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112  structures 140  species 4  interactions 8618  sequences 734  architectures

Family: Ldl_recept_b (PF00058)

Summary: Low-density lipoprotein receptor repeat class B

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

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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.

Low-density lipoprotein receptor repeat class B Provide feedback

This domain is also known as the YWTD motif after the most conserved region of the repeat. The YWTD repeat is found in multiple tandem repeats and has been predicted to form a beta-propeller structure [2].

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. Springer TA; , J Mol Biol 1998;283:837-862.: An Extracellular beta-Propeller Module Predicted in Lipoprotein and Scavenger Receptors, Tyrosine Kinases, Epidermal Growth Factor Precursor, and Extracellular Matrix Components. PUBMED:9790844 EPMC:9790844


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000033

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 classB (YWTD) repeat, the structure of which has been solved [PUBMED:11373616]. The six YWTD repeats together fold into a six-bladed beta-propeller. Each blade of the propeller consists of four antiparallel beta-strands; the innermost strand of each blade is labeled 1 and the outermost strand, 4. The sequence repeats are offset with respect to the blades of the propeller, such that any given 40-residue YWTD repeat spans strands 24 of one propeller blade and strand 1 of the subsequent blade. This offset ensures circularization of the propeller because the last strand of the final sequence repeat acts as an innermost strand 1 of the blade that harbors strands 24 from the first sequence repeat. The repeat is found in a variety of proteins that include, vitellogenin receptor from Drosophila melanogaster, low-density lipoprotein (LDL) receptor [PUBMED:6091915], preproepidermal growth factor, and nidogen (entactin).

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 Beta_propeller (CL0186), which has the following description:

This large clan contains proteins that contain beta propellers. These are composed of between 6 and 8 repeats. The individual repeats are composed of a four stranded sheet. The clan includes families such as WD40 Pfam:PF00400 where the individual repeats are modeled. The clan also includes families where the entire propeller is modeled such as Pfam:PF02239 usually because the individual repeats are not discernible. These proteins carry out a very wide diversity of functions including catalysis.

The clan contains the following 60 members:

Apc4_WD40 Arylesterase Arylsulfotran_2 Arylsulfotrans Beta_propel CNH Coatomer_WDAD CPSF_A Cytochrom_D1 DPPIV_N DUF1513 DUF1668 DUF1900 DUF2415 DUF3312 DUF4652 DUF839 eIF2A FG-GAP FG-GAP_2 Glu_cyclase_2 Gmad1 GSDH IKI3 Kelch_1 Kelch_2 Kelch_3 Kelch_4 Kelch_5 Kelch_6 Lactonase Ldl_recept_b Lgl_C LVIVD Me-amine-dh_H MRJP Nbas_N Neisseria_PilC NHL Nucleoporin_N Nup160 PD40 Pectate_lyase22 Peptidase_S9_N Phytase-like PQQ PQQ_2 PQQ_3 RAG2 RCC1 RCC1_2 Reg_prop SBBP SBP56 SdiA-regulated SGL Str_synth TcdB_toxin_midN VCBS WD40

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
(28)
Full
(8618)
Representative proteomes NCBI
(7279)
Meta
(7)
RP15
(963)
RP35
(1312)
RP55
(2717)
RP75
(4691)
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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
(28)
Full
(8618)
Representative proteomes NCBI
(7279)
Meta
(7)
RP15
(963)
RP35
(1312)
RP55
(2717)
RP75
(4691)
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
(28)
Full
(8618)
Representative proteomes NCBI
(7279)
Meta
(7)
RP15
(963)
RP35
(1312)
RP55
(2717)
RP75
(4691)
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: Swiss-Prot
Previous IDs: ldl_recept_b;
Type: Repeat
Author: Bateman A, Sonnhammer ELL
Number in seed: 28
Number in full: 8618
Average length of the domain: 41.70 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 14.93 %

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 20.8 20.8
Trusted cut-off 20.8 20.8
Noise cut-off 20.7 20.7
Model length: 42
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

EGF_CA Laminin_EGF Ldl_recept_b Ldl_recept_a

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_b domain has been found. There are 112 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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