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Low-density lipoprotein receptor-related protein 4 (LRP-4) (Multiple epidermal growth factor-like domains 7)

 LRP4_RAT                Reviewed;        1905 AA.
Q9QYP1;
13-APR-2004, integrated into UniProtKB/Swiss-Prot.
10-MAY-2004, sequence version 2.
05-DEC-2018, entry version 142.
RecName: Full=Low-density lipoprotein receptor-related protein 4;
Short=LRP-4;
AltName: Full=Multiple epidermal growth factor-like domains 7;
Flags: Precursor;
Name=Lrp4; Synonyms=Megf7;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Brown Norway;
PubMed=15057822; DOI=10.1038/nature02426;
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T.,
Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A.,
Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M.,
Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K.,
Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S.,
Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J.,
Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y.,
Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A.,
Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J.,
D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R.,
Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A.,
Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E.,
Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E.,
Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D.,
Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M.,
Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O.,
Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O.,
Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H.,
Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S.,
Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J.,
Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E.,
Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F.,
Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K.,
Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S.,
Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M.,
Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M.,
Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A.,
Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S.,
Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G.,
Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H.,
Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R.,
Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M.,
Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H.,
Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S.,
Collins F.S.;
"Genome sequence of the Brown Norway rat yields insights into
mammalian evolution.";
Nature 428:493-521(2004).
[2]
NUCLEOTIDE SEQUENCE OF 608-1905, AND TISSUE SPECIFICITY.
STRAIN=Sprague-Dawley; TISSUE=Brain;
PubMed=9693030; DOI=10.1006/geno.1998.5341;
Nakayama M., Nakajima D., Nagase T., Nomura N., Seki N., Ohara O.;
"Identification of high-molecular-weight proteins with multiple EGF-
like motifs by motif-trap screening.";
Genomics 51:27-34(1998).
[3]
INTERACTION WITH MUSK.
PubMed=18848351; DOI=10.1016/j.cell.2008.10.002;
Kim N., Stiegler A.L., Cameron T.O., Hallock P.T., Gomez A.M.,
Huang J.H., Hubbard S.R., Dustin M.L., Burden S.J.;
"Lrp4 is a receptor for Agrin and forms a complex with MuSK.";
Cell 135:334-342(2008).
-!- FUNCTION: Mediates SOST-dependent inhibition of bone formation (By
similarity). Functions as a specific facilitator of SOST-mediated
inhibition of Wnt signaling (By similarity). 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. Plays an essential role in the
process of digit differentiation. {ECO:0000250|UniProtKB:Q8VI56}.
-!- SUBUNIT: Homooligomer. Interacts with MUSK; the heterodimer forms
an AGRIN receptor complex that binds AGRIN resulting in activation
of MUSK (PubMed:18848351). Interacts (via the extracellular
domain) with SOST; the interaction facilitates the inhibition of
Wnt signaling (By similarity). Interacts with MESD; the
interaction promotes glycosylation of LRP4 and its cell-surface
expression (By similarity). {ECO:0000250|UniProtKB:Q8VI56,
ECO:0000269|PubMed:18848351}.
-!- SUBCELLULAR LOCATION: Cell membrane
{ECO:0000250|UniProtKB:Q8VI56}; Single-pass type I membrane
protein {ECO:0000255}.
-!- TISSUE SPECIFICITY: Expressed in different regions of the brain,
mainly in the olfactory bulb, at lower level in the cerebral
cortex and hippocampus. {ECO:0000269|PubMed:9693030}.
-!- PTM: N-glycosylation is required for cell surface location.
{ECO:0000250|UniProtKB:Q8VI56}.
-!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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EMBL; AABR03025549; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AABR03027097; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AABR03027512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AABR03029369; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AB011533; BAA88688.1; -; mRNA.
UniGene; Rn.21381; -.
PDB; 3V64; X-ray; 2.85 A; C/D=396-737.
PDB; 3V65; X-ray; 3.30 A; B/D=353-737.
PDBsum; 3V64; -.
PDBsum; 3V65; -.
ProteinModelPortal; Q9QYP1; -.
SMR; Q9QYP1; -.
CORUM; Q9QYP1; -.
STRING; 10116.ENSRNOP00000021353; -.
iPTMnet; Q9QYP1; -.
PhosphoSitePlus; Q9QYP1; -.
PaxDb; Q9QYP1; -.
PRIDE; Q9QYP1; -.
Ensembl; ENSRNOT00000021353; ENSRNOP00000021353; ENSRNOG00000015285.
UCSC; RGD:619731; rat.
RGD; 619731; Lrp4.
eggNOG; KOG1215; Eukaryota.
eggNOG; ENOG410XPR2; LUCA.
GeneTree; ENSGT00940000158287; -.
HOGENOM; HOG000047507; -.
HOVERGEN; HBG049163; -.
InParanoid; Q9QYP1; -.
OMA; CGRNHFT; -.
OrthoDB; EOG091G0178; -.
PhylomeDB; Q9QYP1; -.
TreeFam; TF315253; -.
PRO; PR:Q9QYP1; -.
Proteomes; UP000002494; Chromosome 3.
Bgee; ENSRNOG00000015285; Expressed in 10 organ(s), highest expression level in lung.
