LRP1_HUMAN
ID LRP1_HUMAN Reviewed; 4544 AA.
AC Q07954; Q2PP12; Q86SW0; Q8IVG8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=Prolow-density lipoprotein receptor-related protein 1 {ECO:0000305};
DE Short=LRP-1;
DE AltName: Full=Alpha-2-macroglobulin receptor {ECO:0000303|PubMed:26142438};
DE Short=A2MR;
DE AltName: Full=Apolipoprotein E receptor;
DE Short=APOER;
DE AltName: CD_antigen=CD91;
DE Contains:
DE RecName: Full=Low-density lipoprotein receptor-related protein 1 85 kDa subunit;
DE Short=LRP-85;
DE Contains:
DE RecName: Full=Low-density lipoprotein receptor-related protein 1 515 kDa subunit;
DE Short=LRP-515;
DE Contains:
DE RecName: Full=Low-density lipoprotein receptor-related protein 1 intracellular domain;
DE Short=LRPICD;
DE Flags: Precursor;
GN Name=LRP1 {ECO:0000312|HGNC:HGNC:6692}; Synonyms=A2MR, APR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PRO-2900.
RC TISSUE=Liver;
RX PubMed=3266596; DOI=10.1002/j.1460-2075.1988.tb03306.x;
RA Herz J., Hamann U., Rogne S., Myklebost O., Gausepohl H., Stanley K.K.;
RT "Surface location and high affinity for calcium of a 500-kd liver membrane
RT protein closely related to the LDL-receptor suggest a physiological role as
RT lipoprotein receptor.";
RL EMBO J. 7:4119-4127(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7534747; DOI=10.1006/geno.1994.1584;
RA Van Leuven F., Stas L., Hilliker C., Lorent K., Umans L., Serneels L.,
RA Overbergh L., Torrekens S., Moechars D., De Strooper B., Van den Berghe H.;
RT "Structure of the gene (LRP1) coding for the human alpha 2-macroglobulin
RT receptor lipoprotein receptor-related protein.";
RL Genomics 24:78-89(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-2900.
RX PubMed=9782078; DOI=10.1006/geno.1998.5408;
RA Van Leuven F., Stas L., Thiry E., Nelissen B., Miyake Y.;
RT "Strategy to sequence the 89 exons of the human LRP1 gene coding for the
RT lipoprotein receptor related protein: identification of one expressed
RT mutation among 48 polymorphisms.";
RL Genomics 52:138-144(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PRO-2900.
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
RX PubMed=2597675; DOI=10.1016/0167-4781(89)90107-3;
RA Kutt H., Herz J., Stanley K.K.;
RT "Structure of the low-density lipoprotein receptor-related protein (LRP)
RT promoter.";
RL Biochim. Biophys. Acta 1009:229-236(1989).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11.
RC TISSUE=Blood;
RA Glaeser C.;
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP PROTEIN SEQUENCE OF 150-166; 234-252; 685-695; 902-916; 1096-1109;
RP 1743-1756; 2863-2874; 2949-2960; 3023-3039 AND 3277-3291.
RC TISSUE=Placenta;
RX PubMed=1698775; DOI=10.1016/s0021-9258(18)38172-9;
RA Strickland D.K., Ashcom J.D., Williams S., Burgess W.H., Migliorini M.,
RA Argraves W.S.;
RT "Sequence identity between the alpha 2-macroglobulin receptor and low
RT density lipoprotein receptor-related protein suggests that this molecule is
RT a multifunctional receptor.";
RL J. Biol. Chem. 265:17401-17404(1990).
RN [10]
RP PROTEOLYTIC PROCESSING.
RX PubMed=2112085; DOI=10.1002/j.1460-2075.1990.tb08301.x;
RA Herz J., Kowal R.C., Goldstein J.L., Brown M.S.;
RT "Proteolytic processing of the 600 kd low density lipoprotein receptor-
RT related protein (LRP) occurs in a trans-Golgi compartment.";
RL EMBO J. 9:1769-1776(1990).
RN [11]
RP FUNCTION.
RX PubMed=1702392; DOI=10.1016/0014-5793(90)80530-v;
RA Kristensen T., Moestrup S.K., Gliemann J., Bendtsen L., Sand O.,
RA Sottrup-Jensen L.;
RT "Evidence that the newly cloned low-density-lipoprotein receptor related
RT protein (LRP) is the alpha 2-macroglobulin receptor.";
RL FEBS Lett. 276:151-155(1990).
RN [12]
RP FUNCTION AS A RECEPTOR FOR P.AERUGINOSA EXOA TOXIN.
RX PubMed=1618748; DOI=10.1016/s0021-9258(18)42291-0;
RA Kounnas M.Z., Morris R.E., Thompson M.R., FitzGerald D.J., Strickland D.K.,
RA Saelinger C.B.;
RT "The alpha 2-macroglobulin receptor/low density lipoprotein receptor-
RT related protein binds and internalizes Pseudomonas exotoxin A.";
RL J. Biol. Chem. 267:12420-12423(1992).
RN [13]
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 [14]
RP INTERACTION WITH GULP1, AND MUTAGENESIS OF ASN-4470 AND ASN-4504.
RX PubMed=11729193; DOI=10.1074/jbc.m109336200;
RA Su H.P., Nakada-Tsukui K., Tosello-Trampont A.-C., Li Y., Bu G.,
RA Henson P.M., Ravichandran K.S.;
RT "Interaction of CED-6/GULP, an adapter protein involved in engulfment of
RT apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-
RT related protein (LRP).";
RL J. Biol. Chem. 277:11772-11779(2002).
RN [15]
RP PHOSPHORYLATION AT TYR-4507, MUTAGENESIS OF 4470-ASN--TYR-4473 AND
RP 4504-ASN--TYR-4507, AND INTERACTION WITH PDGF.
RX PubMed=11854294; DOI=10.1074/jbc.m200427200;
RA Loukinova E., Ranganathan S., Kuznetsov S., Gorlatova N., Migliorini M.M.,
RA Loukinov D., Ulery P.G., Mikhailenko I., Lawrence D.A., Strickland D.K.;
RT "Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of
RT the low density lipoprotein receptor-related protein (LRP). Evidence for
RT integrated co-receptor function between LRP and the PDGF.";
RL J. Biol. Chem. 277:15499-15506(2002).
RN [16]
RP FUNCTION, AND PROTEOLYTIC PROCESSING.
RX PubMed=11907044; DOI=10.1074/jbc.m201979200;
RA May P., Reddy Y.K., Herz J.;
RT "Proteolytic processing of low density lipoprotein receptor-related protein
RT mediates regulated release of its intracellular domain.";
RL J. Biol. Chem. 277:18736-18743(2002).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12888553; DOI=10.1074/jbc.m306403200;
RA Kinoshita A., Shah T., Tangredi M.M., Strickland D.K., Hyman B.T.;
RT "The intracellular domain of the low density lipoprotein receptor-related
RT protein modulates transactivation mediated by amyloid precursor protein and
RT Fe65.";
RL J. Biol. Chem. 278:41182-41188(2003).
RN [18]
RP FUNCTION.
RX PubMed=12713657; DOI=10.1034/j.1600-0854.2003.00086_4_5.x;
RA May P., Herz J.;
RT "LDL receptor-related proteins in neurodevelopment.";
RL Traffic 4:291-301(2003).
RN [19]
RP INTERACTION WITH LRPAP1; PDGFB; PLAU AND SERPINE1.
RX PubMed=15053742; DOI=10.1042/bj20040149;
RA Gliemann J., Hermey G., Nykjaer A., Petersen C.M., Jacobsen C.,
RA Andreasen P.A.;
RT "The mosaic receptor sorLA/LR11 binds components of the plasminogen-
RT activating system and platelet-derived growth factor-BB similarly to LRP1
RT (low-density lipoprotein receptor-related protein), but mediates slow
RT internalization of bound ligand.";
RL Biochem. J. 381:203-212(2004).
RN [20]
RP INTERACTION WITH PLAUR.
RX PubMed=14764453; DOI=10.1161/01.res.0000120862.79154.0f;
RA Zhu Y., Bujo H., Yamazaki H., Ohwaki K., Jiang M., Hirayama S., Kanaki T.,
RA Shibasaki M., Takahashi K., Schneider W.J., Saito Y.;
RT "LR11, an LDL receptor gene family member, is a novel regulator of smooth
RT muscle cell migration.";
RL Circ. Res. 94:752-758(2004).
RN [21]
RP PHOSPHORYLATION AT THR-4460; SER-4517; SER-4520 AND SER-4523, MUTAGENESIS
RP OF THR-4460; THR-4472; SER-4517; SER-4520 AND SER-4523, AND INTERACTION
RP WITH SHC1; GULP1 AND DAB1.
