Uniprot ID:O75197	Protein name: Low-density lipoprotein receptor-related protein 5	Gene : LRP5 LR3 LRP7
Protein Family:LDLR family	Squence Length : 1615

Sequnce	>O75197 1616 MEAAPPGPPWPLLLLLLLLLALCGCPAPAAASPLLLFANRRDVRLVDAGGVKLESTIVVSGLEDAAAVDFQFSKGAVYWTDVSEEAIKQTYLNQTGAAVQNVVISGLVSPDGLACDWVGKKLYWTDSETNRIEVANLNGTSRKVLFWQDLDQPRAIALDPAHGYMYWTDWGETPRIERAGMDGSTRKIIVDSDIYWPNGLTIDLEEQKLYWADAKLSFIHRANLDGSFRQKVVEGSLTHPFALTLSGDTLYWTDWQTRSIHACNKRTGGKRKEILSALYSPMDIQVLSQERQPFFHTRCEEDNGGCSHLCLLSPSEPFYTCACPTGVQLQDNGRTCKAGAEEVLLLARRTDLRRISLDTPDFTDIVLQVDDIRHAIAIDYDPLEGYVYWTDDEVRAIRRAYLDGSGAQTLVNTEINDPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTSRKILVSEDLDEPRAIALHPVMGLMYWTDWGENPKIECANLDGQERRVLVNASLGWPNGLALDLQEGKLYWGDAKTDKIEVINVDGTKRRTLLEDKLPHIFGFTLLGDFIYWTDWQRRSIERVHKVKASRDVIIDQLPDLMGLKAVNVAKVVGTNPCADRNGGCSHLCFFTPHATRCGCPIGLELLSDMKTCIVPEAFLVFTSRAAIHRISLETNNNDVAIPLTGVKEASALDFDVSNNHIYWTDVSLKTISRAFMNGSSVEHVVEFGLDYPEGMAVDWMGKNLYWADTGTNRIEVARLDGQFRQVLVWRDLDNPRSLALDPTKGYIYWTEWGGKPRIVRAFMDGTNCMTLVDKVGRANDLTIDYADQRLYWTDLDTNMIESSNMLGQERVVIADDLPHPFGLTQYSDYIYWTDWNLHSIERADKTSGRNRTLIQGHLDFVMDILVFHSSRQDGLNDCMHNNGQCGQLCLAIPGGHRCGCASHYTLDPSSRNCSPPTTFLLFSQKSAISRMIPDDQHSPDLILPLHGLRNVKAIDYDPLDKFIYWVDGRQNIKRAKDDGTQPFVLTSLSQGQNPDRQPHDLSIDIYSRTLFWTCEATNTINVHRLSGEAMGVVLRGDRDKPRAIVVNAERGYLYFTNMQDRAAKIERAALDGTEREVLFTTGLIRPVALVVDNTLGKLFWVDADLKRIESCDLSGANRLTLEDANIVQPLGLTILGKHLYWIDRQQQMIERVEKTTGDKRTRIQGRVAHLTGIHAVEEVSLEEFSAHPCARDNGGCSHICIAKGDGTPRCSCPVHLVLLQNLLTCGEPPTCSPDQFACATGEIDCIPGAWRCDGFPECDDQSDEEGCPVCSAAQFPCARGQCVDLRLRCDGEADCQDRSDEADCDAICLPNQFRCASGQCVLIKQQCDSFPDCIDGSDELMCEITKPPSDDSPAHSSAIGPVIGIILSLFVMGGVYFVCQRVVCQRYAGANGPFPHEYVSGTPHVPLNFIAPGGSQHGPFTGIACGKSMMSSVSLMGGRGGVPLYDRNHVTGASSSSSSSTKATLYPPILNPPPSPATDPSLYNMDMFYSSNIPATARPYRPYIIRGMAPPTTPCSTDVCDSDYSASRWKASKYYLDLNSDSDPYPPPPTPHSQYLSAEDSCPPSPATERSYFHLFPPPPSPCTDSS
Domains	DOMAIN 295 337 EGF-like 1 DOMAIN 601 641 EGF-like 2 DOMAIN 902 942 EGF-like 3 DOMAIN 1213 1254 EGF-like 4 DOMAIN 1258 1296 LDL-receptor class A 1 DOMAIN 1297 1333 LDL-receptor class A 2 DOMAIN 1335 1371 LDL-receptor class A 3
LDL-receptor class A sequence regions	1258 - 1296 SPDQFACATGEIDCIPGAWRCDGFPECDDQSDEEGCPVC 1297 - 1333 SAAQFPCARGQCVDLRLRCDGEADCQDRSDEADCDAI 1335 - 1371 LPNQFRCASGQCVLIKQQCDSFPDCIDGSDELMCEIT
Function	"Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. Plays a role in norrin (NDP) signal transduction (PubMed:27228167). The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Appears be required for postnatal control of vascular regression in the eye (By similarity). Required for posterior patterning of the epiblast during gastrulation (By similarity)"
Motifs	MOTIF 1500 1506 PPPSP motif A. MOTIF 1538 1545 PPPSP motif B. MOTIF 1574 1581 PPPSP motif C. MOTIF 1591 1596 PPPSP motif D. MOTIF 1605 1612 PPPSP motif E
Disease	"DISEASE: Vitreoretinopathy, exudative 1 (EVR1) [MIM:133780]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness Clinical features can be highly variable, even within the same family Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Vitreoretinopathy, exudative 4 (EVR4) [MIM:601813]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness Clinical features can be highly variable, even within the same family Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone The result is fragile bones and an increased risk of fractures, even after minimal trauma Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs Note=Disease susceptibility is associated with variations affecting the gene represented in this entry ; DISEASE: Osteoporosis-pseudoglioma syndrome (OPPG) [MIM:259770]: A disease characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures Additional clinical manifestations may include microphthalmos, abnormalities of the iris, lens or vitreous, cataracts, short stature, microcephaly, ligamental laxity, mental retardation and hypotonia Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: High bone mass trait (HBM) [MIM:601884]: Rare phenotype characterized by exceptionally dense bones HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Endosteal hyperostosis, Worth type (WENHY) [MIM:144750]: An autosomal dominant sclerosing bone dysplasia clinically characterized by elongation of the mandible, increased gonial angle, flattened forehead, and the presence of a slowly enlarging osseous prominence of the hard palate (torus palatinus) Serum calcium, phosphorus and alkaline phosphatase levels are normal Radiologically, it is characterized by early thickening of the endosteum of long bones, the skull and of the mandible With advancing age, the trabeculae of the metaphysis become thickened WENHY becomes clinically and radiologically evident by adolescence, does not cause deformity except in the skull and mandible, and is not associated with bone pain or fracture Affected patients have normal height, proportion, intelligence and longevity Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Osteopetrosis, autosomal dominant 1 (OPTA1) [MIM:607634]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood OPTA1 is an autosomal dominant form characterized by generalized osteosclerosis most pronounced in the cranial vault Patients are often asymptomatic, but some suffer from pain and hearing loss It appears to be the only type of osteopetrosis not associated with an increased fracture rate Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Van Buchem disease 2 (VBCH2) [MIM:607636]: VBCH2 is an autosomal dominant sclerosing bone dysplasia characterized by cranial osteosclerosis, thickened calvaria and cortices of long bones, enlarged mandible and normal serum alkaline phosphatase levels Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Polycystic liver disease 4 with or without kidney cysts (PCLD4) [MIM:617875]: A form of polycystic liver disease, an autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts PCLD4 patients may also develop kidney cysts that usually do not result in clinically significant renal disease Note=The disease is caused by mutations affecting the gene represented in this entry ; DISEASE: Note=LRP5 variations may act as a disease modifier in autosomal dominant polycystic kidney disease (ADPKD) in patients who have causative mutations in PKD1 May contribute to the disease phenotype heterogeneity and hepatic cystogenesis"

O75197 Proteins LDL-receptor class A domain Repeats