2174/0929867321666140120121158. PMIDÂ 24438523.
- Ma BG, Chen L, Ji HF, Chen ZH, Yang FR, Wang L, etÂ al. (February 2008). "Characters of very ancient proteins". Biochemical and Biophysical Research Communications. 366 (3): 607â€“11. doi:10.1016/j.bbrc.2007.12.014. PMIDÂ 18073136.
- Brindefalk B, Dessailly BH, Yeats C, Orengo C, Werner F, Poole AM (March 2013). "Evolutionary history of the TBP-domain superfamily". Nucleic Acids Research. 41 (5): 2832â€“45. doi:10.1093/nar/gkt045. PMCÂ 3597702. PMIDÂ 23376926.
- Nichols NM, Yue D (2001-01-01). Ribonucleases. Current Protocols in Molecular Biology. Chapter 3. John Wiley & Sons, Inc. pp.Â Unit3.13. doi:10.1002/0471142727.mb0313s84. ISBNÂ 978-0-471-14272-0. PMIDÂ 18972385.
- Loo JF, Wang SS, Peng F, He JA, He L, Guo YC, etÂ al. (July 2015). "A non-PCR SPR platform using RNase H to detect MicroRNA 29a-3p from throat swabs of human subjects with influenza A virus H1N1 infection". The Analyst. 140 (13): 4566â€“75. Bibcode:2015Ana...140.4566L. doi:10.1039/C5AN00679A. PMIDÂ 26000345. S2CIDÂ 28974459.
- Goodrich TT, Lee HJ, Corn RM (April 2004). "Direct detection of genomic DNA by enzymatically amplified SPR imaging measurements of RNA microarrays". Journal of the American Chemical Society. 126 (13): 4086â€“7. CiteSeerXÂ 10.1.1.475.1922. doi:10.1021/ja039823p. PMIDÂ 15053580.
- Dobosy JR, Rose SD, Beltz KR, Rupp SM, Powers KM, Behlke MA, Walder JA (August 2011). "RNase H-dependent PCR (rhPCR): improved specificity and single nucleotide polymorphism detection using blocked cleavable primers". BMC Biotechnology. 11: 80. doi:10.1186/1472-6750-11-80. PMCÂ 3224242. PMIDÂ 21831278.
- Stein H, Hausen P (October 1969). "Enzyme from calf thymus degrading the RNA moiety of DNA-RNA Hybrids: effect on DNA-dependent RNA polymerase". Science. 166 (3903): 393â€“5. Bibcode:1969Sci...166..393S. doi:10.1126/science.166.3903.393. PMIDÂ 5812039. S2CIDÂ 43683241.
- Hausen P, Stein H (June 1970). "Ribonuclease H. An enzyme degrading the RNA moiety of DNA-RNA hybrids". European Journal of Biochemistry. 14 (2): 278â€“83. doi:10.1111/j.1432-1033.1970.tb00287.x. PMIDÂ 5506170.
- Miller HI, Riggs AD, Gill GN (April 1973). "Ribonuclease H (hybrid) in Escherichia coli. Identification and characterization". The Journal of Biological Chemistry. 248 (7): 2621â€“4. doi:10.1016/S0021-9258(19)44152-5. PMIDÂ 4572736.
- MÃ¶lling K, Bolognesi DP, Bauer H, BÃ¼sen W, Plassmann HW, Hausen P (December 1971). "Association of viral reverse transcriptase with an enzyme degrading the RNA moiety of RNA-DNA hybrids". Nature. 234 (51): 240â€“3. doi:10.1038/newbio234240a0. PMIDÂ 4331605.
- Grandgenett DP, Gerard GF, Green M (December 1972). "Ribonuclease H: a ubiquitous activity in virions of ribonucleic acid tumor viruses". Journal of Virology. 10 (6): 1136â€“42. doi:10.1128/jvi.10.6.1136-1142.1972. PMCÂ 356594. PMIDÂ 4118867.
- BÃ¼sen W, Hausen P (March 1975). "Distinct ribonuclease H activities in calf thymus". European Journal of Biochemistry. 52 (1): 179â€“90. doi:10.1111/j.1432-1033.1975.tb03985.x. PMIDÂ 51794.
- Kanaya S, Crouch RJ (January 1983). "DNA sequence of the gene coding for Escherichia coli ribonuclease H". The Journal of Biological Chemistry. 258 (2): 1276â€“81. doi:10.1016/S0021-9258(18)33189-2. PMIDÂ 6296074.
- Itaya M (November 1990). "Isolation and characterization of a second RNase H (RNase HII) of Escherichia coli K-12 encoded by the rnhB gene". Proceedings of the National Academy of Sciences of the United States of America. 87 (21): 8587â€“91. Bibcode:1990PNAS...87.8587I. doi:10.1073/pnas.87.21.8587. PMCÂ 55002. PMIDÂ 2172991.
- Crouch RJ, Arudchandran A, Cerritelli SM (2001-01-01). "RNase H1 of Saccharomyces cerevisiae: methods and nomenclature". Methods in Enzymology. 341: 395â€“413. doi:10.1016/s0076-6879(01)41166-9. ISBNÂ 978-0-12-182242-2. PMIDÂ 11582793.
- Frank P, Braunshofer-Reiter C, Wintersberger U, Grimm R, BÃ¼sen W (October 1998). "Cloning of the cDNA encoding the large subunit of human RNase HI, a homologue of the prokaryotic RNase HII". Proceedings of the National Academy of Sciences of the United States of America. 95 (22): 12872â€“7. Bibcode:1998PNAS...9512872F. doi:10.1073/pnas.95.22.12872. PMCÂ 23637. PMIDÂ 9789007.
- Frank P, Braunshofer-Reiter C, Wintersberger U (January 1998). "Yeast RNase H(35) is the counterpart of the mammalian RNase HI, and is evolutionarily related to prokaryotic RNase HII". FEBS Letters. 421 (1): 23â€“6. doi:10.1016/s0014-5793(97)01528-7. PMIDÂ 9462832.
- Jeong HS, Backlund PS, Chen HC, Karavanov AA, Crouch RJ (2004-01-01). "RNase H2 of Saccharomyces cerevisiae is a complex of three proteins". Nucleic Acids Research. 32 (2): 407â€“14. doi:10.1093/nar/gkh209. PMCÂ 373335. PMIDÂ 14734815.
- GeneReviews/NCBI/NIH/UW entry on Aicardi-GoutiÃ¨res Syndrome
- RNase+H at the US National Library of Medicine Medical Subject Headings (MeSH)
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Ribonuclease HII Provide feedback
No Pfam abstract.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR024567
Ribonuclease HII and HIII are endonucleases that specifically degrade the RNA of RNA-DNA hybrids. Proteins which belong to this family have been found in bacteria, archaea, and eukaryota.
The domain represented by this entry is found in ribonucleases HII.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
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This clan includes a diverse set of nucleases that share a similar structure to Ribonuclease H.
The clan contains the following 70 members:Arena_ncap_C CAF1 DDE_1 DDE_2 DDE_3 DDE_5 DDE_Tnp_1 DDE_Tnp_1_2 DDE_Tnp_1_3 DDE_Tnp_1_4 DDE_Tnp_1_5 DDE_Tnp_1_6 DDE_Tnp_1_7 DDE_Tnp_2 DDE_Tnp_4 DDE_Tnp_IS1 DDE_Tnp_IS1595 DDE_Tnp_IS240 DDE_Tnp_IS66 DDE_Tnp_ISAZ013 DDE_Tnp_ISL3 DDE_Tnp_Tn3 Dimer_Tnp_Tn5 DNA_pol_A_exo1 DNA_pol_B_exo1 DNA_pol_B_exo2 DNA_pol_P_Exo DUF1258 DUF2779 DUF3882 DUF3892 DUF4152 DUF99 Endonuclease_5 KDZ Maelstrom Methyltransf_1N MGMT_N MULE NurA OrfB_IS605 Piwi Plant_tran Plavaka Pox_A22 Ribosomal_S30AE RNase_H RNase_H_2 RNase_HII RNase_T RNaseH_like RT_RNaseH RT_RNaseH_2 RuvC RuvC_1 Rv2179c-like rve rve_2 rve_3 RVT_3 Taq-exonuc TerL_nuclease Terminase_3C Terminase_6C Transposase_1 Transposase_21 Transposase_mut UPF0236 UvrC_RNaseH_dom Ydc2-catalyt
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Bateman A|
|Number in seed:||11|
|Number in full:||10805|
|Average length of the domain:||183.30 aa|
|Average identity of full alignment:||34 %|
|Average coverage of the sequence by the domain:||74.69 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||21|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the RNase_HII domain has been found. There are 36 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...
AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.