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0  structures 139  species 0  interactions 234  sequences 9  architectures

Family: Nicastrin (PF05450)

Summary: Nicastrin

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The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

Nicastrin Provide feedback

Nicastrin and presenilin are two major components of the gamma-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesised in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin) [1]. A region featured in this family has a fold similar to human transferrin receptor (TfR, P02786) and a bacterial aminopeptidase (P80561). It is implicated in the pathogenesis of Alzheimer's disease [4].

Literature references

  1. Herreman A, Van Gassen G, Bentahir M, Nyabi O, Craessaerts K, Mueller U, Annaert W, De Strooper B; , J Cell Sci 2003;116:1127-1136.: gamma-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation. PUBMED:12584255 EPMC:12584255

  2. Bagshaw RD, Pasternak SH, Mahuran DJ, Callahan JW; , Biochem Biophys Res Commun 2003;300:615-618.: Nicastrin is a resident lysosomal membrane protein. PUBMED:12507492 EPMC:12507492

  3. Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorb, Nature 2000;407:48-54.: Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing. PUBMED:10993067 EPMC:10993067

  4. Fagan R, Swindells M, Overington J, Weir M; , Trends Biochem Sci 2001;26:213-214.: Nicastrin, a presenilin-interacting protein, contains an aminopeptidase/transferrin receptor superfamily domain. PUBMED:11295540 EPMC:11295540


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008710

Nicastrin and presenilin are two major components of the gamma-secretase complex, which executes the intramembrane proteolysis of type I integral membrane proteins such as the amyloid precursor protein (APP) and Notch. Nicastrin is synthesised in fibroblasts and neurons as an endoglycosidase-H-sensitive glycosylated precursor protein (immature nicastrin) and is then modified by complex glycosylation in the Golgi apparatus and by sialylation in the trans-Golgi network (mature nicastrin) [PUBMED:12584255].

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 Peptidase_MH (CL0035), which has the following description:

This clan contains peptidases belonging to MEROPS clan MH, MC and MF. We also include Nicastrin that is part of the gamma secretase complex and not known to be a peptidase.

The clan contains the following 12 members:

Amidase_3 AstE_AspA DUF2172 DUF2817 Nicastrin Peptidase_M14 Peptidase_M17 Peptidase_M18 Peptidase_M20 Peptidase_M28 Peptidase_M42 SpoIIP

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
(6)
Full
(234)
Representative proteomes NCBI
(395)
Meta
(62)
RP15
(50)
RP35
(74)
RP55
(112)
RP75
(136)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(6)
Full
(234)
Representative proteomes NCBI
(395)
Meta
(62)
RP15
(50)
RP35
(74)
RP55
(112)
RP75
(136)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(6)
Full
(234)
Representative proteomes NCBI
(395)
Meta
(62)
RP15
(50)
RP35
(74)
RP55
(112)
RP75
(136)
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_15452 (release 8.0)
Previous IDs: none
Type: Family
Author: Moxon SJ
Number in seed: 6
Number in full: 234
Average length of the domain: 196.70 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 32.33 %

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 20.2 20.2
Trusted cut-off 20.2 20.2
Noise cut-off 20.1 20.1
Model length: 234
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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