RX PubMed=15272003; DOI=10.1074/jbc.m407592200;
RA Ranganathan S., Liu C.-X., Migliorini M.M., Von Arnim C.A.F., Peltan I.D.,
RA Mikhailenko I., Hyman B.T., Strickland D.K.;
RT "Serine and threonine phosphorylation of the low density lipoprotein
RT receptor-related protein by protein kinase Calpha regulates endocytosis and
RT association with adaptor molecules.";
RL J. Biol. Chem. 279:40536-40544(2004).
RN [22]
RP INTERACTION WITH SNX17.
RX PubMed=15769472; DOI=10.1016/j.jmb.2005.02.004;
RA Knauth P., Schlueter T., Czubayko M., Kirsch C., Florian V.,
RA Schreckenberger S., Hahn H., Bohnensack R.;
RT "Functions of sorting nexin 17 domains and recognition motif for P-selectin
RT trafficking.";
RL J. Mol. Biol. 347:813-825(2005).
RN [23]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-446; ASN-729; ASN-2127 AND
RP ASN-3048.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [24]
RP IDENTIFICATION IN A COMPLEX WITH CUBN AND PID1, AND INTERACTION WITH CUBN
RP AND PID1.
RX PubMed=17124247; DOI=10.1074/mcp.m600289-mcp200;
RA Caratu G., Allegra D., Bimonte M., Schiattarella G.G., D'Ambrosio C.,
RA Scaloni A., Napolitano M., Russo T., Zambrano N.;
RT "Identification of the ligands of protein interaction domains through a
RT functional approach.";
RL Mol. Cell. Proteomics 6:333-345(2007).
RN [25]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-446; ASN-729; ASN-1511;
RP ASN-1575; ASN-1616; ASN-1645; ASN-1763; ASN-2127; ASN-2815; ASN-3048;
RP ASN-3089; ASN-3488; ASN-3788; ASN-3953; ASN-4075 AND ASN-4125.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [26]
RP GLYCOSYLATION AT ASN-729 AND ASN-1511.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4520, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [29]
RP FUNCTION, AND INTERACTION WITH LRPAP1 AND MAPT1.
RX PubMed=32296178; DOI=10.1038/s41586-020-2156-5;
RA Rauch J.N., Luna G., Guzman E., Challis C., Sibih Y.E., Leshuk C.,
RA Hernandez I., Wegmann S., Hyman B.T., Gradinaru V., Kampmann M.,
RA Kosik K.S.;
RT "LRP1 is a master regulator of tau uptake and spread.";
RL Nature 580:381-385(2020).
RN [30]
RP INTERACTION WITH RVFV GLYCOPROTEIN N (MICROBIAL INFECTION).
RX PubMed=34559985; DOI=10.1016/j.cell.2021.09.001;
RA Ganaie S.S., Schwarz M.M., McMillen C.M., Price D.A., Feng A.X., Albe J.R.,
RA Wang W., Miersch S., Orvedahl A., Cole A.R., Sentmanat M.F., Mishra N.,
RA Boyles D.A., Koenig Z.T., Kujawa M.R., Demers M.A., Hoehl R.M., Moyle A.B.,
RA Wagner N.D., Stubbs S.H., Cardarelli L., Teyra J., McElroy A., Gross M.L.,
RA Whelan S.P.J., Doench J., Cui X., Brett T.J., Sidhu S.S., Virgin H.W.,
RA Egawa T., Leung D.W., Amarasinghe G.K., Hartman A.L.;
RT "Lrp1 is a host entry factor for Rift Valley fever virus.";
RL Cell 184:5163-5178.e24(2021).
RN [31]
RP STRUCTURE BY NMR OF 1059-1100 IN COMPLEX WITH CALCIUM IONS, AND DISULFIDE
RP BONDS.
RX PubMed=10318830; DOI=10.1074/jbc.274.20.14130;
RA Huang W., Dolmer K., Gettins P.G.W.;
RT "NMR solution structure of complement-like repeat CR8 from the low density
RT lipoprotein receptor-related protein.";
RL J. Biol. Chem. 274:14130-14136(1999).
RN [32]
RP STRUCTURE BY NMR OF 851-893 IN COMPLEX WITH CALCIUM IONS, AND DISULFIDE
RP BONDS.
RX PubMed=10652313; DOI=10.1074/jbc.275.5.3264;
RA Dolmer K., Huang W., Gettins P.G.W.;
RT "NMR solution structure of complement-like repeat CR3 from the low density
RT lipoprotein receptor-related protein. Evidence for specific binding to the
RT receptor binding domain of human alpha(2)-macroglobulin.";
RL J. Biol. Chem. 275:3264-3269(2000).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1012-1054 IN COMPLEX WITH CALCIUM
RP IONS, AND DISULFIDE BONDS.
RX PubMed=11735395; DOI=10.1021/bi015688m;
RA Simonovic M., Dolmer K., Huang W., Strickland D.K., Volz K., Gettins P.G.;
RT "Calcium coordination and pH dependence of the calcium affinity of ligand-
RT binding repeat CR7 from the LRP. Comparison with related domains from the
RT LRP and the LDL receptor.";
RL Biochemistry 40:15127-15134(2001).
RN [34]
RP STRUCTURE BY NMR OF 932-1013 IN COMPLEX WITH LRPAP1 AND CALCIUM IONS, AND
RP DISULFIDE BONDS.
RX PubMed=16938309; DOI=10.1016/j.jmb.2006.07.013;
RA Jensen G.A., Andersen O.M.J.J., Bonvin A.M., Bjerrum-Bohr I., Etzerodt M.,
RA Thoegersen H.C., O'Shea C., Poulsen F.M., Kragelund B.B.;
RT "Binding site structure of one LRP-RAP complex: implications for a common
RT ligand-receptor binding motif.";
RL J. Mol. Biol. 362:700-716(2006).
RN [35]
RP VARIANTS [LARGE SCALE ANALYSIS] LYS-869 AND HIS-3760.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [36]
RP VARIANT GLN-3258.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [37]
RP VARIANT KPA ARG-1245, CHARACTERIZATION OF VARIANT KPA ARG-1245, FUNCTION,
RP AND INVOLVEMENT IN KPA.
RX PubMed=26142438; DOI=10.1136/jmedgenet-2014-102931;
RA Klar J., Schuster J., Khan T.N., Jameel M., Maebert K., Forsberg L.,
RA Baig S.A., Baig S.M., Dahl N.;
RT "Whole exome sequencing identifies LRP1 as a pathogenic gene in autosomal
RT recessive keratosis pilaris atrophicans.";
RL J. Med. Genet. 52:599-606(2015).
CC -!- FUNCTION: Endocytic receptor involved in endocytosis and in
CC phagocytosis of apoptotic cells (PubMed:11907044, PubMed:12713657).
CC Required for early embryonic development (By similarity). Involved in
CC cellular lipid homeostasis. Involved in the plasma clearance of
CC chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as
CC well as the local metabolism of complexes between plasminogen
CC activators and their endogenous inhibitors. Acts as an LRPAP1 alpha-2-
CC macroglobulin receptor (PubMed:26142438, PubMed:1702392). Acts as
CC TAU/MAPT receptor and controls the endocytosis of TAU/MAPT as well as
CC its subsequent spread (PubMed:32296178). May modulate cellular events,
CC such as APP metabolism, kinase-dependent intracellular signaling,
CC neuronal calcium signaling as well as neurotransmission
CC (PubMed:12888553). {ECO:0000250|UniProtKB:Q91ZX7,
CC ECO:0000269|PubMed:11907044, ECO:0000269|PubMed:12713657,
CC ECO:0000269|PubMed:12888553, ECO:0000269|PubMed:1702392,
CC ECO:0000269|PubMed:26142438, ECO:0000269|PubMed:32296178}.
CC -!- FUNCTION: (Microbial infection) Functions as a receptor for Pseudomonas
CC aeruginosa exotoxin A. {ECO:0000269|PubMed:1618748}.
CC -!- SUBUNIT: Heterodimer of an 85-kDa membrane-bound carboxyl subunit and a
CC non-covalently attached 515-kDa N-terminal subunit. Intracellular
CC domain interacts with MAFB (By similarity). Found in a complex with
CC PID1/PCLI1, LRP1 and CUBNI (PubMed:17124247). Interacts with SNX17,
CC PID1/PCLI1, PDGF and CUBN. The intracellular domain interacts with
CC SHC1, GULP1 and DAB1. Can weakly interact (via NPXY motif) with DAB2
CC (via PID domain); the interaction is enhanced by tyrosine
CC phosphorylation of the NPXY motif. Interacts with MDK; promotes
CC neuronal survival (PubMed:10772929). Interacts with LRPAP1; this
CC interaction is followed by rapid internalization (PubMed:15053742,
CC PubMed:32296178, PubMed:16938309). Interacts with uPA/PLAU and
CC PAI1/SERPINE1, either individually or in complex with each other,
CC leading to rapid endocytosis; this interaction is abolished in the
CC presence of LRPAP1/RAP (PubMed:15053742). Also interacts with tPA/PLAT
CC alone or in complex with SERPINE1 (PubMed:15053742). Interacts with the
CC urokinase receptor PLAUR; this interaction leads to PLAUR
CC internalization and is impaired in the presence of SORL1
CC (PubMed:14764453). Interacts with PDGFB (PubMed:15053742). Interacts
CC with TAU/MAPT, leading to endocytosis; this interaction is reduced in
CC the presence of LRPAP1/RAP (PubMed:32296178).
