InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LRP4

Summary

InnateDB Protein

IDBP-42512.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LRP4

Protein Name

low density lipoprotein receptor-related protein 4

Synonyms

CLSS; LRP-4; LRP10; MEGF7; SOST2;

Species

Homo sapiens

Ensembl Protein

ENSP00000367888

InnateDB Gene

IDBG-42508 (LRP4)

Protein Structure

UniProt Annotation

Function

Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN- induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Alternatively, may be involved in the negative regulation of the canonical Wnt signaling pathway, being able to antagonize the LRP6-mediated activation of this pathway. More generally, has been proposed to function as a cell surface endocytic receptor binding and internalizing extracellular ligands for degradation by lysosomes. {ECO:0000269PubMed:20381006, ECO:0000269PubMed:21471202}.

Subcellular Localization

Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.

Disease Associations

Cenani-Lenz syndactyly syndrome (CLSS) [MIM:212780]: A congenital malformation syndrome defined as complete and complex syndactyly of the hands combined with malformations of the forearm bones and similar manifestations in the lower limbs. It is characterized by fusion and disorganization of metacarpal and phalangeal bones, radius and ulnar shortening, radioulnar synostosis, and severe syndactyly of hands and feet. {ECO:0000269PubMed:20381006}. Note=The disease is caused by mutations affecting the gene represented in this entry.Sclerosteosis 2 (SOST2) [MIM:614305]: A sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. {ECO:0000269PubMed:21471202}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in bone; present in osteoblasts and osteocytes. No expression is observed in osteoclast. Expressed in several regions of the brain. {ECO:0000269PubMed:21471202}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.

Experimentally validated
Total	9 [view]
Protein-Protein	9 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0030971	receptor tyrosine kinase binding
GO:0034185	apolipoprotein binding
GO:0042803	protein homodimerization activity
GO:0097110	scaffold protein binding

Biological Process

GO:0001822	kidney development
GO:0001932	regulation of protein phosphorylation
GO:0001942	hair follicle development
GO:0006897	endocytosis
GO:0008104	protein localization
GO:0009953	dorsal/ventral pattern formation
GO:0009954	proximal/distal pattern formation
GO:0016055	Wnt signaling pathway
GO:0030178	negative regulation of Wnt signaling pathway
GO:0030198	extracellular matrix organization
GO:0030279	negative regulation of ossification
GO:0030326	embryonic limb morphogenesis
GO:0042475	odontogenesis of dentin-containing tooth
GO:0042733	embryonic digit morphogenesis
GO:0043113	receptor clustering
GO:0048813	dendrite morphogenesis
GO:0048856	anatomical structure development
GO:0050771	negative regulation of axonogenesis
GO:0050808	synapse organization
GO:0051124	synaptic growth at neuromuscular junction
GO:0051290	protein heterotetramerization
GO:0060173	limb development
GO:0071340	skeletal muscle acetylcholine-gated channel clustering
GO:0090090	negative regulation of canonical Wnt signaling pathway
GO:0097104	postsynaptic membrane assembly
GO:0097105	presynaptic membrane assembly
GO:1901631	positive regulation of presynaptic membrane organization

Cellular Component

GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0014069	postsynaptic density
GO:0016021	integral component of membrane
GO:0016600	flotillin complex
GO:0030425	dendrite
GO:0031594	neuromuscular junction
GO:0043025	neuronal cell body
GO:0097060	synaptic membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000033 LDLR class B repeat
IPR000742 Epidermal growth factor-like domain
IPR001881 EGF-like calcium-binding domain
IPR002172 Low-density lipoprotein (LDL) receptor class A repeat
IPR009030 Insulin-like growth factor binding protein, N-terminal

PFAM

PF00058
PF00008
PF07645
PF00057

PRINTS

PR00261

PIRSF

SMART

SM00135
SM00181
SM00179
SM00192

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt