Low-density lipoprotein receptor-related protein 5 precursor

Sequence

>sp|O75197|LRP5_HUMAN Low-density lipoprotein receptor-related protein 5 OS=Homo sapiens GN=LRP5 PE=1 SV=2 MEAAPPGPPWPLLLLLLLLLALCGCPAPAAASPLLLFANRRDVRLVDAGGVKLESTIVVS GLEDAAAVDFQFSKGAVYWTDVSEEAIKQTYLNQTGAAVQNVVISGLVSPDGLACDWVGK KLYWTDSETNRIEVANLNGTSRKVLFWQDLDQPRAIALDPAHGYMYWTDWGETPRIERAG MDGSTRKIIVDSDIYWPNGLTIDLEEQKLYWADAKLSFIHRANLDGSFRQKVVEGSLTHP FALTLSGDTLYWTDWQTRSIHACNKRTGGKRKEILSALYSPMDIQVLSQERQPFFHTRCE EDNGGCSHLCLLSPSEPFYTCACPTGVQLQDNGRTCKAGAEEVLLLARRTDLRRISLDTP DFTDIVLQVDDIRHAIAIDYDPLEGYVYWTDDEVRAIRRAYLDGSGAQTLVNTEINDPDG IAVDWVARNLYWTDTGTDRIEVTRLNGTSRKILVSEDLDEPRAIALHPVMGLMYWTDWGE NPKIECANLDGQERRVLVNASLGWPNGLALDLQEGKLYWGDAKTDKIEVINVDGTKRRTL LEDKLPHIFGFTLLGDFIYWTDWQRRSIERVHKVKASRDVIIDQLPDLMGLKAVNVAKVV GTNPCADRNGGCSHLCFFTPHATRCGCPIGLELLSDMKTCIVPEAFLVFTSRAAIHRISL ETNNNDVAIPLTGVKEASALDFDVSNNHIYWTDVSLKTISRAFMNGSSVEHVVEFGLDYP EGMAVDWMGKNLYWADTGTNRIEVARLDGQFRQVLVWRDLDNPRSLALDPTKGYIYWTEW GGKPRIVRAFMDGTNCMTLVDKVGRANDLTIDYADQRLYWTDLDTNMIESSNMLGQERVV IADDLPHPFGLTQYSDYIYWTDWNLHSIERADKTSGRNRTLIQGHLDFVMDILVFHSSRQ DGLNDCMHNNGQCGQLCLAIPGGHRCGCASHYTLDPSSRNCSPPTTFLLFSQKSAISRMI PDDQHSPDLILPLHGLRNVKAIDYDPLDKFIYWVDGRQNIKRAKDDGTQPFVLTSLSQGQ NPDRQPHDLSIDIYSRTLFWTCEATNTINVHRLSGEAMGVVLRGDRDKPRAIVVNAERGY LYFTNMQDRAAKIERAALDGTEREVLFTTGLIRPVALVVDNTLGKLFWVDADLKRIESCD LSGANRLTLEDANIVQPLGLTILGKHLYWIDRQQQMIERVEKTTGDKRTRIQGRVAHLTG IHAVEEVSLEEFSAHPCARDNGGCSHICIAKGDGTPRCSCPVHLVLLQNLLTCGEPPTCS PDQFACATGEIDCIPGAWRCDGFPECDDQSDEEGCPVCSAAQFPCARGQCVDLRLRCDGE ADCQDRSDEADCDAICLPNQFRCASGQCVLIKQQCDSFPDCIDGSDELMCEITKPPSDDS PAHSSAIGPVIGIILSLFVMGGVYFVCQRVVCQRYAGANGPFPHEYVSGTPHVPLNFIAP GGSQHGPFTGIACGKSMMSSVSLMGGRGGVPLYDRNHVTGASSSSSSSTKATLYPPILNP PPSPATDPSLYNMDMFYSSNIPATARPYRPYIIRGMAPPTTPCSTDVCDSDYSASRWKAS KYYLDLNSDSDPYPPPPTPHSQYLSAEDSCPPSPATERSYFHLFPPPPSPCTDSS

Options »

Blast tips

You can enter:
• a protein or nucleotide sequence
• a valid UniProt identifier, for example:
P00750 or A4_HUMAN or UPI0000000001
More...

Identifiers

O75197

From

To

or

Database identifier mapping tips

To map identifiers to or from UniProtKB:
• enter identifiers, e.g.: 1TTA 1FNS
• select a source database, e.g.: PDB
• or select a target database, e.g.: UniProtKB
More...

Sequence length	1615 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

Function	Involved in the Wnt/beta catenin signaling pathway, probably by acting as a coreceptor together with Frizzled for Wnt.
Subunit structure	Interacts with different Wnt/Frizzled complexes. Interacts with axin.
Subcellular location	Membrane; Single-pass type I membrane proteinPotential.
Tissue specificity	Widely expressed, with the highest level of expression in the liver.
Post-translational modification	Phosphorylation of the PPPSP motif creates an inducible docking site for axin.
Polymorphism	Genetic variation in LRP5 contributes to bone-mass and size determination in the general population.
Involvement in disease	Defects in LRP5 are the cause of vitreoretinopathy exudative type 4 (EVR4) [MIM:601813]. EVR4 is 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. EVR4 inheritance can be autosomal dominant or recessive. Genetic variations in LRP5 may be associated with susceptibility to involutional osteoporosis [MIM:166710]; also known as senile osteoporosis or postmenopausal osteoporosis. Osteoporosis is characterized by reduced bone mineral density, disrutption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture. Defects in LRP5 are the cause of osteoporosis pseudoglioma syndrome (OPPG) [MIM:259770]. OPPG is a recessive disorder characterized by very low bone mass and blindness. Individualy with OPPG are prone to develop bone fractures and deformations and have various eye abnormalities, including phthisis bulbi, retinal detachments, falciform folds or persistent vitreal vasculature. Defects in LRP5 are a cause of high bone mass trait (HBM) [MIM:601884]. HBM is a rare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings. Defects in LRP5 are a cause of endosteal hyperostosis Worth type (WENHY) [MIM:144750]; also known as autosomal dominant osteosclerosis. WENHY is an autosomal dominant sclerosing bone dysplasia clinically characterizd 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. Defects in LRP5 are the cause of osteopetrosis autosomal dominant type 1 (OPTA1) [MIM:607634]. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder 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 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. Defects in LRP5 are the cause of van Buchem disease type 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.
Sequence similarities	Belongs to the LDLR family. Contains 4 EGF-like domains. Contains 3 LDL-receptor class A domains. Contains 20 LDL-receptor class B repeats.

Keywords
Biological process	Endocytosis Wnt signaling pathway
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Osteopetrosis
Domain	EGF-like domain Repeat Signal Transmembrane
Molecular function	Developmental protein Receptor
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW endocytosis Inferred from electronic annotation. Source: UniProtKB-KW lipid metabolic process Ref.1 Traceable author statement. Source: ProtInc positive regulation of cell proliferation Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations