Low-density lipoprotein receptor-related protein 5

UniProt data

UniProt name: LRP5_HUMAN (O75197)

Gene name: LRP5; Synonyms=LR3, LRP7

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. 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). {ECO:0000250|UniProtKB:Q91VN0, ECO:0000269|PubMed:11336703, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:14727154, ECO:0000269|PubMed:14731402, ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:27228167}.

Subcellular location: Membrane; Single-pass type I membrane protein. Endoplasmic reticulum {ECO:0000250}. Note=Chaperoned to the plasma membrane by MESD. {ECO:0000250}.

Transmembrane domains:

  1. 1385-1407, 23 AA, Helical. {ECO:0000255}.

Sequence: 1615 AA

10 20 30 40 50 60 MEAAPPGPPW PLLLLLLLLL ALCGCPAPAA ASPLLLFANR RDVRLVDAGG VKLESTIVVS 70 80 90 100 110 120 GLEDAAAVDF QFSKGAVYWT DVSEEAIKQT YLNQTGAAVQ NVVISGLVSP DGLACDWVGK 130 140 150 160 170 180 KLYWTDSETN RIEVANLNGT SRKVLFWQDL DQPRAIALDP AHGYMYWTDW GETPRIERAG 190 200 210 220 230 240 MDGSTRKIIV DSDIYWPNGL TIDLEEQKLY WADAKLSFIH RANLDGSFRQ KVVEGSLTHP 250 260 270 280 290 300 FALTLSGDTL YWTDWQTRSI HACNKRTGGK RKEILSALYS PMDIQVLSQE RQPFFHTRCE 310 320 330 340 350 360 EDNGGCSHLC LLSPSEPFYT CACPTGVQLQ DNGRTCKAGA EEVLLLARRT DLRRISLDTP 370 380 390 400 410 420 DFTDIVLQVD DIRHAIAIDY DPLEGYVYWT DDEVRAIRRA YLDGSGAQTL VNTEINDPDG 430 440 450 460 470 480 IAVDWVARNL YWTDTGTDRI EVTRLNGTSR KILVSEDLDE PRAIALHPVM GLMYWTDWGE 490 500 510 520 530 540 NPKIECANLD GQERRVLVNA SLGWPNGLAL DLQEGKLYWG DAKTDKIEVI NVDGTKRRTL 550 560 570 580 590 600 LEDKLPHIFG FTLLGDFIYW TDWQRRSIER VHKVKASRDV IIDQLPDLMG LKAVNVAKVV 610 620 630 640 650 660 GTNPCADRNG GCSHLCFFTP HATRCGCPIG LELLSDMKTC IVPEAFLVFT SRAAIHRISL 670 680 690 700 710 720 ETNNNDVAIP LTGVKEASAL DFDVSNNHIY WTDVSLKTIS RAFMNGSSVE HVVEFGLDYP 730 740 750 760 770 780 EGMAVDWMGK NLYWADTGTN RIEVARLDGQ FRQVLVWRDL DNPRSLALDP TKGYIYWTEW 790 800 810 820 830 840 GGKPRIVRAF MDGTNCMTLV DKVGRANDLT IDYADQRLYW TDLDTNMIES SNMLGQERVV 850 860 870 880 890 900 IADDLPHPFG LTQYSDYIYW TDWNLHSIER ADKTSGRNRT LIQGHLDFVM DILVFHSSRQ 910 920 930 940 950 960 DGLNDCMHNN GQCGQLCLAI PGGHRCGCAS HYTLDPSSRN CSPPTTFLLF SQKSAISRMI 970 980 990 1000 1010 1020 PDDQHSPDLI LPLHGLRNVK AIDYDPLDKF IYWVDGRQNI KRAKDDGTQP FVLTSLSQGQ 1030 1040 1050 1060 1070 1080 NPDRQPHDLS IDIYSRTLFW TCEATNTINV HRLSGEAMGV VLRGDRDKPR AIVVNAERGY 1090 1100 1110 1120 1130 1140 LYFTNMQDRA AKIERAALDG TEREVLFTTG LIRPVALVVD NTLGKLFWVD ADLKRIESCD 1150 1160 1170 1180 1190 1200 LSGANRLTLE DANIVQPLGL TILGKHLYWI DRQQQMIERV EKTTGDKRTR IQGRVAHLTG 1210 1220 1230 1240 1250 1260 IHAVEEVSLE EFSAHPCARD NGGCSHICIA KGDGTPRCSC PVHLVLLQNL LTCGEPPTCS 1270 1280 1290 1300 1310 1320 PDQFACATGE IDCIPGAWRC DGFPECDDQS DEEGCPVCSA AQFPCARGQC VDLRLRCDGE 1330 1340 1350 1360 1370 1380 ADCQDRSDEA DCDAICLPNQ FRCASGQCVL IKQQCDSFPD CIDGSDELMC EITKPPSDDS 1390 1400 1410 1420 1430 1440 PAHSSAIGPV IGIILSLFVM GGVYFVCQRV VCQRYAGANG PFPHEYVSGT PHVPLNFIAP 1450 1460 1470 1480 1490 1500 GGSQHGPFTG IACGKSMMSS VSLMGGRGGV PLYDRNHVTG ASSSSSSSTK ATLYPPILNP 1510 1520 1530 1540 1550 1560 PPSPATDPSL YNMDMFYSSN IPATARPYRP YIIRGMAPPT TPCSTDVCDS DYSASRWKAS 1570 1580 1590 1600 1610 KYYLDLNSDS DPYPPPPTPH SQYLSAEDSC PPSPATERSY FHLFPPPPSP CTDSS

CATM prediction

The sequence of LRP5_HUMAN returned 5 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
          1390      1400      1
   +    |    +    |    +    |		 (Å) (°) (Å) (°)  
Model 1 AHSSAIGAVIGIILSLFVMGGVYFVCQRV 6.8 -37.9° 5.7 33.8 -33.1
Model 2 AHSSAIGAVIGIILSLFVMGGVYFVCQRV 6.9 -47.9° 4.3 35.2 -21.9
Model 3 AHSSAIGAVIGIILSLFVMGGVYFVCQRV 7.0 -25.4° 2.7 51.9 -21.8
Model 4 AHSSAIGAVIGIILSLFVMGGVYFVCQRV 6.4 -43.8° 1.8 44.7 -16.8
Model 5 AHSSAIGAVIGIILSLFVMGGVYFVCQRV 7.3 -45.0° 0.1 45.0 -5.2
Prolines* AHSSAIGPVIGIILSLFVMGGVYFVCQRV          

* 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, 1385, SER, HA A, 1385, SER, OG 3.44Å
B, 1388, GLY, HA1 A, 1385, SER, OG 2.97Å
B, 1388, GLY, HA1 A, 1385, SER, O 3.23Å
B, 1389, ALA, HA A, 1388, GLY, O 2.77Å
B, 1392, GLY, HA1 A, 1389, ALA, O 3.14Å
B, 1393, ILE, HA A, 1396, SER, OG 2.65Å
A, 1385, SER, HA B, 1385, SER, OG 3.44Å
A, 1388, GLY, HA1 B, 1385, SER, OG 2.97Å
A, 1388, GLY, HA1 B, 1385, SER, O 3.23Å
A, 1389, ALA, HA B, 1388, GLY, O 2.77Å
A, 1392, GLY, HA1 B, 1389, ALA, O 3.14Å
A, 1393, ILE, HA B, 1396, SER, OG 2.65Å