CC {ECO:0000250|UniProtKB:Q91ZX7, ECO:0000269|PubMed:10772929,
CC ECO:0000269|PubMed:11729193, ECO:0000269|PubMed:11854294,
CC ECO:0000269|PubMed:14764453, ECO:0000269|PubMed:15053742,
CC ECO:0000269|PubMed:15272003, ECO:0000269|PubMed:15769472,
CC ECO:0000269|PubMed:16938309, ECO:0000269|PubMed:17124247,
CC ECO:0000269|PubMed:32296178}.
CC -!- SUBUNIT: (Microbial infection) Interacts with bacterial exotoxins.
CC {ECO:0000269|PubMed:1618748}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Rift valley fever virus
CC (RVFV) glycoprotein N; this interaction facilitates virus entry.
CC {ECO:0000269|PubMed:34559985}.
CC -!- INTERACTION:
CC Q07954; Q92685: ALG3; NbExp=2; IntAct=EBI-1046087, EBI-2848814;
CC Q07954; O00213: APBB1; NbExp=4; IntAct=EBI-1046087, EBI-81694;
CC Q07954; P02649: APOE; NbExp=23; IntAct=EBI-1046087, EBI-1222467;
CC Q07954; P78352: DLG4; NbExp=2; IntAct=EBI-1046087, EBI-80389;
CC Q07954; Q15485: FCN2; NbExp=2; IntAct=EBI-1046087, EBI-7468784;
CC Q07954; Q12879: GRIN2A; NbExp=2; IntAct=EBI-1046087, EBI-7249937;
CC Q07954; P30533: LRPAP1; NbExp=4; IntAct=EBI-1046087, EBI-715927;
CC Q07954; P11226: MBL2; NbExp=5; IntAct=EBI-1046087, EBI-5325353;
CC Q07954; Q63722: Jag1; Xeno; NbExp=4; IntAct=EBI-1046087, EBI-4567800;
CC Q07954; Q03350: Thbs2; Xeno; NbExp=2; IntAct=EBI-1046087, EBI-4567830;
CC Q07954-2; P05067: APP; NbExp=3; IntAct=EBI-25833471, EBI-77613;
CC Q07954-2; Q13867: BLMH; NbExp=3; IntAct=EBI-25833471, EBI-718504;
CC Q07954-2; P04271: S100B; NbExp=3; IntAct=EBI-25833471, EBI-458391;
CC Q07954-2; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-25833471, EBI-357085;
CC Q07954-2; P43405-2: SYK; NbExp=3; IntAct=EBI-25833471, EBI-25892332;
CC Q07954-2; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-25833471, EBI-11141397;
CC -!- SUBCELLULAR LOCATION: [Low-density lipoprotein receptor-related protein
CC 1 85 kDa subunit]: Cell membrane; Single-pass type I membrane protein.
CC Membrane, coated pit.
CC -!- SUBCELLULAR LOCATION: [Low-density lipoprotein receptor-related protein
CC 1 515 kDa subunit]: Cell membrane; Peripheral membrane protein;
CC Extracellular side. Membrane, coated pit.
CC -!- SUBCELLULAR LOCATION: [Low-density lipoprotein receptor-related protein
CC 1 intracellular domain]: Cytoplasm {ECO:0000269|PubMed:12888553}.
CC Nucleus {ECO:0000269|PubMed:12888553}. Note=After cleavage, the
CC intracellular domain (LRPICD) is detected both in the cytoplasm and in
CC the nucleus. {ECO:0000269|PubMed:12888553}.
CC -!- SUBCELLULAR LOCATION: Golgi outpost {ECO:0000250|UniProtKB:G3V928}.
CC Cytoplasm, cytoskeleton, microtubule organizing center
CC {ECO:0000250|UniProtKB:G3V928}. Note=Localizes to the postsynaptic
CC Golgi apparatus region, also named Golgi outpost, which shapes dendrite
CC morphology by functioning as sites of acentrosomal microtubule
CC nucleation. {ECO:0000250|UniProtKB:G3V928}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q07954-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q07954-2; Sequence=VSP_056919, VSP_056920;
CC -!- TISSUE SPECIFICITY: Most abundant in liver, brain and lung.
CC -!- PTM: Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515
CC kDa large extracellular domain (LRP-515) that remains non-covalently
CC associated. Gamma-secretase-dependent cleavage of LRP-85 releases the
CC intracellular domain from the membrane. {ECO:0000269|PubMed:11907044,
CC ECO:0000269|PubMed:2112085}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Phosphorylated on serine and threonine residues.
CC -!- PTM: Phosphorylated on tyrosine residues upon stimulation with PDGF.
CC Tyrosine phosphorylation promotes interaction with SHC1.
CC -!- DISEASE: Keratosis pilaris atrophicans (KPA) [MIM:604093]: A group of
CC rare genodermatoses characterized by keratotic follicular papules,
CC variable degrees of inflammation, and secondary atrophic scarring. Most
CC cases are associated with an atopic diathesis and keratosis pilaris on
CC the extensor extremities. KPA is comprised of three distinct clinical
CC subtypes: keratosis pilaris atrophicans faciei, atrophoderma
CC vermiculatum, and keratosis follicularis spinulosa decalvans. Affected
CC individuals may present with features overlapping the 3 subtypes.
CC {ECO:0000269|PubMed:26142438}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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DR EMBL; X13916; CAA32112.1; -; mRNA.
DR EMBL; AF058427; AAC64265.1; -; Genomic_DNA.
DR EMBL; DQ314873; ABC40732.1; -; Genomic_DNA.
DR EMBL; AC023237; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137628; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC045107; AAH45107.1; -; mRNA.
DR EMBL; X15424; CAA33464.1; -; Genomic_DNA.
DR EMBL; Y18524; CAD57169.1; -; Genomic_DNA.
DR CCDS; CCDS8932.1; -. [Q07954-1]
DR PIR; S02392; S02392.
DR RefSeq; NP_002323.2; NM_002332.2. [Q07954-1]
DR PDB; 1CR8; NMR; -; A=1059-1100.
DR PDB; 1D2L; NMR; -; A=851-893.
DR PDB; 1J8E; X-ray; 1.85 A; A=1011-1054.
DR PDB; 2FYJ; NMR; -; A=932-1013.
DR PDB; 2FYL; NMR; -; B=932-1013.
DR PDB; 2KNX; NMR; -; A=2770-2817.
DR PDB; 2KNY; NMR; -; A=2770-2817.
DR PDBsum; 1CR8; -.
DR PDBsum; 1D2L; -.
DR PDBsum; 1J8E; -.
DR PDBsum; 2FYJ; -.
DR PDBsum; 2FYL; -.
DR PDBsum; 2KNX; -.
DR PDBsum; 2KNY; -.
DR SMR; Q07954; -.
DR BioGRID; 110215; 218.
DR ComplexPortal; CPX-4310; Prolow-density lipoprotein receptor-related protein 1 complex.
DR CORUM; Q07954; -.
DR DIP; DIP-50613N; -.
DR ELM; Q07954; -.
DR IntAct; Q07954; 91.
DR MINT; Q07954; -.
DR STRING; 9606.ENSP00000243077; -.
DR ChEMBL; CHEMBL4630884; -.
DR DrugBank; DB00025; Antihemophilic factor, human recombinant.
DR DrugBank; DB00100; Coagulation Factor IX (Recombinant).
DR DrugBank; DB13152; Coagulation Factor IX Human.
DR DrugBank; DB06245; Lanoteplase.
DR DrugBank; DB13998; Lonoctocog alfa.
DR DrugBank; DB13999; Moroctocog alfa.
DR DrugBank; DB00031; Tenecteplase.
DR TCDB; 9.B.87.1.16; the selenoprotein p receptor (selp-receptor) family.
DR CarbonylDB; Q07954; -.
DR GlyConnect; 1638; 61 N-Linked glycans (38 sites), 1 O-Linked glycan (1 site).
DR GlyGen; Q07954; 74 sites, 62 N-linked glycans (36 sites), 3 O-linked glycans (13 sites).
DR iPTMnet; Q07954; -.
DR MetOSite; Q07954; -.
DR PhosphoSitePlus; Q07954; -.
DR BioMuta; LRP1; -.
DR DMDM; 317373384; -.
DR CPTAC; CPTAC-1617; -.
DR CPTAC; CPTAC-2222; -.
DR CPTAC; CPTAC-2223; -.
DR EPD; Q07954; -.
DR jPOST; Q07954; -.
DR MassIVE; Q07954; -.
DR MaxQB; Q07954; -.
DR PaxDb; Q07954; -.
DR PeptideAtlas; Q07954; -.
DR PRIDE; Q07954; -.
DR ProteomicsDB; 58559; -. [Q07954-1]
DR ProteomicsDB; 69639; -.
DR Antibodypedia; 4353; 1099 antibodies from 40 providers.
DR DNASU; 4035; -.
DR Ensembl; ENST00000243077.8; ENSP00000243077.3; ENSG00000123384.14. [Q07954-1]
DR Ensembl; ENST00000338962.8; ENSP00000341264.4; ENSG00000123384.14. [Q07954-2]
DR GeneID; 4035; -.
DR KEGG; hsa:4035; -.
DR MANE-Select; ENST00000243077.8; ENSP00000243077.3; NM_002332.3; NP_002323.2.
DR UCSC; uc001snd.4; human. [Q07954-1]
DR CTD; 4035; -.
DR DisGeNET; 4035; -.
DR GeneCards; LRP1; -.
DR HGNC; HGNC:6692; LRP1.
DR HPA; ENSG00000123384; Tissue enhanced (adipose).
DR MalaCards; LRP1; -.
DR MIM; 107770; gene.
DR MIM; 604093; phenotype.
DR neXtProt; NX_Q07954; -.
DR OpenTargets; ENSG00000123384; -.
DR Orphanet; 79100; Atrophoderma vermiculata.
DR Orphanet; 2340; Keratosis follicularis spinulosa decalvans.
DR PharmGKB; PA233; -.
DR VEuPathDB; HostDB:ENSG00000123384; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000157899; -.
DR HOGENOM; CLU_000085_1_0_1; -.
DR InParanoid; Q07954; -.
DR OMA; CEYDGTR; -.
DR OrthoDB; 1606at2759; -.
DR PhylomeDB; Q07954; -.
DR TreeFam; TF315253; -.
DR PathwayCommons; Q07954; -.
DR Reactome; R-HSA-2168880; Scavenging of heme from plasma.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR SignaLink; Q07954; -.
DR SIGNOR; Q07954; -.
DR BioGRID-ORCS; 4035; 16 hits in 1075 CRISPR screens.
DR ChiTaRS; LRP1; human.
DR EvolutionaryTrace; Q07954; -.
DR GeneWiki; LRP1; -.
DR GenomeRNAi; 4035; -.
DR Pharos; Q07954; Tbio.
DR PRO; PR:Q07954; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q07954; protein.
DR Bgee; ENSG00000123384; Expressed in stromal cell of endometrium and 201 other tissues.
DR ExpressionAtlas; Q07954; baseline and differential.
DR Genevisible; Q07954; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:ARUK-UCL.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0062136; C:low-density lipoprotein receptor complex; IC:ComplexPortal.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; NAS:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098797; C:plasma membrane protein complex; TAS:ARUK-UCL.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0016964; F:alpha-2 macroglobulin receptor activity; IMP:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
DR GO; GO:0034185; F:apolipoprotein binding; IDA:UniProtKB.
DR GO; GO:0030226; F:apolipoprotein receptor activity; TAS:ARUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0038024; F:cargo receptor activity; IMP:ARUK-UCL.
DR GO; GO:0032050; F:clathrin heavy chain binding; IPI:ARUK-UCL.
DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; TAS:ARUK-UCL.
DR GO; GO:0070325; F:lipoprotein particle receptor binding; IC:BHF-UCL.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; TAS:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0005044; F:scavenger receptor activity; TAS:ARUK-UCL.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0097242; P:amyloid-beta clearance; TAS:BHF-UCL.
DR GO; GO:0150094; P:amyloid-beta clearance by cellular catabolic process; IMP:ARUK-UCL.
DR GO; GO:0150093; P:amyloid-beta clearance by transcytosis; IGI:ARUK-UCL.
DR GO; GO:0035909; P:aorta morphogenesis; ISS:BHF-UCL.
DR GO; GO:0043277; P:apoptotic cell clearance; ISS:BHF-UCL.
DR GO; GO:0002265; P:astrocyte activation involved in immune response; ISS:ARUK-UCL.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; ISS:BHF-UCL.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ARUK-UCL.
DR GO; GO:0042953; P:lipoprotein transport; NAS:UniProtKB.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:BHF-UCL.
DR GO; GO:1905049; P:negative regulation of metallopeptidase activity; IC:ARUK-UCL.
DR GO; GO:0060394; P:negative regulation of pathway-restricted SMAD protein phosphorylation; ISS:BHF-UCL.
DR GO; GO:2000587; P:negative regulation of platelet-derived growth factor receptor-beta signaling pathway; ISS:BHF-UCL.
DR GO; GO:0060392; P:negative regulation of SMAD protein signal transduction; ISS:BHF-UCL.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISS:BHF-UCL.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISS:BHF-UCL.
DR GO; GO:0006909; P:phagocytosis; IMP:ARUK-UCL.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; ISS:ARUK-UCL.
DR GO; GO:0010942; P:positive regulation of cell death; IGI:ARUK-UCL.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISS:BHF-UCL.
DR GO; GO:0045807; P:positive regulation of endocytosis; IGI:ARUK-UCL.
DR GO; GO:0032370; P:positive regulation of lipid transport; ISS:BHF-UCL.
DR GO; GO:1905167; P:positive regulation of lysosomal protein catabolic process; IMP:ARUK-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IGI:ARUK-UCL.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IGI:ARUK-UCL.
DR GO; GO:1904300; P:positive regulation of transcytosis; ISS:ARUK-UCL.
DR GO; GO:0031623; P:receptor internalization; IDA:ComplexPortal.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:ARUK-UCL.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:BHF-UCL.
DR GO; GO:0032374; P:regulation of cholesterol transport; ISS:BHF-UCL.
DR GO; GO:0010715; P:regulation of extracellular matrix disassembly; TAS:ParkinsonsUK-UCL.
DR GO; GO:0032429; P:regulation of phospholipase A2 activity; ISS:BHF-UCL.
DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome.
DR GO; GO:0045056; P:transcytosis; TAS:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; ISS:ARUK-UCL.
DR CDD; cd00112; LDLa; 31.
DR Gene3D; 2.120.10.30; -; 8.
DR Gene3D; 4.10.400.10; -; 30.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR026823; cEGF.
DR InterPro; IPR032485; DUF5050.
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; 1.
DR Pfam; PF16472; DUF5050; 1.
DR Pfam; PF07645; EGF_CA; 2.
DR Pfam; PF00057; Ldl_recept_a; 29.
DR Pfam; PF00058; Ldl_recept_b; 12.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 26.
DR SMART; SM00179; EGF_CA; 7.
DR SMART; SM00192; LDLa; 31.
DR SMART; SM00135; LY; 35.
DR SUPFAM; SSF57184; SSF57184; 4.
DR SUPFAM; SSF57424; SSF57424; 30.
DR PROSITE; PS00010; ASX_HYDROXYL; 3.
DR PROSITE; PS00022; EGF_1; 5.
DR PROSITE; PS01186; EGF_2; 8.
DR PROSITE; PS50026; EGF_3; 6.
DR PROSITE; PS01187; EGF_CA; 2.
DR PROSITE; PS01209; LDLRA_1; 27.
DR PROSITE; PS50068; LDLRA_2; 31.
