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5  structures 592  species 0  interactions 3958  sequences 70  architectures

Family: RRM_8 (PF11835)

Summary: RRM-like domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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. As of 2019, there are almost 4,000 DUF families within the Pfam database representing over 22% of known families. Some DUFs are not named using the nomenclature due to popular usage but are nevertheless DUFs.[1]

The DUF designation is tentative, and such families tend to be renamed to a more specific name (or merged to an existing domain) after a function is identified.[2][3]

History

The DUF naming scheme was introduced by Chris Ponting, through the addition of DUF1 and DUF2 to the SMART database.[4] 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.[2]

Characterisation

Structural genomics programmes have attempted to understand the function of DUFs through structure determination. The structures of over 250 DUF families have been solved. This (2009) 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.[5]

Some DUF families share remote sequence homology with domains that has characterized function. Computational work can be used to link these relationships. An 2015 work was able to assign 20% of the DUFs to characterized structual superfamilies.[6] Pfam also continuously perform the (manually-verified) assignment in "clan" superfamily entries.[1]

Frequency and conservation

Protein domains and DUFs in different domains of life. Left: Annotated domains. Right: domains of unknown function. Not all overlaps shown.[7]

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.[7]

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.[8] 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.[8] 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.[8] It is thus believed that many DUFs (or proteins of unknown function, PUFs) are only required under certain conditions.

Essential DUFs

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.[7]

External links

References

  1. ^ a b El-Gebali S, Mistry J, Bateman A, Eddy SR, Luciani A, Potter SC, Qureshi M, Richardson LJ, Salazar GA, Smart A, Sonnhammer EL, Hirsh L, Paladin L, Piovesan D, Tosatto SC, Finn RD (January 2019). "The Pfam protein families database in 2019". Nucleic Acids Research. 47 (D1): D427–D432. doi:10.1093/nar/gky995. PMC 6324024. PMID 30357350.
  2. ^ a b Bateman A, Coggill P, Finn RD (October 2010). "DUFs: families in search of function". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications. 66 (Pt 10): 1148–52. doi:10.1107/S1744309110001685. PMC 2954198. PMID 20944204.
  3. ^ Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, Pang N, Forslund K, Ceric G, Clements J, Heger A, Holm L, Sonnhammer EL, Eddy SR, Bateman A, Finn RD (January 2012). "The Pfam protein families database". Nucleic Acids Research. 40 (Database issue): D290–301. doi:10.1093/nar/gkr1065. PMC 3245129. PMID 22127870.
  4. ^ Schultz J, Milpetz F, Bork P, Ponting CP (May 1998). "SMART, a simple modular architecture research tool: identification of signaling domains". Proceedings of the National Academy of Sciences of the United States of America. 95 (11): 5857–64. Bibcode:1998PNAS...95.5857S. doi:10.1073/pnas.95.11.5857. PMC 34487. PMID 9600884.
  5. ^ Jaroszewski L, Li Z, Krishna SS, Bakolitsa C, Wooley J, Deacon AM, Wilson IA, Godzik A (September 2009). "Exploration of uncharted regions of the protein universe". PLoS Biology. 7 (9): e1000205. doi:10.1371/journal.pbio.1000205. PMC 2744874. PMID 19787035.
  6. ^ Mudgal R, Sandhya S, Chandra N, Srinivasan N (July 2015). "De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods". Biology Direct. 10 (1): 38. doi:10.1186/s13062-015-0069-2. PMC 4520260. PMID 26228684.
  7. ^ a b c Goodacre NF, Gerloff DL, Uetz P (December 2013). "Protein domains of unknown function are essential in bacteria". mBio. 5 (1): e00744–13. doi:10.1128/mBio.00744-13. PMC 3884060. PMID 24381303.
  8. ^ a b c Häuser R, Pech M, Kijek J, Yamamoto H, Titz B, Naeve F, Tovchigrechko A, Yamamoto K, Szaflarski W, Takeuchi N, Stellberger T, Diefenbacher ME, Nierhaus KH, Uetz P (2012). Hughes D (ed.). "RsfA (YbeB) proteins are conserved ribosomal silencing factors". PLoS Genetics. 8 (7): e1002815. doi:10.1371/journal.pgen.1002815. PMC 3400551. PMID 22829778.

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.

RRM-like domain Provide feedback

This domain is related to the RRM domains suggesting it may have an RNA-binding function.

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR021790

This entry represents the RNA recognition motif 2 (RRM2) of polypyrimidine tract-binding protein 1 (PTBP1) and related proteins. Proteins containing this domain include PTBP1/2/3 (or PTB1/2/3) and heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) proteins.

