LRP2_MOUSE
ID LRP2_MOUSE Reviewed; 4660 AA.
AC A2ARV4; P70215; Q3TL35; Q9JLB3;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Low-density lipoprotein receptor-related protein 2;
DE Short=LRP-2;
DE AltName: Full=Glycoprotein 330;
DE Short=gp330;
DE AltName: Full=Megalin;
DE Flags: Precursor;
GN Name=Lrp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4054-4660.
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4198-4320.
RC STRAIN=NMRI; TISSUE=Kidney;
RA Moll S., Menoud P.A., Izui S.;
RT "Tubular modulation of clusterin in lupus-like glomerulonephritis.";
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4465-4660, AND FUNCTION.
RX PubMed=10766831; DOI=10.1074/jbc.275.16.12003;
RA Hammad S.M., Barth J.L., Knaak C., Argraves W.S.;
RT "Megalin acts in concert with cubilin to mediate endocytosis of high
RT density lipoproteins.";
RL J. Biol. Chem. 275:12003-12008(2000).
RN [5]
RP FUNCTION, INTERACTION WITH GC, AND DISRUPTION PHENOTYPE.
RX PubMed=10052453; DOI=10.1016/s0092-8674(00)80655-8;
RA Nykjaer A., Dragun D., Walther D., Vorum H., Jacobsen C., Herz J.,
RA Melsen F., Christensen E.I., Willnow T.E.;
RT "An endocytic pathway essential for renal uptake and activation of the
RT steroid 25-(OH) vitamin D3.";
RL Cell 96:507-515(1999).
RN [6]
RP INTERACTION WITH MDK.
RX PubMed=10772929; DOI=10.1006/bbrc.2000.2549;
RA Muramatsu H., Zou K., Sakaguchi N., Ikematsu S., Sakuma S., Muramatsu T.;
RT "LDL receptor-related protein as a component of the midkine receptor.";
RL Biochem. Biophys. Res. Commun. 270:936-941(2000).
RN [7]
RP INTERACTION WITH DAB2.
RX PubMed=11247302; DOI=10.1034/j.1600-0854.2001.020206.x;
RA Morris S.M., Cooper J.A.;
RT "Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts
RT with AP-2.";
RL Traffic 2:111-123(2001).
RN [8]
RP INTERACTION WITH SHH.
RX PubMed=11964399; DOI=10.1074/jbc.m201933200;
RA McCarthy R.A., Barth J.L., Chintalapudi M.R., Knaak C., Argraves W.S.;
RT "Megalin functions as an endocytic sonic hedgehog receptor.";
RL J. Biol. Chem. 277:25660-25667(2002).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12724130; DOI=10.1152/ajprenal.00062.2003;
RA Gburek J., Birn H., Verroust P.J., Goj B., Jacobsen C., Moestrup S.K.,
RA Willnow T.E., Christensen E.I.;
RT "Renal uptake of myoglobin is mediated by the endocytic receptors megalin
RT and cubilin.";
RL Am. J. Physiol. 285:F451-F458(2003).
RN [10]
RP INTERACTION WITH ANGIOTENSIN-2.
RX PubMed=15467006; DOI=10.1152/ajprenal.00243.2004;
RA Gonzalez-Villalobos R., Klassen R.B., Allen P.L., Navar L.G., Hammond T.G.;
RT "Megalin binds and internalizes angiotensin II.";
RL Am. J. Physiol. 288:F420-F427(2005).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=16143106; DOI=10.1016/j.cell.2005.06.032;
RA Hammes A., Andreassen T.K., Spoelgen R., Raila J., Hubner N., Schulz H.,
RA Metzger J., Schweigert F.J., Luppa P.B., Nykjaer A., Willnow T.E.;
RT "Role of endocytosis in cellular uptake of sex steroids.";
RL Cell 122:751-762(2005).
RN [12]
RP FUNCTION, INTERACTION WITH BMP4, AND DISRUPTION PHENOTYPE.
RX PubMed=15623804; DOI=10.1242/dev.01580;
RA Spoelgen R., Hammes A., Anzenberger U., Zechner D., Andersen O.M.,
RA Jerchow B., Willnow T.E.;
RT "LRP2/megalin is required for patterning of the ventral telencephalon.";
RL Development 132:405-414(2005).
RN [13]
RP INTERACTION WITH ANGIOTENSIN 1-7.
RX PubMed=16380466; DOI=10.1152/ajprenal.00164.2005;
RA Gonzalez-Villalobos R., Klassen R.B., Allen P.L., Johanson K., Baker C.B.,
RA Kobori H., Navar L.G., Hammond T.G.;
RT "Megalin binds and internalizes angiotensin-(1-7).";
RL Am. J. Physiol. 290:F1270-F1275(2006).
RN [14]
RP INTERACTION WITH APOM, AND DISRUPTION PHENOTYPE.
RX PubMed=16099815; DOI=10.1210/me.2005-0209;
RA Faber K., Hvidberg V., Moestrup S.K., Dahlbaeck B., Nielsen L.B.;
RT "Megalin is a receptor for apolipoprotein M, and kidney-specific megalin-
RT deficiency confers urinary excretion of apolipoprotein M.";
RL Mol. Endocrinol. 20:212-218(2006).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17462596; DOI=10.1016/j.bbrc.2007.04.072;
RA Kaseda R., Iino N., Hosojima M., Takeda T., Hosaka K., Kobayashi A.,
RA Yamamoto K., Suzuki A., Kasai A., Suzuki Y., Gejyo F., Saito A.;
RT "Megalin-mediated endocytosis of cystatin C in proximal tubule cells.";
RL Biochem. Biophys. Res. Commun. 357:1130-1134(2007).
RN [16]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17846082; DOI=10.1096/fj.07-9171com;
RA Koenig O., Ruettiger L., Mueller M., Zimmermann U., Erdmann B.,
RA Kalbacher H., Gross M., Knipper M.;
RT "Estrogen and the inner ear: megalin knockout mice suffer progressive
RT hearing loss.";
RL FASEB J. 22:410-417(2008).
RN [17]
RP FUNCTION, AND INTERACTION WITH SEPP1.
