LRP2_HUMAN
ID LRP2_HUMAN Reviewed; 4655 AA.
AC P98164; O00711; Q16215;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 3.
DT 03-AUG-2022, entry version 213.
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 {ECO:0000312|HGNC:HGNC:6694};
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], AND VARIANT SER-83.
RC TISSUE=Kidney;
RX PubMed=8706697; DOI=10.1111/j.1432-1033.1996.0132u.x;
RA Hjaelm G., Murray E., Crumley G., Harazim W., Lundgren S., Onyango I.,
RA Ek B., Larsson M., Juhlin C., Hellman P., Davis H., Aekerstroem G.,
RA Rask L., Morse B.;
RT "Cloning and sequencing of human gp330, a Ca(2+)-binding receptor with
RT potential intracellular signaling properties.";
RL Eur. J. Biochem. 239:132-137(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2705-4453, AND VARIANTS GLU-4094 AND
RP LEU-4210.
RC TISSUE=Kidney;
RX PubMed=7959795; DOI=10.1006/geno.1994.1348;
RA Korenberg J.R., Argraves K.M., Chen X.N., Tran H., Strickland D.K.,
RA Argraves W.S.;
RT "Chromosomal localization of human genes for the LDL receptor family member
RT glycoprotein 330 (LRP2) and its associated protein RAP (LRPAP1).";
RL Genomics 22:88-93(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4139-4406.
RX PubMed=8187828; DOI=10.1006/excr.1994.1153;
RA Lundgren S., Hjaelm G., Hellman P., Ek B., Juhlin C., Rastad J.,
RA Klareskog L., Aakerstroem G., Rask L.;
RT "A protein involved in calcium sensing of the human parathyroid and
RT placental cytotrophoblast cells belongs to the LDL-receptor protein
RT superfamily.";
RL Exp. Cell Res. 212:344-350(1994).
RN [5]
RP INTERACTION WITH LRPAP1.
RX PubMed=1400426; DOI=10.1016/s0021-9258(19)36811-5;
RA Kounnas M.Z., Argraves W.S., Strickland D.K.;
RT "The 39-kDa receptor-associated protein interacts with two members of the
RT low density lipoprotein receptor family, alpha 2-macroglobulin receptor and
RT glycoprotein 330.";
RL J. Biol. Chem. 267:21162-21166(1992).
RN [6]
RP SUBUNIT, AND INTERACTION WITH CLU.
RX PubMed=7768901; DOI=10.1074/jbc.270.22.13070;
RA Kounnas M.Z., Loukinova E.B., Stefansson S., Harmony J.A.K., Brewer B.H.,
RA Strickland D.K., Argraves W.S.;
RT "Identification of glycoprotein 330 as an endocytic receptor for
RT apolipoprotein J/clusterin.";
RL J. Biol. Chem. 270:13070-13075(1995).
RN [7]
RP INTERACTION WITH DAB2.
RX PubMed=10769163; DOI=10.1042/bj3470613;
RA Oleinikov A.V., Zhao J., Makker S.P.;
RT "Cytosolic adaptor protein Dab2 is an intracellular ligand of endocytic
RT receptor gp600/megalin.";
RL Biochem. J. 347:613-621(2000).
RN [8]
RP INTERACTION WITH LRP2BP.
RX PubMed=12508107; DOI=10.1242/jcs.00243;
RA Petersen H.H., Hilpert J., Militz D., Zandler V., Jacobsen C.,
RA Roebroek A.J.M., Willnow T.E.;
RT "Functional interaction of megalin with the megalin-binding protein
RT (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule.";
RL J. Cell Sci. 116:453-461(2003).
RN [9]
RP FUNCTION.
RX PubMed=15126248; DOI=10.1152/ajprenal.00233.2003;
RA Klassen R.B., Crenshaw K., Kozyraki R., Verroust P.J., Tio L., Atrian S.,
RA Allen P.L., Hammond T.G.;
RT "Megalin mediates renal uptake of heavy metal metallothionein complexes.";
RL Am. J. Physiol. 287:F393-F403(2004).
RN [10]
RP INTERACTION WITH DAB2.
RX PubMed=15134832; DOI=10.1016/j.biochi.2004.03.001;
RA Gallagher H., Oleinikov A.V., Fenske C., Newman D.J.;
RT "The adaptor disabled-2 binds to the third psi xNPxY sequence on the
RT cytoplasmic tail of megalin.";
RL Biochimie 86:179-182(2004).
RN [11]
RP INTERACTION WITH SHBG.
RX PubMed=16143106; DOI=10.1016/j.cell.2005.06.032;
RA Hammes A., Andreassen T.K., Spoelgen R., Raila J., Hubner N., Schulz H.,
RA Metzger J., Schweigert F.J., Luppa P.B., Nykjaer A., Willnow T.E.;
RT "Role of endocytosis in cellular uptake of sex steroids.";
RL Cell 122:751-762(2005).
RN [12]
RP INTERACTION WITH CST3.
RX PubMed=17462596; DOI=10.1016/j.bbrc.2007.04.072;
RA Kaseda R., Iino N., Hosojima M., Takeda T., Hosaka K., Kobayashi A.,
RA Yamamoto K., Suzuki A., Kasai A., Suzuki Y., Gejyo F., Saito A.;
RT "Megalin-mediated endocytosis of cystatin C in proximal tubule cells.";
RL Biochem. Biophys. Res. Commun. 357:1130-1134(2007).
