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36  structures 8621  species 0  interactions 10805  sequences 67  architectures

Family: RNase_HII (PF01351)

Summary: Ribonuclease HII

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Ribonuclease H Edit Wikipedia article

ribonuclease H
RNase H fix.png
Crystallographic structure of E. coli RNase HI.[1]
Identifiers
EC no.3.1.26.4
CAS no.9050-76-4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
retroviral ribonuclease H
Identifiers
EC no.3.1.26.13
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB 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.[2] 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 Aicardi–Goutières syndrome.[3] A third type, closely related to H2, is found only in a few prokaryotes,[4] whereas H1 and H2 occur in all domains of life.[4] 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.[5][6]

In eukaryotes, ribonuclease H1 is involved in DNA replication of the mitochondrial genome. Both H1 and H2 are involved in genome maintenance tasks such as processing of R-loop structures.[2][7]

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.[7] 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.[8][9]

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.[2][7] 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.[4]

Structure

Comparison of the structures of representative ribonuclease H proteins from each subtype. In the E. coli protein (beige, top left), the four conserved active site residues are shown as spheres. In the H. sapiens proteins, the structural core common between the H1 and H2 subtypes is shown in red. Structures are rendered from: E. coli, PDB: 2RN2​; T. maritima, PDB: 303F​; B. stearothermophilus, PDB: 2D0B​; H. sapiens H1, PDB: 2QK9​; H. sapiens, PDB: 3P56​.

The structure of RNase H commonly consists of a 5-stranded β-sheet surrounded by a distribution of α-helices.[10] 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.[7][5]

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.[2][7][11] While all members of the H1 group and the prokaryotic members of the H2 group function as monomers, eukaryotic H2 enzymes are obligate heterotrimers.[2][7] 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.[7] Retroviral RNase H domains occurring in multidomain reverse transcriptase proteins have structures closely resembling the H1 group.[5]

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.[12][13][14] 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.[15][16]

Function

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.[17] Depending on the differences in their amino acid sequences, these RNases H are classified into type 1 and type 2 RNases H.[7][18] 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.[19][20] 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.[2] 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.[21][22]

Ribonuclease H1

Identifiers
SymbolRNase H
PfamPF00075
Pfam clanCL0219
InterProIPR002156
PROSITEPS50879

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.[2] RNase H1 is not essential in unicellular organisms where it has been investigated; in E. coli, RNase H1 knockouts confer a temperature-sensitive phenotype,[7] and in S. cerevisiae, they produce defects in stress response.[23]

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.[2][24][25] The defects in mitochondrial DNA replication induced by loss of RNase H1 are likely due to defects in R-loop processing.[22]

Ribonuclease H2

Identifiers
SymbolRNase HII
PfamPF01351
Pfam clanCL0219
InterProIPR024567

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.[26][27] The B subunit mediates protein-protein interactions between the H2 complex and PCNA, which localizes H2 to replication foci.[28]

Both prokaryotic and eukaryotic H2 enzymes can cleave single ribonucleotides in a strand.[2] 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.[2][27] 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.[29][30][28] 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.[28]

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.[7][31] 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.[32]

Mechanism

RNase H reaction mechanism
Reaction mechanism for RNase H catalysis using two metal ions in the HIV-1 RNase H domain

The active site of nearly all RNases H contains four negatively charged amino acid residues, known as the DEDD motif; often a histidine e.g. in HIV-1, human or E. coli is also present.[2][7]

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,[2][7] while calcium or high concentration of Mg2+ inhibits activity.[11][33][34]

Based on experimental evidence and computer simulations the enzyme activates a water molecule bound to one of the metal ions with the conserved histidine.[33][35] The transition state is associative in nature [17] and forms an intermediate with protonated phosphate and deprotonated alkoxide leaving group.[35] 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. [36][37]

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.[38] 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.[39][40][41]

Role in disease

The structure of the trimeric human H2 complex, with the catalytic A subunit in blue, the structural B subunit in brown, and the structural C subunit in pink. Although the B and C subunits do not interact with the active site, they are required for activity. The catalytic residues in the active site are shown in magenta. Positions shown in yellow are those with known AGS mutations. The most common AGS mutation - alanine to threonine at position 177 of subunit B - is shown as a green sphere. Many of these mutations do not disrupt catalytic activity in vitro, but do destabilize the complex or interfere with protein-protein interactions with other proteins in the cell.[42]