RX PubMed=18174160; DOI=10.1074/jbc.m709945200;
RA Olson G.E., Winfrey V.P., Hill K.E., Burk R.F.;
RT "Megalin mediates selenoprotein P uptake by kidney proximal tubule
RT epithelial cells.";
RL J. Biol. Chem. 283:6854-6860(2008).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-387.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4464; SER-4467; SER-4577;
RP THR-4637 AND SER-4658, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Kidney, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=20460439; DOI=10.1242/jcs.065912;
RA Gajera C.R., Emich H., Lioubinski O., Christ A.,
RA Beckervordersandforth-Bonk R., Yoshikawa K., Bachmann S., Christensen E.I.,
RA Goetz M., Kempermann G., Peterson A.S., Willnow T.E., Hammes A.;
RT "LRP2 in ependymal cells regulates BMP signaling in the adult neurogenic
RT niche.";
RL J. Cell Sci. 123:1922-1930(2010).
RN [21]
RP FUNCTION, INTERACTION WITH APPB1 AND APP, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=20637285; DOI=10.1016/j.mcn.2010.07.005;
RA Alvira-Botero X., Perez-Gonzalez R., Spuch C., Vargas T., Antequera D.,
RA Garzon M., Bermejo-Pareja F., Carro E.;
RT "Megalin interacts with APP and the intracellular adapter protein FE65 in
RT neurons.";
RL Mol. Cell. Neurosci. 45:306-315(2010).
RN [22]
RP FUNCTION, AND INDUCTION BY CANNABINOIDS.
RX PubMed=22841573; DOI=10.1016/j.cmet.2012.07.002;
RA Tam J., Cinar R., Liu J., Godlewski G., Wesley D., Jourdan T., Szanda G.,
RA Mukhopadhyay B., Chedester L., Liow J.S., Innis R.B., Cheng K., Rice K.C.,
RA Deschamps J.R., Chorvat R.J., McElroy J.F., Kunos G.;
RT "Peripheral cannabinoid-1 receptor inverse agonism reduces obesity by
RT reversing leptin resistance.";
RL Cell Metab. 16:167-179(2012).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=22340494; DOI=10.1016/j.devcel.2011.11.023;
RA Christ A., Christa A., Kur E., Lioubinski O., Bachmann S., Willnow T.E.,
RA Hammes A.;
RT "LRP2 is an auxiliary SHH receptor required to condition the forebrain
RT ventral midline for inductive signals.";
RL Dev. Cell 22:268-278(2012).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=22354480; DOI=10.1002/glia.22316;
RA Ortega M.C., Cases O., Merchan P., Kozyraki R., Clemente D., de Castro F.;
RT "Megalin mediates the influence of sonic hedgehog on oligodendrocyte
RT precursor cell migration and proliferation during development.";
RL Glia 60:851-866(2012).
RN [25]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23825075; DOI=10.1152/ajprenal.00546.2012;
RA Jobst-Schwan T., Knaup K.X., Nielsen R., Hackenbeck T., Buettner-Herold M.,
RA Lechler P., Kroening S., Goppelt-Struebe M., Schloetzer-Schrehardt U.,
RA Fuernrohr B.G., Voll R.E., Amann K., Eckardt K.U., Christensen E.I.,
RA Wiesener M.S.;
RT "Renal uptake of the antiapoptotic protein survivin is mediated by megalin
RT at the apical membrane of the proximal tubule.";
RL Am. J. Physiol. 305:F734-F744(2013).
RN [26]
RP FUNCTION.
RX PubMed=24825475; DOI=10.15252/embr.201338317;
RA Byun K., Gil S.Y., Namkoong C., Youn B.S., Huang H., Shin M.S., Kang G.M.,
RA Kim H.K., Lee B., Kim Y.B., Kim M.S.;
RT "Clusterin/ApoJ enhances central leptin signaling through Lrp2-mediated
RT endocytosis.";
RL EMBO Rep. 15:801-808(2014).
RN [27]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24639464; DOI=10.1242/jcs.140145;
RA Kur E., Mecklenburg N., Cabrera R.M., Willnow T.E., Hammes A.;
RT "LRP2 mediates folate uptake in the developing neural tube.";
RL J. Cell Sci. 127:2261-2268(2014).
RN [28]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26439398; DOI=10.1016/j.devcel.2015.09.001;
RA Christ A., Christa A., Klippert J., Eule J.C., Bachmann S., Wallace V.A.,
RA Hammes A., Willnow T.E.;
RT "LRP2 acts as SHH clearance receptor to protect the retinal margin from
RT mitogenic stimuli.";
RL Dev. Cell 35:36-48(2015).
RN [29]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26822476; DOI=10.1242/dmm.022053;
RA Baardman M.E., Zwier M.V., Wisse L.J., Gittenberger-de Groot A.C.,
RA Kerstjens-Frederikse W.S., Hofstra R.M., Jurdzinski A., Hierck B.P.,
RA Jongbloed M.R., Berger R.M., Ploesch T., DeRuiter M.C.;
RT "Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice
RT indicate a crucial role of LRP2 in cardiac development.";
RL Dis. Model. Mech. 9:413-425(2016).
RN [30]
RP GLYCOSYLATION.
RX PubMed=27773703; DOI=10.1016/j.bbagen.2016.10.015;
RA Hirano M., Totani K., Fukuda T., Gu J., Suzuki A.;
RT "N-glycoform-dependent interactions of megalin with its ligands.";
RL Biochim. Biophys. Acta 1861:3106-3118(2017).
RN [31]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28659595; DOI=10.1038/s41598-017-04648-y;
RA Johanns M., Lemoine P., Janssens V., Grieco G., Moestrup S.K., Nielsen R.,
RA Christensen E.I., Courtoy P.J., Emonard H., Marbaix E., Henriet P.;
RT "Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor
RT megalin/LRP-2.";
RL Sci. Rep. 7:4328-4328(2017).
CC -!- FUNCTION: Multiligand endocytic receptor. Acts together with CUBN to
CC mediate endocytosis of high-density lipoproteins (PubMed:10766831).
CC Mediates receptor-mediated uptake of polybasic drugs such as aprotinin,
CC aminoglycosides and polymyxin B (By similarity). In the kidney,
CC mediates the tubular uptake and clearance of leptin (PubMed:22841573).
CC Also mediates transport of leptin across the blood-brain barrier
CC through endocytosis at the choroid plexus epithelium (By similarity).
CC Endocytosis of leptin in neuronal cells is required for hypothalamic
CC leptin signaling and leptin-mediated regulation of feeding and body
CC weight (PubMed:24825475). Mediates endocytosis and subsequent lysosomal
CC degradation of CST3 in kidney proximal tubule cells (PubMed:17462596).
CC Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the
CC vitamin D3 transporter GC/DBP (PubMed:10052453). Mediates renal uptake
CC of metallothionein-bound heavy metals (By similarity). Together with
CC CUBN, mediates renal reabsorption of myoglobin (By similarity).
CC Mediates renal uptake and subsequent lysosomal degradation of APOM (By
CC similarity). Plays a role in kidney selenium homeostasis by mediating
CC renal endocytosis of selenoprotein SEPP1 (PubMed:18174160). Mediates
CC renal uptake of the antiapoptotic protein BIRC5/survivin which may be
CC important for functional integrity of the kidney (PubMed:23825075).
CC Mediates renal uptake of matrix metalloproteinase MMP2 in complex with
CC metalloproteinase inhibitor TIMP1 (PubMed:28659595). Mediates
CC endocytosis of Sonic hedgehog protein N-product (ShhN), the active
CC product of SHH (By similarity). Also mediates ShhN transcytosis (By
CC similarity). In the embryonic neuroepithelium, mediates endocytic
CC uptake and degradation of BMP4, is required for correct SHH
CC localization in the ventral neural tube and plays a role in patterning
CC of the ventral telencephalon (PubMed:15623804). Required at the onset
CC of neurulation to sequester SHH on the apical surface of
CC neuroepithelial cells of the rostral diencephalon ventral midline and
CC to control PTCH1-dependent uptake and intracellular trafficking of SHH
CC (PubMed:22340494). During neurulation, required in neuroepithelial
CC cells for uptake of folate bound to the folate receptor FOLR1 which is
CC necessary for neural tube closure (PubMed:24639464). In the adult
CC brain, negatively regulates BMP signaling in the subependymal zone
CC which enables neurogenesis to proceed (PubMed:20460439). In astrocytes,
CC mediates endocytosis of ALB which is required for the synthesis of the
CC neurotrophic factor oleic acid (By similarity). Involved in neurite
CC branching (PubMed:20637285). During optic nerve development, required
CC for SHH-mediated migration and proliferation of oligodendrocyte
CC precursor cells (PubMed:22354480). Mediates endocytic uptake and
CC clearance of SHH in the retinal margin which protects retinal
CC progenitor cells from mitogenic stimuli and keeps them quiescent
CC (PubMed:26439398). Plays a role in reproductive organ development by
CC mediating uptake in reproductive tissues of androgen and estrogen bound
CC to the sex hormone binding protein SHBG (PubMed:16143106). Mediates
CC endocytosis of angiotensin-2 (By similarity). Also mediates endocytosis
CC of angiotensin 1-7 (By similarity). Binds to the complex composed of
CC beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and
CC lysosomal degradation (By similarity). Required for embryonic heart
CC development (PubMed:26822476). Required for normal hearing, possibly
CC through interaction with estrogen in the inner ear (PubMed:17846082).
CC {ECO:0000250|UniProtKB:C0HL13, ECO:0000250|UniProtKB:P98158,
CC ECO:0000250|UniProtKB:P98164, ECO:0000269|PubMed:10052453,
CC ECO:0000269|PubMed:10766831, ECO:0000269|PubMed:15623804,
CC ECO:0000269|PubMed:16143106, ECO:0000269|PubMed:16380466,
CC ECO:0000269|PubMed:17462596, ECO:0000269|PubMed:17846082,
CC ECO:0000269|PubMed:18174160, ECO:0000269|PubMed:20460439,
CC ECO:0000269|PubMed:20637285, ECO:0000269|PubMed:22340494,
CC ECO:0000269|PubMed:22354480, ECO:0000269|PubMed:22841573,
CC ECO:0000269|PubMed:23825075, ECO:0000269|PubMed:24639464,
CC ECO:0000269|PubMed:24825475, ECO:0000269|PubMed:26439398,
CC ECO:0000269|PubMed:26822476, ECO:0000269|PubMed:28659595}.
CC -!- SUBUNIT: Binds plasminogen, extracellular matrix components,
CC plasminogen activator-plasminogen activator inhibitor type I complex,
CC apolipoprotein E-enriched beta-VLDL, lipoprotein lipase, lactoferrin,
CC CLU/clusterin and calcium. Forms a multimeric complex together with
CC LRPAP1 (By similarity). Interacts (via PxLPxI/L motif) with ANKRA2 (via
CC ankyrin repeats) (By similarity). Interacts with LRP2BP. Interacts (via
CC NPXY motif) with DAB2; the interaction is not affected by tyrosine
CC phosphorylation of the NPXY motif (PubMed:11247302). Interacts with MB
CC (By similarity). Interacts with BMP4 (PubMed:15623804). Interacts with
CC the Sonic hedgehog protein N-product which is the active product of SHH
CC (PubMed:11964399). Interacts with CST3 in a calcium-dependent manner
CC (By similarity). Interacts with the vitamin-D binding protein GC/DBP
CC (PubMed:10052453). Interacts with sex hormone-binding protein SHBG (By
CC similarity). Interacts with angiotensin-2 (PubMed:15467006). Also
CC interacts with angiotensin 1-7 (PubMed:16380466). Interacts with APOM
CC (PubMed:16099815). Interacts with selenoprotein SEPP1
CC (PubMed:18174160). Interacts with LEP (By similarity). Interacts with
CC ALB (By similarity). Interacts with the antiapoptotic protein
CC BIRC5/survivin (By similarity). Interacts with matrix metalloproteinase
CC MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity).
CC In neurons, forms a trimeric complex with APP and APPB1/FE65
CC (PubMed:20637285). Interacts with LDLRAP1/ARH; mediates trafficking of
CC LRP2 to the endocytic recycling compartment (By similarity). Does not
CC interact with beta-amyloid protein 40 alone but interacts with the
CC complex composed of beta-amyloid protein 40 and CLU/APOJ (By
CC similarity). Interacts with MDK (PubMed:10772929).
CC {ECO:0000250|UniProtKB:C0HL13, ECO:0000250|UniProtKB:P98158,
CC ECO:0000250|UniProtKB:P98164, ECO:0000269|PubMed:10052453,
CC ECO:0000269|PubMed:10772929, ECO:0000269|PubMed:11247302,
CC ECO:0000269|PubMed:11964399, ECO:0000269|PubMed:15467006,
CC ECO:0000269|PubMed:15623804, ECO:0000269|PubMed:16099815,
CC ECO:0000269|PubMed:16380466, ECO:0000269|PubMed:18174160,
CC ECO:0000269|PubMed:20637285}.
CC -!- INTERACTION:
CC A2ARV4; P97318: Dab1; NbExp=2; IntAct=EBI-300875, EBI-81680;
CC A2ARV4; Q62108: Dlg4; NbExp=2; IntAct=EBI-300875, EBI-300895;
CC A2ARV4; Q9Z0G0: Gipc1; NbExp=2; IntAct=EBI-300875, EBI-300855;
CC A2ARV4; Q9WVI9: Mapk8ip1; NbExp=2; IntAct=EBI-300875, EBI-74515;
CC A2ARV4; Q9ERE9: Mapk8ip2; NbExp=2; IntAct=EBI-300875, EBI-74576;
CC A2ARV4; Q9D6K5: Synj2bp; NbExp=2; IntAct=EBI-300875, EBI-300910;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:16143106, ECO:0000269|PubMed:20460439,
CC ECO:0000269|PubMed:22340494, ECO:0000269|PubMed:22354480}; Single-pass
CC type I membrane protein {ECO:0000255}. Endosome lumen
CC {ECO:0000250|UniProtKB:P98158}. Membrane, coated pit
CC {ECO:0000269|PubMed:22340494}. Cell projection, dendrite
CC {ECO:0000269|PubMed:20637285}. Cell projection, axon
CC {ECO:0000269|PubMed:20637285}. Note=Localizes to brush border membranes
CC in the kidney. In the endolymphatic sac of the inner ear, located in
CC the lumen of endosomes as a soluble form.
CC {ECO:0000250|UniProtKB:P98158}.
CC -!- TISSUE SPECIFICITY: In the inner ear, strongly expressed in the
CC marginal cells of the stria vascularis (at protein level)
CC (PubMed:17846082). In the female reproductive tract, expressed on the
CC luminal side of the uterine epithelium (at protein level)
CC (PubMed:16143106). In the adult brain, expressed in ependymal cells of
CC the lateral ventricles where expression is restricted to the ependyma
CC that faces the stem cell niche (at protein level) (PubMed:20460439).
CC Expressed in neurons throughout the brain including in the hippocampus,
CC limbic cortices and cerebellum (at protein level) (PubMed:20637285). In
CC the developing optic nerve, expressed exclusively in astrocytes at 14.5
CC dpc, 16.5 dpc and 18.5 dpc (at protein level) (PubMed:22354480).
CC {ECO:0000269|PubMed:16143106, ECO:0000269|PubMed:17846082,
CC ECO:0000269|PubMed:20460439, ECO:0000269|PubMed:20637285,
CC ECO:0000269|PubMed:22354480}.
CC -!- DEVELOPMENTAL STAGE: In the developing optic nerve, more strongly
CC expressed at 14.5 dpc and 16.5 dpc than at 18.5 dpc (at protein level)
CC (PubMed:22354480). In the embryo, expression is detected from 7.5 dpc
CC on the apical side of the developing neural plate and persists
CC throughout later stages of development (PubMed:22340494). After neural
CC tube closure at 9.5 dpc, becomes progressively restricted to the
CC midline region (PubMed:22340494). During the estrus cycle, expression
CC is highest in metestrus II and diestrus (PubMed:16143106).
CC {ECO:0000269|PubMed:16143106, ECO:0000269|PubMed:22340494,
CC ECO:0000269|PubMed:22354480}.
CC -!- INDUCTION: Down-regulated in the kidney by cannabinoids, such as
CC endocannabinoid anandamide and synthetic cannabinoid HU-210.
CC {ECO:0000269|PubMed:22841573}.
CC -!- DOMAIN: Two overlapping PxLPxI/L motifs mediate interaction with
CC ankyrin repeats of ANKRA2. {ECO:0000250|UniProtKB:P98158}.
CC -!- DOMAIN: The cytoplasmic domain is required for sorting to the apical
CC cell membrane. {ECO:0000250|UniProtKB:P98158}.
CC -!- PTM: A fraction undergoes proteolytic cleavage of the extracellular
CC domain at the cell membrane to generate a cytoplasmic tail fragment.
CC This is internalized into the early endosome from where it trafficks in
CC an LDLRAP1/ARH-dependent manner to the endocytic recycling compartment
CC (ERC). In the ERC, it is further cleaved by gamma-secretase to release
CC a fragment which translocates to the nucleus and mediates
CC transcriptional repression. {ECO:0000250|UniProtKB:P98158}.
CC -!- PTM: N-glycosylation is required for ligand binding. Contains core-
CC fucosylated N-glycans in kidney proximal convoluted tubules (PCTs) and
CC hybrid-type N-glycans in proximal straight tubules (PSTs). Interacts
CC with ligands in a glycoform-dependent manner. Retinol-binding protein
CC and the vitamin D carrier GC/DBP are endocytosed primarily by PCTs,
CC albumin is endocytosed equally by PCTs and PSTs, and the aminoglycoside
CC kanamycin is endocytosed primarily by PSTs.
CC {ECO:0000269|PubMed:27773703}.
CC -!- DISRUPTION PHENOTYPE: Severe facial dysgenesis and impaired forebrain
CC development around mid-gestation, absence of Shh expression and
CC decreased cell proliferation in the ventral neural tube, and aberrant
CC expression of morphogens Fgf8 and Bmp4 (PubMed:15623804). Reduced
CC expression of homeobox protein Six3 at 8.0 dpc in the prospective
CC forebrain and impaired Shh expression at the ventral midline with
CC resulting midline formation defects and holoprosencephaly
CC (PubMed:22340494). At 9.5 dpc, loss of Shh in the ventral anterior
CC diencephalon and increased Bmp4 expression in the dorsal forebrain
CC (PubMed:22340494). Increased Bmp4 expression and impaired proliferation
CC of neural precursor cells in the subependymal zone of the brain which
CC results in decreased numbers of neuroblasts reaching the olfactory bulb
CC (PubMed:20460439). Compound heterozygotes display enlarged and
CC exophthalmic eyes with thinning of the retina (PubMed:26439398). Severe
CC cardiovascular abnormalities including aortic arch anomalies,
CC persistent truncus arteriosus with coronary artery anomalies,
CC ventricular septal defects, overriding of the tricuspid valve, marked
CC thinning of the ventricular myocardium, and abnormal positioning of the
CC neural crest cells and second heart field (PubMed:26822476). Impaired
CC endocytosis of folate bound to the folate receptor FOLR1, reduced
CC folate levels in embryos and impaired closure of the rostral neural
CC tube (PubMed:24639464). High lethality at and after birth with
CC survivors showing profound hearing loss, elevated lipofuscin granule
CC levels and irregular apical surfaces in marginal cells of the stria
CC vascularis, complete loss of potassium ion channel KCQN1 in basal and
CC midbasal cochlear turns, and reduced estrogen uptake in the stria
CC vascularis (PubMed:17846082). Survivors also display severe vitamin D
CC deficiency and bone formation defects (PubMed:10052453). Failure of the
CC vaginal cavity to open after birth in females and impaired testis
CC descent in males with the left testis poorly developed and severely
CC retarded in size (PubMed:16143106). Conditional knockout in the kidney
CC results in reduced expression of CUBN in kidney cells and little or no
CC uptake of myoglobin (PubMed:12724130). It also results in reduced
CC uptake of Cst3 by kidney proximal tubule cells (PubMed:17462596). In
CC addition, it causes pronounced urinary excretion of Apom,
CC Birc5/survivin, and Mmp2 together with Timp1 (PubMed:16099815,
CC PubMed:23825075, PubMed:28659595). {ECO:0000269|PubMed:10052453,
CC ECO:0000269|PubMed:12724130, ECO:0000269|PubMed:15623804,
CC ECO:0000269|PubMed:16099815, ECO:0000269|PubMed:16143106,
CC ECO:0000269|PubMed:17462596, ECO:0000269|PubMed:17846082,
CC ECO:0000269|PubMed:20460439, ECO:0000269|PubMed:22340494,
CC ECO:0000269|PubMed:23825075, ECO:0000269|PubMed:24639464,
CC ECO:0000269|PubMed:26439398, ECO:0000269|PubMed:26822476,
CC ECO:0000269|PubMed:28659595}.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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DR EMBL; AL845489; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK166702; BAE38957.1; -; mRNA.
DR EMBL; Y08566; CAA69877.1; -; mRNA.
DR EMBL; AF197160; AAF61488.1; -; mRNA.
DR CCDS; CCDS38135.1; -.
DR RefSeq; NP_001074557.1; NM_001081088.1.
DR SMR; A2ARV4; -.
DR BioGRID; 200005; 8.
DR CORUM; A2ARV4; -.
DR IntAct; A2ARV4; 9.
DR STRING; 10090.ENSMUSP00000079752; -.
DR TCDB; 9.B.87.1.1; the selenoprotein p receptor (selp-receptor) family.
DR GlyGen; A2ARV4; 43 sites.
DR iPTMnet; A2ARV4; -.
DR PhosphoSitePlus; A2ARV4; -.
DR jPOST; A2ARV4; -.
DR MaxQB; A2ARV4; -.
DR PaxDb; A2ARV4; -.
DR PeptideAtlas; A2ARV4; -.
DR PRIDE; A2ARV4; -.
DR ProteomicsDB; 252677; -.
DR Antibodypedia; 962; 370 antibodies from 35 providers.
DR Ensembl; ENSMUST00000080953; ENSMUSP00000079752; ENSMUSG00000027070.
DR GeneID; 14725; -.
DR KEGG; mmu:14725; -.
DR UCSC; uc008jyc.1; mouse.
DR CTD; 4036; -.
DR MGI; MGI:95794; Lrp2.
DR VEuPathDB; HostDB:ENSMUSG00000027070; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000157232; -.
DR HOGENOM; CLU_000085_1_1_1; -.
DR InParanoid; A2ARV4; -.
DR OrthoDB; 1606at2759; -.
DR PhylomeDB; A2ARV4; -.
DR TreeFam; TF315253; -.
DR BioGRID-ORCS; 14725; 4 hits in 71 CRISPR screens.
DR ChiTaRS; Lrp2; mouse.
DR PRO; PR:A2ARV4; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; A2ARV4; protein.
DR Bgee; ENSMUSG00000027070; Expressed in vestibular membrane of cochlear duct and 138 other tissues.
DR ExpressionAtlas; A2ARV4; baseline and differential.
DR Genevisible; A2ARV4; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0044295; C:axonal growth cone; ISO:MGI.
DR GO; GO:0005903; C:brush border; IDA:MGI.
DR GO; GO:0031526; C:brush border membrane; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0030492; F:hemoglobin binding; ISO:MGI.
DR GO; GO:0042562; F:hormone binding; ISO:MGI.
DR GO; GO:0031994; F:insulin-like growth factor I binding; ISO:MGI.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:MGI.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0140318; F:protein transporter activity; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0097242; P:amyloid-beta clearance; ISO:MGI.
DR GO; GO:0035904; P:aorta development; IMP:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:MGI.
DR GO; GO:0061642; P:chemoattraction of axon; ISO:MGI.
DR GO; GO:0060982; P:coronary artery morphogenesis; IMP:UniProtKB.
DR GO; GO:0060976; P:coronary vasculature development; IMP:MGI.
DR GO; GO:0034311; P:diol metabolic process; IMP:MGI.
DR GO; GO:0020028; P:endocytic hemoglobin import into cell; ISO:MGI.
DR GO; GO:0006897; P:endocytosis; ISO:MGI.
DR GO; GO:0016197; P:endosomal transport; ISO:MGI.
DR GO; GO:1904447; P:folate import across plasma membrane; IMP:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0046879; P:hormone secretion; ISO:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:UniProtKB.
DR GO; GO:0030001; P:metal ion transport; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IMP:UniProtKB.
DR GO; GO:0140058; P:neuron projection arborization; IMP:UniProtKB.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:UniProtKB.
DR GO; GO:0045807; P:positive regulation of endocytosis; ISO:MGI.
DR GO; GO:0140077; P:positive regulation of lipoprotein transport; ISO:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; IMP:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IDA:ARUK-UCL.
DR GO; GO:0061156; P:pulmonary artery morphogenesis; IMP:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:UniProtKB.
DR GO; GO:0044321; P:response to leptin; IDA:ARUK-UCL.
DR GO; GO:0010165; P:response to X-ray; ISO:MGI.
DR GO; GO:0003139; P:secondary heart field specification; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB.
DR GO; GO:0045056; P:transcytosis; ISO:MGI.
DR GO; GO:0060068; P:vagina development; IMP:UniProtKB.
DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; IMP:UniProtKB.
DR GO; GO:0003281; P:ventricular septum development; IMP:MGI.
DR GO; GO:0042359; P:vitamin D metabolic process; IMP:MGI.
DR CDD; cd00112; LDLa; 36.
DR Gene3D; 2.120.10.30; -; 8.
DR Gene3D; 4.10.400.10; -; 36.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR026823; cEGF.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR Pfam; PF12662; cEGF; 2.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00057; Ldl_recept_a; 34.
DR Pfam; PF00058; Ldl_recept_b; 17.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 25.
DR SMART; SM00179; EGF_CA; 9.
DR SMART; SM00192; LDLa; 36.
