Summary: UBA/TS-N domain

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Wikipedia: UBA protein domain
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UBA protein domain Edit Wikipedia article

UBA

elongation factor complex ef-tu/ef-ts from escherichia coli

Identifiers

Symbol

UBA

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

In molecular biology, the protein domain UBA is short for ubiquitin-associated domains. Ubiquitin is a signal added to an incorrectly folded protein, which allows it to be degraded by the proteasome, and the amino acid constituents can be recycled. It is thought to be encoded for by STS-1 gene in humans.

Function[edit]

This family of proteins is involved in a variety of additional cell processes, such as nucleotide excision repair (NER), spindle pole body duplication, and cell growth.^[1]

Protein degradation via the ubiquitin proteasome system (UPS) allows the cell to selectively negatively regulate intracellular proteins. Protein degradation helps to maintain protein quality control, signalling, and cell cycle progression.^[2]^[3] UBA has be proposed to limit ubiquitin chain elongation and to target polyubiquitinated proteins to the 26S proteasome for degradation.^[4]They have been identified in modular proteins involved in protein trafficking, DNA repair, proteasomal degradation, and cell cycle regulation. UBA bind to ubiquitin and aids all the cellular processes involved with ubiquitin; this includes:

Antigen processing
Apoptosis
Biogenesis of organelles
Cell cycle and division
DNA transcription and DNA repair
Differentiation and development
Immune response and inflammation
Neural and muscular degeneration
Morphogenesis of neural networks
Modulation of cell surface receptors, ion channels and the secretory pathway
Response to stress and extracellular modulators
Ribosome biogenesis
Viral infection

Localisation[edit]

The ubiquitin-associated (UBA) protein domain is found to be localized in the cytoplasm and nucleus.^[4]

Structure[edit]

UBA domains are a commonly occurring sequence motif of approximately 45 amino acid residues.^[5]

Examples[edit]

The human homologue of yeast Rad23A is one example of a nucleotide excision-repair protein that contains both an internal and a C-terminal UBA domain. The solution structure of human Rad23A UBA(2) showed that the domain forms a compact three-helix bundle.^[6]

Comparison of the structures of UBA(1) and UBA(2) reveals that both form very similar folds and have a conserved large hydrophobic surface patch which may be a common protein-interacting surface present in diverse UBA domains. Evidence that ubiquitin binds to UBA domains leads to the prediction that the hydrophobic surface patch of UBA domains interacts with the hydrophobic surface on the five-stranded beta-sheet of ubiquitin.^[7]

This domain is similar in sequence to the N-terminal domain of translation elongation factor EF1B (or EF-Ts) from bacteria, mitochondria and chloroplasts.

More information about EF1B (EF-Ts) proteins can be found at Protein of the Month: Elongation Factors .

References[edit]

^ Su V, Lau AF (2009). "Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation.". Cell Mol Life Sci 66 (17): 2819–33. doi:10.1007/s00018-009-0048-9. PMC 2725189. PMID 19468686.
^ Gomez TA, Kolawa N, Gee M, Sweredoski MJ, Deshaies RJ (2011). "Identification of a functional docking site in the Rpn1 LRR domain for the UBA-UBL domain protein Ddi1.". BMC Biol 9: 33. doi:10.1186/1741-7007-9-33. PMC 3126750. PMID 21627799.
^ Tse MK, Hui SK, Yang Y, Yin ST, Hu HY, Zou B et al. (2011). "Structural analysis of the UBA domain of X-linked inhibitor of apoptosis protein reveals different surfaces for ubiquitin-binding and self-association.". PLoS ONE 6 (12): e28511. doi:10.1371/journal.pone.0028511. PMC 3240630. PMID 22194841.
^ ^a ^b Li J, Chu H, Zhang Y, Mou T, Wu C, Zhang Q et al. (2012). "The rice HGW gene encodes a ubiquitin-associated (UBA) domain protein that regulates heading date and grain weight.". PLoS ONE 7 (3): e34231. doi:10.1371/journal.pone.0034231. PMC 3311617. PMID 22457828.
^ Hofmann K, Bucher P (May 1996). "The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway". Trends Biochem. Sci. 21 (5): 172–3. doi:10.1016/S0968-0004(96)30015-7. PMID 8871400.
^ Dieckmann T, Withers-Ward ES, Jarosinski MA, Liu CF, Chen IS, Feigon J (December 1998). "Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr". Nat. Struct. Biol. 5 (12): 1042–7. doi:10.1038/4220. PMID 9846873.
^ Mueller TD, Feigon J (June 2002). "Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions". J. Mol. Biol. 319 (5): 1243–55. doi:10.1016/S0022-2836(02)00302-9. PMID 12079361.

This article incorporates text from the public domain Pfam and InterPro IPR000449

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.

