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Database: UniProt
Entry: A2ARV4
LinkDB: A2ARV4
Original site: A2ARV4 
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   31-JUL-2019, entry version 121.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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.,
RA   She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA   Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA   Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA   Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA   Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of
RT   the 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.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   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.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   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;
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.,
RA   Muramatsu T.;
RT   "LDL receptor-related protein as a component of the midkine
RT   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
RT   interacts 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
RT   megalin 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.,
RA   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
RP   STAGE, 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.,
RA   Schulz H., Metzger J., Schweigert F.J., Luppa P.B., Nykjaer A.,
RA   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
RT   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.,
RA   Baker C.B., 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
RT   megalin-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
RT   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-
RT   linked cell surface glycoproteins.";
RL   Nat. Biotechnol. 27:378-386(2009).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4464; SER-4467;
RP   SER-4577; THR-4637 AND SER-4658, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE 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
RT   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.,
RA   Christensen E.I., Goetz M., Kempermann G., Peterson A.S.,
RA   Willnow T.E., Hammes A.;
RT   "LRP2 in ependymal cells regulates BMP signaling in the adult
RT   neurogenic niche.";
RL   J. Cell Sci. 123:1922-1930(2010).
RN   [21]
RP   FUNCTION, INTERACTION WITH APPB1 AND APP, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=20637285; DOI=10.1016/j.mcn.2010.07.005;
RA   Alvira-Botero X., Perez-Gonzalez R., Spuch C., Vargas T.,
RA   Antequera D., Garzon M., Bermejo-Pareja F., Carro E.;
RT   "Megalin interacts with APP and the intracellular adapter protein FE65
RT   in 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.,
RA   Szanda G., Mukhopadhyay B., Chedester L., Liow J.S., Innis R.B.,
RA   Cheng K., Rice K.C., Deschamps J.R., Chorvat R.J., McElroy J.F.,
RA   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.,
RA   Willnow T.E., 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.,
RA   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.,
RA   Buettner-Herold M., Lechler P., Kroening S., Goppelt-Struebe M.,
RA   Schloetzer-Schrehardt U., Fuernrohr B.G., Voll R.E., Amann K.,
RA   Eckardt K.U., Christensen E.I., Wiesener M.S.;
RT   "Renal uptake of the antiapoptotic protein survivin is mediated by
RT   megalin 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.,
RA   Kang G.M., Kim H.K., Lee B., Kim Y.B., Kim M.S.;
RT   "Clusterin/ApoJ enhances central leptin signaling through Lrp2-
RT   mediated 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.,
RA   Wallace V.A., Hammes A., Willnow T.E.;
RT   "LRP2 acts as SHH clearance receptor to protect the retinal margin
RT   from 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
RT   mice 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.,
RA   Nielsen R., Christensen E.I., Courtoy P.J., Emonard H., Marbaix E.,
RA   Henriet P.;
RT   "Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic
RT   receptor megalin/LRP-2.";
RL   Sci. Rep. 7:4328-4328(2017).
CC   -!- FUNCTION: Multiligand endocytic receptor. Acts together with CUBN
CC       to mediate endocytosis of high-density lipoproteins
CC       (PubMed:10766831). Mediates receptor-mediated uptake of polybasic
CC       drugs such as aprotinin, aminoglycosides and polymyxin B (By
CC       similarity). In the kidney, mediates the tubular uptake and
CC       clearance of leptin (PubMed:22841573). Also mediates transport of
CC       leptin across the blood-brain barrier through endocytosis at the
CC       choroid plexus epithelium (By similarity). Endocytosis of leptin
CC       in neuronal cells is required for hypothalamic leptin signaling
CC       and leptin-mediated regulation of feeding and body weight
CC       (PubMed:24825475). Mediates endocytosis and subsequent lysosomal
CC       degradation of CST3 in kidney proximal tubule cells
CC       (PubMed:17462596). Mediates renal uptake of 25-hydroxyvitamin D3
CC       in complex with the vitamin D3 transporter GC/DBP
CC       (PubMed:10052453). Mediates renal uptake of metallothionein-bound
CC       heavy metals (By similarity). Together with CUBN, mediates renal
CC       reabsorption of myoglobin (By similarity). Mediates renal uptake
CC       and subsequent lysosomal degradation of APOM (By similarity).