DR SMART; SM00135; LY; 37.
DR SUPFAM; SSF57184; SSF57184; 2.
DR SUPFAM; SSF57424; SSF57424; 35.
DR PROSITE; PS00010; ASX_HYDROXYL; 4.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 8.
DR PROSITE; PS50026; EGF_3; 6.
DR PROSITE; PS01187; EGF_CA; 3.
DR PROSITE; PS01209; LDLRA_1; 31.
DR PROSITE; PS50068; LDLRA_2; 36.
DR PROSITE; PS51120; LDLRB; 36.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cell projection; Coated pit; Disulfide bond;
KW EGF-like domain; Endocytosis; Endosome; Glycoprotein; Hearing; Membrane;
KW Metal-binding; Neurogenesis; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; SH3-binding; Signal; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..4660
FT /note="Low-density lipoprotein receptor-related protein 2"
FT /id="PRO_0000309845"
FT TOPO_DOM 26..4425
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 4426..4446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 4447..4660
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..63
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 66..104
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 107..143
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 146..180
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 182..218
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 221..257
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 264..307
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT REPEAT 435..477
FT /note="LDL-receptor class B 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 478..520
FT /note="LDL-receptor class B 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 521..567
FT /note="LDL-receptor class B 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 568..612
FT /note="LDL-receptor class B 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 752..794
FT /note="LDL-receptor class B 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 795..836
FT /note="LDL-receptor class B 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 837..880
FT /note="LDL-receptor class B 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 881..924
FT /note="LDL-receptor class B 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 1024..1060
FT /note="LDL-receptor class A 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1065..1102
FT /note="LDL-receptor class A 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1109..1145
FT /note="LDL-receptor class A 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1149..1185
FT /note="LDL-receptor class A 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1187..1224
FT /note="LDL-receptor class A 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1230..1268
FT /note="LDL-receptor class A 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1271..1307
FT /note="LDL-receptor class A 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1312..1350
FT /note="LDL-receptor class A 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1350..1390
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1391..1430
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1479..1521
FT /note="LDL-receptor class B 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1522..1564
FT /note="LDL-receptor class B 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1567..1610
FT /note="LDL-receptor class B 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1611..1655
FT /note="LDL-receptor class B 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1656..1696
FT /note="LDL-receptor class B 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1791..1833
FT /note="LDL-receptor class B 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1834..1883
FT /note="LDL-receptor class B 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1884..1931
FT /note="LDL-receptor class B 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1932..1973
FT /note="LDL-receptor class B 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1974..2014
FT /note="LDL-receptor class B 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2108..2157
FT /note="LDL-receptor class B 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2158..2202
FT /note="LDL-receptor class B 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2203..2246
FT /note="LDL-receptor class B 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2247..2290
FT /note="LDL-receptor class B 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2291..2333
FT /note="LDL-receptor class B 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2432..2478
FT /note="LDL-receptor class B 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2479..2519
FT /note="LDL-receptor class B 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2520..2563
FT /note="LDL-receptor class B 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2564..2605
FT /note="LDL-receptor class B 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2606..2647
FT /note="LDL-receptor class B 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 2700..2738
FT /note="LDL-receptor class A 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2741..2777
FT /note="LDL-receptor class A 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2780..2819
FT /note="LDL-receptor class A 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2822..2861
FT /note="LDL-receptor class A 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2864..2902
FT /note="LDL-receptor class A 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2907..2946
FT /note="LDL-receptor class A 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2949..2991
FT /note="LDL-receptor class A 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2994..3030
FT /note="LDL-receptor class A 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3033..3071
FT /note="LDL-receptor class A 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3076..3112
FT /note="LDL-receptor class A 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3112..3153
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 3154..3194
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 3241..3283
FT /note="LDL-receptor class B 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3284..3326
FT /note="LDL-receptor class B 30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3335..3378
FT /note="LDL-receptor class B 31"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3379..3421
FT /note="LDL-receptor class B 32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3422..3462
FT /note="LDL-receptor class B 33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 3513..3551
FT /note="LDL-receptor class A 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3554..3592
FT /note="LDL-receptor class A 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3595..3633
FT /note="LDL-receptor class A 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3636..3674
FT /note="LDL-receptor class A 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3679..3717
FT /note="LDL-receptor class A 30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3720..3757
FT /note="LDL-receptor class A 31"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3760..3796
FT /note="LDL-receptor class A 32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3799..3835
FT /note="LDL-receptor class A 33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3843..3881
FT /note="LDL-receptor class A 34"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3884..3923
FT /note="LDL-receptor class A 35"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3929..3965
FT /note="LDL-receptor class A 36"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 4009..4050
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 4156..4198
FT /note="LDL-receptor class B 34"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 4199..4242
FT /note="LDL-receptor class B 35"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 4244..4285
FT /note="LDL-receptor class B 36"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 4379..4413
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 4558..4660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4597..4610