RN [13]
RP DEVELOPMENTAL STAGE.
RX PubMed=17324488; DOI=10.1016/j.neurobiolaging.2007.01.008;
RA Dietrich M.O., Spuch C., Antequera D., Rodal I., de Yebenes J.G.,
RA Molina J.A., Bermejo F., Carro E.;
RT "Megalin mediates the transport of leptin across the blood-CSF barrier.";
RL Neurobiol. Aging 29:902-912(2008).
RN [14]
RP FUNCTION, INTERACTION WITH BIRC5, AND SUBCELLULAR LOCATION.
RX PubMed=23825075; DOI=10.1152/ajprenal.00546.2012;
RA Jobst-Schwan T., Knaup K.X., Nielsen R., Hackenbeck T., Buettner-Herold M.,
RA Lechler P., Kroening S., Goppelt-Struebe M., Schloetzer-Schrehardt U.,
RA Fuernrohr B.G., Voll R.E., Amann K., Eckardt K.U., Christensen E.I.,
RA Wiesener M.S.;
RT "Renal uptake of the antiapoptotic protein survivin is mediated by megalin
RT at the apical membrane of the proximal tubule.";
RL Am. J. Physiol. 305:F734-F744(2013).
RN [15]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=27798286; DOI=10.1369/0022155416672210;
RA Storm T., Christensen E.I., Christensen J.N., Kjaergaard T., Uldbjerg N.,
RA Larsen A., Honore B., Madsen M.;
RT "Megalin is predominantly observed in vesicular structures in first and
RT third trimester cytotrophoblasts of the human placenta.";
RL J. Histochem. Cytochem. 64:769-784(2016).
RN [16]
RP STRUCTURE BY NMR OF 1103-1148 IN COMPLEX WITH CALCIUM, AND DISULFIDE BONDS.
RX PubMed=23275343; DOI=10.1074/jbc.m112.434159;
RA Dagil R., O'Shea C., Nykjaer A., Bonvin A.M., Kragelund B.B.;
RT "Gentamicin binds to the megalin receptor as a competitive inhibitor using
RT the common ligand binding motif of complement type repeats: insight from
RT the NMR structure of the 10th complement type repeat domain alone and in
RT complex with gentamicin.";
RL J. Biol. Chem. 288:4424-4435(2013).
RN [17]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-4272.
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 [18]
RP VARIANT DBS HIS-2522.
RX PubMed=17632512; DOI=10.1038/ng2063;
RA Kantarci S., Al-Gazali L., Hill R.S., Donnai D., Black G.C.M., Bieth E.,
RA Chassaing N., Lacombe D., Devriendt K., Teebi A., Loscertales M.,
RA Robson C., Liu T., MacLaughlin D.T., Noonan K.M., Russell M.K., Walsh C.A.,
RA Donahoe P.K., Pober B.R.;
RT "Mutations in LRP2, which encodes the multiligand receptor megalin, cause
RT Donnai-Barrow and facio-oculo-acoustico-renal syndromes.";
RL Nat. Genet. 39:957-959(2007).
RN [19]
RP VARIANT ARG-103.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
RN [20]
RP VARIANT GLY-3828.
RX PubMed=23992033; DOI=10.1111/cge.12265;
RA Schrauwen I., Sommen M., Claes C., Pinner J., Flaherty M., Collins F.,
RA Van Camp G.;
RT "Broadening the phenotype of LRP2 mutations: a new mutation in LRP2 causes
RT a predominantly ocular phenotype suggestive of Stickler syndrome.";
RL Clin. Genet. 86:282-286(2014).
RN [21]
RP VARIANT ASN-3779.
RX PubMed=26529358; DOI=10.1097/ypg.0000000000000114;
RA Vasli N., Ahmed I., Mittal K., Ohadi M., Mikhailov A., Rafiq M.A.,
RA Bhatti A., Carter M.T., Andrade D.M., Ayub M., Vincent J.B., John P.;
RT "Identification of a homozygous missense mutation in LRP2 and a hemizygous
RT missense mutation in TSPYL2 in a family with mild intellectual
RT disability.";
RL Psychiatr. Genet. 26:66-73(2016).
CC -!- FUNCTION: Multiligand endocytic receptor (By similarity). Acts together
CC with CUBN to mediate endocytosis of high-density lipoproteins (By
CC similarity). Mediates receptor-mediated uptake of polybasic drugs such
CC as aprotinin, aminoglycosides and polymyxin B (By similarity). In the
CC kidney, mediates the tubular uptake and clearance of leptin (By
CC similarity). Also mediates transport of leptin across the blood-brain
CC barrier through endocytosis at the choroid plexus epithelium (By
CC similarity). Endocytosis of leptin in neuronal cells is required for
CC hypothalamic leptin signaling and leptin-mediated regulation of feeding
CC and body weight (By similarity). Mediates endocytosis and subsequent
CC lysosomal degradation of CST3 in kidney proximal tubule cells (By
CC similarity). Mediates renal uptake of 25-hydroxyvitamin D3 in complex
CC with the vitamin D3 transporter GC/DBP (By similarity). Mediates renal
CC uptake of metallothionein-bound heavy metals (PubMed:15126248).
