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19  structures 294  species 0  interactions 473  sequences 22  architectures

Family: Nucleoporin2 (PF04096)

Summary: Nucleoporin autopeptidase

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Nucleoporin autopeptidase Provide feedback

No Pfam abstract.

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


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR007230

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

  • Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
  • Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

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].

This group of autocatalytic serine endopeptidases belong to MEROPS peptidase family S59 (clan SP).

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

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Domain organisation

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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...

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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
(57)
Full
(473)
Representative proteomes NCBI
(507)
Meta
(1)
RP15
(113)
RP35
(182)
RP55
(263)
RP75
(304)
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Format an alignment

  Seed
(57)
Full
(473)
Representative proteomes NCBI
(507)
Meta
(1)
RP15
(113)
RP35
(182)
RP55
(263)
RP75
(304)
Alignment:
Format:
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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
(57)
Full
(473)
Representative proteomes NCBI
(507)
Meta
(1)
RP15
(113)
RP35
(182)
RP55
(263)
RP75
(304)
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.

Pfam alignments:

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
Author: Wood V, Finn RD, Rawlings N
Number in seed: 57
Number in full: 473
Average length of the domain: 137.20 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 10.65 %

HMM information View help on HMM parameters

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 21.9 21.9
Trusted cut-off 23.8 24.9
Noise cut-off 21.8 21.0
Model length: 141
Family (HMM) version: 9
Download: download the raw HMM for this family

Species distribution

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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 Nucleoporin2 domain has been found. There are 19 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.

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