Human Gene LRP4 (ENST00000378623.6) from GENCODE V44
Description: Homo sapiens LDL receptor related protein 4 (LRP4), mRNA. (from RefSeq NM_002334) RefSeq Summary (NM_002334): This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000378623.6 Gencode Gene: ENSG00000134569.10 Transcript (Including UTRs) Position: hg38 chr11:46,856,717-46,918,550 Size: 61,834 Total Exon Count: 38 Strand: - Coding Region Position: hg38 chr11:46,858,983-46,918,379 Size: 59,397 Coding Exon Count: 38
ID:LRP4_HUMAN DESCRIPTION: RecName: Full=Low-density lipoprotein receptor-related protein 4; Short=LRP-4; AltName: Full=Multiple epidermal growth factor-like domains 7; Flags: Precursor; 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. 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. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (Potential). TISSUE SPECIFICITY: Expressed in bone; present in osteoblasts and osteocytes. No expression is observed in osteoclast. Expressed in several regions of the brain. DISEASE: Defects in LRP4 are the cause of Cenani-Lenz syndactyly syndrome (CLSS) [MIM:212780]. It is 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. DISEASE: Defects in LRP4 are the cause of sclerosteosis type 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. SIMILARITY: Belongs to the LDLR family. SIMILARITY: Contains 3 EGF-like domains. SIMILARITY: Contains 8 LDL-receptor class A domains. SIMILARITY: Contains 20 LDL-receptor class B repeats. SEQUENCE CAUTION: Sequence=BAE19679.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00057 - Low-density lipoprotein receptor domain class A PF00058 - Low-density lipoprotein receptor repeat class B
ModBase Predicted Comparative 3D Structure on O75096
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
