LRP4_HUMAN » Low-density lipoprotein receptor-related protein 4

LRP4_HUMAN » Low-density lipoprotein receptor-related protein 4
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
LRP4_HUMAN » Low-density lipoprotein receptor-related protein 4 » LRP-4; Multiple epidermal growth factor-like domains 7;
Hydrophobic Thickness 34.2 ± 1.9 Å
Tilt Angle 3 ± 3°
ΔGtransfer -25.3 kcal/mol
ΔGfold -24.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 1726-1748 (1724-1752)
Pathways none
PDB none
OPM none
Complexes none
Interactions none
Domains

AA: 25-66, PDBID: 2FYJ, Subunit A, Seq Identity:48%, Low-density lipoprotein receptor domain class A

AA: 69-105, PDBID: 2FYJ, Subunit A, Seq Identity:57%, Low-density lipoprotein receptor domain class A

AA: 108-143, PDBID: 1D2L, Subunit A, Seq Identity:55%, Low-density lipoprotein receptor domain class A

AA: 146-182, PDBID: 1AJJ, Subunit A, Seq Identity:61%, Low-density lipoprotein receptor domain class A

AA: 189-225, PDBID: 2FYJ, Subunit A, Seq Identity:55%, Low-density lipoprotein receptor domain class A

AA: 229-265, PDBID: 1AJJ, Subunit A, Seq Identity:61%, Low-density lipoprotein receptor domain class A

AA: 268-304, PDBID: 1AJJ, Subunit A, Seq Identity:64%, Low-density lipoprotein receptor domain class A

AA: 310-349, PDBID: 2FYJ, Subunit A, Seq Identity:55%, Low-density lipoprotein receptor domain class A

AA: 376-398, PDBID: 3V65, Subunit D, Seq Identity:96%, Complement Clr-like EGF-like

AA: 480-520, PDBID: 3V64, Subunit D, Seq Identity:100%, Low-density lipoprotein receptor repeat class B

AA: 523-563, PDBID: 3V64, Subunit D, Seq Identity:97%, Low-density lipoprotein receptor repeat class B

AA: 566-607, PDBID: 3V64, Subunit D, Seq Identity:100%, Low-density lipoprotein receptor repeat class B

AA: 610-650, PDBID: 3V64, Subunit D, Seq Identity:100%, Low-density lipoprotein receptor repeat class B

AA: 785-825, PDBID: 3V64, Subunit D, Seq Identity:56%, Low-density lipoprotein receptor repeat class B

AA: 828-866, PDBID: 3S94, Subunit B, Seq Identity:60%, Low-density lipoprotein receptor repeat class B

AA: 871-912, PDBID: 3S94, Subunit B, Seq Identity:69%, Low-density lipoprotein receptor repeat class B

AA: 915-954, PDBID: 3V64, Subunit D, Seq Identity:54%, Low-density lipoprotein receptor repeat class B

AA: 956-996, PDBID: 1IJQ, Subunit A, Seq Identity:36%, Low-density lipoprotein receptor repeat class B

AA: 1006-1043, PDBID: 3S94, Subunit A, Seq Identity:64%, Coagulation Factor Xa inhibitory site

AA: 1093-1133, PDBID: 3V64, Subunit D, Seq Identity:55%, Low-density lipoprotein receptor repeat class B

AA: 1136-1176, PDBID: 3S94, Subunit B, Seq Identity:72%, Low-density lipoprotein receptor repeat class B

AA: 1179-1220, PDBID: 3S94, Subunit B, Seq Identity:65%, Low-density lipoprotein receptor repeat class B

AA: 1313-1348, PDBID: 3S94, Subunit A, Seq Identity:64%, Coagulation Factor Xa inhibitory site

AA: 1397-1437, PDBID: 3V64, Subunit D, Seq Identity:56%, Low-density lipoprotein receptor repeat class B

AA: 1440-1480, PDBID: 3S94, Subunit B, Seq Identity:62%, Low-density lipoprotein receptor repeat class B

AA: 1483-1524, PDBID: 3S94, Subunit B, Seq Identity:76%, Low-density lipoprotein receptor repeat class B

AA: 1527-1563, PDBID: 3V64, Subunit D, Seq Identity:47%, Low-density lipoprotein receptor repeat class B

UniProt annotation for LRP4_HUMAN » Low-density lipoprotein receptor-related protein 4
FUNCTION: Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN- induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the transcription of specific genes and the clustering of AChR in the postsynaptic membrane. Alternatively, may be involved in the negative regulation of the canonical Wnt signaling pathway, being able to antagonize the LRP6-mediated activation of this pathway. More generally, has been proposed to function as a cell surface endocytic receptor binding and internalizing extracellular ligands for degradation by lysosomes.

SUBUNIT: Homooligomer. Interacts with MUSK; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK (By similarity). Interacts (via the extracellular domain) with SOST; the interaction facilitates the inhibition of Wnt signaling.

TISSUE SPECIFICITY: Expressed in bone; present in osteoblasts and osteocytes. No expression is observed in osteoclast. Expressed in several regions of the brain.

DISEASE: Cenani-Lenz syndactyly syndrome (CLSS) OMIM: A congenital malformation syndrome defined as complete and complex syndactyly of the hands combined with malformations of the forearm bones and similar manifestations in the lower limbs. It is characterized by fusion and disorganization of metacarpal and phalangeal bones, radius and ulnar shortening, radioulnar synostosis, and severe syndactyly of hands and feet. mutations affecting the gene represented in this entry.

DISEASE: Sclerosteosis 2 (SOST2) OMIM: A sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. mutations affecting the gene represented in this entry.

UniProt features for LRP4_HUMAN » Low-density lipoprotein receptor-related protein 4
SIGNAL 1 20 Potential.
CHAIN 21 1905 Low-density lipoprotein receptor-related protein 4.
DOMAIN 26 67 LDL-receptor class A 1.
DOMAIN 70 106 LDL-receptor class A 2.
DOMAIN 109 144 LDL-receptor class A 3.
DOMAIN 147 183 LDL-receptor class A 4.
DOMAIN 190 226 LDL-receptor class A 5.
DOMAIN 230 266 LDL-receptor class A 6.
DOMAIN 269 305 LDL-receptor class A 7.
DOMAIN 311 350 LDL-receptor class A 8.
DOMAIN 354 394 EGF-like 1; calcium-binding (Potential).
DOMAIN 395 434 EGF-like 2; calcium-binding (Potential).
REPEAT 480 522 LDL-receptor class B 1.
REPEAT 523 565 LDL-receptor class B 2.
REPEAT 566 609 LDL-receptor class B 3.
REPEAT 610 652 LDL-receptor class B 4.
REPEAT 653 693 LDL-receptor class B 5.
DOMAIN 698 737 EGF-like 3.
REPEAT 785 827 LDL-receptor class B 6.
REPEAT 828 870 LDL-receptor class B 7.
REPEAT 871 914 LDL-receptor class B 8.
REPEAT 915 956 LDL-receptor class B 9.
REPEAT 957 998 LDL-receptor class B 10.
REPEAT 1093 1135 LDL-receptor class B 11.
REPEAT 1136 1178 LDL-receptor class B 12.
REPEAT 1179 1222 LDL-receptor class B 13.
REPEAT 1223 1263 LDL-receptor class B 14.
REPEAT 1264 1306 LDL-receptor class B 15.
REPEAT 1397 1439 LDL-receptor class B 16.
REPEAT 1440 1482 LDL-receptor class B 17.
REPEAT 1483 1526 LDL-receptor class B 18.
REPEAT 1527 1568 LDL-receptor class B 19.
REPEAT 1569 1610 LDL-receptor class B 20.
MOTIF 1766 1769 Endocytosis signal (Potential).
DISULFID 27 44 By similarity.
DISULFID 34 57 By similarity.
DISULFID 51 66 By similarity.
DISULFID 71 83 By similarity.
DISULFID 78 96 By similarity.
DISULFID 90 105 By similarity.
DISULFID 110 122 By similarity.
DISULFID 117 135 By similarity.
DISULFID 129 143 By similarity.
DISULFID 148 160 By similarity.
DISULFID 155 173 By similarity.
DISULFID 167 182 By similarity.
DISULFID 191 203 By similarity.
DISULFID 198 216 By similarity.
DISULFID 210 225 By similarity.
DISULFID 231 243 By similarity.
DISULFID 238 256 By similarity.
DISULFID 250 265 By similarity.
DISULFID 270 282 By similarity.
DISULFID 277 295 By similarity.
DISULFID 289 304 By similarity.
DISULFID 312 324 By similarity.
DISULFID 319 337 By similarity.
DISULFID 331 349 By similarity.
DISULFID 358 369 By similarity.
DISULFID 365 378 By similarity.
DISULFID 380 393 By similarity.
DISULFID 399 409 By similarity.
DISULFID 405 418 By similarity.
DISULFID 420 433 By similarity.
DISULFID 702 713 By similarity.
DISULFID 709 722 By similarity.
DISULFID 724 736 By similarity.
Amino Acid Sequence for LRP4_HUMAN » Low-density lipoprotein receptor-related protein 4
MRRQWGALLL GALLCAHGLA SSPECACGRS HFTCAVSALG ECTCIPAQWQ CDGDNDCGDH SDEDGCILPT CSPLDFHCDN GKCIRRSWVC DGDNDCEDDS DEQDCPPREC EEDEFPCQNG YCIRSLWHCD GDNDCGDNSD EQCDMRKCSD KEFRCSDGSC IAEHWYCDGD TDCKDGSDEE NCPSAVPAPP CNLEEFQCAY GRCILDIYHC DGDDDCGDWS DESDCSSHQP CRSGEFMCDS GLCINAGWRC DGDADCDDQS DERNCTTSMC TAEQFRCHSG RCVRLSWRCD GEDDCADNSD EENCENTGSP QCALDQFLCW NGRCIGQRKL CNGVNDCGDN SDESPQQNCR PRTGEENCNV NNGGCAQKCQ MVRGAVQCTC HTGYRLTEDG HTCQDVNECA EEGYCSQGCT NSEGAFQCWC ETGYELRPDR RSCKALGPEP VLLFANRIDI RQVLPHRSEY TLLLNNLENA IALDFHHRRE LVFWSDVTLD RILRANLNGS NVEEVVSTGL ESPGGLAVDW VHDKLYWTDS GTSRIEVANL DGAHRKVLLW QNLEKPRAIA LHPMEGTIYW TDWGNTPRIE ASSMDGSGRR IIADTHLFWP NGLTIDYAGR RMYWVDAKHH VIERANLDGS HRKAVISQGL PHPFAITVFE DSLYWTDWHT KSINSANKFT GKNQEIIRNK LHFPMDIHTL HPQRQPAGKN RCGDNNGGCT HLCLPSGQNY TCACPTGFRK ISSHACAQSL DKFLLFARRM DIRRISFDTE DLSDDVIPLA DVRSAVALDW DSRDDHVYWT DVSTDTISRA KWDGTGQEVV VDTSLESPAG LAIDWVTNKL YWTDAGTDRI EVANTDGSMR TVLIWENLDR PRDIVVEPMG GYMYWTDWGA SPKIERAGMD ASGRQVIISS NLTWPNGLAI DYGSQRLYWA DAGMKTIEFA GLDGSKRKVL IGSQLPHPFG LTLYGERIYW TDWQTKSIQS ADRLTGLDRE TLQENLENLM DIHVFHRRRP PVSTPCAMEN GGCSHLCLRS PNPSGFSCTC PTGINLLSDG KTCSPGMNSF LIFARRIDIR MVSLDIPYFA DVVVPINITM KNTIAVGVDP QEGKVYWSDS TLHRISRANL DGSQHEDIIT TGLQTTDGLA VDAIGRKVYW TDTGTNRIEV GNLDGSMRKV LVWQNLDSPR AIVLYHEMGF MYWTDWGENA KLERSGMDGS DRAVLINNNL GWPNGLTVDK ASSQLLWADA HTERIEAADL NGANRHTLVS PVQHPYGLTL LDSYIYWTDW QTRSIHRADK GTGSNVILVR SNLPGLMDMQ AVDRAQPLGF NKCGSRNGGC SHLCLPRPSG FSCACPTGIQ LKGDGKTCDP SPETYLLFSS RGSIRRISLD TSDHTDVHVP VPELNNVISL DYDSVDGKVY YTDVFLDVIR RADLNGSNME TVIGRGLKTT DGLAVDWVAR NLYWTDTGRN TIEASRLDGS CRKVLINNSL DEPRAIAVFP RKGYLFWTDW GHIAKIERAN LDGSERKVLI NTDLGWPNGL TLDYDTRRIY WVDAHLDRIE SADLNGKLRQ VLVGHVSHPF ALTQQDRWIY WTDWQTKSIQ RVDKYSGRNK ETVLANVEGL MDIIVVSPQR QTGTNACGVN NGGCTHLCFA RASDFVCACP DEPDSQPCSL VPGLVPPAPR ATGMSEKSPV LPNTPPTTLY SSTTRTRTSL EEVEGRCSER DARLGLCARS NDAVPAAPGE GLHISYAIGG LLSILLILVV IAALMLYRHK KSKFTDPGMG NLTYSNPSYR TSTQEVKIEA IPKPAMYNQL CYKKEGGPDH NYTKEKIKIV EGICLLSGDD AEWDDLKQLR SSRGGLLRDH VCMKTDTVSI QASSGSLDDT ETEQLLQEEQ SECSSVHTAA TPERRGSLPD TGWKHERKLS SESQV