PUA

Putative RNA-binding Domain in PseudoUridine synthase and Archaeosine transglycosylase

• SMART accession number: SM00359
• Interpro abstract (IPR002478):

  The PUA (PseudoUridine synthase and Archaeosine transglycosylase) domain was named after the proteins in which it was first found [(PUBMED:10093218)]. PUA is a highly conserved RNA-binding motif found in a wide range of archaeal, bacterial and eukaryotic proteins, including enzymes that catalyse tRNA and rRNA post-transcriptional modifications, proteins involved in ribosome biogenesis and translation, as well as in enzymes involved in proline biosynthesis [(PUBMED:16793063), (PUBMED:16407303)]. The structures of several PUA-RNA complexes reveal a common RNA recognition surface, but also some versatility in the way in which the motif binds to RNA [(PUBMED:17803682)]. PUA motifs are involved in dyskeratosis congenita and cancer, pointing to links between RNA metabolism and human diseases [(PUBMED:16943774)].

• GO function: RNA binding (GO:0003723)

There are 2664 PUA domains in 2664 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Binding / catalysis: RNA-binding

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Aravind L, Koonin EV
• Novel predicted RNA-binding domains associated with the translation machinery.
• J Mol Evol. 1999; 48: 291-302

Two previously undetected domains were identified in a variety of RNA-binding proteins, particularly RNA-modifying enzymes, using methods for sequence profile analysis. A small domain consisting of 60-65 amino acid residues was detected in the ribosomal protein S4, two families of pseudouridine synthases, a novel family of predicted RNA methylases, a yeast protein containing a pseudouridine synthetase and a deaminase domain, bacterial tyrosyl-tRNA synthetases, and a number of uncharacterized, small proteins that may be involved in translation regulation. Another novel domain, designated PUA domain, after PseudoUridine synthase and Archaeosine transglycosylase, was detected in archaeal and eukaryotic pseudouridine synthases, archaeal archaeosine synthases, a family of predicted ATPases that may be involved in RNA modification, a family of predicted archaeal and bacterial rRNA methylases. Additionally, the PUA domain was detected in a family of eukaryotic proteins that also contain a domain homologous to the translation initiation factor eIF1/SUI1; these proteins may comprise a novel type of translation factors. Unexpectedly, the PUA domain was detected also in bacterial and yeast glutamate kinases; this is compatible with the demonstrated role of these enzymes in the regulation of the expression of other genes. We propose that the S4 domain and the PUA domain bind RNA molecules with complex folded structures, adding to the growing collection of nucleic acid-binding domains associated with DNA and RNA modification enzymes. The evolution of the translation machinery components containing the S4, PUA, and SUI1 domains must have included several events of lateral gene transfer and gene loss as well as lineage-specific domain fusions.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the PUA domain.

Protein	Disease
H/ACA ribonucleoprotein complex subunit 4 (O60832) (SMART)	OMIM:300126: Dyskeratosis congenita-1 OMIM:305000: Hoyeraal-Hreidarsson syndrome OMIM:300240:

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
84.48	map00220	Urea cycle and metabolism of amino groups
3.58	map00240	Pyrimidine metabolism
1.79	map00380	Tryptophan metabolism
1.79	map00450	Selenoamino acid metabolism
1.49	map00350	Tyrosine metabolism
1.49	map00440	Aminophosphonate metabolism
1.49	map00150	Androgen and estrogen metabolism
1.49	map00626	Naphthalene and anthracene degradation
1.49	map00340	Histidine metabolism
0.60	map00920	Sulfur metabolism
0.30	map00230	Purine metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PUA domain which could be assigned to a KEGG orthologous group, and not all proteins containing PUA domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of PUA domains in PDB

PDB code	Title
1iq8	Crystal structure of archaeosine trna-guanine transglycosylase from pyrococcus horikoshii
1it7	Crystal structure of archaeosine trna-guanine transglycosylase complexed with guanine
1it8	Crystal structure of archaeosine trna-guanine transglycosylase from pyrococcus horikoshii complexed with archaeosine precursor, preq0
1j2b	Crystal structure of archaeosine trna-guanine transglycosylase complexed with lambda-form trna(val)
1q7h	Structure of a conserved pua domain protein from thermoplasma acidophilum
1r3e	Crystal structure of trna pseudouridine synthase trub and its rna complex: rna-protein recognition through a combination of rigid docking and induced fit
1sqw	Crystal structure of kd93, a novel protein expressed in the human pro
1t5y	Crystal structure of northeast structural genomics consortium target hr2118: a human homolog of saccharomyces cerevisiae nip7p
1ze1	Conformational change of pseudouridine 55 synthase upon its association with rna substrate
1ze2	Conformational change of pseudouridine 55 synthase upon its association with rna substrate
1zs7	The structure of gene product ape0525 from aeropyrum pernix
2ab4	Dissecting the roles of a strictly conserved tyrosine in substrate recognition and catalysis by pseudouridine 55 synthase
2apo	Crystal structure of the methanococcus jannaschii cbf5 nop10 complex
2as0	Crystal structure of ph1915 (apc 5817): a hypothetical rna methyltransferase
2aus	Crystal structure of the archaeal box h/aca srnp nop10-cbf5 complex
2cx0	Crystal structure of a pua domain (ape0525) from the aeropyrum pernix k1 (sulfate complex)
2cx1	Crystal structure of a pua domain (ape0525) from the aeropyrum pernix k1 (tartrate complex)
2ey4	Crystal structure of a cbf5-nop10-gar1 complex
2hvy	Crystal structure of an h/aca box rnp from pyrococcus furiosus
2j5t	Glutamate 5-kinase from escherichia coli complexed with glutamate
2j5v	Glutamate 5-kinase from escherichia coli complexed with glutamyl-5-phosphate and pyroglutamic acid
2q07	Crystal structure of af0587, a protein of unknown function
2rfk	Substrate rna positioning in the archaeal h/aca ribonucleoprotein complex
3c0k	Crystal structure of a ribosomal rna methyltranferase
3d79	Crystal structure of hypothetical protein ph0734.1 from hyperthermophilic archaea pyrococcus horikoshii ot3
3hax	Crystal structure of a substrate-bound gar1-minus h/aca rnp from pyrococcus furiosus
3hay	Crystal structure of a substrate-bound full h/aca rnp from pyrococcus furiosus
3hjw	Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate rna
3hjy	Structure of a functional ribonucleoprotein pseudouridine synthase bound to a substrate rna

Links (links to other resources describing this domain)

• INTERPRO: IPR002478