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LDL receptor-like module superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   Small proteins [ 56992] (90)
Fold:   LDL receptor-like module [ 57423]
Superfamily:   LDL receptor-like module [ 57424]
Families:   LDL receptor-like module [ 57425] (6)

Superfamily statistics
Genomes (213) Uniprot 2018_03 genome PDB chains (SCOP 1.75)
Domains 32,315 103,788 26
Proteins 7,777 23,713 18

Functional annotation
General category Processes_IC
Detailed category Transport

Function annotation of SCOP domain superfamilies

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEO levelAnnotation (direct or inherited)
Enzyme Commission (EC)Acting on peptide bonds (peptide hydrolases)0Least InformativeDirect
Enzyme Commission (EC)Serine endopeptidases0Moderately InformativeDirect

Document: EC annotation of SCOP domains

Human Phenotype (HP)

(show details)
HP termFDR (all)SDHP levelAnnotation (direct or inherited)
Phenotypic Abnormality (PA)Abnormality of the eye0.7575Least InformativeInherited
Phenotypic Abnormality (PA)Abnormal posterior eye segment morphology0.309Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.51Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of complement system0.00003059InformativeDirect
Phenotypic Abnormality (PA)Recurrent infections0.4337InformativeInherited
Phenotypic Abnormality (PA)Abnormal retinal morphology0.5495InformativeInherited
Phenotypic Abnormality (PA)Recurrent Neisserial infections0.000003097Highly InformativeDirect
Phenotypic Abnormality (PA)Yellow/white lesions of the retina0.0009574Highly InformativeDirect

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)abnormal homeostasis0.6387Least InformativeInherited
Mammalian Phenotype (MP)abnormal reproductive system morphology0.3686Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal gland morphology0.6027Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal ion homeostasis0.03012InformativeInherited
Mammalian Phenotype (MP)abnormal male reproductive gland morphology0.5276InformativeInherited
Mammalian Phenotype (MP)abnormal internal male genitalia morphology0.929InformativeInherited

Document: MP annotation of SCOP domains

Worm Phenotype (WP)

(show details)
WP termFDR (all)SDWP levelAnnotation (direct or inherited)
Worm Phenotype (WP)organism behavior variant0.1854Least InformativeInherited
Worm Phenotype (WP)movement variant0.09218Moderately InformativeInherited
Worm Phenotype (WP)locomotion variant0.6565Moderately InformativeInherited
Worm Phenotype (WP)locomotion reduced0.04104InformativeInherited
Worm Phenotype (WP)paralyzed0.0004496Highly InformativeDirect

Document: WP annotation of SCOP domains

Fly Anatomy (FA)

(show details) Document: FA annotation of SCOP domains

Zebrafish Anatomy (ZA)

(show details)
ZA termFDR (all)SDZA levelAnnotation (direct or inherited)
Zebrafish Anatomy (ZA)organism subdivision0Least InformativeDirect
Zebrafish Anatomy (ZA)multi-tissue structure0Least InformativeDirect

Document: ZA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)embryo0.9507Least InformativeInherited
Xenopus ANatomical entity (XAN)alimentary system0.3336Moderately InformativeInherited
Xenopus ANatomical entity (XAN)embryonic structure0.5633Moderately InformativeInherited
Xenopus ANatomical entity (XAN)hindgut0.0006582Highly InformativeDirect

Document: XA annotation of SCOP domains

Enzyme Commission (EC)

(show details)
EC termFDR (all)SDEC levelAnnotation (direct or inherited)
Enzyme Commission (EC)Hydrolases0.00000007461Least InformativeDirect
Enzyme Commission (EC)Acting on peptide bonds (peptidases)0Moderately InformativeDirect
Enzyme Commission (EC)Serine endopeptidases0InformativeDirect

Document: EC annotation of SCOP domains

InterPro annotation
Cross references IPR002172 SSF57424 Protein matches

Low density lipoprotein (LDL) is the major cholesterol-carrying lipoprotein of plasma. The receptor protein binds LDL and transports it into cells by endocytosis. In order to be internalised, the receptor-ligand complex must first cluster into clathrin-coated pits. Seven successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein [PubMed6091915].

The LDL-receptor class A domain contains 6 disulphide-bound cysteines [PubMed7548065] and a highly conserved cluster of negatively charged amino acids, of which many are clustered on one face of the module [PubMed7603991]. A schematic representation of this domain is shown here:

   +---------------------+        +--------------------------------+
   |                     |        |                                |
                |                            |

'C': conserved cysteine involved in a disulphide bond.
'x': any residue.

In LDL-receptors the class A domains form the binding site for LDL [PubMed6091915] and calcium [PubMed3320043]. The acidic residues between the fourth and sixth cysteines are important for high-affinity binding of positively charged sequences in LDLR's ligands [PubMed3283935]. The repeat has been shown [PubMed7603991] to consist 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 [PubMed6327078, PubMed6091915].

Similar domains have been found (see references in [PubMed7603991]) in several extracellular and membrane proteins (see examples).

Numerous familial hypercholestorolemia mutations of the LDL receptor alter the calcium coordinating residue of LDL-A domains or other crucial scaffolding residues.

InterPro database

PDBeMotif information about ligands, sequence and structure motifs
Cross references PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Enzyme Commission (EC) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Enzyme Commission (EC) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.

Alignments of sequences to 16 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.

Browse and view proteins in genomes which have different domain combinations including a LDL receptor-like module domain.

Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.

Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 16 hidden Markov models representing the LDL receptor-like module superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Enzyme Commission (EC) · Human Phenotype (HP) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Anatomy (FA) · Zebrafish Anatomy (ZA) · Xenopus Anatomy (XA) · Enzyme Commission (EC) · Internal database links ]