CC       Plays a role in kidney selenium homeostasis by mediating renal
CC       endocytosis of selenoprotein SEPP1 (PubMed:18174160). Mediates
CC       renal uptake of the antiapoptotic protein BIRC5/survivin which may
CC       be important for functional integrity of the kidney
CC       (PubMed:23825075). Mediates renal uptake of matrix
CC       metalloproteinase MMP2 in complex with metalloproteinase inhibitor
CC       TIMP1 (PubMed:28659595). Mediates endocytosis of Sonic hedgehog
CC       protein N-product (ShhN), the active product of SHH (By
CC       similarity). Also mediates ShhN transcytosis (By similarity). In
CC       the embryonic neuroepithelium, mediates endocytic uptake and
CC       degradation of BMP4, is required for correct SHH localization in
CC       the ventral neural tube and plays a role in patterning of the
CC       ventral telencephalon (PubMed:15623804). Required at the onset of
CC       neurulation to sequester SHH on the apical surface of
CC       neuroepithelial cells of the rostral diencephalon ventral midline
CC       and to control PTCH1-dependent uptake and intracellular
CC       trafficking of SHH (PubMed:22340494). During neurulation, required
CC       in neuroepithelial cells for uptake of folate bound to the folate
CC       receptor FOLR1 which is necessary for neural tube closure
CC       (PubMed:24639464). In the adult brain, negatively regulates BMP
CC       signaling in the subependymal zone which enables neurogenesis to
CC       proceed (PubMed:20460439). In astrocytes, mediates endocytosis of
CC       ALB which is required for the synthesis of the neurotrophic factor
CC       oleic acid (By similarity). Involved in neurite branching
CC       (PubMed:20637285). During optic nerve development, required for
CC       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
CC       by mediating uptake in reproductive tissues of androgen and
CC       estrogen bound to the sex hormone binding protein SHBG
CC       (PubMed:16143106). Mediates endocytosis of angiotensin-2 (By
CC       similarity). Also mediates endocytosis of angiotensin 1-7 (By
CC       similarity). Binds to the complex composed of beta-amyloid protein
CC       40 and CLU/APOJ and mediates its endocytosis and lysosomal
CC       degradation (By similarity). Required for embryonic heart
CC       development (PubMed:26822476). Required for normal hearing,
CC       possibly through interaction with estrogen in the inner ear
CC       (PubMed:17846082). {ECO:0000250|UniProtKB:C0HL13,
CC       ECO:0000250|UniProtKB:P98158, ECO:0000250|UniProtKB:P98164,
CC       ECO:0000269|PubMed:10052453, ECO:0000269|PubMed:10766831,
CC       ECO:0000269|PubMed:15623804, ECO:0000269|PubMed:16143106,
CC       ECO:0000269|PubMed:16380466, ECO:0000269|PubMed:17462596,
CC       ECO:0000269|PubMed:17846082, ECO:0000269|PubMed:18174160,
CC       ECO:0000269|PubMed:20460439, ECO:0000269|PubMed:20637285,
CC       ECO:0000269|PubMed:22340494, ECO:0000269|PubMed:22354480,
CC       ECO:0000269|PubMed:22841573, ECO:0000269|PubMed:23825075,
CC       ECO:0000269|PubMed:24639464, ECO:0000269|PubMed:24825475,
CC       ECO:0000269|PubMed:26439398, ECO:0000269|PubMed:26822476,
CC       ECO:0000269|PubMed:28659595}.
CC   -!- SUBUNIT: Binds plasminogen, extracellular matrix components,
CC       plasminogen activator-plasminogen activator inhibitor type I
CC       complex, apolipoprotein E-enriched beta-VLDL, lipoprotein lipase,
CC       lactoferrin, CLU/clusterin and calcium. Forms a multimeric complex
CC       together with LRPAP1 (By similarity). Interacts (via PxLPxI/L
CC       motif) with ANKRA2 (via ankyrin repeats) (By similarity).