ExpressionAtlas; Q9QYP1; baseline and differential.
Genevisible; Q9QYP1; RN.
GO; GO:0009986; C:cell surface; IDA:UniProtKB.
GO; GO:0030425; C:dendrite; IDA:UniProtKB.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB.
GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0044853; C:plasma membrane raft; IDA:UniProtKB.
GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
GO; GO:0097060; C:synaptic membrane; IDA:UniProtKB.
GO; GO:0034185; F:apolipoprotein binding; IPI:UniProtKB.
GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
GO; GO:0097110; F:scaffold protein binding; IPI:UniProtKB.
GO; GO:0030509; P:BMP signaling pathway; IEA:InterPro.
GO; GO:0048813; P:dendrite morphogenesis; IMP:UniProtKB.
GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl.
GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
GO; GO:0001822; P:kidney development; IEA:Ensembl.
GO; GO:0050771; P:negative regulation of axonogenesis; ISS:UniProtKB.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
GO; GO:1901631; P:positive regulation of presynaptic membrane organization; ISS:UniProtKB.
GO; GO:1904395; P:positive regulation of skeletal muscle acetylcholine-gated channel clustering; IEA:Ensembl.
GO; GO:0097104; P:postsynaptic membrane assembly; ISS:UniProtKB.
GO; GO:0097105; P:presynaptic membrane assembly; ISS:UniProtKB.
GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
GO; GO:0071340; P:skeletal muscle acetylcholine-gated channel clustering; ISS:UniProtKB.
GO; GO:0050808; P:synapse organization; IMP:UniProtKB.
GO; GO:0051124; P:synaptic growth at neuromuscular junction; ISS:UniProtKB.
GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
CDD; cd00112; LDLa; 7.
Gene3D; 2.120.10.30; -; 4.
InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
InterPro; IPR026823; cEGF.
InterPro; IPR001881; EGF-like_Ca-bd_dom.
InterPro; IPR013032; EGF-like_CS.
InterPro; IPR000742; EGF-like_dom.
InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
InterPro; IPR018097; EGF_Ca-bd_CS.
InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
InterPro; IPR036055; LDL_receptor-like_sf.
InterPro; IPR023415; LDLR_class-A_CS.
InterPro; IPR000033; LDLR_classB_rpt.
InterPro; IPR002172; LDrepeatLR_classA_rpt.
InterPro; IPR030799; LRP4.
PANTHER; PTHR44017:SF4; PTHR44017:SF4; 1.
Pfam; PF12662; cEGF; 1.
Pfam; PF00057; Ldl_recept_a; 8.
Pfam; PF00058; Ldl_recept_b; 16.
PRINTS; PR00261; LDLRECEPTOR.
SMART; SM00181; EGF; 7.
SMART; SM00179; EGF_CA; 2.
SMART; SM00192; LDLa; 8.
SMART; SM00135; LY; 20.
SUPFAM; SSF57184; SSF57184; 1.
SUPFAM; SSF57424; SSF57424; 8.
PROSITE; PS00010; ASX_HYDROXYL; 1.
PROSITE; PS01186; EGF_2; 3.
PROSITE; PS01187; EGF_CA; 1.
PROSITE; PS01209; LDLRA_1; 8.
PROSITE; PS50068; LDLRA_2; 8.
PROSITE; PS51120; LDLRB; 20.
1: Evidence at protein level;
3D-structure; Calcium; Cell membrane; Complete proteome;
Developmental protein; Differentiation; Disulfide bond;
EGF-like domain; Endocytosis; Glycoprotein; Membrane; Receptor;
Reference proteome; Repeat; Signal; Transmembrane;
Transmembrane helix; Wnt signaling pathway.
SIGNAL 1 20 {ECO:0000255}.
CHAIN 21 1905 Low-density lipoprotein receptor-related
protein 4.
/FTId=PRO_0000017327.
TOPO_DOM 21 1723 Extracellular. {ECO:0000255}.
TRANSMEM 1724 1746 Helical. {ECO:0000255}.
TOPO_DOM 1747 1905 Cytoplasmic. {ECO:0000255}.
DOMAIN 26 67 LDL-receptor class A 1.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 70 106 LDL-receptor class A 2.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 109 144 LDL-receptor class A 3.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 147 183 LDL-receptor class A 4.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 190 226 LDL-receptor class A 5.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 230 266 LDL-receptor class A 6.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 269 305 LDL-receptor class A 7.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 311 350 LDL-receptor class A 8.
{ECO:0000255|PROSITE-ProRule:PRU00124}.
DOMAIN 354 394 EGF-like 1; atypical.
DOMAIN 395 434 EGF-like 2; calcium-binding.
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.
CARBOHYD 264 264 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 498 498 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 719 719 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 901 901 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1077 1077 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1415 1415 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 1467 1467 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 27 44 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 34 57 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 51 66 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 71 83 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 78 96 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 90 105 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 110 122 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 117 135 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 129 143 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 148 160 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 155 173 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 167 182 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 191 203 {ECO:0000255|PROSITE-ProRule:PRU00124}.
DISULFID 198