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000250|UniProtKB:P98164"
FT MOTIF 4454..4463
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 4457..4462
FT /note="PxLPxI/L motif 1; mediates interaction with ANKRA2"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOTIF 4460..4465
FT /note="PxLPxI/L motif 2; mediates interaction with ANKRA2"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOTIF 4522..4527
FT /note="Endocytosis signal"
FT /evidence="ECO:0000255"
FT MOTIF 4603..4606
FT /note="NPXY motif"
FT MOTIF 4606..4609
FT /note="SH2-binding"
FT /evidence="ECO:0000255"
FT MOTIF 4619..4630
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 4590..4606
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4629..4648
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98164"
FT BINDING 1130
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98164"
FT BINDING 1132
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98164"
FT BINDING 1134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98164"
FT BINDING 1140
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98164"
FT BINDING 1141
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98164"
FT BINDING 1206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1211
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1213
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1220
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOD_RES 4464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 4467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 4577
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 4624
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOD_RES 4637
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 4658
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 462
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 657
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 865
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1063
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1551
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1676
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1733
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1811
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2225
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2548
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2782
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2810
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2949
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2989
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3213
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3448
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3682
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3840
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3969
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3980
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4070
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..40
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 35..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 47..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 67..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 74..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 87..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 108..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 115..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 127..142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 147..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 152..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 164..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 183..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 190..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 202..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 222..234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 229..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 241..256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 265..278
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 272..291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 285..306
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1025..1037
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1032..1050
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1044..1059
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1066..1079
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1073..1092
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1086..1101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1110..1122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1117..1135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1129..1144
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1150..1162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1157..1175
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1169..1184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1188..1201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1195..1214
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1208..1223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1231..1244
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1238..1257
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1251..1267
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1272..1284
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1279..1297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1291..1306
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1313..1326
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1320..1339
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1333..1349
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1354..1365
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1361..1374
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1376..1389
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1395..1405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1401..1414
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1416..1429
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2701..2713
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2708..2726
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2720..2737
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2742..2754
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2749..2767
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2761..2776
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2781..2794
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2789..2807
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2801..2818
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2823..2836
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2830..2849
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2843..2860
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2865..2878
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2872..2891
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2885..2901
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2908..2920
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2915..2933
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2927..2945
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2950..2967
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2957..2980
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2974..2990
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2995..3007
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3002..3020
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3014..3029
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3034..3046
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3041..3059
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3053..3070
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3077..3089
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3084..3102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3096..3111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3116..3128
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3124..3137