CC       Interacts with LRP2BP. Interacts (via NPXY motif) with DAB2; the
CC       interaction is not affected by tyrosine phosphorylation of the
CC       NPXY motif (PubMed:11247302). Interacts with MB (By similarity).
CC       Interacts with BMP4 (PubMed:15623804). Interacts with the Sonic
CC       hedgehog protein N-product which is the active product of SHH
CC       (PubMed:11964399). Interacts with CST3 in a calcium-dependent
CC       manner (By similarity). Interacts with the vitamin-D binding
CC       protein GC/DBP (PubMed:10052453). Interacts with sex hormone-
CC       binding protein SHBG (By similarity). Interacts with angiotensin-2
CC       (PubMed:15467006). Also interacts with angiotensin 1-7
CC       (PubMed:16380466). Interacts with APOM (PubMed:16099815).
CC       Interacts with selenoprotein SEPP1 (PubMed:18174160). Interacts
CC       with LEP (By similarity). Interacts with ALB (By similarity).
CC       Interacts with the antiapoptotic protein BIRC5/survivin (By
CC       similarity). Interacts with matrix metalloproteinase MMP2 in
CC       complex with metalloproteinase inhibitor TIMP1 (By similarity). In
CC       neurons, forms a trimeric complex with APP and APPB1/FE65
CC       (PubMed:20637285). Interacts with LDLRAP1/ARH; mediates
CC       trafficking of LRP2 to the endocytic recycling compartment (By
CC       similarity). Does not interact with beta-amyloid protein 40 alone
CC       but interacts with the complex composed of beta-amyloid protein 40
CC       and CLU/APOJ (By similarity). Interacts with MDK
CC       (PubMed:10772929). {ECO:0000250|UniProtKB:C0HL13,
CC       ECO:0000250|UniProtKB:P98158, ECO:0000250|UniProtKB:P98164,
CC       ECO:0000269|PubMed:10052453, ECO:0000269|PubMed:10772929,
CC       ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:11964399,
CC       ECO:0000269|PubMed:15467006, ECO:0000269|PubMed:15623804,
CC       ECO:0000269|PubMed:16099815, ECO:0000269|PubMed:16380466,
CC       ECO:0000269|PubMed:18174160, ECO:0000269|PubMed:20637285}.
CC   -!- INTERACTION:
CC       P97318:Dab1; NbExp=2; IntAct=EBI-300875, EBI-81680;
CC       Q62108:Dlg4; NbExp=2; IntAct=EBI-300875, EBI-300895;
CC       Q9Z0G0:Gipc1; NbExp=2; IntAct=EBI-300875, EBI-300855;
CC       Q9WVI9:Mapk8ip1; NbExp=2; IntAct=EBI-300875, EBI-74515;
CC       Q9ERE9:Mapk8ip2; NbExp=2; IntAct=EBI-300875, EBI-74576;
CC       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-
CC       pass 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
CC       membranes in the kidney. In the endolymphatic sac of the inner
CC       ear, located in 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
CC       the luminal side of the uterine epithelium (at protein level)
CC       (PubMed:16143106). In the adult brain, expressed in ependymal
CC       cells of the lateral ventricles where expression is restricted to
CC       the ependyma that faces the stem cell niche (at protein level)
CC       (PubMed:20460439). Expressed in neurons throughout the brain
CC       including in the hippocampus, limbic cortices and cerebellum (at
CC       protein level) (PubMed:20637285). In the developing optic nerve,
CC       expressed exclusively in astrocytes at 14.5 dpc, 16.5 dpc and 18.5
CC       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
CC       level) (PubMed:22354480). In the embryo, expression is detected
CC       from 7.5 dpc on the apical side of the developing neural plate and
CC       persists throughout later stages of development (PubMed:22340494).
CC       After neural tube closure at 9.5 dpc, becomes progressively
CC       restricted to the midline region (PubMed:22340494). During the
CC       estrus cycle, expression is highest in metestrus II and diestrus
CC       (PubMed:16143106). {ECO:0000269|PubMed:16143106,
CC       ECO:0000269|PubMed:22340494, 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
CC       apical cell membrane. {ECO:0000250|UniProtKB:P98158}.
