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2  structures 1441  species 0  interactions 1724  sequences 19  architectures

Family: Hva1_TUDOR (PF11160)

Summary: Hypervirulence associated proteins TUDOR domain

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This is the Wikipedia entry entitled "Domain of unknown function". More...

Domain of unknown function Edit Wikipedia article

A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. There are now over 3,000 DUF families within the Pfam database representing over 20% of known families.[1]

History

The DUF naming scheme was introduced by Chris Ponting, through the addition of DUF1 and DUF2 to the SMART database.[2] These two domains were found to be widely distributed in bacterial signaling proteins. Subsequently, the functions of these domains were identified and they have since been renamed as the GGDEF domain and EAL domain respectively.

Structure

Structural genomics programmes have attempted to understand the function of DUFs through structure determination. The structures of over 250 DUF families have been solved.[3] This work showed that about two thirds of DUF families had a structure similar to a previously solved one and therefore likely to be divergent members of existing protein superfamilies, whereas about one third possessed a novel protein fold.

Frequency and conservation

Protein domains and DUFs in different domains of life. Left: Annotated domains. Right: domains of unknown function. Not all overlaps shown.[4]

More than 20% of all protein domains were annotated as DUFs in 2013. About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs.[4]

Role in biology

Many DUFs are highly conserved, indicating an important role in biology. However, many such DUFs are not essential, hence their biological role often remains unknown. For instance, DUF143 is present in most bacteria and eukaryotic genomes.[5] However, when it was deleted in Escherichia coli no obvious phenotype was detected. Later it was shown that the proteins that contain DUF143, are ribosomal silencing factors that block the assembly of the two ribosomal subunits.[5] While this function is not essential, it helps the cells to adapt to low nutrient conditions by shutting down protein biosynthesis. As a result, these proteins and the DUF only become relevant when the cells starve.[5] It is thus believed that many DUFs (or proteins of unknown function, PUFs) are only required under certain conditions.

Essential DUFs (eDUFs)

Goodacre et al. identified 238 DUFs in 355 essential proteins (in 16 model bacterial species), most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. These DUFs are called "essential DUFs" or eDUFs.[4]

External links

References

  1. ^ Bateman A, Coggill P, Finn RD (October 2010). "DUFs: families in search of function". Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 66 (Pt 10): 1148–52. PMC 2954198Freely accessible. PMID 20944204. doi:10.1107/S1744309110001685. 
  2. ^ Schultz J, Milpetz F, Bork P, Ponting CP (May 1998). "SMART, a simple modular architecture research tool: identification of signaling domains". Proc. Natl. Acad. Sci. U.S.A. 95 (11): 5857–64. PMC 34487Freely accessible. PMID 9600884. doi:10.1073/pnas.95.11.5857. 
  3. ^ Jaroszewski L, Li Z, Krishna SS, et al. (September 2009). "Exploration of uncharted regions of the protein universe". PLoS Biol. 7 (9): e1000205. PMC 2744874Freely accessible. PMID 19787035. doi:10.1371/journal.pbio.1000205. 
  4. ^ a b c Goodacre, N. F.; Gerloff, D. L.; Uetz, P. (2013). "Protein Domains of Unknown Function Are Essential in Bacteria". MBio. 5 (1): e00744–e00713. PMC 3884060Freely accessible. PMID 24381303. doi:10.1128/mBio.00744-13. 
  5. ^ a b c Häuser, R.; Pech, M.; Kijek, J.; Yamamoto, H.; Titz, B. R.; Naeve, F.; Tovchigrechko, A.; Yamamoto, K.; Szaflarski, W.; Takeuchi, N.; Stellberger, T.; Diefenbacher, M. E.; Nierhaus, K. H.; Uetz, P. (2012). Hughes, Diarmaid, ed. "RsfA (YbeB) Proteins Are Conserved Ribosomal Silencing Factors". PLoS Genetics. 8 (7): e1002815. PMC 3400551Freely accessible. PMID 22829778. doi:10.1371/journal.pgen.1002815. 

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

This is the Wikipedia entry entitled "Tudor domain". More...

Tudor domain Edit Wikipedia article

TUDOR domain
PDB 2diq EBI.jpg
Structure of a TUDOR domain.
Identifiers
Symbol TUDOR
Pfam PF00567
Pfam clan CL0049
InterPro IPR008191
SMART TUDOR
PROSITE PDOC50304
SCOP 3fdr
SUPERFAMILY 3fdr
CDD cd04508

In molecular biology a tudor domain is a conserved protein structural domain originally identified as a region of 50 amino acids found in the Tudor protein encoded in Drosophila. The structurally characterized Tudor domain in human SMN (survival of motor neuron) is a strongly bent anti-parallel β-sheet consisting of five β-strands with a barrel-like fold and recognizes symmetrically dimethylated arginine.[1]

The proteins TP53BP1 (Tumor suppressor p53-binding protein 1) and its fission yeast homolog Crb2[2] and JMJD2A (Jumonji domain containing 2A) contain either tandem or double Tudor domains and recognize methylated histones.[3][4]

Other tudor domain containing proteins include AKAP1 (A-kinase anchor protein 1)[5] and ARID4A (AT rich interactive domain 4A) among others. A well known Tudor domain containing protein is Staphylococcal Nuclease Domain Containing 1 (SND1)/Tudor-SN/p100 co activator.[6] SND1 is involved in RISC complex and interacts with AEG-1 oncogene.[7] SND1 is also acts as an oncogene and plays a very important role in HCC and colon cancer.[8] The SND1 tudor domain binds to methylated arginine in the PIWIL1 protein.[9] Tudor containing SND1 promotes tumor angiogenesis in human hepatocellular carcinoma through a novel pathway which involves NF-kappaB and miR-221.[10] Tudor SND1 is also present in the Drosophila melanogaster. [11]

References

  1. ^ Sprangers R, Groves MR, Sinning I, Sattler M (March 2003). "High-resolution X-ray and NMR structures of the SMN Tudor domain: conformational variation in the binding site for symmetrically dimethylated arginine residues". J. Mol. Biol. 327 (2): 507–20. PMID 12628254. doi:10.1016/S0022-2836(03)00148-7. 
  2. ^ Botuyan MV, Lee J, Ward IM, et al. (December 2006). "Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair". Cell. 127 (7): 1361–73. PMC 1804291Freely accessible. PMID 17190600. doi:10.1016/j.cell.2006.10.043. 
  3. ^ Huang Y, Fang J, Bedford MT, Zhang Y, Xu RM (May 2006). "Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A". Science. 312 (5774): 748–51. PMID 16601153. doi:10.1126/science.1125162. 
  4. ^ Lee J, Thompson JR, Botuyan MV, Mer G (January 2008). "Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor". Nat. Struct. Mol. Biol. 15 (1): 109–11. PMC 2211384Freely accessible. PMID 18084306. doi:10.1038/nsmb1326. 
  5. ^ Rogne M, Landsverk HB, Van Eynde A, et al. (December 2006). "The KH-Tudor domain of a-kinase anchoring protein 149 mediates RNA-dependent self-association". Biochemistry. 45 (50): 14980–9. PMID 17154535. doi:10.1021/bi061418y. 
  6. ^ Caudy AA, Ketting RF, Hammond SM, Denli AM, Bathoorn AM, Tops BB, Silva JM, Myers MM, Hannon GJ, Plasterk RH (September 2003). "A micrococcal nuclease homologue in RNAi effector complexes". Nature. 425 (6956): 411–4. PMID 14508492. doi:10.1038/nature01956. 
  7. ^ Yoo BK, Santhekadur PK, Gredler R, Chen D, Emdad L, Bhutia S, Pannell L, Fisher PB, Sarkar D (2011). "Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma". Hepatology. 53 (5): 1538–48. PMC 3081619Freely accessible. PMID 21520169. doi:10.1002/hep.24216. 
  8. ^ Yoo BK, Emdad L, Lee SG, Su ZZ, Santhekadur P, Chen D, Gredler R, Fisher PB, Sarkar D (April 2011). "Astrocyte elevated gene-1 (AEG-1): A multifunctional regulator of normal and abnormal physiology". Pharmacol. Ther. 130 (1): 1–8. PMC 3043119Freely accessible. PMID 21256156. doi:10.1016/j.pharmthera.2011.01.008. 
  9. ^ Liu K, Chen C, Guo Y, et al. (October 2010). "Structural basis for recognition of arginine methylated Piwi proteins by the extended Tudor domain". Proc. Natl. Acad. Sci. U.S.A. 107 (43): 18398–403. PMC 2972943Freely accessible. PMID 20937909. doi:10.1073/pnas.1013106107. 
  10. ^ Santhekadur PK, Das SK, Gredler R, et al. (April 2012). "Multifunction Protein Staphylococcal Nuclease Domain Containing 1 (SND1) Promotes Tumor Angiogenesis in Human Hepatocellular Carcinoma through Novel Pathway That Involves Nuclear Factor κB and miR-221". J. Biol. Chem. 287 (17): 13952–8. PMC 3340184Freely accessible. PMID 22396537. doi:10.1074/jbc.M111.321646. 
  11. ^ Muying Ying; Dahua Chen (2012). "Tudor domain-containing proteins of Drosophila melanogaster.". Development, Growth & Differentiation. 


