Protein Domain : IPR002172

Type:  Repeat Name:  Low-density lipoprotein (LDL) receptor class A 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. Short Name:  LDrepeatLR_classA_rpt
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0 Child Features

0 Contains

6 Cross Referencess

Identifier
PF00057
PR00261
PS50068
SM00192
G3DSA:4.10.400.10
SSF57424

10 Found Ins

DB identifier Type Name
IPR017118 Family Peptidase S1A, matriptase-2
IPR012111 Family Hemolectin/hemocytin
IPR017343 Family Uncharacterised conserved protein UCP037987
IPR017052 Family Atrial natriuretic peptide-converting enzyme corin
IPR017049 Family Low density lipoprotein receptor-related protein, 5/6
IPR017324 Family Transmembrane protease serine 9
IPR011163 Family Peptidase S1A, enteropeptidase
IPR008112 Family Relaxin receptor
IPR017327 Family Peptidase S1A, TMPRSS13
IPR017051 Family Peptidase S1A, matripase

1 GO Annotation

GO Term Gene Name
GO:0005515 IPR002172

1 Ontology Annotations

GO Term Gene Name
GO:0005515 IPR002172

0 Parent Features

3256 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
evm.model.supercontig_119.26 PAC:16406541 Carica papaya 503  
evm.model.supercontig_209.5 PAC:16413361 Carica papaya 201  
29950.m001160 B9SHI5 PAC:16814434 Ricinus communis 593  
29646.m001111 B9SGN0 PAC:16804621 Ricinus communis 210  
28842.m000929 B9SBM9 PAC:16801818 Ricinus communis 683  
Cucsa.152660.2 PAC:16964564 Cucumis sativus 645  
Cucsa.152660.6 PAC:16964568 Cucumis sativus 644  
Cucsa.152660.12 PAC:16964560 Cucumis sativus 642  
Cucsa.152660.13 PAC:16964561 Cucumis sativus 641  
Cucsa.152660.15 PAC:16964563 Cucumis sativus 607  
Cucsa.152660.1 PAC:16964557 Cucumis sativus 651  
Cucsa.152660.3 PAC:16964565 Cucumis sativus 644  
Cucsa.152660.10 PAC:16964558 Cucumis sativus 644  
Cucsa.148850.1 A0A0A0K1G3 PAC:16964210 Cucumis sativus 199  
Cucsa.148850.2 A0A0A0K1G3 PAC:16964211 Cucumis sativus 199  
orange1.1g018864m A0A067GI98 PAC:18112493 Citrus sinensis 349  
orange1.1g036153m A0A067EQG1 PAC:18126821 Citrus sinensis 291  
orange1.1g027304m A0A067E4F6 PAC:18125576 Citrus sinensis 225  
orange1.1g031060m A0A067E3F3 PAC:18125577 Citrus sinensis 166  
orange1.1g007310m A0A067EKS7 PAC:18110145 Citrus sinensis 608  
orange1.1g008507m A0A067EUA9 PAC:18110146 Citrus sinensis 563  
orange1.1g006056m A0A067EHE7 PAC:18110143 Citrus sinensis 663  
AT4G13950.1 Q2HIM9 PAC:19646232 Arabidopsis thaliana 113  
AT5G56360.1 Q9FM96 PAC:19670989 Arabidopsis thaliana 647  
AT2G42390.1 Q9SLC0 PAC:19642367 Arabidopsis thaliana 212  
Thhalv10017307m V4LQR0 PAC:20180723 Eutrema salsugineum 178  
Thhalv10012935m V4LGC4 PAC:20206427 Eutrema salsugineum 644  
Thhalv10012928m V4KXR0 PAC:20206426 Eutrema salsugineum 648  
Ciclev10015546m V4UL40 PAC:20818719 Citrus clementina 389  
Ciclev10016674m V4U799 PAC:20819149 Citrus clementina 214  

6 Publications

First Author Title Year Journal Volume Pages PubMed ID
            6091915
            9790844
            7603991
            17457719
            3513311
            3494949