CC   -!- PTM: A fraction undergoes proteolytic cleavage of the
CC       extracellular domain at the cell membrane to generate a
CC       cytoplasmic tail fragment. This is internalized into the early
CC       endosome from where it trafficks in an LDLRAP1/ARH-dependent
CC       manner to the endocytic recycling compartment (ERC). In the ERC,
CC       it is further cleaved by gamma-secretase to release a fragment
CC       which translocates to the nucleus and mediates transcriptional
CC       repression. {ECO:0000250|UniProtKB:P98158}.
CC   -!- PTM: N-glycosylation is required for ligand binding. Contains
CC       core-fucosylated N-glycans in kidney proximal convoluted tubules
CC       (PCTs) and hybrid-type N-glycans in proximal straight tubules
CC       (PSTs). Interacts with ligands in a glycoform-dependent manner.
CC       Retinol-binding protein and the vitamin D carrier GC/DBP are
CC       endocytosed primarily by PCTs, albumin is endocytosed equally by
CC       PCTs and PSTs, and the aminoglycoside kanamycin is endocytosed
CC       primarily by PSTs. {ECO:0000269|PubMed:27773703}.
CC   -!- DISRUPTION PHENOTYPE: Severe facial dysgenesis and impaired
CC       forebrain development around mid-gestation, absence of Shh
CC       expression and decreased cell proliferation in the ventral neural
CC       tube, and aberrant expression of morphogens Fgf8 and Bmp4
CC       (PubMed:15623804). Reduced expression of homeobox protein Six3 at
CC       8.0 dpc in the prospective forebrain and impaired Shh expression
CC       at the ventral midline with resulting midline formation defects
CC       and holoprosencephaly (PubMed:22340494). At 9.5 dpc, loss of Shh
CC       in the ventral anterior diencephalon and increased Bmp4 expression
CC       in the dorsal forebrain (PubMed:22340494). Increased Bmp4
CC       expression and impaired proliferation of neural precursor cells in
CC       the subependymal zone of the brain which results in decreased
CC       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).
CC       Severe cardiovascular abnormalities including aortic arch
CC       anomalies, persistent truncus arteriosus with coronary artery
CC       anomalies, ventricular septal defects, overriding of the tricuspid
CC       valve, marked thinning of the ventricular myocardium, and abnormal
CC       positioning of the neural crest cells and second heart field
CC       (PubMed:26822476). Impaired endocytosis of folate bound to the
CC       folate receptor FOLR1, reduced folate levels in embryos and
CC       impaired closure of the rostral neural tube (PubMed:24639464).
CC       High lethality at and after birth with survivors showing profound
CC       hearing loss, elevated lipofuscin granule levels and irregular
CC       apical surfaces in marginal cells of the stria vascularis,
CC       complete loss of potassium ion channel KCQN1 in basal and midbasal
CC       cochlear turns, and reduced estrogen uptake in the stria
CC       vascularis (PubMed:17846082). Survivors also display severe
CC       vitamin D deficiency and bone formation defects (PubMed:10052453).
CC       Failure of the vaginal cavity to open after birth in females and
CC       impaired testis descent in males with the left testis poorly
CC       developed and severely retarded in size (PubMed:16143106).
CC       Conditional knockout in the kidney results in reduced expression
CC       of CUBN in kidney cells and little or no uptake of myoglobin
CC       (PubMed:12724130). It also results in reduced uptake of Cst3 by
CC       kidney proximal tubule cells (PubMed:17462596). In addition, it
CC       causes pronounced urinary excretion of Apom, Birc5/survivin, and
CC       Mmp2 together with Timp1 (PubMed:16099815, PubMed:23825075,
CC       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}.
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; 5.
DR   CORUM; A2ARV4; -.
DR   IntAct; A2ARV4; 11.
DR   MINT; A2ARV4; -.
DR   STRING; 10090.ENSMUSP00000079752; -.
