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MGP001837

UniProt Annotations

Entry Information

Gene Name	low density lipoprotein receptor-related protein 4
Protein Entry	LRP4_HUMAN
UniProt ID	O75096
Species	Human

Comments

Comment type	Description
Disease	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:0000269\|PubMed:20381006}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	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:0000269\|PubMed:21471202}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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:0000269\|PubMed:20381006, ECO:0000269\|PubMed:21471202}.
Sequence Caution	Sequence=BAE19679.1; Type=Erroneous initiation; Evidence={ECO:0000305};
Similarity	Belongs to the LDLR family. {ECO:0000305}.
Similarity	Contains 20 LDL-receptor class B repeats. {ECO:0000255\|PROSITE-ProRule:PRU00461}.
Similarity	Contains 3 EGF-like domains. {ECO:0000305}.
Similarity	Contains 8 LDL-receptor class A domains. {ECO:0000255\|PROSITE-ProRule:PRU00124}.
Subcellular Location	Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}.
Subunit	Homooligomer. Interacts with MUSK; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK (By similarity). Interacts (via the extracellular domain) with SOST; the interaction facilitates the inhibition of Wnt signaling. {ECO:0000250, ECO:0000269\|PubMed:21471202}.
Tissue Specificity	Expressed in bone; present in osteoblasts and osteocytes. No expression is observed in osteoclast. Expressed in several regions of the brain. {ECO:0000269\|PubMed:21471202}.