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0LRP5_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameLRP5
DescriptionLow-density lipoprotein receptor-related protein 5 precursor.
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0016021 integral to membrane (TAS)
0006629 lipid metabolism (TAS)
0008284 positive regulation of cell proliferation (TAS)
0007165 signal transduction (NAS)

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schematic display of those terms with internal associations, click the node and browse the corresponding GO term
Domain Architecture (Details)
InterPro domains unassigned to SynO:
Low density lipoprotein (LDL) is the major cholesterol-carrying lipoprotein of plasma. The receptor protein binds LDL and transports it into cells by endocytosis. In order to be internalised.he receptor-ligand complex must first cluster into clathrin-coated pits. Seven successive cysteine-rich repeats of about 40 amino acids are present in the N-terminal of this multidomain membrane protein .The LDL-receptor class A domain contains 6 disulphide-bound cysteines and a highly conserved cluster of negatively charged amino acids.f which many are clustered on one face of the module . A schematic representation of this domain is shown here:In LDL-receptors the class A domains form the binding site for LDL and calcium . The acidic residues between the fourth and sixth cysteines are important for high-affinity binding of positively charged sequences in LDLRs ligands . The repeat has been shown to consist of a beta-hairpin structure followed by a series of beta turns. In the absence of calcium.DL-A domains are unstructured; the bound calcium ion imparts structural integrity.Following these repeats is a 350 residue domain that resembles part of the epidermal growth factor (EGF) precursor .Similar domains have been found (see references in ) in several extracellular and membrane proteins (see examples).Numerous familial hypercholestorolemia mutations of the LDL receptor alter the calcium coordinating residue of LDL-A domains or other crucial scaffolding residues.
  IPR002172:Low density lipoprotein-receptor, class A
A sequence of about thirty to forty amino-acid residues long found in the sequence of epidermal growth factor (EGF)has been shown to be present.n a moreor less conserved form.n a large number of other.ostly animal proteins. The list of proteins currently known tocontain one or more copies of an EGF-like pattern is large and varied. The functional significance of EGF domains inwhat appear to be unrelated proteins is not yet clear. However. common feature is that these repeats are found inthe extracellular domain of membrane-bound proteins or in proteins known to be secreted (exception: prostaglandinG/H synthase). The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphidebonds. The main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet.Subdomains between the conserved cysteines vary in length.
  IPR006209:EGF-like
The low-density lipoprotein receptor (LDLR) regulates cholesterol homeostasis in mammalian cells. LDLR binds cholesterol-carrying LDL.ssociates with clathrin-coated pits.nd is internalized into acidic endosomes where it separates from its ligand. The ligand is degraded in lysosomes.hile the receptor returns to the cell surface . The LDLR has several domains. The ligand-binding domain contains seven LDL receptor class A repeats.ach with three disulfide bonds and a coordinated Ca2+ ion. The second conserved region contains two EGF repeats.ollowed by six YWTD or LDL receptor class B repeats and another EGF repeat . This conserved region is critical for ligand release and recycling of the receptor . The structure of the six YWTD repeats of LDL receptor have been solved . The six YWTD repeats together fold into a six-bladed beta-propeller. Each blade of the propeller consists of four antiparallel beta-strands; the innermost strand of each blade is labeled 1 and the outermost strand.. The sequence repeats are offset with respect to the blades of the propeller.uch that any given 40-residue YWTD repeat spans strands 24 of one propeller blade and strand 1 of the subsequent blade. This offset ensures circularization of the propeller because the last strand of the final sequence repeat acts as an innermost strand 1 of the blade that harbors strands 24 from the first sequence repeat. The repeat is found in a variety of proteins that include.itellogenin receptor from Drosophila melanogaster.ow-density lipoprotein (LDL) receptor .reproepidermal growth factor.nd nidogen (entactin).
  IPR000033:Low-density lipoprotein receptor, YWTD repeat
Epidermal growth factors and transforming growth factors belong to a general class of proteins that share a repeat pattern involving a number of conserved Cys residues. Growth factors are involved in cell recognition and division . The repeating pattern.specially of cysteines (the so-called EGF repeat).s thought to be important to the 3D structure of the proteins.nd hence its recognition by receptors and other molecules. The type 1 EGF signature includes six conserved cysteines believed to be involved in disulphide bond formation. The EGF motif is found frequently in nature.articularly in extracellular proteins.