PTB can shuttle between nucleus and cytoplasm. It is a splicing repressor factor implicated in the control of alternative exon selection during mRNA processing of many different transcribed genes, including its own pre-mRNA. It is also involved in internal ribosome entry site (IRES)-mediated translation initiation. It may also be involved in the 3'-end processing, localization, and stability of several mRNAs. Two PTB homologues, PTBP2 and PTBP3, are generally expressed in mammalian tissues. PTBP2 is expressed at high levels in adult brain, muscle and testis, while PTBP3 is expressed preferentially in haematopoietic cells [ PUBMED:24264039 ]. PTB and PTBP2 bind to the same RNA sequences and have similar effects on alternative splicing events. However, differential expression of PTB and PTBP2 can lead to the generation of alternatively spliced mRNAs [ PUBMED:24688880 ]. During neuronal differentiation, MicroRNA miR-124 downregulates PTBP1 expression, which in turn leads to upregulation of PTBP2. Later in development, the expression of PTBP2 decreases and this leads to a second wave of alternative splicing changes characteristic of adult brain and essential for brain development [ PUBMED:25940628 ]. PTBP3 may be involved in nonsense-mediated mRNA decay [ PUBMED:22575643 ].

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 RRM (CL0221), which has the following description:

This clan contains families that are related to the RNA recognition motif domains. However, not all these families are RNA binding.

The clan contains the following 32 members:

BRAP2 Calcipressin DbpA DUF1743 DUF1866 DUF4523 GlcNAc-1_reg GUCT Limkain-b1 Nup35_RRM Nup35_RRM_2 PHM7_cyt RL RNA_bind RRM_1 RRM_2 RRM_3 RRM_5 RRM_7 RRM_8 RRM_9 RRM_occluded RRM_Rrp7 SET_assoc Smg4_UPF3 Spo7_2_N Tap-RNA_bind Transposase_22 U1snRNP70_N xRRM XS YlmH_RBD

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...

View options

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
(10)
Full
(3958)
Representative proteomes UniProt
(7026)
RP15
(404)
RP35
(1287)
RP55
(3248)
RP75
(4611)
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PP/heatmap 1 View           

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

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

Format an alignment

  Seed
(10)
Full
(3958)
Representative proteomes UniProt
(7026)
RP15
(404)
RP35
(1287)
RP55
(3248)
RP75
(4611)
Alignment:
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Sequence:
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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
(10)
Full
(3958)
Representative proteomes UniProt
(7026)
RP15
(404)
RP35
(1287)
RP55
(3248)
RP75
(4611)
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: PFAM-B_2268 (release 23.0)
Previous IDs: DUF3355;
Type: Domain
Sequence Ontology: SO:0000417
Author: Assefa S , Coggill P , Bateman A
Number in seed: 10
Number in full: 3958
Average length of the domain: 87.40 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 17.30 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.2 26.2
Trusted cut-off 26.2 26.2
Noise cut-off 26.1 26.1
Model length: 89
Family (HMM) version: 10
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 RRM_8 domain has been found. There are 5 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
A0A0B4K6W9 View 3D Structure Click here
A0A0B4K7I2 View 3D Structure Click here
A0A0P0Y491 View 3D Structure Click here
A0A0R0G0X8 View 3D Structure Click here
A0A0R0HTT1 View 3D Structure Click here
A0A0R0HXC9 View 3D Structure Click here
A0A0R0KL81 View 3D Structure Click here
A0A0R4IZG6 View 3D Structure Click here
A0A1D6FPL6 View 3D Structure Click here
A0A1D6GIJ4 View 3D Structure Click here
A0A1D6K4D6 View 3D Structure Click here
A0A1D6KP33 View 3D Structure Click here
A0A1D6M5G3 View 3D Structure Click here
A0A2R8RN29 View 3D Structure Click here
A4I7Q0 View 3D Structure Click here
A5PM68 View 3D Structure Click here
A8KC22 View 3D Structure Click here
C6KSR3 View 3D Structure Click here
D4A3E1 View 3D Structure Click here
E7FB37 View 3D Structure Click here
F1LQ48 View 3D Structure Click here
F1M040 View 3D Structure Click here
F1QKG2 View 3D Structure Click here
I1JDD2 View 3D Structure Click here
I1LX73 View 3D Structure Click here
I1MAI0 View 3D Structure Click here
I1N4F1 View 3D Structure Click here
I1NH38 View 3D Structure Click here
K7KUR7 View 3D Structure Click here
K7LFQ1 View 3D Structure Click here
O95758 View 3D Structure Click here
P14866 View 3D Structure Click here
P17225 View 3D Structure Click here
Q00438 View 3D Structure Click here
Q0DHV7 View 3D Structure Click here
Q0JHE8 View 3D Structure Click here
Q10KN8 View 3D Structure Click here
Q18999 View 3D Structure Click here
Q503D3 View 3D Structure Click here
Q54YS7 View 3D Structure Click here
Q5ZBG2 View 3D Structure Click here
Q66H20 View 3D Structure Click here
Q6ICX4 View 3D Structure Click here
Q6K4M7 View 3D Structure Click here
Q6YWJ5 View 3D Structure Click here
Q80XZ1 View 3D Structure Click here
Q8BHD7 View 3D Structure Click here
Q8R081 View 3D Structure Click here
Q8WVV9 View 3D Structure Click here
Q91Z31 View 3D Structure Click here
Q921F4 View 3D Structure Click here
Q95QR5 View 3D Structure Click here
Q9FGL9 View 3D Structure Click here
Q9MAC5 View 3D Structure Click here
Q9UKA9 View 3D Structure Click here
Q9Z118 View 3D Structure Click here