CC Together with CUBN, mediates renal reabsorption of myoglobin (By
CC similarity). Mediates renal uptake and subsequent lysosomal degradation
CC of APOM (By similarity). Plays a role in kidney selenium homeostasis by
CC mediating renal endocytosis of selenoprotein SEPP1 (By similarity).
CC Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which
CC may be important for functional integrity of the kidney
CC (PubMed:23825075). Mediates renal uptake of matrix metalloproteinase
CC MMP2 in complex with metalloproteinase inhibitor TIMP1 (By similarity).
CC Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the
CC active product of SHH (By similarity). Also mediates ShhN transcytosis
CC (By similarity). In the embryonic neuroepithelium, mediates endocytic
CC uptake and degradation of BMP4, is required for correct SHH
CC localization in the ventral neural tube and plays a role in patterning
CC of the ventral telencephalon (By similarity). Required at the onset of
CC neurulation to sequester SHH on the apical surface of neuroepithelial
CC cells of the rostral diencephalon ventral midline and to control PTCH1-
CC dependent uptake and intracellular trafficking of SHH (By similarity).
CC During neurulation, required in neuroepithelial cells for uptake of
CC folate bound to the folate receptor FOLR1 which is necessary for neural
CC tube closure (By similarity). In the adult brain, negatively regulates
CC BMP signaling in the subependymal zone which enables neurogenesis to
CC proceed (By similarity). In astrocytes, mediates endocytosis of ALB
CC which is required for the synthesis of the neurotrophic factor oleic
CC acid (By similarity). Involved in neurite branching (By similarity).
CC During optic nerve development, required for SHH-mediated migration and
CC proliferation of oligodendrocyte precursor cells (By similarity).
CC Mediates endocytic uptake and clearance of SHH in the retinal margin
CC which protects retinal progenitor cells from mitogenic stimuli and
CC keeps them quiescent (By similarity). Plays a role in reproductive
CC organ development by mediating uptake in reproductive tissues of
CC androgen and estrogen bound to the sex hormone binding protein SHBG (By
CC similarity). Mediates endocytosis of angiotensin-2 (By similarity).
CC Also mediates endocytosis of angiotensis 1-7 (By similarity). Binds to
CC the complex composed of beta-amyloid protein 40 and CLU/APOJ and
CC mediates its endocytosis and lysosomal degradation (By similarity).
CC Required for embryonic heart development (By similarity). Required for
CC normal hearing, possibly through interaction with estrogen in the inner
CC ear (By similarity). {ECO:0000250|UniProtKB:A2ARV4,
CC ECO:0000250|UniProtKB:C0HL13, ECO:0000250|UniProtKB:P98158,
CC ECO:0000269|PubMed:15126248, ECO:0000269|PubMed:23825075}.
CC -!- SUBUNIT: Binds plasminogen, extracellular matrix components,
CC plasminogen activator-plasminogen activator inhibitor type I complex,
CC apolipoprotein E-enriched beta-VLDL, lipoprotein lipase, lactoferrin,
CC CLU/clusterin and calcium (PubMed:7768901). Forms a multimeric complex
CC together with LRPAP1 (PubMed:1400426). Interacts (via PxLPxI/L motif)
CC with ANKRA2 (via ankyrin repeats) (By similarity). Interacts with
CC LRP2BP (PubMed:12508107). Interacts (via NPXY motif) with DAB2; the
CC interaction is not affected by tyrosine phosphorylation of the NPXY
CC motif (PubMed:10769163, PubMed:15134832). Interacts with MB (By
CC similarity). Interacts with BMP4 (By similarity). Interacts with the
CC Sonic hedgehog protein N-product which is the active product of SHH (By
CC similarity). Interacts with CST3 in a calcium-dependent manner
CC (PubMed:17462596). Interacts with the vitamin-D binding protein GC/DBP
CC (By similarity). Interacts with sex hormone-binding protein SHBG
CC (PubMed:16143106). Interacts with angiotensin-2 (By similarity). Also
CC interacts with angiotensin 1-7 (By similarity). Interacts with APOM (By
CC similarity). Interacts with selenoprotein SEPP1 (By similarity).
CC Interacts with LEP (By similarity). Interacts with ALB (By similarity).
CC Interacts with the antiapoptotic protein BIRC5/survivin
CC (PubMed:23825075). 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 (By
CC similarity). Interacts with LDLRAP1/ARH; mediates trafficking of LRP2
CC to the endocytic recycling compartment (By similarity). Does not
CC interact with beta-amyloid protein 40 alone but interacts with the
CC complex composed of beta-amyloid protein 40 and CLU/APOJ (By
CC similarity). Interacts with MDK (By similarity).