DR   TCDB; 9.B.87.1.1; the selenoprotein p receptor (selp-receptor) family.
DR   iPTMnet; A2ARV4; -.
DR   PhosphoSitePlus; A2ARV4; -.
DR   jPOST; A2ARV4; -.
DR   MaxQB; A2ARV4; -.
DR   PaxDb; A2ARV4; -.
DR   PeptideAtlas; A2ARV4; -.
DR   PRIDE; A2ARV4; -.
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   eggNOG; KOG1215; Eukaryota.
DR   eggNOG; ENOG410XP34; LUCA.
DR   GeneTree; ENSGT00940000157232; -.
DR   HOGENOM; HOG000230574; -.
DR   InParanoid; A2ARV4; -.
DR   KO; K06233; -.
DR   OrthoDB; 1606at2759; -.
DR   PhylomeDB; A2ARV4; -.
DR   TreeFam; TF315253; -.
DR   Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-MMU-975634; Retinoid metabolism and transport.
DR   PRO; PR:A2ARV4; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   Bgee; ENSMUSG00000027070; Expressed in 154 organ(s), highest expression level in kidney.
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:0032991; C:protein-containing complex; ISO:MGI.
DR   GO; GO:0043235; C:receptor complex; ISO:MGI.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR   GO; GO:0008144; F:drug binding; ISS:UniProtKB.
DR   GO; GO:0030492; F:hemoglobin binding; ISO:MGI.
DR   GO; GO:0042562; F:hormone binding; ISO:MGI.
DR   GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:MGI.
DR   GO; GO:0030165; F:PDZ domain binding; 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:0035258; F:steroid hormone receptor binding; ISO:MGI.
DR   GO; GO:0035904; P:aorta development; IMP:MGI.
DR   GO; GO:0008283; P:cell population proliferation; IMP: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:0020028; P:endocytic hemoglobin import; 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: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; IEA:Ensembl.
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; IEA:Ensembl.
DR   GO; GO:0061156; P:pulmonary artery morphogenesis; IMP:UniProtKB.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; IDA:UniProtKB.
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:0006766; P:vitamin 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; IPR013032; EGF-like_CS.
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;
KW   Complete proteome; Disulfide bond; EGF-like domain; Endocytosis;
KW   Endosome; Glycoprotein; Hearing; Membrane; Metal-binding;
KW   Neurogenesis; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW   SH3-binding; Signal; Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL        1     25       {ECO:0000255}.
FT   CHAIN        26   4660       Low-density lipoprotein receptor-related
FT                                protein 2.
FT                                /FTId=PRO_0000309845.
FT   TOPO_DOM     26   4425       Extracellular. {ECO:0000255}.
FT   TRANSMEM   4426   4446       Helical. {ECO:0000255}.
FT   TOPO_DOM   4447   4660       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       27     63       LDL-receptor class A 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN       66    104       LDL-receptor class A 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      107    143       LDL-receptor class A 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      146    180       LDL-receptor class A 4.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      182    218       LDL-receptor class A 5.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      221    257       LDL-receptor class A 6.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      264    307       LDL-receptor class A 7.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   REPEAT      435    477       LDL-receptor class B 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      478    520       LDL-receptor class B 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      521    567       LDL-receptor class B 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      568    612       LDL-receptor class B 4.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      752    794       LDL-receptor class B 5.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      795    836       LDL-receptor class B 6.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      837    880       LDL-receptor class B 7.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT      881    924       LDL-receptor class B 8.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   DOMAIN     1024   1060       LDL-receptor class A 8.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1065   1102       LDL-receptor class A 9.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1109   1145       LDL-receptor class A 10.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1149   1185       LDL-receptor class A 11.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1187   1224       LDL-receptor class A 12.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1230   1268       LDL-receptor class A 13.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1271   1307       LDL-receptor class A 14.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1312   1350       LDL-receptor class A 15.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1350   1390       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN     1391   1430       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   REPEAT     1479   1521       LDL-receptor class B 9.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1522   1564       LDL-receptor class B 10.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1567   1610       LDL-receptor class B 11.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1611   1655       LDL-receptor class B 12.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1656   1696       LDL-receptor class B 13.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1791   1833       LDL-receptor class B 14.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1834   1883       LDL-receptor class B 15.