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.

Hypervirulence associated proteins TUDOR domain Provide feedback

Family members include HVA1 (hypervirulence-associated protein 1) whose absence is associated with a hypervirulent phenotype in mice. Metabolomics analysis suggests that when HVA1 is absent there is a block in the citric acid cycle, while structural analysis of the Hva1 protein suggests a potential interaction with NADPH. The structural architecture of Hva1 bears similarity with Tudor domains [1].

Literature references

  1. McClelland EE, Ramagopal UA, Rivera J, Cox J, Nakouzi A, Prabu MM, Almo SC, Casadevall A;, PLoS Pathog. 2016;12:e1005849.: A Small Protein Associated with Fungal Energy Metabolism Affects the Virulence of Cryptococcus neoformans in Mammals. PUBMED:27583447 EPMC:27583447


This tab holds annotation information from the InterPro database.

InterPro entry IPR021331

This family of proteins has no known function.

Domain organisation

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

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Pfam Clan

This family is a member of clan Tudor (CL0049), which has the following description:

This clan covers the Tudor domain 'royal family' [1]. This includes chromo, MBT, PWWP and tudor domains. The chromo domain is a comprised of approximately 50 amino acid residues. There are usually one to three Chromo domains found in a single protein. In some chromo domain containing proteins, a second related chromo domain has been found and is referred to as the Chromo-shadow domain. The structure of the Chromo and Chromo-shadow domains reveal an OB-fold, a fold found in a variety of prokaryotic and eukaryotic nucleic acid binding proteins. More specifically,the chromo-domain structure reveals a three beta strands that are packed against an alpha helix. Interestingly, a similar structure is found in the archaeal chromatin proteins (7kDa DNA-binding domain). These are sequence neutral DNA binding proteins. The DNA binding in these archaeal proteins is mediated through the triple stranded beta sheet. These archaeal domains are though to represent an ancestral chromo domain. Homologs of the chromo domain have been found in fission yeast, ciliated protozoa and all animal species, but appear to be absent in eubacteria, budding yeast and plants [2]. The precise function of the chromo domain is unclear, but the chromo domain is thought to act as a targeting module for chromosomal proteins, although the chromosomal contexts and functional contexts being targeted vary. In all cases studies, the chromo domains are found in proteins that are involved in transcription regulation, positive and negative [2].

The clan contains the following 33 members:

53-BP1_Tudor 7kD_DNA_binding Agenet Chromo Chromo_2 Chromo_shadow Cul7 DUF1325 DUF4537 DUF4819 GEN1_C Hva1_TUDOR LBR_tudor LytTR MBT Mtf2_C ProQ_C PWWP Rad9_Rad53_bind RBB1NT SAWADEE SMN SNase TTD TUDOR Tudor-knot Tudor_1_RapA Tudor_2 Tudor_3 Tudor_4 TUDOR_5 Tudor_FRX1 Tudor_RapA

Alignments

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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
(200)
Full
(1724)
Representative proteomes UniProt
(3355)
NCBI
(4016)
Meta
(47)
RP15
(276)
RP35
(937)
RP55
(1566)
RP75
(2287)
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  Seed
(200)
Full
(1724)
Representative proteomes UniProt
(3355)
NCBI
(4016)
Meta
(47)
RP15
(276)
RP35
(937)
RP55
(1566)
RP75
(2287)
Alignment:
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  Seed
(200)
Full
(1724)
Representative proteomes UniProt
(3355)
NCBI
(4016)
Meta
(47)
RP15
(276)
RP35
(937)
RP55
(1566)
RP75
(2287)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   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: Pfam-B_002448 (release 23.0)
Previous IDs: DUF2945;
Type: Domain
Sequence Ontology: SO:0000417
Author: Pollington J , Finn RD , El-Gebali S
Number in seed: 200
Number in full: 1724
Average length of the domain: 59.80 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 56.65 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.1 24.1
Trusted cut-off 24.2 24.2
Noise cut-off 24.0 24.0
Model length: 59
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

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

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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 Hva1_TUDOR domain has been found. There are 2 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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