DR PROSITE; PS51120; LDLRB; 34.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Calcium; Cell membrane;
KW Coated pit; Cytoplasm; Cytoskeleton; Developmental protein;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW EGF-like domain; Endocytosis; Glycoprotein; Golgi apparatus;
KW Host-virus interaction; Membrane; Metal-binding; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..4544
FT /note="Prolow-density lipoprotein receptor-related protein
FT 1"
FT /id="PRO_0000017317"
FT CHAIN 20..?3943
FT /note="Low-density lipoprotein receptor-related protein 1
FT 515 kDa subunit"
FT /id="PRO_0000302750"
FT CHAIN ?3944..4544
FT /note="Low-density lipoprotein receptor-related protein 1
FT 85 kDa subunit"
FT /id="PRO_0000302751"
FT CHAIN ?4441..4544
FT /note="Low-density lipoprotein receptor-related protein 1
FT intracellular domain"
FT /id="PRO_0000302752"
FT TOPO_DOM 20..4419
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 4420..4444
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 4445..4544
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..66
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 70..110
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 111..149
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 150..189
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 292..334
FT /note="LDL-receptor class B 1"
FT REPEAT 335..378
FT /note="LDL-receptor class B 2"
FT REPEAT 379..422
FT /note="LDL-receptor class B 3"
FT DOMAIN 474..520
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 571..613
FT /note="LDL-receptor class B 4"
FT REPEAT 614..659
FT /note="LDL-receptor class B 5"
FT REPEAT 660..710
FT /note="LDL-receptor class B 6"
FT REPEAT 711..754
FT /note="LDL-receptor class B 7"
FT DOMAIN 803..843
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 852..892
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 893..933
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 934..973
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 974..1013
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1013..1053
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1060..1099
FT /note="LDL-receptor class A 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1102..1142
FT /note="LDL-receptor class A 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1143..1182
FT /note="LDL-receptor class A 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1183..1222
FT /note="EGF-like 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 1223..1262
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1309..1355
FT /note="LDL-receptor class B 8"
FT REPEAT 1356..1398
FT /note="LDL-receptor class B 9"
FT REPEAT 1399..1445
FT /note="LDL-receptor class B 10"
FT REPEAT 1446..1490
FT /note="LDL-receptor class B 11"
FT REPEAT 1491..1531
FT /note="LDL-receptor class B 12"
FT DOMAIN 1536..1579
FT /note="EGF-like 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1627..1669
FT /note="LDL-receptor class B 13"
FT REPEAT 1670..1713
FT /note="LDL-receptor class B 14"
FT REPEAT 1714..1753
FT /note="LDL-receptor class B 15"
FT REPEAT 1754..1798
FT /note="LDL-receptor class B 16"
FT DOMAIN 1846..1887
FT /note="EGF-like 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1934..1976
FT /note="LDL-receptor class B 17"
FT REPEAT 1977..2019
FT /note="LDL-receptor class B 18"
FT REPEAT 2020..2063
FT /note="LDL-receptor class B 19"
FT REPEAT 2064..2107
FT /note="LDL-receptor class B 20"
FT DOMAIN 2155..2195
FT /note="EGF-like 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 2253..2294
FT /note="LDL-receptor class B 21"
FT REPEAT 2295..2343
FT /note="LDL-receptor class B 22"
FT REPEAT 2344..2388
FT /note="LDL-receptor class B 23"
FT REPEAT 2389..2431
FT /note="LDL-receptor class B 24"
FT REPEAT 2432..2473
FT /note="LDL-receptor class B 25"
FT DOMAIN 2478..2518
FT /note="EGF-like 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 2522..2563
FT /note="LDL-receptor class A 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2564..2602
FT /note="LDL-receptor class A 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2603..2641
FT /note="LDL-receptor class A 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2642..2690
FT /note="LDL-receptor class A 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2694..2732
FT /note="LDL-receptor class A 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2732..2771
FT /note="LDL-receptor class A 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2772..2814
FT /note="LDL-receptor class A 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2816..2855
FT /note="LDL-receptor class A 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2856..2899
FT /note="LDL-receptor class A 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2902..2940
FT /note="LDL-receptor class A 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2941..2981
FT /note="EGF-like 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 2982..3022
FT /note="EGF-like 12; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 3069..3113
FT /note="LDL-receptor class B 26"
FT REPEAT 3114..3156
FT /note="LDL-receptor class B 27"
FT REPEAT 3157..3200
FT /note="LDL-receptor class B 28"
FT REPEAT 3201..3243
FT /note="LDL-receptor class B 29"
FT REPEAT 3244..3284
FT /note="LDL-receptor class B 30"
FT DOMAIN 3290..3331
FT /note="EGF-like 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 3332..3371
FT /note="LDL-receptor class A 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3372..3410
FT /note="LDL-receptor class A 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3411..3450
FT /note="LDL-receptor class A 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3451..3491
FT /note="LDL-receptor class A 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3492..3533
FT /note="LDL-receptor class A 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3534..3572
FT /note="LDL-receptor class A 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3573..3611
FT /note="LDL-receptor class A 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3611..3649
FT /note="LDL-receptor class A 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3652..3692
FT /note="LDL-receptor class A 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3693..3733
FT /note="LDL-receptor class A 30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3739..3778
FT /note="LDL-receptor class A 31"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3781..3823
FT /note="EGF-like 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 3824..3861
FT /note="EGF-like 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 3912..3954
FT /note="LDL-receptor class B 31"
FT REPEAT 3970..4012
FT /note="LDL-receptor class B 32"
FT REPEAT 4013..4056
FT /note="LDL-receptor class B 33"
FT REPEAT 4057..4101
FT /note="LDL-receptor class B 34"
FT DOMAIN 4147..4183
FT /note="EGF-like 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4196..4232
FT /note="EGF-like 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4232..4268
FT /note="EGF-like 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4268..4304
FT /note="EGF-like 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4304..4340
FT /note="EGF-like 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4340..4375
FT /note="EGF-like 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 4373..4409
FT /note="EGF-like 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 4445..4544
FT /note="Interaction with MAFB"
FT /evidence="ECO:0000250|UniProtKB:Q91ZX7"
FT MOTIF 3940..3943
FT /note="Recognition site for proteolytical processing"
FT /evidence="ECO:0000255"
FT MOTIF 4502..4507
FT /note="NPXY motif"
FT BINDING 871
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10652313"
FT BINDING 874
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10652313"
FT BINDING 876
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10652313"
FT BINDING 878
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10652313"
FT BINDING 884
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10652313"
FT BINDING 885
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10652313"
FT BINDING 1032
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11735395"
FT BINDING 1035
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11735395"
FT BINDING 1037
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11735395"
FT BINDING 1039
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11735395"
FT BINDING 1045
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11735395"
FT BINDING 1046
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11735395"
FT BINDING 1080
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10318830"
FT BINDING 1083
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10318830"
FT BINDING 1085
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10318830"
FT BINDING 1087
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10318830"
FT BINDING 1093
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10318830"
FT BINDING 1094
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:10318830"
FT MOD_RES 2009
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZX7"
FT MOD_RES 4460
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:15272003"
FT MOD_RES 4507
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11854294"
FT MOD_RES 4517
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15272003"
FT MOD_RES 4520
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 4523
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15272003"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 357
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 729
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218"
FT CARBOHYD 928
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1050
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1154
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1511
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 1558
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1575
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 1616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 1645
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 1723
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 1763
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 1825
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1933
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1995
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2048
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 2472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2502
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2521
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2539
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2601
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2620
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2638
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2815
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 2905
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3048
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 3089
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 3264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 3662
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3788
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 3839
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3953
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 4075
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 4125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 4179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4278
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 27..40
FT /evidence="ECO:0000250"
FT DISULFID 34..53
FT /evidence="ECO:0000250"
FT DISULFID 47..64
FT /evidence="ECO:0000250"
FT DISULFID 72..85
FT /evidence="ECO:0000250"
FT DISULFID 79..98
FT /evidence="ECO:0000250"
FT DISULFID 92..108
FT /evidence="ECO:0000250"
FT DISULFID 115..124
FT /evidence="ECO:0000250"
FT DISULFID 120..133
FT /evidence="ECO:0000250"
FT DISULFID 135..148
FT /evidence="ECO:0000250"
FT DISULFID 154..164
FT /evidence="ECO:0000250"
FT DISULFID 160..173
FT /evidence="ECO:0000250"
FT DISULFID 175..188
FT /evidence="ECO:0000250"
FT DISULFID 478..493
FT /evidence="ECO:0000250"
FT DISULFID 489..504
FT /evidence="ECO:0000250"
FT DISULFID 506..519
FT /evidence="ECO:0000250"
FT DISULFID 807..818
FT /evidence="ECO:0000250"
FT DISULFID 814..827
FT /evidence="ECO:0000250"
FT DISULFID 829..842
FT /evidence="ECO:0000250"
FT DISULFID 854..866
FT DISULFID 861..879
FT DISULFID 873..890
FT DISULFID 895..907
FT /evidence="ECO:0000250"
FT DISULFID 902..920
FT /evidence="ECO:0000250"
FT DISULFID 914..931
FT /evidence="ECO:0000250"
FT DISULFID 936..948
FT DISULFID 943..961
FT DISULFID 955..971
FT DISULFID 976..989
FT DISULFID 984..1002
FT DISULFID 996..1011
FT DISULFID 1015..1027
FT DISULFID 1022..1040
FT DISULFID 1034..1051
FT DISULFID 1062..1075
FT DISULFID 1069..1088
FT DISULFID 1082..1097
FT DISULFID 1104..1118
FT /evidence="ECO:0000250"
FT DISULFID 1112..1131
FT /evidence="ECO:0000250"
FT DISULFID 1125..1140
FT /evidence="ECO:0000250"
FT DISULFID 1145..1159
FT /evidence="ECO:0000250"
FT DISULFID 1152..1172
FT /evidence="ECO:0000250"
FT DISULFID 1166..1182
FT /evidence="ECO:0000250"
FT DISULFID 1185..1196
FT /evidence="ECO:0000250"
FT DISULFID 1192..1206
FT /evidence="ECO:0000250"
FT DISULFID 1208..1221
FT /evidence="ECO:0000250"
FT DISULFID 1227..1237
FT /evidence="ECO:0000250"
FT DISULFID 1233..1246
FT /evidence="ECO:0000250"
FT DISULFID 1248..1261
FT /evidence="ECO:0000250"
FT DISULFID 1540..1553
FT /evidence="ECO:0000250"
FT DISULFID 1549..1563
FT /evidence="ECO:0000250"
FT DISULFID 1565..1578
FT /evidence="ECO:0000250"
FT DISULFID 1850..1861
FT /evidence="ECO:0000250"
FT DISULFID 1857..1871
FT /evidence="ECO:0000250"
FT DISULFID 1873..1886
FT /evidence="ECO:0000250"
FT DISULFID 2159..2170
FT /evidence="ECO:0000250"
FT DISULFID 2166..2180
FT /evidence="ECO:0000250"
FT DISULFID 2182..2194
FT /evidence="ECO:0000250"
FT DISULFID 2482..2493
FT /evidence="ECO:0000250"
FT DISULFID 2489..2503
FT /evidence="ECO:0000250"
FT DISULFID 2505..2517
FT /evidence="ECO:0000250"
FT DISULFID 2524..2537
FT /evidence="ECO:0000250"
FT DISULFID 2532..2550
FT /evidence="ECO:0000250"
FT DISULFID 2544..2561
FT /evidence="ECO:0000250"
FT DISULFID 2566..2578
FT /evidence="ECO:0000250"
FT DISULFID 2573..2591
FT /evidence="ECO:0000250"
FT DISULFID 2585..2600
FT /evidence="ECO:0000250"
FT DISULFID 2605..2617
FT /evidence="ECO:0000250"
FT DISULFID 2612..2630
FT /evidence="ECO:0000250"
FT DISULFID 2624..2639
FT /evidence="ECO:0000250"
FT DISULFID 2644..2666
FT /evidence="ECO:0000250"
FT DISULFID 2660..2679
FT /evidence="ECO:0000250"
FT DISULFID 2673..2688
FT /evidence="ECO:0000250"
FT DISULFID 2696..2708
FT /evidence="ECO:0000250"
FT DISULFID 2703..2721
FT /evidence="ECO:0000250"
FT DISULFID 2715..2730
FT /evidence="ECO:0000250"
FT DISULFID 2734..2746
FT /evidence="ECO:0000250"
FT DISULFID 2741..2759
FT /evidence="ECO:0000250"
FT DISULFID 2753..2769
FT /evidence="ECO:0000250"
FT DISULFID 2774..2787
FT /evidence="ECO:0000250"
FT DISULFID 2781..2800
FT /evidence="ECO:0000250"
FT DISULFID 2794..2812
FT /evidence="ECO:0000250"
FT DISULFID 2818..2830
FT /evidence="ECO:0000250"
FT DISULFID 2825..2843
FT /evidence="ECO:0000250"
FT DISULFID 2837..2853
FT /evidence="ECO:0000250"
FT DISULFID 2858..2870
FT /evidence="ECO:0000250"
FT DISULFID 2865..2884
FT /evidence="ECO:0000250"
FT DISULFID 2878..2897
FT /evidence="ECO:0000250"
FT DISULFID 2904..2917
FT /evidence="ECO:0000250"
FT DISULFID 2912..2930
FT /evidence="ECO:0000250"
FT DISULFID 2924..2939
FT /evidence="ECO:0000250"
FT DISULFID 2944..2956
FT /evidence="ECO:0000250"
FT DISULFID 2952..2965
FT /evidence="ECO:0000250"
FT DISULFID 2967..2980
FT /evidence="ECO:0000250"
FT DISULFID 2986..2996
FT /evidence="ECO:0000250"
FT DISULFID 2992..3005
FT /evidence="ECO:0000250"
FT DISULFID 3007..3021
FT /evidence="ECO:0000250"
FT DISULFID 3294..3305
FT /evidence="ECO:0000250"
FT DISULFID 3301..3315
FT /evidence="ECO:0000250"
FT DISULFID 3317..3330
FT /evidence="ECO:0000250"
FT DISULFID 3334..3346
FT /evidence="ECO:0000250"
FT DISULFID 3341..3359
FT /evidence="ECO:0000250"
FT DISULFID 3353..3369
FT /evidence="ECO:0000250"
FT DISULFID 3374..3386
FT /evidence="ECO:0000250"
FT DISULFID 3381..3399
FT /evidence="ECO:0000250"
FT DISULFID 3393..3408
FT /evidence="ECO:0000250"
FT DISULFID 3413..3426
FT /evidence="ECO:0000250"
FT DISULFID 3420..3439
FT /evidence="ECO:0000250"
FT DISULFID 3433..3448
FT /evidence="ECO:0000250"
FT DISULFID 3453..3466
FT /evidence="ECO:0000250"
FT DISULFID 3460..3479
FT /evidence="ECO:0000250"
FT DISULFID 3473..3489
FT /evidence="ECO:0000250"
FT DISULFID 3494..3507
FT /evidence="ECO:0000250"
FT DISULFID 3501..3520
FT /evidence="ECO:0000250"
FT DISULFID 3514..3531
FT /evidence="ECO:0000250"
FT DISULFID 3536..3548
FT /evidence="ECO:0000250"
FT DISULFID 3543..3561
FT /evidence="ECO:0000250"
FT DISULFID 3555..3570
FT /evidence="ECO:0000250"
FT DISULFID 3575..3587
FT /evidence="ECO:0000250"
FT DISULFID 3582..3600
FT /evidence="ECO:0000250"
FT DISULFID 3594..3609
FT /evidence="ECO:0000250"
FT DISULFID 3613..3625
FT /evidence="ECO:0000250"
FT DISULFID 3620..3638
FT /evidence="ECO:0000250"
FT DISULFID 3632..3647
FT /evidence="ECO:0000250"
FT DISULFID 3654..3666
FT /evidence="ECO:0000250"
FT DISULFID 3661..3679
FT /evidence="ECO:0000250"
FT DISULFID 3673..3690
FT /evidence="ECO:0000250"
FT DISULFID 3695..3709
FT /evidence="ECO:0000250"
FT DISULFID 3703..3722
FT /evidence="ECO:0000250"
FT DISULFID 3716..3731
FT /evidence="ECO:0000250"
FT DISULFID 3741..3754
FT /evidence="ECO:0000250"
FT DISULFID 3749..3767
FT /evidence="ECO:0000250"
FT DISULFID 3761..3776
FT /evidence="ECO:0000250"
FT DISULFID 3785..3798
FT /evidence="ECO:0000250"
FT DISULFID 3792..3807
FT /evidence="ECO:0000250"
FT DISULFID 3809..3822
FT /evidence="ECO:0000250"
FT DISULFID 3828..3838
FT /evidence="ECO:0000250"
FT DISULFID 3834..3847
FT /evidence="ECO:0000250"
FT DISULFID 3849..3860
FT /evidence="ECO:0000250"
FT DISULFID 4151..4160
FT /evidence="ECO:0000250"
FT DISULFID 4156..4169
FT /evidence="ECO:0000250"
FT DISULFID 4171..4182
FT /evidence="ECO:0000250"
FT DISULFID 4200..4210
FT /evidence="ECO:0000250"
FT DISULFID 4204..4220
FT /evidence="ECO:0000250"
FT DISULFID 4222..4231
FT /evidence="ECO:0000250"
FT DISULFID 4236..4246
FT /evidence="ECO:0000250"
FT DISULFID 4240..4256
FT /evidence="ECO:0000250"
FT DISULFID 4258..4267
FT /evidence="ECO:0000250"
FT DISULFID 4272..4282
FT /evidence="ECO:0000250"
FT DISULFID 4276..4292
FT /evidence="ECO:0000250"
FT DISULFID 4294..4303
FT /evidence="ECO:0000250"
FT DISULFID 4308..4318
FT /evidence="ECO:0000250"
FT DISULFID 4312..4328
FT /evidence="ECO:0000250"
FT DISULFID 4330..4339
FT /evidence="ECO:0000250"
FT DISULFID 4344..4352
FT /evidence="ECO:0000250"
FT DISULFID 4347..4363
FT /evidence="ECO:0000250"
FT DISULFID 4365..4374
FT /evidence="ECO:0000250"
FT DISULFID 4377..4387
FT /evidence="ECO:0000250"
FT DISULFID 4381..4397
FT /evidence="ECO:0000250"
FT DISULFID 4399..4408
FT /evidence="ECO:0000250"
FT VAR_SEQ 281..292
FT /note="HVEQMAIDWLTG -> LCVFSKSQQEMG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056919"
FT VAR_SEQ 293..4544
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056920"
FT VARIANT 166
FT /note="N -> D (in dbSNP:rs2306691)"
FT /id="VAR_021885"
FT VARIANT 217
FT /note="A -> V (in dbSNP:rs1800127)"
FT /id="VAR_014725"
FT VARIANT 869
FT /note="E -> K (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1207947902)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035994"
FT VARIANT 1245
FT /note="K -> R (in KPA; reduced alpha-2 macroglobulin
FT receptor activity; reduced protein abundance;
FT dbSNP:rs483353013)"
FT /evidence="ECO:0000269|PubMed:26142438"
FT /id="VAR_077982"
FT VARIANT 2059
FT /note="V -> L (in dbSNP:rs2229278)"
FT /id="VAR_029181"
FT VARIANT 2080
FT /note="D -> N (in dbSNP:rs34577247)"
FT /id="VAR_047525"
FT VARIANT 2900
FT /note="Q -> P (in dbSNP:rs7397167)"
FT /evidence="ECO:0000269|PubMed:3266596,
FT ECO:0000269|PubMed:9782078, ECO:0000269|Ref.4"
FT /id="VAR_047526"
FT VARIANT 3258
FT /note="H -> Q (found in a patient with severe intellectual
FT disability, seizures, stereotypic behavior, high pain
FT threshold and sleep disturbances; dbSNP:rs1565750061)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069388"
FT VARIANT 3760
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs569866427)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035995"
FT VARIANT 4536
FT /note="E -> G (in dbSNP:rs17357542)"
FT /id="VAR_047527"
FT MUTAGEN 4460
FT /note="T->A: Strongly reduced phosphorylation and loss of
FT interaction with SHC1; when associated with A-4517; A-4520
FT and A-4523."
FT /evidence="ECO:0000269|PubMed:15272003"
FT MUTAGEN 4470..4473
FT /note="NPTY->APTA: No effect on tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:11854294"
FT MUTAGEN 4470
FT /note="N->A: No effect on interaction with GULP1."
FT /evidence="ECO:0000269|PubMed:11729193"
FT MUTAGEN 4472
FT /note="T->A: No detectable effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:15272003"
FT MUTAGEN 4504..4507
FT /note="NPVY->APVA: Loss of tyrosine phosphorylation.
FT Abolishes interaction with SHC1 and GULP1."
FT /evidence="ECO:0000269|PubMed:11854294"
FT MUTAGEN 4504
FT /note="N->A: Loss of interaction with GULP1."
FT /evidence="ECO:0000269|PubMed:11729193"
FT MUTAGEN 4517
FT /note="S->A: Strongly reduced phosphorylation and loss of
FT interaction with SHC1; when associated with A-4460; A-4520
FT and A-4523."
FT /evidence="ECO:0000269|PubMed:15272003"
FT MUTAGEN 4520
FT /note="S->A: Strongly reduced phosphorylation and loss of
FT interaction with SHC1; when associated with A-4460; A-4517
FT and A-4523."
FT /evidence="ECO:0000269|PubMed:15272003"
FT MUTAGEN 4523
FT /note="S->A: Strongly reduced phosphorylation and loss of
FT interaction with SHC1; when associated with A-4460; A-4517
FT and A-4520."
FT /evidence="ECO:0000269|PubMed:15272003"
FT CONFLICT 685
FT /note="D -> G (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1743
FT /note="G -> S (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 2871..2872
FT /note="LS -> IA (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 3036
FT /note="R -> M (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT TURN 853..857
FT /evidence="ECO:0007829|PDB:1D2L"
FT STRAND 859..861
FT /evidence="ECO:0007829|PDB:1D2L"
FT TURN 862..864
FT /evidence="ECO:0007829|PDB:1D2L"
FT STRAND 865..867
FT /evidence="ECO:0007829|PDB:1D2L"
FT HELIX 869..871
FT /evidence="ECO:0007829|PDB:1D2L"
FT STRAND 874..876
FT /evidence="ECO:0007829|PDB:1D2L"
FT TURN 878..881
FT /evidence="ECO:0007829|PDB:1D2L"
FT STRAND 934..936
FT /evidence="ECO:0007829|PDB:2FYJ"
FT STRAND 940..942
FT /evidence="ECO:0007829|PDB:2FYJ"
FT TURN 944..946
FT /evidence="ECO:0007829|PDB:2FYL"
FT STRAND 948..950
FT /evidence="ECO:0007829|PDB:2FYJ"
FT STRAND 953..956
FT /evidence="ECO:0007829|PDB:2FYJ"
FT STRAND 958..961
FT /evidence="ECO:0007829|PDB:2FYJ"
FT TURN 964..968
FT /evidence="ECO:0007829|PDB:2FYJ"
FT TURN 969..971
FT /evidence="ECO:0007829|PDB:2FYL"
FT STRAND 974..976
FT /evidence="ECO:0007829|PDB:2FYJ"
FT STRAND 978..983
FT /evidence="ECO:0007829|PDB:2FYJ"
FT TURN 985..987
FT /evidence="ECO:0007829|PDB:2FYL"
FT STRAND 989..991
FT /evidence="ECO:0007829|PDB:2FYJ"
FT STRAND 995..1000
FT /evidence="ECO:0007829|PDB:2FYJ"
FT STRAND 1003..1007
FT /evidence="ECO:0007829|PDB:2FYJ"
FT STRAND 1009..1011
FT /evidence="ECO:0007829|PDB:2FYL"
FT STRAND 1013..1015
FT /evidence="ECO:0007829|PDB:1J8E"
FT STRAND 1019..1021
FT /evidence="ECO:0007829|PDB:1J8E"
FT STRAND 1027..1029
FT /evidence="ECO:0007829|PDB:1J8E"
FT HELIX 1030..1032
FT /evidence="ECO:0007829|PDB:1J8E"
FT STRAND 1035..1037
FT /evidence="ECO:0007829|PDB:1J8E"
FT STRAND 1040..1043
FT /evidence="ECO:0007829|PDB:1J8E"
FT HELIX 1044..1046
FT /evidence="ECO:0007829|PDB:1J8E"
FT HELIX 1048..1051
FT /evidence="ECO:0007829|PDB:1J8E"
FT TURN 1070..1072
FT /evidence="ECO:0007829|PDB:1CR8"
FT HELIX 1078..1080
FT /evidence="ECO:0007829|PDB:1CR8"
FT STRAND 1081..1085
FT /evidence="ECO:0007829|PDB:1CR8"
FT STRAND 1088..1091
FT /evidence="ECO:0007829|PDB:1CR8"
FT TURN 1092..1096
FT /evidence="ECO:0007829|PDB:1CR8"
FT STRAND 2778..2781
FT /evidence="ECO:0007829|PDB:2KNX"
FT TURN 2782..2785
FT /evidence="ECO:0007829|PDB:2KNX"
FT STRAND 2786..2789
FT /evidence="ECO:0007829|PDB:2KNX"
FT TURN 2790..2794
FT /evidence="ECO:0007829|PDB:2KNX"
FT STRAND 2795..2797
FT /evidence="ECO:0007829|PDB:2KNX"
FT STRAND 2800..2803
FT /evidence="ECO:0007829|PDB:2KNY"
FT HELIX 2804..2806
FT /evidence="ECO:0007829|PDB:2KNX"
FT HELIX 2808..2810
FT /evidence="ECO:0007829|PDB:2KNX"
FT STRAND 2813..2816
FT /evidence="ECO:0007829|PDB:2KNY"
SQ SEQUENCE 4544 AA; 504606 MW; 5A11CC02FAB127BE CRC64;
MLTPPLLLLL PLLSALVAAA IDAPKTCSPK QFACRDQITC ISKGWRCDGE RDCPDGSDEA
PEICPQSKAQ RCQPNEHNCL GTELCVPMSR LCNGVQDCMD GSDEGPHCRE LQGNCSRLGC
QHHCVPTLDG PTCYCNSSFQ LQADGKTCKD FDECSVYGTC SQLCTNTDGS FICGCVEGYL
LQPDNRSCKA KNEPVDRPPV LLIANSQNIL ATYLSGAQVS TITPTSTRQT TAMDFSYANE
TVCWVHVGDS AAQTQLKCAR MPGLKGFVDE HTINISLSLH HVEQMAIDWL TGNFYFVDDI
DDRIFVCNRN GDTCVTLLDL ELYNPKGIAL DPAMGKVFFT DYGQIPKVER CDMDGQNRTK
LVDSKIVFPH GITLDLVSRL VYWADAYLDY IEVVDYEGKG RQTIIQGILI EHLYGLTVFE