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1884   1931       LDL-receptor class B 16.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1932   1973       LDL-receptor class B 17.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     1974   2014       LDL-receptor class B 18.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2108   2157       LDL-receptor class B 19.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2158   2202       LDL-receptor class B 20.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2203   2246       LDL-receptor class B 21.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2247   2290       LDL-receptor class B 22.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2291   2333       LDL-receptor class B 23.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2432   2478       LDL-receptor class B 24.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2479   2519       LDL-receptor class B 25.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2520   2563       LDL-receptor class B 26.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2564   2605       LDL-receptor class B 27.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     2606   2647       LDL-receptor class B 28.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   DOMAIN     2700   2738       LDL-receptor class A 16.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     2741   2777       LDL-receptor class A 17.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     2780   2819       LDL-receptor class A 18.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     2822   2861       LDL-receptor class A 19.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     2864   2902       LDL-receptor class A 20.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     2907   2946       LDL-receptor class A 21.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     2949   2991       LDL-receptor class A 22.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     2994   3030       LDL-receptor class A 23.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3033   3071       LDL-receptor class A 24.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3076   3112       LDL-receptor class A 25.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3112   3153       EGF-like 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN     3154   3194       EGF-like 4; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   REPEAT     3241   3283       LDL-receptor class B 29.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     3284   3326       LDL-receptor class B 30.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     3335   3378       LDL-receptor class B 31.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     3379   3421       LDL-receptor class B 32.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     3422   3462       LDL-receptor class B 33.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   DOMAIN     3513   3551       LDL-receptor class A 26.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3554   3592       LDL-receptor class A 27.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3595   3633       LDL-receptor class A 28.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3636   3674       LDL-receptor class A 29.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3679   3717       LDL-receptor class A 30.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3720   3757       LDL-receptor class A 31.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3760   3796       LDL-receptor class A 32.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3799   3835       LDL-receptor class A 33.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3843   3881       LDL-receptor class A 34.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3884   3923       LDL-receptor class A 35.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     3929   3965       LDL-receptor class A 36.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     4009   4050       EGF-like 5; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   REPEAT     4156   4198       LDL-receptor class B 34.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     4199   4242       LDL-receptor class B 35.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   REPEAT     4244   4285       LDL-receptor class B 36.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00461}.
FT   DOMAIN     4379   4413       EGF-like 6. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   REGION     4597   4610       Interaction with DAB2.
FT                                {ECO:0000250|UniProtKB:P98164}.
FT   MOTIF      4454   4463       SH3-binding. {ECO:0000255}.
FT   MOTIF      4457   4462       PxLPxI/L motif 1; mediates interaction
FT                                with ANKRA2.
FT                                {ECO:0000250|UniProtKB:P98158}.
FT   MOTIF      4460   4465       PxLPxI/L motif 2; mediates interaction
FT                                with ANKRA2.
FT                                {ECO:0000250|UniProtKB:P98158}.
FT   MOTIF      4522   4527       Endocytosis signal. {ECO:0000255}.
FT   MOTIF      4603   4606       NPXY motif.
FT   MOTIF      4606   4609       SH2-binding. {ECO:0000255}.
FT   MOTIF      4619   4630       SH3-binding. {ECO:0000255}.
FT   METAL      1127   1127       Calcium; via carbonyl oxygen.
FT                                {ECO:0000250|UniProtKB:P98164}.
FT   METAL      1130   1130       Calcium. {ECO:0000250|UniProtKB:P98164}.
FT   METAL      1132   1132       Calcium; via carbonyl oxygen.
FT                                {ECO:0000250|UniProtKB:P98164}.
FT   METAL      1134   1134       Calcium. {ECO:0000250|UniProtKB:P98164}.
FT   METAL      1140   1140       Calcium. {ECO:0000250|UniProtKB:P98164}.
FT   METAL      1141   1141       Calcium. {ECO:0000250|UniProtKB:P98164}.
