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27  structures 1005  species 1  interaction 1615  sequences 62  architectures

Family: Nucleoporin2 (PF04096)

Summary: Nucleoporin autopeptidase

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Nucleoporin autopeptidase Provide feedback

The nuclear pore complex protein plays a role in bidirectional transport across the nucleoporin complex in nucleocytoplasmic transport. The mammalian nuclear pore complex (NPC) is comprised of approximately 30 unique proteins, collectively known as nucleoporins [2]. This family includes yeast family members such as Nup145p as well as vertebrate Nup98. The NUP C-terminal domains of Nup98 and Nup145 possess peptidase S59 autoproteolytic activity. The autoproteolytic sites of Nup98 and Nup145 each occur immediately C-terminal to the NUP C-terminal domain. Thus, although this domain occurs in the middle of each precursor polypeptide, it winds up at the C-terminal end of the N-terminal cleavage product. Cleavage of the peptide chains are necessary for the proper targeting to the nuclear pore [3] [4].

Literature references

  1. Hodel AE, Hodel MR, Griffis ER, Hennig KA, Ratner GA, Xu S, Powers MA; , Mol Cell 2002;10:347-358.: The three-dimensional structure of the autoproteolytic, nuclear pore-targeting domain of the human nucleoporin Nup98. PUBMED:12191480 EPMC:12191480

  2. Capitanio JS, Montpetit B, Wozniak RW;, Elife. 2017; [Epub ahead of print]: Human Nup98 regulates the localization and activity of DExH/D-box helicase DHX9. PUBMED:28221134 EPMC:28221134

  3. Hodel AE, Hodel MR, Griffis ER, Hennig KA, Ratner GA, Xu S, Powers MA; , Mol Cell 2002;10:347-358.: The three-dimensional structure of the autoproteolytic, nuclear pore-targeting domain of the human nucleoporin Nup98. PUBMED:12191480 EPMC:12191480

  4. Robinson MA, Park S, Sun ZY, Silver PA, Wagner G, Hogle JM;, J Biol Chem. 2005;280:35723-35732.: Multiple conformations in the ligand-binding site of the yeast nuclear pore-targeting domain of Nup116p. PUBMED:16105837 EPMC:16105837


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR007230

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [PUBMED:7845208]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence [PUBMED:7845208]. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [PUBMED:7845208].

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [PUBMED:7845208]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds [PUBMED:7845208]. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [PUBMED:7845208, PUBMED:8439290].

The nuclear pore complex protein plays a role in bidirectional transport across the nucleoporin complex in nucleocytoplasmic transport. The mammalian nuclear pore complex (NPC) is comprised of approximately 50 unique proteins, collectively known as nucleoporins. A number of the peptides are synthesised as precursors and undergo self-catalyzed cleavage.

The proteolytic cleavage site of yeast Nup145p has been mapped upstream of an evolutionary conserved serine residue. Cleavage occurs at the same site when a precursor is artificially expressed in Escherichia coli. A hydroxyl-containing residue is critical for the reaction, although a thiol-containing residue offers an acceptable replacement. In vitro kinetics experiments using a purified precursor molecule demonstrate that the cleavage is self-catalyzed and that the catalytic domain lies within the N-terminal moiety. Taken altogether, the data are consistent with a proteolytic mechanism involving an N>O acyl rearrangement and a subsequent ester intermediate uncovered in other self-processing proteins [PUBMED:10542288].

Nup98 is a component of the nuclear pore that plays its primary role in the export of RNAs. Nup98 is expressed in two forms, derived from alternate mRNA splicing. Both forms are processed into two peptides through autoproteolysis mediated by the C-terminal domain of hNup98. The three-dimensional structure of the C-terminal domain reveals a novel protein fold, and thus a new class of autocatalytic proteases. The structure further reveals that the suggested nucleoporin RNA binding motif is unlikely to bind to RNA [PUBMED:12191480].

The following nucleoporins share an ~150-residue C-terminal domain responsible for NPC targeting [PUBMED:12191480, PUBMED:16105837]:

  • Vertebrate Nup98, a component of the nuclear pore that plays its primary role in the export of RNAs.
  • Yeast Nup100, plays an important role in several nuclear export and import pathways including poly(A)+ RNA and protein transport.
  • Yeast Nup116, involved in mRNA export and protein transport.
  • Yeast Nup145, involved in nuclear poly(A)+ RNA and tRNA export.

The NUP C-terminal domains of Nup98 and Nup145 possess peptidase S59 autoproteolytic activity. The autoproteolytic sites of Nup98 and Nup145 each occur immediately C-terminal to the NUP C-terminal domain. Thus, although this domain occurs in the middle of each precursor polypeptide, it winds up at the C-terminal end of the N-terminal cleavage product. Cleavage of the peptide chains are necessary for the proper targeting to the nuclear pore [PUBMED:12191480, PUBMED:16105837].

The NUP C-terminal domain adopts a predominantly beta-strand structure. The molecule consists of a six-stranded beta-sheet sandwiched against a two-stranded beta-sheet and flanked by alpha-helical regions. The N-terminal helical region consists of two short helices, whereas the stretch on the opposite side of molecule consists of a single, longer helix [PUBMED:12191480, PUBMED:16105837].

Gene Ontology

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

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 Gain (CL0661), which has the following description:

Members of this clan belong to GAIN domain with an autoproteolytic motif. The G-protein-coupled receptor (GPCR) autoproteolysis-inducing (GAIN) domain, includes GPCRs involved in adhesion with a characteristic autoproteolysis motif of HLT/S known as the GPCR proteolysis site (GPS). GPS is also shared by polycystic kidney disease (PKD) proteins. GAIN has been shown to be both necessary and sufficient for autoproteolysis [1].

The clan contains the following 6 members:

DUF1191 GAIN GPS Nucleoporin2 UPF0560 ZU5

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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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
(214)
Full
(1615)
Representative proteomes UniProt
(2423)
NCBI
(3438)
Meta
(1)
RP15
(425)
RP35
(860)
RP55
(1217)
RP75
(1453)
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  Seed
(214)
Full
(1615)
Representative proteomes UniProt
(2423)
NCBI
(3438)
Meta
(1)
RP15
(425)
RP35
(860)
RP55
(1217)
RP75
(1453)
Alignment:
Format:
Order:
Sequence:
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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
(214)
Full
(1615)
Representative proteomes UniProt
(2423)
NCBI
(3438)
Meta
(1)
RP15
(425)
RP35
(860)
RP55
(1217)
RP75
(1453)
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_5132 (release 7.3);
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Wood V , Finn RD , Rawlings ND , El-Gebali S
Number in seed: 214
Number in full: 1615
Average length of the domain: 142.60 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 10.62 %

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 28.0 28.0
Trusted cut-off 28.2 28.1
Noise cut-off 27.3 27.9
Model length: 149
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There is 1 interaction for this family. More...

Nucleoporin2

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 Nucleoporin2 domain has been found. There are 27 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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