In small studies, mutations in human RNase H1 have been associated with chronic progressive external ophthalmoplegia, a common feature of mitochondrial disease.[25]

Mutations in any of the three RNase H2 subunits are well-established as causes of a rare genetic disorder known as Aicardi–Goutières syndrome (AGS),[3] which manifests as neurological and dermatological symptoms at an early age.[43] 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.[44] Characterization of mutational distribution in an AGS patient population found 5% of all AGS mutations in RNASEH2A, 36% in 2B, and 12% in 2C.[45] Mutations in 2B have been associated with somewhat milder neurological impairment[46] and with an absence of interferon-induced gene upregulation that can be detected in patients with other AGS-associated genotypes.[44]

In viruses

The crystal structure of the HIV reverse transcriptase heterodimer (yellow and green), with the RNase H domain shown in blue (active site in magenta spheres). The orange nucleic acid strand is RNA, the red strand is DNA.[47]

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.[48][49]

Retroviral RT proteins from HIV-1 and murine leukemia virus are the best-studied members of the family.[50][51] 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.[5][6][52][53]

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.[54] 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.[53]

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.[55] 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.[52][56]

Evolution

RNases H are widely distributed and occur in all domains of life. The family belongs to a larger superfamily of nuclease enzymes[8][9] and is considered to be evolutionarily ancient.[57] 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.[7][32] RNase HIII, which is unique to prokaryotes, has a scattered taxonomic distribution and is found in both bacteria and archaea;[32] it is believed to have diverged from HII fairly early.[58]

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.[2][27]

Applications

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.[59] Highly sensitive techniques such as surface plasmon resonance can be used for detection.[60][61] 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.[59] 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.[62] Of note, the ribonuclease inhibitor protein commonly used as a reagent is not effective at inhibiting the activity of either HI or HII.[59]

History

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.[26][63][64] RNase H activity was subsequently discovered in E. coli[65] and in a sample of oncoviruses with RNA genomes during early studies of viral reverse transcription.[66][67] It later became clear that calf thymus extract contained more than one protein with RNase H activity[68] and that E. coli contained two RNase H genes.[69][70] 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.[2][26][31][71] The prokaryotic RNase HIII, reported in 1999, was the last RNase H subtype to be identified.[31]

Characterizing eukaryotic RNase H2 was historically a challenge, in part due to its low abundance.[2] Careful efforts at purification of the enzyme suggested that, unlike the E. coli RNase H2, the eukaryotic enzyme had multiple subunits.[72] 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,[73] but the corresponding protein was found not to have enzymatic activity in isolation.[2][23] Eventually, the yeast B and C subunits were isolated by co-purification and found to be required for enzymatic activity.[74] 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 Aicardi–Goutières syndrome.[2][3]

References

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  42. ^ 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-Goutières syndrome defects". The Journal of Biological Chemistry. 286 (12): 10540–50. doi:10.1074/jbc.M110.181974. PMC 3060507. PMID 21177858.
  43. ^ Orcesi S, La Piana R, Fazzi E (2009). "Aicardi-Goutieres syndrome". British Medical Bulletin. 89: 183–201. doi:10.1093/bmb/ldn049. PMID 19129251.
  44. ^ a b Crow YJ, Manel N (July 2015). "Aicardi-Goutières syndrome and the type I interferonopathies". Nature Reviews. Immunology. 15 (7): 429–40. doi:10.1038/nri3850. PMID 26052098. S2CID 34259643.
  45. ^ Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GM, Gornall HL, et 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): 296–312. doi:10.1002/ajmg.a.36887. PMC 4382202. PMID 25604658.
  46. ^ Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, et al. (October 2007). "Clinical and molecular phenotype of Aicardi-Goutieres syndrome". American Journal of Human Genetics. 81 (4): 713–25. doi:10.1086/521373. PMC 2227922. PMID 17846997.
  47. ^ Sarafianos SG, Das K, Tantillo C, Clark AD, Ding J, Whitcomb JM, et al. (March 2001). "Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA". The EMBO Journal. 20 (6): 1449–61. doi:10.1093/emboj/20.6.1449. PMC 145536. PMID 11250910.
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  50. ^ 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): 440–2. doi:10.1271/bbb.90777. PMID 20139597. S2CID 28110533.
  51. ^ Coté ML, Roth MJ (June 2008). "Murine leukemia virus reverse transcriptase: structural comparison with HIV-1 reverse transcriptase". Virus Research. 134 (1–2): 186–202. doi:10.1016/j.virusres.2008.01.001. PMC 2443788. PMID 18294720.
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  53. ^ a b Beilhartz GL, Götte M (April 2010). "HIV-1 Ribonuclease H: Structure, Catalytic Mechanism and Inhibitors". Viruses. 2 (4): 900–26. doi:10.3390/v2040900. PMC 3185654. PMID 21994660.
  54. ^ 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): 183–94. PMID 12555693.
  55. ^ Tramontano E, Di Santo R (2010). "HIV-1 RT-associated RNase H function inhibitors: Recent advances in drug development". Current Medicinal Chemistry. 17 (26): 2837–53. doi:10.2174/092986710792065045. PMID 20858167.
  56. ^ 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): 1956–67. doi:10.2174/0929867321666140120121158. PMID 24438523.
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  60. ^ Loo JF, Wang SS, Peng F, He JA, He L, Guo YC, et 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): 4566–75. Bibcode:2015Ana...140.4566L. doi:10.1039/C5AN00679A. PMID 26000345. S2CID 28974459.
  61. ^ 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): 4086–7. CiteSeerX 10.1.1.475.1922. doi:10.1021/ja039823p. PMID 15053580.
  62. ^ 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. PMC 3224242. PMID 21831278.
  63. ^ 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): 393–5. Bibcode:1969Sci...166..393S. doi:10.1126/science.166.3903.393. PMID 5812039. S2CID 43683241.
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External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Literature references

