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51  structures 160  species 2  interactions 1259  sequences 55  architectures

Family: NTR (PF01759)

Summary: UNC-6/NTR/C345C module

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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.

UNC-6/NTR/C345C module Provide feedback

Sequence similarity between netrin UNC-6 and C345C complement protein family members, and hence the existence of the UNC-6 module, was first reported in [1]. Subsequently, many additional members of the family were identified on the basis of sequence similarity between the C-terminal domains of netrins, complement proteins C3, C4, C5, secreted frizzled-related proteins, and type I pro-collagen C-proteinase enhancer proteins (PCOLCEs), which are homologous with the N-terminal domains of tissue inhibitors of metalloproteinases (TIMPs). The TIMPs are classified as a separate family in Pfam (PF00965) [2]. This expanded domain family has been named as the NTR module [2].

Literature references

  1. Ishii N, Wadsworth WG, Stern BD, Culotti JG, Hedgecock EM; , Neuron 1992;9:873-881.: UNC-6, a laminin-related protein, guides cell and pioneer axon migrations in C. elegans. PUBMED:1329863 EPMC:1329863

  2. Banyai L, Patthy L; , Protein Sci 1999;8:1636-1642.: The NTR module: domains of netrins, secreted frizzled related proteins, and type I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors of metalloproteases. PUBMED:10452607 EPMC:10452607


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR018933

The netrin (NTR) module is an about 130-residue domain found in the C-terminal parts of netrins, complement proteins C3, C4, and C5, secreted frizzled-related proteins, and type I procollagen C-proteinase enhancer proteins (PCOLCEs), as well as in the N-terminal parts of tissue inhibitors of metalloproteinases (TIMPs). The proteins harboring the NTR domain fulfill diverse biological roles ranging from axon guidance, regulation of Wnt signalling, to the control of the activity of metalloproteinases. The NTR domain can be found associated to other domains such as CUB, WAP, Kazal, Kunitz, Ig-like, laminin N-terminal, laminin-type EGF or frizzled. The NTR domain is implicated in inhibition of zinc metalloproteinases of the metzincin family [PUBMED:10452607, PUBMED:11274388].

The NTR module is a basic domain containing six conserved cysteines, which are likely to form internal disulphide bonds, and several conserved blocks of hydrophobic residues (including an YLLLG-like motif). The NTR module consists of a beta-barrel with two terminal alpha-helices packed side by side against the face of the beta-barrel (see SWISSPROT) [PUBMED:10452607].

This entry includes most netrin modules, but excludes those found in TIMPs.

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 TIMP-like (CL0353), which contains the following 2 members:

NTR TIMP

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
(103)
Full
(1259)
Representative proteomes NCBI
(1076)
Meta
(0)
RP15
(82)
RP35
(136)
RP55
(315)
RP75
(605)
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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
(103)
Full
(1259)
Representative proteomes NCBI
(1076)
Meta
(0)
RP15
(82)
RP35
(136)
RP55
(315)
RP75
(605)
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
(103)
Full
(1259)
Representative proteomes NCBI
(1076)
Meta
(0)
RP15
(82)
RP35
(136)
RP55
(315)
RP75
(605)
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.

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: [1]
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 103
Number in full: 1259
Average length of the domain: 105.20 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 14.37 %

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 21.9 21.9
Noise cut-off 21.8 21.6
Model length: 111
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

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

A2M_recep A2M

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 NTR domain has been found. There are 51 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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