CC {ECO:0000250|UniProtKB:A2ARV4, ECO:0000250|UniProtKB:C0HL13,
CC ECO:0000250|UniProtKB:P98158, ECO:0000269|PubMed:10769163,
CC ECO:0000269|PubMed:12508107, ECO:0000269|PubMed:1400426,
CC ECO:0000269|PubMed:15134832, ECO:0000269|PubMed:16143106,
CC ECO:0000269|PubMed:17462596, ECO:0000269|PubMed:23825075,
CC ECO:0000269|PubMed:7768901}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:23825075, ECO:0000269|PubMed:27798286}; Single-pass
CC type I membrane protein {ECO:0000255}. Endosome lumen
CC {ECO:0000250|UniProtKB:P98158}. Membrane, coated pit
CC {ECO:0000250|UniProtKB:A2ARV4}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:A2ARV4}. Cell projection, axon
CC {ECO:0000250|UniProtKB:A2ARV4}. Note=Localizes to brush border
CC membranes in the kidney. In the endolymphatic sac of the inner ear,
CC located in the lumen of endosomes as a soluble form.
CC {ECO:0000250|UniProtKB:P98158}.
CC -!- TISSUE SPECIFICITY: Expressed in first and third trimester
CC cytotrophoblasts in the placenta (at protein level) (PubMed:27798286).
CC Absorptive epithelia, including renal proximal tubules.
CC {ECO:0000269|PubMed:27798286}.
CC -!- DEVELOPMENTAL STAGE: Expression in the choroid plexus of the brain is
CC markedly reduced in aging subjects when compared with younger adults.
CC {ECO:0000269|PubMed:17324488}.
CC -!- DOMAIN: Two overlapping PxLPxI/L motifs mediate interaction with
CC ankyrin repeats of ANKRA2. {ECO:0000250|UniProtKB:P98158}.
CC -!- DOMAIN: The cytoplasmic domain is required for sorting to the apical
CC cell membrane. {ECO:0000250|UniProtKB:P98158}.
CC -!- PTM: A fraction undergoes proteolytic cleavage of the extracellular
CC domain at the cell membrane to generate a cytoplasmic tail fragment.
CC This is internalized into the early endosome from where it trafficks in
CC an LDLRAP1/ARH-dependent manner to the endocytic recycling compartment
CC (ERC). In the ERC, it is further cleaved by gamma-secretase to release
CC a fragment which translocates to the nucleus and mediates
CC transcriptional repression. {ECO:0000250|UniProtKB:P98158}.
CC -!- PTM: N-glycosylation is required for ligand binding.
CC {ECO:0000250|UniProtKB:A2ARV4}.
CC -!- DISEASE: Donnai-Barrow syndrome (DBS) [MIM:222448]: Rare autosomal
CC recessive disorder characterized by major malformations including
CC agenesis of the corpus callosum, congenital diaphragmatic hernia,
CC facial dysmorphology, ocular anomalies, sensorineural hearing loss and
CC developmental delay. The FOAR syndrome was first described as
CC comprising facial anomalies, ocular anomalies, sensorineural hearing
CC loss, and proteinuria. DBS and FOAR were first described as distinct
CC disorders but the classic distinguishing features between the 2
CC disorders were presence of proteinuria and absence of diaphragmatic
CC hernia and corpus callosum anomalies in FOAR. Early reports noted that
CC the 2 disorders shared many phenotypic features and may be identical.
CC Although there is variability in the expression of some features (e.g.,
CC agenesis of the corpus callosum and proteinuria), DBS and FOAR are now
CC considered to represent the same entity. {ECO:0000269|PubMed:17632512}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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DR EMBL; U33837; AAB41649.1; -; mRNA.
DR EMBL; AC007556; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC008178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U04441; AAB02882.1; -; mRNA.
DR EMBL; S73145; AAB30825.1; -; mRNA.
DR CCDS; CCDS2232.1; -.
DR PIR; I38467; I38467.
DR PIR; I53413; I53413.
DR RefSeq; NP_004516.2; NM_004525.2.
DR PDB; 2M0P; NMR; -; A=1103-1148.
DR PDBsum; 2M0P; -.
DR SMR; P98164; -.
DR BioGRID; 110216; 129.
DR IntAct; P98164; 43.
DR MINT; P98164; -.
DR STRING; 9606.ENSP00000263816; -.
DR DrugBank; DB00115; Cyanocobalamin.
DR DrugBank; DB00798; Gentamicin.
DR DrugBank; DB00030; Insulin human.
DR DrugBank; DB00013; Urokinase.
DR TCDB; 9.B.87.1.14; the selenoprotein p receptor (selp-receptor) family.
DR GlyConnect; 1467; 7 N-Linked glycans (3 sites).
DR GlyGen; P98164; 66 sites, 7 N-linked glycans (3 sites), 5 O-linked glycans (26 sites).
DR iPTMnet; P98164; -.
DR PhosphoSitePlus; P98164; -.
DR BioMuta; LRP2; -.
DR DMDM; 160332309; -.
DR EPD; P98164; -.
DR jPOST; P98164; -.
DR MassIVE; P98164; -.
DR MaxQB; P98164; -.
DR PaxDb; P98164; -.
DR PeptideAtlas; P98164; -.
DR PRIDE; P98164; -.
DR ProteomicsDB; 57800; -.
DR Antibodypedia; 962; 370 antibodies from 35 providers.
DR DNASU; 4036; -.
DR Ensembl; ENST00000649046.1; ENSP00000496870.1; ENSG00000081479.15.
DR GeneID; 4036; -.
DR KEGG; hsa:4036; -.
DR MANE-Select; ENST00000649046.1; ENSP00000496870.1; NM_004525.3; NP_004516.2.
DR UCSC; uc002ues.4; human.
