The domain within your query sequence starts at position 822 and ends at position 857; the E-value for the Pumilio domain shown below is 3.2e-9.

ELHQHTEQLVQDQYGNYVIQHVLEHGRPEDKSKIVS

Pumilio

Pumilio-like repeats

• SMART accession number: SM00025
• Description: Pumilio-like repeats that bind RNA.
• Interpro abstract (IPR001313):

  Members of the Pumilio family of proteins (Puf) regulate translation and mRNA stability in a wide variety of eukaryotic organisms including mammals, flies, worms, slime mold, and yeast [ (PUBMED:10662662) ]. Pumilio family members are characterised by the presence of eight tandem copies of an imperfectly repeated 36 amino acids sequence motif, the Pumilio repeat, surrounded by a short N- and C-terminal conserved region. The eight repeats and the N- and C-terminal regions form the Pumilio homology domain (PUM-HD). The PUM-HD domain is a sequence-specific RNA binding domain. The Puf family of proteins are mainly post-transcriptional regulators. Several Puf members have been shown to bind specific RNA sequences mainly found in the 3' UTR of mRNA and repress their translation [ (PUBMED:14584586) (PUBMED:29385744) ]. Frequently, Puf proteins function asymmetrically to create protein gradients, thus causing asymmetric cell division and regulating cell fate specification [ (PUBMED:1459455) ].

  Crystal structure of Pumilio repeats has been solved [ (PUBMED:11336708) ]. The PUM repeat with the N- and C-terminal regions pack together to form a right-handed superhelix that approximates a half doughnut structurally similar to the Armadillo (ARM) repeat proteins, beta-catenin and karyopherin alpha. The RNA binds the concave surface of the molecule, where each of the protein's eight repeats makes contacts with a different RNA base via three amino acid side chains at conserved positions [ (PUBMED:12202039) ].

  This entry represents the Pumilio repeat.

• GO function: RNA binding (GO:0003723)

There are 66335 Pumilio domains in 9739 proteins in SMART's nrdb database.

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.

• Wharton RP, Sonoda J, Lee T, Patterson M, Murata Y
• The Pumilio RNA-binding domain is also a translational regulator.
• Mol Cell. 1998; 1: 863-72

Posterior patterning in the Drosophila embryo requires the action of Nanos (Nos) and Pumilio (Pum), which collaborate to regulate the translation of maternal hunchback (hb) mRNA. Previous work demonstrated that Pum recognizes sites in the 3' UTR of hb mRNA. In this report, we first define the RNA-binding domain of Pum and then show that residues essential for translational repression are embedded within this domain. We also show that Nos and Pum can repress cap-independent translation from an internal ribosome entry site (IRES) in vivo, suggesting that they act downstream of the initial steps of normal, cap-dependent translation.

• Curtis D, Treiber DK, Tao F, Zamore PD, Williamson JR, Lehmann R
• A CCHC metal-binding domain in Nanos is essential for translational regulation.
• EMBO J. 1997; 16: 834-43

The Drosophila Nanos protein is a localized repressor of hunchback mRNA translation in the early embryo, and is required for the establishment of the anterior-posterior body axis. Analysis of nanos mutants reveals that a small, evolutionarily conserved, C-terminal region is essential for Nanos function in vivo, while no other single portion of the Nanos protein is absolutely required. Within the C-terminal region are two unusual Cys-Cys-His-Cys (CCHC) motifs that are potential zinc-binding sites. Using absorption spectroscopy and NMR we demonstrate that the CCHC motifs each bind one equivalent of zinc with high affinity. nanos mutations disrupting metal binding at either of these two sites in vitro abolish Nanos translational repression activity in vivo. We show that full-length and C-terminal Nanos proteins bind to RNA in vitro with high affinity, but with little sequence specificity. Mutations affecting the hunchback mRNA target sites for Nanos-dependent translational repression were found to disrupt translational repression in vivo, but had little effect on Nanos RNA binding in vitro. Thus, the Nanos zinc domain does not specifically recognize target hunchback RNA sequences, but might interact with RNA in the context of a larger ribonucleoprotein complex.

• Zamore PD, Williamson JR, Lehmann R
• The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins.
• RNA. 1997; 3: 1421-33

Translation of hunchback(mat) (hb[mat]) mRNA must be repressed in the posterior of the pre-blastoderm Drosophila embryo to permit formation of abdominal segments. This translational repression requires two copies of the Nanos Response Element (NRE), a 16-nt sequence in the hb[mat] 3' untranslated region. Translational repression also requires the action of two proteins: Pumilio (PUM), a sequence-specific RNA-binding protein; and Nanos, a protein that determines the location of repression. Binding of PUM to the NRE is thought to target hb(mat) mRNA for repression. Here, we show the RNA-binding domain of PUM to be an evolutionarily conserved, 334-amino acid region at the carboxy-terminus of the approximately 158-kDa PUM protein. This contiguous region of PUM retains the RNA-binding specificity of full-length PUM protein. Proteins with sequences homologous to the PUM RNA-binding domain are found in animals, plants, and fungi. The high degree of sequence conservation of the PUM RNA-binding domain in other far-flung species suggests that the domain is an ancient protein motif, and we show that conservation of sequence reflects conservation of function: that is, the homologous region from a human protein binds RNA with sequence specificity related to but distinct from Drosophila PUM.

• Zhang B et al.
• A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line.
• Nature. 1997; 390: 477-84

The nematode Caenorhabditis elegans has two sexes, males and hermaphrodites. Hermaphrodites Initially produce sperm but switch to producing oocytes. This switch appears to be controlled by the 3' untranslated region of fem-3 messenger RNA. We have now identified a binding factor (FBF) which is a cytoplasmic protein that binds specifically to the regulatory region of fem-3 3'UTR and mediates the sperm/oocyte switch. The RNA-binding domain of FBF consists of a stretch of eight tandem repeats and two short flanking regions. This structural element is conserved in several proteins including Drosophila Pumilio, a regulatory protein that controls pattern formation in the fly by binding to a 3'UTR. We propose that FBF and Pumilio are members of a widespread family of sequence-specific RNA-binding proteins.

