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54  structures 198  species 5  interactions 19728  sequences 1237  architectures

Family: Ldl_recept_a (PF00057)

Summary: Low-density lipoprotein receptor domain class A

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 "Low density lipoprotein receptor gene family". More...

Low density lipoprotein receptor gene family Edit Wikipedia article

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.

Low-density lipoprotein receptor domain class A Provide feedback

No Pfam abstract.

Literature references

  1. Yamamoto T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, Russell DW; , Cell 1984;39:27-38.: The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. PUBMED:6091915 EPMC:6091915

  2. Fass D, Blacklow S, Kim PS, Berger JM; , Nature 1997;388:691-693.: Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module PUBMED:9262405 EPMC:9262405


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002172

The low-density lipoprotein receptor (LDLR) is the major cholesterol-carrying lipoprotein of plasma, acting to regulate cholesterol homeostasis in mammalian cells. The LDL receptor binds LDL and transports it into cells by acidic endocytosis. In order to be internalized, the receptor-ligand complex must first cluster into clathrin-coated pits. Once inside the cell, the LDLR separates from its ligand, which is degraded in the lysosomes, while the receptor returns to the cell surface [PUBMED:3513311]. The internal dissociation of the LDLR with its ligand is mediated by proton pumps within the walls of the endosome that lower the pH. The LDLR is a multi-domain protein, containing:

  • The ligand-binding domain contains seven or eight 40-amino acid LDLR class A (cysteine-rich) repeats, each of which contains a coordinated calcium ion and six cysteine residues involved in disulphide bond formation [PUBMED:6091915]. Similar domains have been found in other extracellular and membrane proteins [PUBMED:7603991].

  • The second conserved region contains two EGF repeats, followed by six LDLR class B (YWTD) repeats, and another EGF repeat. The LDLR class B repeats each contain a conserved YWTD motif, and is predicted to form a beta-propeller structure [PUBMED:9790844]. This region is critical for ligand release and recycling of the receptor [PUBMED:3494949].

  • The third domain is rich in serine and threonine residues and contains clustered O-linked carbohydrate chains.

  • The fourth domain is the hydrophobic transmembrane region.

  • The fifth domain is the cytoplasmic tail that directs the receptor to clathrin-coated pits.

LDLR is closely related in structure to several other receptors, including LRP1, LRP1b, megalin/LRP2, VLDL receptor, lipoprotein receptor, MEGF7/LRP4, and LRP8/apolipoprotein E receptor2); these proteins participate in a wide range of physiological processes, including the regulation of lipid metabolism, protection against atherosclerosis, neurodevelopment, and transport of nutrients and vitamins [PUBMED:17457719].

This entry represents the LDLR class A (cyateine-rich) repeat, which contains 6 disulphide-bound cysteines and a highly conserved cluster of negatively charged amino acids, of which many are clustered on one face of the module [PUBMED:7603991]. In LDL receptors, the class A domains form the binding site for LDL and calcium. The acidic residues between the fourth and sixth cysteines are important for high-affinity binding of positively charged sequences in LDLR's ligands. The repeat consists of a beta-hairpin structure followed by a series of beta turns. In the absence of calcium, LDL-A domains are unstructured; the bound calcium ion imparts structural integrity. Following these repeats is a 350 residue domain that resembles part of the epidermal growth factor (EGF) precursor. Numerous familial hypercholestorolemia mutations of the LDL receptor alter the calcium coordinating residue of LDL-A domains or other crucial scaffolding residues.

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
(19728)
Representative proteomes NCBI
(17417)
Meta
(67)
RP15
(3071)
RP35
(3990)
RP55
(7792)
RP75
(11586)
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Format an alignment

  Seed
(53)
Full
(19728)
Representative proteomes NCBI
(17417)
Meta
(67)
RP15
(3071)
RP35
(3990)
RP55
(7792)
RP75
(11586)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

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
(53)
Full
(19728)
Representative proteomes NCBI
(17417)
Meta
(67)
RP15
(3071)
RP35
(3990)
RP55
(7792)
RP75
(11586)
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: ldl_recept_a;
Type: Repeat
Author: Sonnhammer ELL
Number in seed: 53
Number in full: 19728
Average length of the domain: 38.20 aa
Average identity of full alignment: 41 %
Average coverage of the sequence by the domain: 15.75 %

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 24.1 24.1
Trusted cut-off 24.1 24.1
Noise cut-off 24.0 24.0
Model length: 37
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 5 interactions for this family. More...

Ldl_recept_b Ldl_recept_a Globin Rhv EGF

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 Ldl_recept_a domain has been found. There are 54 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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