DR CTD; 4036; -.
DR DisGeNET; 4036; -.
DR GeneCards; LRP2; -.
DR GeneReviews; LRP2; -.
DR HGNC; HGNC:6694; LRP2.
DR HPA; ENSG00000081479; Group enriched (brain, kidney, parathyroid gland, retina, thyroid gland).
DR MalaCards; LRP2; -.
DR MIM; 222448; phenotype.
DR MIM; 600073; gene.
DR neXtProt; NX_P98164; -.
DR OpenTargets; ENSG00000081479; -.
DR Orphanet; 2143; Donnai-Barrow syndrome.
DR PharmGKB; PA30452; -.
DR VEuPathDB; HostDB:ENSG00000081479; -.
DR eggNOG; KOG1215; Eukaryota.
DR GeneTree; ENSGT00940000157232; -.
DR HOGENOM; CLU_000085_1_1_1; -.
DR InParanoid; P98164; -.
DR OrthoDB; 1606at2759; -.
DR PhylomeDB; P98164; -.
DR TreeFam; TF315253; -.
DR PathwayCommons; P98164; -.
DR Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-975634; Retinoid metabolism and transport.
DR Reactome; R-HSA-9758890; Transport of RCbl within the body.
DR SignaLink; P98164; -.
DR SIGNOR; P98164; -.
DR BioGRID-ORCS; 4036; 6 hits in 1069 CRISPR screens.
DR ChiTaRS; LRP2; human.
DR GeneWiki; LRP2; -.
DR GenomeRNAi; 4036; -.
DR Pharos; P98164; Tbio.
DR PRO; PR:P98164; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P98164; protein.
DR Bgee; ENSG00000081479; Expressed in adult organism and 121 other tissues.
DR ExpressionAtlas; P98164; baseline and differential.
DR Genevisible; P98164; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0031904; C:endosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0038024; F:cargo receptor activity; TAS:Reactome.
DR GO; GO:0051087; F:chaperone binding; IPI:ARUK-UCL.
DR GO; GO:0042562; F:hormone binding; IBA:GO_Central.
DR GO; GO:0031994; F:insulin-like growth factor I binding; ISS:ARUK-UCL.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; TAS:Reactome.
DR GO; GO:0140318; F:protein transporter activity; ISS:ARUK-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0097242; P:amyloid-beta clearance; ISS:ARUK-UCL.
DR GO; GO:0035904; P:aorta development; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:ARUK-UCL.
DR GO; GO:0060982; P:coronary artery morphogenesis; ISS:UniProtKB.
DR GO; GO:0034311; P:diol metabolic process; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:1904447; P:folate import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0008584; P:male gonad development; ISS:UniProtKB.
DR GO; GO:0030001; P:metal ion transport; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IGI:ARUK-UCL.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB.
DR GO; GO:0140058; P:neuron projection arborization; ISS:UniProtKB.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:UniProtKB.
DR GO; GO:1905167; P:positive regulation of lysosomal protein catabolic process; ISS:ARUK-UCL.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:UniProtKB.
DR GO; GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; ISS:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:ARUK-UCL.
DR GO; GO:0015031; P:protein transport; IDA:ARUK-UCL.
DR GO; GO:0061156; P:pulmonary artery morphogenesis; ISS:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IDA:UniProtKB.
DR GO; GO:0044321; P:response to leptin; IDA:ARUK-UCL.
DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome.
DR GO; GO:0003139; P:secondary heart field specification; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0045056; P:transcytosis; ISS:ARUK-UCL.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0060068; P:vagina development; ISS:UniProtKB.
DR GO; GO:0003223; P:ventricular compact myocardium morphogenesis; ISS:UniProtKB.
DR GO; GO:0003281; P:ventricular septum development; IEA:Ensembl.
DR GO; GO:0042359; P:vitamin D metabolic process; TAS:Reactome.
DR CDD; cd00112; LDLa; 34.
DR Gene3D; 2.120.10.30; -; 8.
DR Gene3D; 4.10.400.10; -; 36.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR026823; cEGF.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR019825; Lectin_legB_Mn/Ca_BS.
DR Pfam; PF12662; cEGF; 1.
DR Pfam; PF07645; EGF_CA; 2.
DR Pfam; PF00057; Ldl_recept_a; 34.
DR Pfam; PF00058; Ldl_recept_b; 14.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 26.
DR SMART; SM00179; EGF_CA; 10.
DR SMART; SM00192; LDLa; 36.
DR SMART; SM00135; LY; 38.
DR SUPFAM; SSF57184; SSF57184; 2.
DR SUPFAM; SSF57424; SSF57424; 36.
DR PROSITE; PS00010; ASX_HYDROXYL; 4.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 9.
