Low-density lipoprotein receptor-related protein 6

UniProt data

UniProt name: LRP6_HUMAN (O75581)

Gene name: LRP6

Organism: Homo sapiens (Human).

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. 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. Required for posterior patterning of the epiblast during gastrulation (By similarity). {ECO:0000250, ECO:0000269|PubMed:11357136, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:16341017, ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17326769, ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:19107203, ECO:0000269|PubMed:19293931, ECO:0000269|PubMed:19801552}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:26387593}; Single-pass type I membrane protein. Endoplasmic reticulum {ECO:0000269|PubMed:26387593}. Note=On Wnt signaling, undergoes a cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane location. Released from the endoplasmic reticulum on palmitoylation. Mono-ubiquitination retains it in the endoplasmic reticulum in the absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-signalsomes. Chaperoned to the plasma membrane by MESD (By similarity). {ECO:0000250}.

Transmembrane domains:

  1. 1371-1393, 23 AA, Helical. {ECO:0000255}.

Sequence: 1613 AA

10 20 30 40 50 60 MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF 70 80 90 100 110 120 SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE 130 140 150 160 170 180 VSNLDGSLRK VLFWQELDQP RAIALDPSSG FMYWTDWGEV PKIERAGMDG SSRFIIINSE 190 200 210 220 230 240 IYWPNGLTLD YEEQKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT 250 260 270 280 290 300 DWSTHSILAC NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 310 320 330 340 350 360 PVKPFYQCAC PTGVKLLENG KTCKDGATEL LLLARRTDLR RISLDTPDFT DIVLQLEDIR 370 380 390 400 410 420 HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA QIAHPDGIAV DWVARNLYWT 430 440 450 460 470 480 DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA IVLDPMVGYM YWTDWGEIPK IERAALDGSD 490 500 510 520 530 540 RVVLVNTSLG WPNGLALDYD EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL 550 560 570 580 590 600 LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS 610 620 630 640 650 660 HLCLYRPQGL RCACPIGFEL ISDMKTCIVP EAFLLFSRRA DIRRISLETN NNNVAIPLTG 670 680 690 700 710 720 VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV EFGLDYPEGM AVDWLGKNLY 730 740 750 760 770 780 WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP RALALDPAEG FMYWTEWGGK PKIDRAAMDG 790 800 810 820 830 840 SERTTLVPNV GRANGLTIDY AKRRLYWTDL DTNLIESSNM LGLNREVIAD DLPHPFGLTQ 850 860 870 880 890 900 YQDYIYWTDW SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQSGW NECASSNGHC 910 920 930 940 950 960 SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APTTFLLFSQ KSAINRMVID EQQSPDIILP 970 980 990 1000 1010 1020 IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF TVVVSSVPSQ NLEIQPYDLS 1030 1040 1050 1060 1070 1080 IDIYSRYIYW TCEATNVINV TRLDGRSVGV VLKGEQDRPR AVVVNPEKGY MYFTNLQERS 1090 1100 1110 1120 1130 1140 PKIERAALDG TEREVLFFSG LSKPIALALD SRLGKLFWAD SDLRRIESSD LSGANRIVLE 1150 1160 1170 1180 1190 1200 DSNILQPVGL TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ 1210 1220 1230 1240 1250 1260 EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS PQQFTCFTGE 1270 1280 1290 1300 1310 1320 IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC IDGALRCNGD ANCQDKSDEK 1330 1340 1350 1360 1370 1380 NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD CSDKSDELDC YPTEEPAPQA TNTVGSVIGV 1390 1400 1410 1420 1430 1440 IVTIFVSGTV YFICQRMLCP RMKGDGETMT NDYVVHGPAS VPLGYVPHPS SLSGSLPGMS 1450 1460 1470 1480 1490 1500 RGKSMISSLS IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM 1510 1520 1530 1540 1550 1560 EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV ATAKGYTSDL 1570 1580 1590 1600 1610 NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS

CATM prediction

The sequence of LRP6_HUMAN returned 2 potential models

The positions at the dimer's interface are highlighted in yellow. The position at the crossing point is highlighted in orange.

# Sequence and interface d θ Z' ω' Score
    1370      1380      1390   
  |    +    |    +    |    + 		 (Å) (°) (Å) (°)  
Model 1 AQATNTVGSVIGVIVTIFVSGTVYFICQR 7.1 -40.1° 4.1 37.9 -22.1
Model 2 AQATNTVGSVIGVIVTIFVSGTVYFICQR 6.8 -50.9° 4.8 56.9 -6.1
Prolines* PQATNTVGSVIGVIVTIFVSGTVYFICQR          

* Note: this sequence contains Pro residues. CATM substituted them with Ala during the modeling. The positions are marked.

Click on the model number to visualize its details below.

MODEL 1 DETAILS

Precited structure:


Click on the image to enlarge

Download model 1 structure: PDB, PyMOL session

List of hydrogen bonds:

Donor Acceptor Distance
B, 1372, ASN, HA A, 1372, ASN, OD1 2.95Å
B, 1376, SER, HA A, 1375, GLY, O 3.10Å
B, 1379, GLY, HA1 A, 1376, SER, O 3.19Å
B, 1380, VAL, HA A, 1383, THR, OG1 2.56Å
A, 1372, ASN, HA B, 1372, ASN, OD1 2.62Å
A, 1376, SER, HA B, 1375, GLY, O 3.10Å
A, 1379, GLY, HA1 B, 1376, SER, O 3.19Å
A, 1380, VAL, HA B, 1383, THR, OG1 2.56Å
A, 1391, TYR, HH B, 1391, TYR, OH 2.09Å