  IPR006210:EGF
IPR002172:Ldl_recept_a 
Evalue:-18.7447280883789 
Location:1257-1295IPR002172:Ldl_recept_a 
Evalue:-17.1674919128418 
Location:1334-1370IPR002172:Ldl_recept_a 
Evalue:-17.0915145874023 
Location:1296-1332IPR000033:LY 
Evalue:-15.7958800173441 
Location:451-494IPR000033:Ldl_recept_b 
Evalue:-15.508638381958 
Location:163-205IPR000033:LY 
Evalue:-15.3872161432803 
Location:408-450IPR000033:LY 
Evalue:-14.4685210829577 
Location:495-537IPR000033:Ldl_recept_b 
Evalue:-13.4436979293823 
Location:120-161IPR000033:LY 
Evalue:-13.2146701649892 
Location:710-752IPR000033:LY 
Evalue:-10.4089353929735 
Location:753-796IPR000033:LY 
Evalue:-8.10237290870956 
Location:1104-1146IPR006209:EGF 
Evalue:-7.56863641738892 
Location:299-336IPR000033:LY 
Evalue:-7.53760200210104 
Location:365-407IPR000033:LY 
Evalue:-7.22914798835785 
Location:667-709IPR006209:EGF 
Evalue:-7.17392539978027 
Location:1217-1253IPR006209:EGF 
Evalue:-7.02227640151977 
Location:605-640IPR000033:Ldl_recept_b 
Evalue:-5.76955127716064 
Location:856-897IPR000033:LY 
Evalue:-5.44369749923271 
Location:797-838IPR000033:LY 
Evalue:-4.69897000433602 
Location:1059-1103IPR000033:LY 
Evalue:-4.63827216398241 
Location:538-578IPR000033:LY 
Evalue:-4.09151498112135 
Location:230-271IPR000033:Ldl_recept_b 
Evalue:-3.07572078704834 
Location:75-118IPR000033:LY 
Evalue:-2.95860731484177 
Location:969-1010IPR000033:Ldl_recept_b 
Evalue:-0.795880019664764 
Location:1165-1207IPR013032:EGF_1 
Evalue:0 
Location:0-0IPR006210:EGF 
Evalue:0.230448921378274 
Location:905-942IPR000033:LY 
Evalue:0.591064607026499 
Location:1013-1058
SequencesProtein: LRP5_HUMAN (1615 aa)
mRNA: NM_002335
Local Annotation
Synapse Ontology
endocytosis may be initiated or blocked by all kinds of signal.
sdb:0257 regulation of endocytosis  (Evidence:keywords)
Microglias, one kind of glias in CNS, are responsible for removing most of the waste and cellular debris from the CNS
sdb:0267 removing metabolic mass  (Evidence:keywords)
KO assignmentK03068
  Level 3 annotation:
    low density lipoprotein receptor-related protein 5/6
  Level 2 annotation:
    Wnt signaling pathway
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 47 residues, 67836710-67836849Exon2: 134 residues, 67871890-67872287Exon3: 68 residues, 67881693-67881891Exon4: 67 residues, 67887790-67887987Exon5: 46 residues, 67889614-67889746Exon6: 134 residues, 67910359-67910756Exon7: 59 residues, 67913924-67914096Exon8: 74 residues, 67927526-67927743Exon9: 98 residues, 67930567-67930857Exon10: 77 residues, 67933957-67934184Exon11: 63 residues, 67935479-67935664Exon12: 110 residues, 67937732-67938056Exon13: 68 residues, 67940371-67940571Exon14: 71 residues, 67947532-67947741Exon15: 65 residues, 67949145-67949336Exon16: 72 residues, 67950021-67950231Exon17: 44 residues, 67953618-67953744Exon18: 81 residues, 67957645-67957882Exon19: 39 residues, 67960932-67961043Exon20: 81 residues, 67962489-67962726Exon21: 48 residues, 67963820-67963960Exon22: 34 residues, 67970479-67970577Exon23: 157 residues, 67972852-67973317Exon24: 2 residues, -Jump to LRP5_HUMAN  
Tune and view alternative isoforms
Loci Cluster (Details)Loci: 2672 63498654-63500590 ~-2K 6992(COX8A)(+)Loci: 2673 63758841-63762834 ~-4K 7008(VEGFB)(+)Loci: 2674 63775570-63791969 ~-16K 7011(PLCB3)(+)Loci: 2675 63883200-63896262 ~-13K 7031(RPS6KA4)(+)Loci: 3958 64130223-64247236 ~-117K 7042(NRXN2)(-)Loci: 3959 64376783-64402767 ~-26K 7059(EHD1)(-)Loci: 2676 64551485-64564618 ~-13K 7071(SNX15)(+)Loci: 2677 64635935-64640274 ~-4K 7081(TM7SF2)(+)Loci: 2678 64705918-64736052 ~-30K 7088(CAPN1)(+)Loci: 2679 65049159-65062750 ~-14K 7102(+)Loci: 3960 65121802-65138296 ~-16K 7115(MAP3K11)(-)Loci: 3961 65407787-65412586 ~-5K 7136(FIBP)(-)Loci: 3962 65416267-65424573 ~-8K 7139(FOSL1)(-)Loci: 2680 65594399-65768789 ~-174K 7153(PACS1)(+)Loci: 2681 65792680-65801537 ~-9K 7155(RAB1B)(+)Loci: 2682 65815916-65820707 ~-5K 7159(+)Loci: 3963 65856117-65860576 ~-4K 7162(RIN1)(-)Loci: 2683 66140672-66151387 ~-11K 7189(RBM14)(+)Loci: 2684 66162753-66170514 ~-8K 7192(RBM4)(+)Loci: 3964 66209298-66245446 ~-36K 7194(SPTBN2)(-)Loci: 3965 66372572-66478456 ~-106K 7198(PC)(-)Loci: 2685 66547466-66574905 ~-27K 7200(SYT12)(+)Loci: 2686 66580896-66596059 ~-15K 7201(RHOD)(+)Loci: 3966 66922227-66925952 ~-4K 7219(PPP1CA)(-)Loci: 2687 66979393-66983261 ~-4K 7229(CABP4)(+)Loci: 2688 67130982-67136581 ~-6K 7239(NDUFV1)(+)Loci: 2689 67554684-67560690 ~-6K 7248(NDUFS8)(+)Loci: 2690 67836710-67973317 ~-137K 7259(LRP5)(+)Loci: 2671 63412650-63433621 ~-21K 6988(MARK2)(+)Link out to UCSC