NYLYATNSDN ANAQQKTSVI RVNRFNSTEY QVVTRVDKGG ALHIYHQRRQ PRVRSHACEN
DQYGKPGGCS DICLLANSHK ARTCRCRSGF SLGSDGKSCK KPEHELFLVY GKGRPGIIRG
MDMGAKVPDE HMIPIENLMN PRALDFHAET GFIYFADTTS YLIGRQKIDG TERETILKDG
IHNVEGVAVD WMGDNLYWTD DGPKKTISVA RLEKAAQTRK TLIEGKMTHP RAIVVDPLNG
WMYWTDWEED PKDSRRGRLE RAWMDGSHRD IFVTSKTVLW PNGLSLDIPA GRLYWVDAFY
DRIETILLNG TDRKIVYEGP ELNHAFGLCH HGNYLFWTEY RSGSVYRLER GVGGAPPTVT
LLRSERPPIF EIRMYDAQQQ QVGTNKCRVN NGGCSSLCLA TPGSRQCACA EDQVLDADGV
TCLANPSYVP PPQCQPGEFA CANSRCIQER WKCDGDNDCL DNSDEAPALC HQHTCPSDRF
KCENNRCIPN RWLCDGDNDC GNSEDESNAT CSARTCPPNQ FSCASGRCIP ISWTCDLDDD
CGDRSDESAS CAYPTCFPLT QFTCNNGRCI NINWRCDNDN DCGDNSDEAG CSHSCSSTQF
KCNSGRCIPE HWTCDGDNDC GDYSDETHAN CTNQATRPPG GCHTDEFQCR LDGLCIPLRW
RCDGDTDCMD SSDEKSCEGV THVCDPSVKF GCKDSARCIS KAWVCDGDND CEDNSDEENC
ESLACRPPSH PCANNTSVCL PPDKLCDGND DCGDGSDEGE LCDQCSLNNG GCSHNCSVAP
GEGIVCSCPL GMELGPDNHT CQIQSYCAKH LKCSQKCDQN KFSVKCSCYE GWVLEPDGES
CRSLDPFKPF IIFSNRHEIR RIDLHKGDYS VLVPGLRNTI ALDFHLSQSA LYWTDVVEDK
IYRGKLLDNG ALTSFEVVIQ YGLATPEGLA VDWIAGNIYW VESNLDQIEV AKLDGTLRTT
LLAGDIEHPR AIALDPRDGI LFWTDWDASL PRIEAASMSG AGRRTVHRET GSGGWPNGLT
VDYLEKRILW IDARSDAIYS ARYDGSGHME VLRGHEFLSH PFAVTLYGGE VYWTDWRTNT
LAKANKWTGH NVTVVQRTNT QPFDLQVYHP SRQPMAPNPC EANGGQGPCS HLCLINYNRT
VSCACPHLMK LHKDNTTCYE FKKFLLYARQ MEIRGVDLDA PYYNYIISFT VPDIDNVTVL
DYDAREQRVY WSDVRTQAIK RAFINGTGVE TVVSADLPNA HGLAVDWVSR NLFWTSYDTN
KKQINVARLD GSFKNAVVQG LEQPHGLVVH PLRGKLYWTD GDNISMANMD GSNRTLLFSG
QKGPVGLAID FPESKLYWIS SGNHTINRCN LDGSGLEVID AMRSQLGKAT ALAIMGDKLW
WADQVSEKMG TCSKADGSGS VVLRNSTTLV MHMKVYDESI QLDHKGTNPC SVNNGDCSQL
CLPTSETTRS CMCTAGYSLR SGQQACEGVG SFLLYSVHEG IRGIPLDPND KSDALVPVSG
TSLAVGIDFH AENDTIYWVD MGLSTISRAK RDQTWREDVV TNGIGRVEGI AVDWIAGNIY
WTDQGFDVIE VARLNGSFRY VVISQGLDKP RAITVHPEKG YLFWTEWGQY PRIERSRLDG
TERVVLVNVS ISWPNGISVD YQDGKLYWCD ARTDKIERID LETGENREVV LSSNNMDMFS
VSVFEDFIYW SDRTHANGSI KRGSKDNATD SVPLRTGIGV QLKDIKVFNR DRQKGTNVCA
VANGGCQQLC LYRGRGQRAC ACAHGMLAED GASCREYAGY LLYSERTILK SIHLSDERNL
NAPVQPFEDP EHMKNVIALA FDYRAGTSPG TPNRIFFSDI HFGNIQQIND DGSRRITIVE
NVGSVEGLAY HRGWDTLYWT SYTTSTITRH TVDQTRPGAF ERETVITMSG DDHPRAFVLD
ECQNLMFWTN WNEQHPSIMR AALSGANVLT LIEKDIRTPN GLAIDHRAEK LYFSDATLDK
IERCEYDGSH RYVILKSEPV HPFGLAVYGE HIFWTDWVRR AVQRANKHVG SNMKLLRVDI
PQQPMGIIAV ANDTNSCELS PCRINNGGCQ DLCLLTHQGH VNCSCRGGRI LQDDLTCRAV
NSSCRAQDEF ECANGECINF SLTCDGVPHC KDKSDEKPSY CNSRRCKKTF RQCSNGRCVS
NMLWCNGADD CGDGSDEIPC NKTACGVGEF RCRDGTCIGN SSRCNQFVDC EDASDEMNCS
ATDCSSYFRL GVKGVLFQPC ERTSLCYAPS WVCDGANDCG DYSDERDCPG VKRPRCPLNY
FACPSGRCIP MSWTCDKEDD CEHGEDETHC NKFCSEAQFE CQNHRCISKQ WLCDGSDDCG
DGSDEAAHCE GKTCGPSSFS CPGTHVCVPE RWLCDGDKDC ADGADESIAA GCLYNSTCDD
REFMCQNRQC IPKHFVCDHD RDCADGSDES PECEYPTCGP SEFRCANGRC LSSRQWECDG
ENDCHDQSDE APKNPHCTSQ EHKCNASSQF LCSSGRCVAE ALLCNGQDDC GDSSDERGCH
INECLSRKLS GCSQDCEDLK IGFKCRCRPG FRLKDDGRTC ADVDECSTTF PCSQRCINTH
GSYKCLCVEG YAPRGGDPHS CKAVTDEEPF LIFANRYYLR KLNLDGSNYT LLKQGLNNAV
ALDFDYREQM IYWTDVTTQG SMIRRMHLNG SNVQVLHRTG LSNPDGLAVD WVGGNLYWCD
KGRDTIEVSK LNGAYRTVLV SSGLREPRAL VVDVQNGYLY WTDWGDHSLI GRIGMDGSSR
SVIVDTKITW PNGLTLDYVT ERIYWADARE DYIEFASLDG SNRHVVLSQD IPHIFALTLF
EDYVYWTDWE TKSINRAHKT TGTNKTLLIS TLHRPMDLHV FHALRQPDVP NHPCKVNNGG
CSNLCLLSPG GGHKCACPTN FYLGSDGRTC VSNCTASQFV CKNDKCIPFW WKCDTEDDCG
DHSDEPPDCP EFKCRPGQFQ CSTGICTNPA FICDGDNDCQ DNSDEANCDI HVCLPSQFKC
TNTNRCIPGI FRCNGQDNCG DGEDERDCPE VTCAPNQFQC SITKRCIPRV WVCDRDNDCV
DGSDEPANCT QMTCGVDEFR CKDSGRCIPA RWKCDGEDDC GDGSDEPKEE CDERTCEPYQ
FRCKNNRCVP GRWQCDYDND CGDNSDEESC TPRPCSESEF SCANGRCIAG RWKCDGDHDC
ADGSDEKDCT PRCDMDQFQC KSGHCIPLRW RCDADADCMD GSDEEACGTG VRTCPLDEFQ
CNNTLCKPLA WKCDGEDDCG DNSDENPEEC ARFVCPPNRP FRCKNDRVCL WIGRQCDGTD
NCGDGTDEED CEPPTAHTTH CKDKKEFLCR NQRCLSSSLR CNMFDDCGDG SDEEDCSIDP
KLTSCATNAS ICGDEARCVR TEKAAYCACR SGFHTVPGQP GCQDINECLR FGTCSQLCNN
TKGGHLCSCA RNFMKTHNTC KAEGSEYQVL YIADDNEIRS LFPGHPHSAY EQAFQGDESV
RIDAMDVHVK AGRVYWTNWH TGTISYRSLP PAAPPTTSNR HRRQIDRGVT HLNISGLKMP
RGIAIDWVAG NVYWTDSGRD VIEVAQMKGE NRKTLISGMI DEPHAIVVDP LRGTMYWSDW
GNHPKIETAA MDGTLRETLV QDNIQWPTGL AVDYHNERLY WADAKLSVIG SIRLNGTDPI
VAADSKRGLS HPFSIDVFED YIYGVTYINN RVFKIHKFGH SPLVNLTGGL SHASDVVLYH
QHKQPEVTNP CDRKKCEWLC LLSPSGPVCT CPNGKRLDNG TCVPVPSPTP PPDAPRPGTC
NLQCFNGGSC FLNARRQPKC RCQPRYTGDK CELDQCWEHC RNGGTCAASP SGMPTCRCPT
GFTGPKCTQQ VCAGYCANNS TCTVNQGNQP QCRCLPGFLG DRCQYRQCSG YCENFGTCQM
AADGSRQCRC TAYFEGSRCE VNKCSRCLEG ACVVNKQSGD VTCNCTDGRV APSCLTCVGH
CSNGGSCTMN SKMMPECQCP PHMTGPRCEE HVFSQQQPGH IASILIPLLL LLLLVLVAGV
VFWYKRRVQG AKGFQHQRMT NGAMNVEIGN PTYKMYEGGE PDDVGGLLDA DFALDPDKPT
NFTNPVYATL YMGGHGSRHS LASTDEKREL LGRGPEDEIG DPLA