• Macdonald PM
• The Drosophila pumilio gene: an unusually long transcription unit and an unusual protein.
• Development. 1992; 114: 221-32

Specification of the posterior body plan in Drosophila requires the action of a determinant prelocalized to the posterior pole of the embryo. During embryogenesis this determinant appears to move anteriorly in a process dependent on the pumilio (pum) gene. This report describes the cloning and molecular characterization of a cDNA derived from the pum gene, and the analysis of pum mRNA and protein expression during early Drosophila development. The pum gene is unusually large; comparison of genomic and cDNA sequences reveals that the pum transcription unit is at least 160 kb in length. The pum cDNA encodes a 157 x 10(3) M(r) protein which consists mainly of regions enriched in a single amino acid, usually glycine, alanine, glutamine or serine/threonine. Six tandem repeats of a 36 amino acid repeat unit are also present. Pum protein is cytoplasmic and is concentrated in a subcortical region of the embryo. The distribution of pum protein exhibits no asymmetry along the anteroposterior axis of the embryo.

Structure (3D structures containing this domain)

3D Structures of Pumilio domains in PDB

PDB code	Title
1ib2	CRYSTAL STRUCTURE OF A PUMILIO-HOMOLOGY DOMAIN
1m8w	CRYSTAL STRUCTURE OF THE PUMILIO-HOMOLOGY DOMAIN FROM HUMAN PUMILIO1 IN COMPLEX WITH NRE1-19 RNA
1m8x	CRYSTAL STRUCTURE OF THE PUMILIO-HOMOLOGY DOMAIN FROM HUMAN PUMILIO1 IN COMPLEX WITH NRE1-14 RNA
1m8y	CRYSTAL STRUCTURE OF THE PUMILIO-HOMOLOGY DOMAIN FROM HUMAN PUMILIO1 IN COMPLEX WITH NRE2-10 RNA
1m8z	Crystal Structure Of A Pumilio-Homology Domain
2yjy	A specific and modular binding code for cytosine recognition in PUF domains
3bsb	Crystal Structure of Human Pumilio1 in Complex with CyclinB reverse RNA
3bsx	Crystal Structure of Human Pumilio 1 in complex with Puf5 RNA
3bwt	Crystal structure of the RNA binding domain of Puf4 from Saccharomyces cerevisiae
3bx2	Puf4 RNA binding domain bound to HO endonuclease RNA 3' UTR recognition sequence
3bx3	Puf4 T650C/C724R Mutant bound to Cox17 RNA 3' UTR recognition sequence
3gvo	Structure and RNA binding of the mouse Pumilio-2 Puf Domain
3gvt	Structure and RNA binding of the mouse Pumilio-2 Puf Domain
3h3d	Drosophila Pumilio RNA binding domain (Puf domain)
3k49	Puf3 RNA binding domain bound to Cox17 RNA 3' UTR recognition sequence site B
3k4e	Puf3 RNA binding domain bound to Cox17 RNA 3' UTR recognition sequence site A
3k5q	Crystal structure of FBF-2/FBE complex
3k5y	Crystal structure of FBF-2/gld-1 FBEa complex
3k5z	Crystal structure of FBF-2/gld-1 FBEa G4A mutant complex
3k61	Crystal structure of FBF-2/fog-1 FBEa complex
3k62	Crystal structure of FBF-2/gld-1 FBEb complex
3k64	Crystal structure of FBF-2/fem-3 PME complex
3q0l	Crystal structure of the PUMILIO-homology domain from Human PUMILIO1 in complex with p38alpha NREa
3q0m	Crystal structure of the PUMILIO-homology domain from Human PUMILIO1 in complex with p38alpha NREb
3q0n	Crystal structure of the PUMILIO-homology domain from Human PUMILIO1 in complex with erk2 NRE
3q0o	Crystal structure of the PUMILIO-homology domain from Human PUMILIO1 in complex with erk2 NRE
3q0p	Crystal structure of the PUMILIO-homology domain from Human PUMILIO1 in complex with hunchback NRE
3q0q	Crystal structure of the PUMILIO-homology domain from Human PUMILIO2 in complex with p38alpha NREa
3q0r	Crystal structure of the PUMILIO-homology domain from Human PUMILIO2 in complex with p38alpha NREb
3q0s	Crystal structure of the PUMILIO-homology domain from Human PUMILIO2 in complex with erk2 NRE
3qg9	crystal structure of FBF-2/gld-1 FBEa A7U mutant complex
3qgb	Crystal structure of FBF-2 R288Y mutant in complex with gld-1 FBEa
3qgc	Crystal structure of FBF-2 R288Y mutant in complex with gld-1 FBEa A7U mutant
3v6y	crystal structure of FBF-2 in complex with a mutant gld-1 FBEa13 RNA
3v71	Crystal structure of PUF-6 in complex with 5BE13 RNA
3v74	crystal structure of FBF-2 in complex with gld-1 FBEa13 RNA
4dzs	Crystal structure of yeast Puf4p RNA binding domain in complex with HO-4BE mutant RNA
4wzr	4WZR
4wzw	4WZW
5bym	5BYM
5bz1	5BZ1
5bz5	5BZ5
5bzu	5BZU
5bzv	5BZV
5kl1	5KL1
5kl8	5KL8
5kla	5KLA
5svd	5SVD

Links (links to other resources describing this domain)

• INTERPRO: IPR001313