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40  structures 472  species 0  interactions 6090  sequences 1319  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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This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

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


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 Ca 2+ , 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 Ca 2+ binding, and thereby contribute to the native fold.

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

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
(108)
Full
(6090)
Representative proteomes UniProt
(12566)
RP15
(1016)
RP35
(2213)
RP55
(5119)
RP75
(6633)
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HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(108)
Full
(6090)
Representative proteomes UniProt
(12566)
RP15
(1016)
RP35
(2213)
RP55
(5119)
RP75
(6633)
Alignment:
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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
(108)
Full
(6090)
Representative proteomes UniProt
(12566)
RP15
(1016)
RP35
(2213)
RP55
(5119)
RP75
(6633)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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: Swissprot_feature_table
Previous IDs: notch;
Type: Domain
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL , Bateman A
Number in seed: 108
Number in full: 6090
Average length of the domain: 35.60 aa
Average identity of full alignment: 40 %
Average coverage of the sequence by the domain: 4.85 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.2 21.2
Trusted cut-off 21.2 21.2
Noise cut-off 21.1 21.1
Model length: 36
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 Notch domain has been found. There are 40 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A1Z7S7 View 3D Structure Click here
D3ZKE0 View 3D Structure Click here
D3ZKE0 View 3D Structure Click here
F1QCA7 View 3D Structure Click here
F1QCA7 View 3D Structure Click here
F1QCA7 View 3D Structure Click here
F1QZF2 View 3D Structure Click here
F1QZF2 View 3D Structure Click here
F1QZF2 View 3D Structure Click here
F1RCH4 View 3D Structure Click here
F1RCH4 View 3D Structure Click here
F1RCH4 View 3D Structure Click here
O35516 View 3D Structure Click here
O35516 View 3D Structure Click here
O35516 View 3D Structure Click here
P13508 View 3D Structure Click here
P13508 View 3D Structure Click here
P13508 View 3D Structure Click here
P14585 View 3D Structure Click here
P14585 View 3D Structure Click here
P14585 View 3D Structure Click here
P31695 View 3D Structure Click here
P31695 View 3D Structure Click here
P31695 View 3D Structure Click here
P46530 View 3D Structure Click here
P46530 View 3D Structure Click here
P46530 View 3D Structure Click here
P46531 View 3D Structure Click here
P46531 View 3D Structure Click here
P46531 View 3D Structure Click here
Q01705 View 3D Structure Click here
Q01705 View 3D Structure Click here
Q01705 View 3D Structure Click here
Q04721 View 3D Structure Click here
Q04721 View 3D Structure Click here
Q04721 View 3D Structure Click here
Q07008 View 3D Structure Click here
Q07008 View 3D Structure Click here
Q07008 View 3D Structure Click here
Q3T906 View 3D Structure Click here
Q3T906 View 3D Structure Click here
Q54MP1 View 3D Structure Click here
Q54MP1 View 3D Structure Click here
Q5RGJ8 View 3D Structure Click here
Q5RGJ8 View 3D Structure Click here
Q61982 View 3D Structure Click here
Q61982 View 3D Structure Click here
Q61982 View 3D Structure Click here
Q69ZN6 View 3D Structure Click here
Q69ZN6 View 3D Structure Click here
Q6MG89 View 3D Structure Click here
Q6MG89 View 3D Structure Click here
Q6MG89 View 3D Structure Click here
Q99466 View 3D Structure Click here
Q99466 View 3D Structure Click here
Q99466 View 3D Structure Click here
Q9QW30 View 3D Structure Click here
Q9QW30 View 3D Structure Click here
Q9QW30 View 3D Structure Click here
Q9R172 View 3D Structure Click here
Q9R172 View 3D Structure Click here
Q9R172 View 3D Structure Click here
Q9UM47 View 3D Structure Click here
Q9UM47 View 3D Structure Click here
Q9UM47 View 3D Structure Click here
X1WEZ2 View 3D Structure Click here
X1WEZ2 View 3D Structure Click here