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Protein Domain : IPR002172

Name  Low-density lipoprotein (LDL) receptor class A repeat Short Name  LDrepeatLR_classA_rpt
Type  Repeat Description  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 []. 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 []. Similar domains have been found in other extracellular and membrane proteins []. 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 []. This region is critical for ligand release and recycling of the receptor [].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 [].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 []. 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.

Publication Counts Displayer

0 Child Features

0 Contains

6 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PF00057 PFAM IPR002172
PR00261 PRINTS IPR002172
PS50068 PROFILE IPR002172
SM00192 SMART IPR002172
G3DSA:4.10.400.10 GENE3D IPR002172
SSF57424 SSF IPR002172

3 Data Sets

Name URL
TrEMBL data set http://www.ebi.ac.uk/trembl/
InterPro data set  
InterPro GO Annotation data set  

10 Found In

DB identifier Name Short Name Type
IPR008112 Relaxin receptor Relaxin_rcpt Family
IPR012111 Hemolectin/hemocytin Hml Family
IPR017049 Low density lipoprotein receptor-related protein, 5/6 Low_density_Lipo_rcpt-rel_p5/6 Family
IPR017343 Uncharacterised conserved protein UCP037987 UCP037987 Family
IPR011163 Peptidase S1A, enteropeptidase Pept_S1A_enterop Family
IPR017118 Peptidase S1A, matriptase-2 Pept_S1A_matriptase-2 Family
IPR017052 Peptidase S1A, corin Peptidase_S1A_corin Family
IPR017051 Peptidase S1A, matripase Peptidase_S1A_matripase Family
IPR017327 Peptidase S1A, TMPRSS13 Peptidase_S1A_TMPRSS13 Family
IPR017324 Peptidase S1A, polyserase-1 Pept_S1A_polyserase-1 Family

1 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Low-density lipoprotein (LDL) receptor class A repeat   GO:0005515 protein binding

1 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Low-density lipoprotein (LDL) receptor class A repeat   GO:0005515 protein binding

0 Parent Features

501 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0081098 Q9VI89 Drosophila melanogaster
FBpp0288558 Q9VM55 Drosophila melanogaster
FBpp0291372 E1JHA6 Drosophila melanogaster
FBpp0076693 P98159 Drosophila melanogaster
FBpp0073715 P98163 Drosophila melanogaster
FBpp0087983 A1Z709 Drosophila melanogaster
FBpp0081059 Q8INT3 Drosophila melanogaster
FBpp0112077 Q5BIG2 Drosophila melanogaster
FBpp0076399 Q8IQA8 Drosophila melanogaster
FBpp0076398 Q9VSI3 Drosophila melanogaster
FBpp0076397 Q8IQA9 Drosophila melanogaster
FBpp0079165 Q9VLT3 Drosophila melanogaster
FBpp0086264 Q7KJ08 Drosophila melanogaster
FBpp0079096 Q9VLZ6 Drosophila melanogaster
FBpp0075495 Q9VU94 Drosophila melanogaster
FBpp0086821 A1Z9D7 Drosophila melanogaster
FBpp0086492 Q7K3C2 Drosophila melanogaster
FBpp0076333 Q7KUB3 Drosophila melanogaster
FBpp0076252 Q8IQB8 Drosophila melanogaster
FBpp0071118 Q9W3H0 Drosophila melanogaster
FBpp0083050 Q9VE71 Drosophila melanogaster
FBpp0308759 Q9VYC7 Drosophila melanogaster
FBpp0308760 G4LU05 Drosophila melanogaster
FBpp0080551 Q9VJD1 Drosophila melanogaster
FBpp0073931 Q9VXM0 Drosophila melanogaster
FBpp0071605 Q9I7V5 Drosophila melanogaster
FBpp0084302 Q86B77 Drosophila melanogaster
FBpp0086768 Q4V6B0 Drosophila melanogaster
FBpp0083176 Q7JRL9 Drosophila melanogaster
FBpp0087128 Q95NU8 Drosophila melanogaster