FT   METAL      1206   1206       Calcium; via carbonyl oxygen.
FT                                {ECO:0000250|UniProtKB:P98158}.
FT   METAL      1209   1209       Calcium. {ECO:0000250|UniProtKB:P98158}.
FT   METAL      1211   1211       Calcium; via carbonyl oxygen.
FT                                {ECO:0000250|UniProtKB:P98158}.
FT   METAL      1213   1213       Calcium. {ECO:0000250|UniProtKB:P98158}.
FT   METAL      1219   1219       Calcium. {ECO:0000250|UniProtKB:P98158}.
FT   METAL      1220   1220       Calcium. {ECO:0000250|UniProtKB:P98158}.
FT   MOD_RES    4464   4464       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    4467   4467       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    4577   4577       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    4624   4624       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P98158}.
FT   MOD_RES    4637   4637       Phosphothreonine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES    4658   4658       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   CARBOHYD    159    159       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    178    178       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    299    299       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    340    340       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    387    387       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:19349973}.
FT   CARBOHYD    462    462       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    657    657       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    865    865       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1063   1063       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1187   1187       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1328   1328       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1341   1341       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1384   1384       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1451   1451       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1497   1497       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1551   1551       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1676   1676       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1733   1733       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   1811   1811       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2131   2131       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2134   2134       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2178   2178       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2225   2225       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2396   2396       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2488   2488       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2548   2548       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2782   2782       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2810   2810       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2949   2949       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   2989   2989       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3127   3127       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3213   3213       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3259   3259       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3317   3317       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3357   3357       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3448   3448       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3566   3566       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3682   3682       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3840   3840       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3969   3969       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   3980   3980       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   4070   4070       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD   4329   4329       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     28     40       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     35     53       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     47     62       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     67     80       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     74     93       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID     87    103       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    108    120       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    115    133       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    127    142       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    147    157       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    152    170       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    164    179       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    183    195       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    190    208       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    202    217       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    222    234       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    229    247       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    241    256       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    265    278       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    272    291       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    285    306       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1025   1037       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1032   1050       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1044   1059       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1066   1079       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1073   1092       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1086   1101       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1110   1122       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1117   1135       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1129   1144       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1150   1162       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1157   1175       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1169   1184       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1188   1201       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1195   1214       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1208   1223       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1231   1244       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1238   1257       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1251   1267       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1272   1284       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1279   1297       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1291   1306       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1313   1326       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1320   1339       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1333   1349       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1354   1365       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   1361   1374       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   1376   1389       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   1395   1405       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   1401   1414       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   1416   1429       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   2701   2713       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2708   2726       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2720   2737       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2742   2754       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2749   2767       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2761   2776       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2781   2794       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2789   2807       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2801   2818       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2823   2836       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2830   2849       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2843   2860       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2865   2878       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2872   2891       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2885   2901       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2908   2920       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2915   2933       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2927   2945       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2950   2967       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2957   2980       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2974   2990       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   2995   3007       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3002   3020       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3014   3029       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3034   3046       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3041   3059       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3053   3070       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3077   3089       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3084   3102       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3096   3111       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3116   3128       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   3124   3137       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   3139   3152       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   3158   3169       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   3165   3178       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   3180   3193       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   3514   3527       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3521   3540       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3534   3550       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3555   3567       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3562   3580       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3574   3591       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3596   3608       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3603   3621       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3615   3632       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3637   3649       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3644   3662       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3656   3673       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3680   3694       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3688   3707       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3701   3716       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3721   3734       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3729   3747       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3741   3756       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3761   3773       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3768   3786       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3780   3795       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3800   3812       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3807   3825       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3819   3834       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3844   3856       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3851   3869       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3863   3880       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3885   3898       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3893   3911       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3905   3922       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3930   3942       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3937   3955       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   3949   3964       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   4013   4023       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   4019   4032       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   4034   4049       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   4383   4391       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   4385   4401       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID   4403   4412       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   CONFLICT   4198   4198       L -> F (in Ref. 3; CAA69877).
FT                                {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
//
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