UBA/TS-N domain Provide feedback

This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle [1]. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU [2]. The domain has been found in non EF-TS proteins such as alpha-NAC P70670 and MJ0280 Q57728 [1].

Literature references

Dieckmann T, Withers-Ward ES, Jarosinski MA, Liu CF, Chen IS, Feigon J; , Nat Struct Biol 1998;5:1042-1047.: Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr. PUBMED:9846873 EPMC:9846873
Makarova KS, Aravind L, Galperin MY, Grishin NV, Tatusov RL, Wolf YI, Koonin EV; , Genome Res 1999;9:608-628.: Comparative genomics of the Archaea (Euryarchaeota): evolution of conserved protein families, the stable core, and the variable shell. PUBMED:10413400 EPMC:10413400
Kawashima T, Berthet-Colominas C, Wulff M, Cusack S, Leberman R; , Nature 1996;379:511-518.: The structure of the Escherichia coli EF-Tu.EF-Ts complex at 2.5 A resolution. PUBMED:8596629 EPMC:8596629

External database links

HOMSTRAD:	EF_TS
PANDIT:	PF00627
PROSITE:	PDOC50015
PROSITE profile:	PS50030
Pseudofam:	PF00627
SCOP:	1uba 1efu
SYSTERS:	UBA

This tab holds annotation information from the InterPro database.

InterPro entry IPR000449

UBA domains are a commonly occurring sequence motif of approximately 45 amino acid residues that are found in diverse proteins involved in the ubiquitin/proteasome pathway, DNA excision-repair, and cell signalling via protein kinases [PUBMED:8871400]. The human homologue of yeast Rad23A is one example of a nucleotide excision-repair protein that contains both an internal and a C-terminal UBA domain. The solution structure of human Rad23A UBA(2) showed that the domain forms a compact three-helix bundle [PUBMED:9846873]. Comparison of the structures of UBA(1) and UBA(2) reveals that both form very similar folds and have a conserved large hydrophobic surface patch which may be a common protein-interacting surface present in diverse UBA domains. Evidence that ubiquitin binds to UBA domains leads to the prediction that the hydrophobic surface patch of UBA domains interacts with the hydrophobic surface on the five-stranded beta-sheet of ubiquitin [PUBMED:12079361].

This domain is similar in sequence to the N-terminal domain of translation elongation factor EF1B (or EF-Ts) from bacteria, mitochondria and chloroplasts.

More information about EF1B (EF-Ts) proteins can be found at Protein of the Month: Elongation Factors [PUBMED:].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function

protein binding (GO:0005515)

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan UBA (CL0214), which has the following description:

This superfamily includes domains related to the UBA domain. These domains are often involved in ubiquitin binding.

The clan contains the following 9 members:

CUE DMA DUF1296 RuvA_C TAP_C UBA UBA_2 UBA_3 UBA_4

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: 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
PP/Heatmap: 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.
Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

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.

Downloading

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.

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 (141)	Full (9566)	Representative proteomes				NCBI (7764)	Meta (1831)
	Seed (141)	Full (9566)	RP15 (1308)	RP35 (2242)	RP55 (3222)	RP75 (4154)	NCBI (7764)	Meta (1831)
Jalview	View	View	View	View	View	View	View	View
HTML	View		View	View	View	View
PP/heatmap	₁		View	View	View	View
Pfam viewer	View	View

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

Key: available, not generated, — not available.

Format an alignment

	Seed (141)	Full (9566)	Representative proteomes				NCBI (7764)	Meta (1831)
	Seed (141)	Full (9566)	RP15 (1308)	RP35 (2242)	RP55 (3222)	RP75 (4154)	NCBI (7764)	Meta (1831)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

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 (141)	Full (9566)	Representative proteomes				NCBI (7764)	Meta (1831)
	Seed (141)	Full (9566)	RP15 (1308)	RP35 (2242)	RP55 (3222)	RP75 (4154)	NCBI (7764)	Meta (1831)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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

Seed source:

Bateman A

Previous IDs:

none

Type:

Domain

Author:

Bateman A

Number in seed:

141

Number in full:

9566

Average length of the domain:

37.30 aa

Average identity of full alignment:

34 %

Average coverage of the sequence by the domain:

8.50 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	21.1	21.1
Trusted cut-off	21.1	21.1
Noise cut-off	21.0	21.0

Model length:

37

Family (HMM) version:

26

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Show

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...

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:

superkingdom
kingdom
phylum
class
order
family
genus
species

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".

Sub-species

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.

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

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.

Interactive tree

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

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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.

Interactions

There are 6 interactions for this family. More...

Pkinase UBA GTP_EFTU EF_TS ubiquitin UQ_con

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 UBA domain has been found. There are 104 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 seqence.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: UBA (PF00627)

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