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24  structures 1472  species 0  interactions 5112  sequences 191  architectures

Family: Sortilin-Vps10 (PF15902)

Summary: Sortilin, neurotensin receptor 3,

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Sortilin, neurotensin receptor 3, Provide feedback

Sortilin, also known in mammals as neurotensin receptor-3, is the archetypical member of a Vps10-domain (Vps10-D) that binds neurotrophic factors and neuropeptides. This domain constitutes the entire luminal part of Sortilin and is activated in the trans-Golgi network by enzymatic propeptide cleavage [1,2]. The structure of the domain has been determined as a ten-bladed propeller, with up to 9 BNR or beta-hairpin turns in it. The mature receptor binds various ligands, including its own propeptide (Sort-pro), neurotensin, the pro-forms of nerve growth factor-beta (NGF)6 and brain-derived neurotrophic factor (BDNF)7, lipoprotein lipase (LpL), apo lipoprotein AV14 and the receptor-associated protein (RAP)1 [4,5].

Literature references

  1. Petersen CM, Nielsen MS, Nykjaer A, Jacobsen L, Tommerup N, Rasmussen HH, Roigaard H, Gliemann J, Madsen P, Moestrup SK;, J Biol Chem. 1997;272:3599-3605.: Molecular identification of a novel candidate sorting receptor purified from human brain by receptor-associated protein affinity chromatography. PUBMED:9013611 EPMC:9013611

  2. Mazella J, Zsurger N, Navarro V, Chabry J, Kaghad M, Caput D, Ferrara P, Vita N, Gully D, Maffrand JP, Vincent JP;, J Biol Chem. 1998;273:26273-26276.: The 100-kDa neurotensin receptor is gp95/sortilin, a non-G-protein-coupled receptor. PUBMED:9756851 EPMC:9756851

  3. Nielsen MS, Jacobsen C, Olivecrona G, Gliemann J, Petersen CM;, J Biol Chem. 1999;274:8832-8836.: Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. PUBMED:10085125 EPMC:10085125

  4. Quistgaard EM, Madsen P, Groftehauge MK, Nissen P, Petersen CM, Thirup SS;, Nat Struct Mol Biol. 2009;16:96-98.: Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain. PUBMED:19122660 EPMC:19122660


Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR031778

Sortilin, also known in mammals as neurotensin receptor-3, is the archetypical member of the vacuolar protein sorting 10 protein domain (Vps10-D) receptor family that binds neurotrophic factors and neuropeptides [PUBMED:25345507]. This entry represents a domain that constitutes the entire luminal part of Sortilin and is activated in the trans-Golgi network by enzymatic propeptide cleavage [PUBMED:9013611, PUBMED:9756851]. The structure of the domain has been determined as a ten-bladed propeller, with up to 9 BNR or beta-hairpin turns in it [PUBMED:19122660]. The mature receptor binds various ligands, including its own propeptide (Sort-pro), neurotensin, the pro-forms of nerve growth factor-beta (NGF)-6 and brain-derived neurotrophic factor (BDNF)-7, lipoprotein lipase (LpL), apo lipoprotein AV14 and the receptor-associated protein (RAP)1 [PUBMED:19122660, PUBMED:10085125].

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 Sialidase (CL0434), which has the following description:

This superfamily includes sialidases enzymes. Several viruses use sialic acid as a cell surface receptor for host invasion. These viruses then have cell surface neuraminidase enzymes to cleave sialic acid from cell surface proteins allowing them to leave the host cell after replication. This superfamily are composed of six beta-sheets that form a six-fold beta-propeller structure. Many members of this superfamily contain BNR sequence motifs Pfam:PF02012.

The clan contains the following 16 members:

BNR BNR_2 BNR_3 BNR_4 BNR_6 End_beta_barrel End_beta_propel Fungal_lectin HN Mcl1_mid Neur Neuraminidase OLF Phytase PSII_BNR Sortilin-Vps10

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, the UniProtKB sequence database, 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
(132)
Full
(5112)
Representative proteomes UniProt
(14456)
NCBI
(18336)
Meta
(673)
RP15
(766)
RP35
(2012)
RP55
(4250)
RP75
(6245)
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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
(132)
Full
(5112)
Representative proteomes UniProt
(14456)
NCBI
(18336)
Meta
(673)
RP15
(766)
RP35
(2012)
RP55
(4250)
RP75
(6245)
Alignment:
Format:
Order:
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
(132)
Full
(5112)
Representative proteomes UniProt
(14456)
NCBI
(18336)
Meta
(673)
RP15
(766)
RP35
(2012)
RP55
(4250)
RP75
(6245)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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: Jackhmmer:Q99523
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Coggill P
Number in seed: 132
Number in full: 5112
Average length of the domain: 305.80 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 37.04 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 33.0 33.0
Trusted cut-off 33.0 33.0
Noise cut-off 32.9 32.9
Model length: 446
Family (HMM) version: 6
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 Sortilin-Vps10 domain has been found. There are 24 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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