  1. Mian IS; , Nucleic Acids Res 1997;25:3187-3189.: Comparative sequence analysis of ribonucleases HII, III, II PH and D. PUBMED:9241229 EPMC:9241229


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.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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...

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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.

  Seed
(11)
Full
(10805)
Representative proteomes UniProt
(52243)
RP15
(1766)
RP35
(5487)
RP55
(10798)
RP75
(17899)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(11)
Full
(10805)
Representative proteomes UniProt
(52243)
RP15
(1766)
RP35
(5487)
RP55
(10798)
RP75
(17899)
Alignment:
Format:
Order:
Sequence:
Gaps:
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Download options

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.

  Seed
(11)
Full
(10805)
Representative proteomes UniProt
(52243)
RP15
(1766)
RP35
(5487)
RP55
(10798)
RP75
(17899)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

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...

Trees

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.

Curation View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: 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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.8 25.8
Trusted cut-off 26.0 25.9
Noise cut-off 25.0 25.7
Model length: 198
Family (HMM) version: 21
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Structures

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.

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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.

Protein Predicted structure External Information
A0A0R0J8M8 View 3D Structure Click here
A0B796 View 3D Structure Click here
A0JXT5 View 3D Structure Click here
A0KHH7 View 3D Structure Click here
A0L4Z0 View 3D Structure Click here
A0LMM5 View 3D Structure Click here
A0LV66 View 3D Structure Click here
A0Q0X7 View 3D Structure Click here
A0QV44 View 3D Structure Click here
A0RV25 View 3D Structure Click here
A1AMZ7 View 3D Structure Click here
A1B3V0 View 3D Structure Click here
A1BCI1 View 3D Structure Click here
A1K6Q7 View 3D Structure Click here
A1RYM0 View 3D Structure Click here
A1S4Q4 View 3D Structure Click here
A1SLS0 View 3D Structure Click here
A1SYU9 View 3D Structure Click here
A1T759 View 3D Structure Click here
A1TN83 View 3D Structure Click here
A1UEF9 View 3D Structure Click here
A1URV4 View 3D Structure Click here
A1VN54 View 3D Structure Click here
A1W904 View 3D Structure Click here
A1WHV6 View 3D Structure Click here
A1WX09 View 3D Structure Click here
A2BL34 View 3D Structure Click here
A2SH85 View 3D Structure Click here
A2SMZ3 View 3D Structure Click here
A2STJ6 View 3D Structure Click here
A3CN38 View 3D Structure Click here
A3DDG7 View 3D Structure Click here
A3MYK1 View 3D Structure Click here
A3PEZ1 View 3D Structure Click here
A3QG89 View 3D Structure Click here
A4FME5 View 3D Structure Click here
A4G4T5 View 3D Structure Click here
A4HVE1 View 3D Structure Click here
A4ICS0 View 3D Structure Click here
A4ICV4 View 3D Structure Click here