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4  structures 228  species 0  interactions 604  sequences 95  architectures

Family: NtA (PF03146)

Summary: Agrin NtA domain

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This is the Wikipedia entry entitled "Agrin". More...

Agrin Edit Wikipedia article


Large proteoglycan that is required for the formation of the neuromuscular junction

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.

Agrin NtA domain Provide feedback

Agrin is a multidomain heparan sulphate proteoglycan, that is a key organiser for the induction of postsynaptic specialisations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain [2]. This region mediates high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to non-neuronal cell such as motor neurons. The structure of this domain is an OB-fold [1].

Literature references

  1. Stetefeld J, Jenny M, Schulthess T, Landwehr R, Schumacher B, Frank S, Ruegg MA, Engel J, Kammerer RA; , Nat Struct Biol 2001;8:705-709.: The laminin-binding domain of agrin is structurally related to N-TIMP-1. PUBMED:11473262 EPMC:11473262

  2. Denzer AJ, Hauser DM, Gesemann M, Ruegg MA; , Cell Tissue Res 1997;290:357-365.: Synaptic differentiation: the role of agrin in the formation and maintenance of the neuromuscular junction. PUBMED:9321698 EPMC:9321698


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004850

Agrin is a multidomain heparan sulphate proteoglycan, that is a key organiser for the induction of postsynaptic specializations at the neuromuscular junction. Binding of agrin to basement membranes requires the amino terminal (NtA) domain [ PUBMED:9321698 ]. This region mediates high affinity interaction with the coiled-coil domain of laminins. The binding of agrin to laminins via the NtA domain is subject to tissue-specific regulation. The NtA domain-containing form of agrin is expressed in non-neuronal cells or in neurons that project to non-neuronal cell such as motor neurons. The NtA domain forms the most N-terminal part, followed by 9 Kazal-like domains and 2 LE domains. The C-terminal part consists of a SEA domain, 4 EGF-like domains and 3 Laminin G domains, responsible for the clustering of acetylcholine receptors [ PUBMED:11473262 ].

Tertiairy structures show that the NtA domain folds as a beta-barrel core flanked by N- and C-terminal helical regions. The core of the domain consists of 5 beta-strands that form 2 beta-sheets. The structure belongs to the OB fold family and shows similarity with the protease inhibition domain of TIMP-1, suggesting alternative functions for agrin in addition to synaptogenic activity [ PUBMED:11473262 ]. Residues Leu 117 and Val 124 in helix 3 of the NtA domain are essential for binding to the laminin gamma1 chain [ PUBMED:12554653 ].

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 TIMP-like (CL0353), which has the following description:

This superfamily consists of the C-terminal domains of netrins, complement proteins C3, C4, C5, secreted frizzled-related proteins, and type I procollagen C-proteinase enhancer proteins, as well as the homologous N-terminal domains of tissue inhibitors of metalloproteinases (TIMPs).

The clan contains the following 3 members:

NtA 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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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
(604)
Representative proteomes UniProt
(842)
RP15
(102)
RP35
(181)
RP55
(458)
RP75
(617)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

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  Seed
(6)
Full
(604)
Representative proteomes UniProt
(842)
RP15
(102)
RP35
(181)
RP55
(458)
RP75
(617)
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  Seed
(6)
Full
(604)
Representative proteomes UniProt
(842)
RP15
(102)
RP35
(181)
RP55
(458)
RP75
(617)
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.

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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: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 6
Number in full: 604
Average length of the domain: 112.1 aa
Average identity of full alignment: 67 %
Average coverage of the sequence by the domain: 6.72 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.1 25.1
Trusted cut-off 25.7 25.3
Noise cut-off 24.9 23.3
Model length: 116
Family (HMM) version: 18
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 NtA domain has been found. There are 4 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
A0A044QTT2 View 3D Structure Click here
A0A077Z0H1 View 3D Structure Click here
A0A3P7EEG4 View 3D Structure Click here
F1R074 View 3D Structure Click here
O00468 View 3D Structure Click here
P31696 View 3D Structure Click here