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3139..3152
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3158..3169
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3165..3178
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3180..3193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3514..3527
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3521..3540
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3534..3550
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3555..3567
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3562..3580
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3574..3591
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3596..3608
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3603..3621
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3615..3632
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3637..3649
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3644..3662
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3656..3673
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3680..3694
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3688..3707
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3701..3716
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3721..3734
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3729..3747
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3741..3756
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3761..3773
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3768..3786
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3780..3795
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3800..3812
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3807..3825
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3819..3834
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3844..3856
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3851..3869
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3863..3880
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3885..3898
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3893..3911
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3905..3922
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3930..3942
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3937..3955
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3949..3964
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 4013..4023
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4019..4032
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4034..4049
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4383..4391
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4385..4401
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4403..4412
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CONFLICT 4198
FT /note="L -> F (in Ref. 3; CAA69877)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 4660 AA; 519208 MW; 4CF399C24DF2FAA4 CRC64;
MERGAAAAAW MLLLAIAACL APVSGQECGS GNFRCDNGYC IPASWRCDGT RDCLDDTDEI
GCPPRSCGSG FFLCPAEGTC IPSSWVCDQD KDCSDGADEQ QNCPGTTCSS QQLTCSNGQC
VPIEYRCDHV SDCPDGSDER NCYYPTCDQL TCANGACYNT SQKCDHKVDC RDSSDEANCT
TLCSQKEFQC GSGECILRAY VCDHDNDCED NSDEHNCNYD TCGGHQFTCS NGQCINQNWV
CDGDDDCQDS GDEDGCESNQ RHHTCYPREW ACPGSGRCIS MDKVCDGVPD CPEGEDENNA
TSGRYCGTGL CSILNCEYQC HQTPYGGECF CPPGHIINSN DSRTCIDFDD CQIWGICDQK
CESRQGRHQC LCEEGYILER GQHCKSNDSF SAASIIFSNG RDLLVGDLHG RNFRILAESK
NRGIVMGVDF HYQKHRVFWT DPMQAKVFST DINGLNTQEI LNVSIDAPEN LAVDWINNKL
YLVETRVNRI DVVNLEGNQR VTLITENLGH PRGIALDPTV GYLFFSDWGS LSGQPKVERA
FMDGSNRKDL VTTKLGWPAG ITLDLVSKRV YWVDSRYDYI ETVTYDGIQR KTVARGGSLV
PHPFGISLFE EHVFFTDWTK MAVMKANKFT DTNPQVYHQS SLTPFGVTVY HALRQPNATN
PCGNNNGGCA QICVLSHRTD NGGLGYRCKC EFGFELDADE HHCVAVKNFL LFSSQTAVRG
IPFTLSTQED VMVPVTGSPS FFVGIDFDAQ HSTIFYSDLS KNIIYQQKID GTGKEVITAN
RLQNVECLSF DWISRNLYWT DGGSKSVTVM KLADKSRRQI ISNLNNPRSI VVHPAAGYMF
LSDWFRPAKI MRAWSDGSHL MPIVNTSLGW PNGLAIDWST SRLYWVDAFF DKIEHSNLDG
LDRKRLGHVD QMTHPFGLTV FKDNVFLTDW RLGAIIRVRK SDGGDMTVVR RGISSIMHVK
AYDADLQTGT NYCSQTTHPN GDCSHFCFPV PNFQRVCGCP YGMKLQRDQM TCEGDPAREP
PTQQCGSSSF PCNNGKCVPS IFRCDGVDDC HDNSDEHQCG ALNNTCSSSA FTCVHGGQCI
PGQWRCDKQN DCLDGSDEQN CPTRSPSSTC PPTSFTCDNH MCIPKEWVCD TDNDCSDGSD
EKNCQASGTC HPTQFRCPDH RCISPLYVCD GDKDCVDGSD EAGCVLNCTS SQFKCADGSS
CINSRYRCDG VYDCKDNSDE AGCPTRPPGM CHPDEFQCQG DGTCIPNTWE CDGHPDCIQG
SDEHNGCVPK TCSPSHFLCD NGNCIYNSWV CDGDNDCRDM SDEKDCPTQP FHCPSSQWQC
PGYSICVNLS ALCDGVFDCP NGTDESPLCN QDSCLHFNGG CTHRCIQGPF GATCVCPIGY
QLANDTKTCE DVNECDIPGF CSQHCVNMRG SFRCACDPEY TLESDGRTCK VTASENLLLV
VASRDKIIMD NITAHTHNIY SLVQDVSFVV ALDFDSVTGR VFWSDLLEGK TWSAFQNGTD
KRVVHDSGLS LTEMIAVDWI GRNIYWTDYT LETIEVSKID GSHRTVLISK NVTKPRGLAL
DPRMGDNVMF WSDWGHHPRI ERASMDGTMR TVIVQEKIYW PCGLSIDYPN RLIYFMDAYL
DYIEFCDYDG QNRRQVIASD LVLHHPHALT LFEDSVFWTD RGTHQVMQAN KWHGRNQSVV
MYSVPQPLGI IAIHPSRQPS SPNPCASATC SHLCLLSAQE PRHYSCACPS GWNLSDDSVN
CVRGDQPFLI SVRENVIFGI SLDPEVKSND AMVPISGIQH GYDVEFDDSE QFIYWVENPG
EIHRVKTDGS NRTAFAPLSL LGSSLGLALD WVSRNIYYTT PASRSIEVLT LRGDTRYGKT
LITNDGTPLG VGFPVGIAVD PARGKLYWSD HGTDSGVPAK IASANMDGTS LKILFTGNME
HLEVVTLDIQ EQKLYWAVTS RGVIERGNVD GTERMILVHH LAHPWGLVVH GSFLYYSDEQ
YEVIERVDKS SGSNKVVFRD NIPYLRGLRV YHHRNAADSS NGCSNNPNAC QQICLPVPGG
MFSCACASGF KLSPDGRSCS PYNSFIVVSM LPAVRGFSLE LSDHSEAMVP VAGQGRNVLH
ADVDVANGFI YWCDFSSSVR SSNGIRRIKP NGSNFTNIVT YGIGANGIRG VAVDWVAGNL
YFTNAFVYET LIEVIRINTT YRRVLLKVSV DMPRHIVVDP KHRYLFWADY GQKPKIERSF
LDCTNRTVLV SEGIVTPRGL AVDHDTGYIY WVDDSLDIIA RIHRDGGESQ VVRYGSRYPT
PYGITVFGES IIWVDRNLRK VFQASKQPGN TDPPTVIRDS INLLRDVTIF DEHVQPLSPA
ELNNNPCLQS NGGCSHFCFA LPELPTPKCG CAFGTLEDDG KNCATSREDF LIYSLNNSLR
SLHFDPQDHN LPFQAISVEG MAIALDYDRR NNRIFFTQKL NPIRGQISYV NLYSGASSPT
ILLSNIGVTD GIAFDWINRR IYYSDFSNQT INSMAEDGSN RAVIARVSKP RAIVLDPCRG
YMYWTDWGTN AKIERATLGG NFRVPIVNTS LVWPNGLTLD LETDLLYWAD ASLQKIERST
LTGSNREVVI STAFHSFGLT VYGQYIYWTD FYTKKIYRAN KYDGSDLIAM TTRLPTQPSG
ISTVVKTQQQ QCSNPCDQFN GGCSHICAPG PNGAECQCPH EGSWYLANDN KYCVVDTGAR
CNQFQFTCLN GRCISQDWKC DNDNDCGDGS DELPTVCAFH TCRSTAFTCA NGRCVPYHYR
CDFYNDCGDN SDEAGCLFRS CNSTTEFTCS NGRCIPLSYV CNGINNCHDN DTSDEKNCPP
ITCQPDFAKC QTTNICVPRA FLCDGDNDCG DGSDENPIYC ASHTCRSNEF QCVSPHRCIP
SYWFCDGEAD CVDSSDEPDT CGHSLNSCSA NQFHCDNGRC ISSSWVCDGD NDCGDMSDED
QRHHCELQNC SSTEFTCINS RPPNRRCIPQ HWVCDGDADC ADALDELQNC TMRACSTGEF
SCANGRCIRQ SFRCDRRNDC GDYSDERGCS YPPCRDDQFT CQNGQCITKL YVCDEDNDCG
DGSDEQEHLC HTPEPTCPPH QFRCDNGHCI EMGTVCNHVD DCSDNSDEKG CGINECQDSS
ISHCDHNCTD TITSFYCSCL PGYKLMSDKR TCVDIDECKE TPQLCSQKCE NVIGSYICKC
APGYIREPDG KSCRQNSNIE PYLVFSNRYY IRNLTIDGTS YSLILQGLGN VVALDFDRVE
ERLYWIDAEK QIIERMFLNK TNQETIISHR LRRAESLAVD WVSRKLYWLD AILDCLFVSD
LEGRQRKMLA QHCVDANNTF CFENPRGIVL HPQRGYVYWA DWGDHAYIAR IGMDGTNKTV
IISTKIEWPN AITIDYTNDL LYWADAHLGY IEFSDLEGHH RHTVYDGTLP HPFALTIFED
TVFWTDWNTR TVEKGNKYDG SGRVVLVNTT HKPFDIHVLH PYRQPIMSNP CATNNGGCSH
LCLIKAGGRG FTCECPDDFQ TVQLRDRTLC MPMCSSTQFL CGNNEKCIPI WWKCDGQKDC
SDGSDESDLC PHRFCRLGQF QCRDGNCTSP QALCNARQDC ADGSDEDRVL CEHHRCEANE
WQCANKRCIP EYWQCDSVDD CLDNSDEDPS HCASRTCRPG QFKCNNGRCI PQSWKCDVDN
DCGDYSDEPI HECMTAAYNC DNHTEFSCKT NYRCIPQWAV CNGFDDCRDN SDEQGCESVP
CHPSGDFRCG NHHCIPLRWK CDGIDDCGDN SDEESCVPRE CTESEFRCAD QQCIPSRWVC
DQENDCGDNS DERDCEMKTC HPEHFQCTSG HCVPKALACD GRADCLDASD ESACPTRFPN
GTYCPAAMFE CKNHVCIQSF WICDGENDCV DGSDEEIHLC FNVPCESPQR FRCDNSRCIY
GHQLCNGVDD CGDGSDEKEE HCRKPTHKPC TDTEYKCSNG NCVSQHYVCD NVDDCGDLSD
ETGCNLGENR TCAEKICEQN CTQLSNGGFI CSCRPGFKPS TLDKNSCQDI NECEEFGICP
QSCRNSKGSY ECFCVDGFKS MSTHYGERCA ADGSPPLLLL PENVRIRKYN ISSEKFSEYL
EEEEHIQAID YDWDPEGIGL SVVYYTVLSQ GSQFGAIKRA YLPDFESGSN NPVREVDLGL
KYLMQPDGLA VDWVGRHIYW SDAKSQRIEV ATLDGRYRKW LITTQLDQPA AIAVNPKLGL
MFWTDQGKQP KIESAWMNGE HRSVLASANL GWPNGLSIDY LNGDRIYWSD SKEDVIESIK
YDGTDRRLII NDAMKPFSLD IFEDQLYWVA KEKGEVWRQN KFGKGNKEKL LVVNPWLTQV
RIFHQLRYNQ SVSNPCKQVC SHLCLLRPGG YSCACPQGSD FVTGSTVECD AASELPITMP
SPCRCMHGGS CYFDENDLPK CKCSSGYSGE YCEIGLSRGI PPGTTMALLL TFAMVIIVGA
LVLVGFFHYR KTGSLLPSLP KLPSLSSLAK PSENGNGVTF RSGADVNMDI GVSPFGPETI
IDRSMAMNEQ FVMEVGKQPV IFENPMYAAK DSTSKVGLAV QGPSVSSQVT VPENVENQNY
GRSIDPSEIV PEPKPASPGA DETQGTKWNI FKRKPKQTTN FENPIYAEMD TEQKEAVAVA
PPPSPSLPAK ASKRSSTPGY TATEDTFKDT ANLVKEDSDV
