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25  structures 120  species 2  interactions 1456  sequences 302  architectures

Family: Notch (PF00066)

Summary: LNR domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "NOTCH proteins". More...

NOTCH proteins Edit Wikipedia article

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LNR domain Provide feedback

The LNR (Lin-12/Notch repeat) domain is found in three tandem copies in Notch related proteins. The structure of the domain has been determined by NMR [1] and was shown to contain three disulphide bonds and coordinate a calcium ion. Three repeats are also found in the PAPP-A peptidase [2].

Literature references

  1. Vardar D, North CL, Sanchez-Irizarry C, Aster JC, Blacklow SC; , Biochemistry. 2003;42:7061-7067.: Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1. PUBMED:12795601 EPMC:12795601

  2. Boldt HB, Kjaer-Sorensen K, Overgaard MT, Weyer K, Poulsen CB, Sottrup-Jensen L, Conover CA, Giudice LC, Oxvig C; , J Biol Chem. 2004;279:38525-38531.: The Lin12-notch repeats of pregnancy-associated plasma protein-A bind calcium and determine its proteolytic specificity. PUBMED:15262980 EPMC:15262980


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000800

The Notch domain is also called the 'DSL' domain or the Lin-12/Notch repeat (LNR). The LNR region is present only in Notch related proteins C-terminal to EGF repeats. The lin-12/Notch proteins act as transmembrane receptors for intercellular signals that specify cell fates during animal development. In response to a ligand, proteolytic cleavages release the intracellular domain of Notch, which then gains access to the nucleus and acts as a transcriptional co-activator [PUBMED:3119223]. The LNR region is supposed to negatively regulate the Lin-12/Notch proteins activity. It is a triplication of an around 35-40 amino acids module present on the extracellular part of the protein [PUBMED:7697721, PUBMED:8139658]. Each module contains six cysteine residues engaged in three disulphide bonds and three conserved aspartate and asparagine residues [PUBMED:3119223]. The biochemical characterisation of a recombinantly expressed LIN-12.1 module from the human Notch1 receptor indicate that the disulphide bonds are formed between the first and fifth, second and fourth, and third and sixth cysteines. The formation of this particular disulphide isomer is favored by the presence of Ca2+, which is also required to maintain the structural integrity of the rLIN-12.1 module. The conserved aspartate and asparagine residues are likely to be important for Ca2+ binding, and thereby contribute to the native fold.

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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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
(53)
Full
(1456)
Representative proteomes NCBI
(1259)
Meta
(39)
RP15
(251)
RP35
(317)
RP55
(518)
RP75
(783)
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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
(53)
Full
(1456)
Representative proteomes NCBI
(1259)
Meta
(39)
RP15
(251)
RP35
(317)
RP55
(518)
RP75
(783)
Alignment:
Format:
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Sequence:
Gaps:
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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
(53)
Full
(1456)
Representative proteomes NCBI
(1259)
Meta
(39)
RP15
(251)
RP35
(317)
RP55
(518)
RP75
(783)
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.

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: Swissprot_feature_table
Previous IDs: notch;
Type: Domain
Author: Sonnhammer ELL, Bateman A
Number in seed: 53
Number in full: 1456
Average length of the domain: 37.40 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 5.70 %

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 21.2 21.2
Trusted cut-off 21.2 21.3
Noise cut-off 21.1 21.1
Model length: 38
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

NODP Notch

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 Notch domain has been found. There are 25 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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