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; 35.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell membrane; Cell projection; Coated pit;
KW Disease variant; Disulfide bond; EGF-like domain; Endocytosis; Endosome;
KW Glycoprotein; Hearing; Membrane; Metal-binding; Neurogenesis;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; SH3-binding; Signal;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..4655
FT /note="Low-density lipoprotein receptor-related protein 2"
FT /id="PRO_0000017321"
FT TOPO_DOM 26..4423
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 4424..4446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 4447..4655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..63
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 66..104
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 107..143
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 146..180
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 182..218
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 221..257
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 265..308
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT REPEAT 436..478
FT /note="LDL-receptor class B 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 479..521
FT /note="LDL-receptor class B 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 522..568
FT /note="LDL-receptor class B 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 569..613
FT /note="LDL-receptor class B 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 753..795
FT /note="LDL-receptor class B 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 796..837
FT /note="LDL-receptor class B 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 838..881
FT /note="LDL-receptor class B 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 882..925
FT /note="LDL-receptor class B 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 1025..1061
FT /note="LDL-receptor class A 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1066..1102
FT /note="LDL-receptor class A 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1108..1144
FT /note="LDL-receptor class A 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1148..1184
FT /note="LDL-receptor class A 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1186..1223
FT /note="LDL-receptor class A 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1229..1267
FT /note="LDL-receptor class A 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1270..1306
FT /note="LDL-receptor class A 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1304..1349
FT /note="LDL-receptor class A 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1390..1429
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1478..1520
FT /note="LDL-receptor class B 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1521..1563
FT /note="LDL-receptor class B 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1566..1609
FT /note="LDL-receptor class B 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1610..1654
FT /note="LDL-receptor class B 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1655..1695
FT /note="LDL-receptor class B 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 1700..1741
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 1790..1832
FT /note="LDL-receptor class B 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1833..1882
FT /note="LDL-receptor class B 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1883..1930
FT /note="LDL-receptor class B 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1931..1972
FT /note="LDL-receptor class B 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 1973..2013
FT /note="LDL-receptor class B 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2107..2156
FT /note="LDL-receptor class B 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2157..2201
FT /note="LDL-receptor class B 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2202..2245
FT /note="LDL-receptor class B 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2246..2289
FT /note="LDL-receptor class B 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2431..2477
FT /note="LDL-receptor class B 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2478..2518
FT /note="LDL-receptor class B 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2519..2562
FT /note="LDL-receptor class B 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2563..2604
FT /note="LDL-receptor class B 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 2605..2646
FT /note="LDL-receptor class B 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 2699..2737
FT /note="LDL-receptor class A 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2740..2776
FT /note="LDL-receptor class A 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2779..2818
FT /note="LDL-receptor class A 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2821..2860
FT /note="LDL-receptor class A 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2863..2900
FT /note="LDL-receptor class A 20"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2905..2944
FT /note="LDL-receptor class A 21"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2947..2989
FT /note="LDL-receptor class A 22"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 2992..3028
FT /note="LDL-receptor class A 23"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3031..3069
FT /note="LDL-receptor class A 24"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3074..3110
FT /note="LDL-receptor class A 25"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3110..3151
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 3152..3192
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 3239..3281
FT /note="LDL-receptor class B 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3282..3324
FT /note="LDL-receptor class B 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3333..3376
FT /note="LDL-receptor class B 30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3377..3419
FT /note="LDL-receptor class B 31"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 3420..3460
FT /note="LDL-receptor class B 32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 3511..3549
FT /note="LDL-receptor class A 26"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3552..3590
FT /note="LDL-receptor class A 27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3593..3631
FT /note="LDL-receptor class A 28"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3634..3672
FT /note="LDL-receptor class A 29"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3677..3715
FT /note="LDL-receptor class A 30"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3718..3755
FT /note="LDL-receptor class A 31"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3758..3794
FT /note="LDL-receptor class A 32"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3797..3833
FT /note="LDL-receptor class A 33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3841..3879
FT /note="LDL-receptor class A 34"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3882..3921
FT /note="LDL-receptor class A 35"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 3927..3963
FT /note="LDL-receptor class A 36"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 4007..4048
FT /note="EGF-like 5; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 4154..4196
FT /note="LDL-receptor class B 33"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 4197..4240
FT /note="LDL-receptor class B 34"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT REPEAT 4242..4283
FT /note="LDL-receptor class B 35"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00461"
FT DOMAIN 4377..4411
FT /note="EGF-like 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 4550..4574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4589..4602
FT /note="Interaction with DAB2"
FT /evidence="ECO:0000269|PubMed:10769163"
FT REGION 4601..4655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4453..4462
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 4456..4461
FT /note="PxLPxI/L motif 1; mediates interaction with ANKRA2"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOTIF 4459..4464
FT /note="PxLPxI/L motif 2; mediates interaction with ANKRA2"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOTIF 4521..4526
FT /note="Endocytosis signal"
FT /evidence="ECO:0000255"
FT MOTIF 4595..4598
FT /note="NPXY motif"
FT MOTIF 4598..4601
FT /note="SH2-binding"
FT /evidence="ECO:0000255"
FT MOTIF 4611..4622
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 4613..4630
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23275343,
FT ECO:0007744|PDB:2M0P"
FT BINDING 1129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23275343,
FT ECO:0007744|PDB:2M0P"
FT BINDING 1131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23275343,
FT ECO:0007744|PDB:2M0P"
FT BINDING 1133
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23275343,
FT ECO:0007744|PDB:2M0P"
FT BINDING 1139
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23275343,
FT ECO:0007744|PDB:2M0P"
FT BINDING 1140
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:23275343,
FT ECO:0007744|PDB:2M0P"
FT BINDING 1208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1212
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1218
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT BINDING 1219
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOD_RES 4463
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2ARV4"
FT MOD_RES 4466
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2ARV4"
FT MOD_RES 4569
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2ARV4"
FT MOD_RES 4616
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P98158"
FT MOD_RES 4632
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:A2ARV4"
FT MOD_RES 4653
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A2ARV4"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 463
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 866
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1064
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1383
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1496
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1550
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1675
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1810
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2055
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2224
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2547
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2809
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2810
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2947
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2987
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3564
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3680
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 3978
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4068
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 4327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..40
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 35..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 47..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 67..80
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 74..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 87..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 108..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 115..133
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 127..142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 147..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 152..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 164..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 183..195
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 190..208
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 202..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 222..234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 229..247
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 241..256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 266..279
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 273..292
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 286..307
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1026..1038
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1033..1051
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1045..1060
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1067..1079
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1074..1092
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1086..1101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1109..1121
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:23275343"
FT DISULFID 1116..1134
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:23275343"
FT DISULFID 1128..1143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124,
FT ECO:0000269|PubMed:23275343"
FT DISULFID 1149..1161
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1156..1174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1168..1183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1187..1200
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1194..1213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1207..1222
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1230..1243
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1237..1256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1250..1266
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1271..1283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1278..1296
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1290..1305
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1305..1325
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1312..1338
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1332..1348
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1394..1404
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1400..1413
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1415..1428
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1704..1713
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1709..1725
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 1727..1740
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 2700..2712
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2707..2725
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2719..2736
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2741..2753
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2748..2766
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2760..2775
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2780..2793
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2788..2806
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2800..2817
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2822..2835
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2829..2848
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2842..2859
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2864..2876
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2871..2889
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2883..2899
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2906..2918
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2913..2931
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2925..2943
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2948..2965
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2955..2978
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2972..2988
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 2993..3005
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3000..3018
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3012..3027
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3032..3044
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3039..3057
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3051..3068
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3075..3087
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3082..3100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3094..3109
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3114..3126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3122..3135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3137..3150
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3156..3167
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3163..3176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3178..3191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 3512..3525
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3519..3538
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3532..3548
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3553..3565
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3560..3578
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3572..3589
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3594..3606
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3601..3619
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3613..3630
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3635..3647
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3642..3660
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3654..3671
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3678..3692
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3686..3705
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3699..3714
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3719..3732
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3727..3745
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3739..3754
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3759..3771
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3766..3784
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3778..3793
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3798..3810
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3805..3823
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3817..3832
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3842..3854
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3849..3867
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3861..3878
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3883..3896
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3891..3909
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3903..3920
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3928..3940
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3935..3953
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 3947..3962
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 4011..4021
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4017..4030
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4032..4047
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4381..4389
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4383..4399
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 4401..4410
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VARIANT 83
FT /note="N -> S (in dbSNP:rs2229263)"
FT /evidence="ECO:0000269|PubMed:8706697"
FT /id="VAR_037009"
FT VARIANT 103
FT /note="C -> R (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064727"
FT VARIANT 259
FT /note="G -> R (in dbSNP:rs34693334)"
FT /id="VAR_061294"
FT VARIANT 669
FT /note="G -> D (in dbSNP:rs34291900)"
FT /id="VAR_037010"
FT VARIANT 909
FT /note="H -> R (in dbSNP:rs36082715)"
FT /id="VAR_037011"
FT VARIANT 1083
FT /note="H -> Q (in dbSNP:rs2302691)"
FT /id="VAR_037012"
FT VARIANT 1279
FT /note="D -> A (in dbSNP:rs17848149)"
FT /id="VAR_029182"
FT VARIANT 1287
FT /note="A -> P"
FT /id="VAR_005421"
FT VARIANT 2012
FT /note="R -> K (in dbSNP:rs4667596)"
FT /id="VAR_029183"
FT VARIANT 2065
FT /note="I -> T (in dbSNP:rs2228168)"
FT /id="VAR_020218"
FT VARIANT 2522
FT /note="Y -> H (in DBS; dbSNP:rs80338747)"
FT /evidence="ECO:0000269|PubMed:17632512"
FT /id="VAR_037013"
FT VARIANT 2632
FT /note="N -> D (in dbSNP:rs17848169)"
FT /id="VAR_029184"
FT VARIANT 2872
FT /note="A -> T (in dbSNP:rs2228171)"
FT /id="VAR_005422"
FT VARIANT 3011
FT /note="R -> M (in dbSNP:rs11674973)"
FT /id="VAR_037014"
FT VARIANT 3305
FT /note="R -> H (in dbSNP:rs3213760)"
FT /id="VAR_020219"
FT VARIANT 3779
FT /note="D -> N (found in patients with mild intellectual
FT disability; unknown pathological significance;
FT dbSNP:rs199583537)"
FT /evidence="ECO:0000269|PubMed:26529358"
FT /id="VAR_075534"
FT VARIANT 3828
FT /note="D -> G (found in patients with a phenotype
FT suggestive of Stickler syndrome; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23992033"
FT /id="VAR_075535"
FT VARIANT 4094
FT /note="K -> E (in dbSNP:rs2075252)"
FT /evidence="ECO:0000269|PubMed:7959795"
FT /id="VAR_005423"
FT VARIANT 4210
FT /note="I -> L (in dbSNP:rs4667591)"
FT /evidence="ECO:0000269|PubMed:7959795"
FT /id="VAR_005424"
FT VARIANT 4272
FT /note="M -> V (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035996"
FT CONFLICT 2724
FT /note="D -> G (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2773
FT /note="A -> T (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2827
FT /note="T -> P (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2880..2882
FT /note="HWY -> TFGI (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2897
FT /note="A -> S (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2908
FT /note="A -> S (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2921
FT /note="S -> N (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2954
FT /note="L -> P (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2971..2972
FT /note="VC -> PP (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2982
FT /note="Y -> H (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2985
FT /note="N -> I (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 3615
FT /note="T -> S (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 3738
FT /note="Q -> K (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 3784
FT /note="C -> LW (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 3810
FT /note="C -> R (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT CONFLICT 4220
FT /note="R -> P (in Ref. 3; AAB02882)"
FT /evidence="ECO:0000305"
FT STRAND 1111..1115
FT /evidence="ECO:0007829|PDB:2M0P"
FT STRAND 1121..1123
FT /evidence="ECO:0007829|PDB:2M0P"
FT STRAND 1129..1131
FT /evidence="ECO:0007829|PDB:2M0P"
FT STRAND 1133..1136
FT /evidence="ECO:0007829|PDB:2M0P"
FT HELIX 1138..1141
FT /evidence="ECO:0007829|PDB:2M0P"
SQ SEQUENCE 4655 AA; 521958 MW; C73C4206B8B28CE0 CRC64;
MDRGPAAVAC TLLLALVACL APASGQECDS AHFRCGSGHC IPADWRCDGT KDCSDDADEI
GCAVVTCQQG YFKCQSEGQC IPNSWVCDQD QDCDDGSDER QDCSQSTCSS HQITCSNGQC
IPSEYRCDHV RDCPDGADEN DCQYPTCEQL TCDNGACYNT SQKCDWKVDC RDSSDEINCT
EICLHNEFSC GNGECIPRAY VCDHDNDCQD GSDEHACNYP TCGGYQFTCP SGRCIYQNWV
CDGEDDCKDN GDEDGCESGP HDVHKCSPRE WSCPESGRCI SIYKVCDGIL DCPGREDENN
TSTGKYCSMT LCSALNCQYQ CHETPYGGAC FCPPGYIINH NDSRTCVEFD DCQIWGICDQ
KCESRPGRHL CHCEEGYILE RGQYCKANDS FGEASIIFSN GRDLLIGDIH GRSFRILVES
QNRGVAVGVA FHYHLQRVFW TDTVQNKVFS VDINGLNIQE VLNVSVETPE NLAVDWVNNK
IYLVETKVNR IDMVNLDGSY RVTLITENLG HPRGIAVDPT VGYLFFSDWE SLSGEPKLER
AFMDGSNRKD LVKTKLGWPA GVTLDMISKR VYWVDSRFDY IETVTYDGIQ RKTVVHGGSL
IPHPFGVSLF EGQVFFTDWT KMAVLKANKF TETNPQVYYQ ASLRPYGVTV YHSLRQPYAT
NPCKDNNGGC EQVCVLSHRT DNDGLGFRCK CTFGFQLDTD ERHCIAVQNF LIFSSQVAIR
GIPFTLSTQE DVMVPVSGNP SFFVGIDFDA QDSTIFFSDM SKHMIFKQKI DGTGREILAA
NRVENVESLA FDWISKNLYW TDSHYKSISV MRLADKTRRT VVQYLNNPRS VVVHPFAGYL
FFTDWFRPAK IMRAWSDGSH LLPVINTTLG WPNGLAIDWA ASRLYWVDAY FDKIEHSTFD
GLDRRRLGHI EQMTHPFGLA IFGEHLFFTD WRLGAIIRVR KADGGEMTVI RSGIAYILHL
KSYDVNIQTG SNACNQPTHP NGDCSHFCFP VPNFQRVCGC PYGMRLASNH LTCEGDPTNE
PPTEQCGLFS FPCKNGRCVP NYYLCDGVDD CHDNSDEQLC GTLNNTCSSS AFTCGHGECI
PAHWRCDKRN DCVDGSDEHN CPTHAPASCL DTQYTCDNHQ CISKNWVCDT DNDCGDGSDE
KNCNSTETCQ PSQFNCPNHR CIDLSFVCDG DKDCVDGSDE VGCVLNCTAS QFKCASGDKC
IGVTNRCDGV FDCSDNSDEA GCPTRPPGMC HSDEFQCQED GICIPNFWEC DGHPDCLYGS
DEHNACVPKT CPSSYFHCDN GNCIHRAWLC DRDNDCGDMS DEKDCPTQPF RCPSWQWQCL
GHNICVNLSV VCDGIFDCPN GTDESPLCNG NSCSDFNGGC THECVQEPFG AKCLCPLGFL
LANDSKTCED IDECDILGSC SQHCYNMRGS FRCSCDTGYM LESDGRTCKV TASESLLLLV
ASQNKIIADS VTSQVHNIYS LVENGSYIVA VDFDSISGRI FWSDATQGKT WSAFQNGTDR
RVVFDSSIIL TETIAIDWVG RNLYWTDYAL ETIEVSKIDG SHRTVLISKN LTNPRGLALD
PRMNEHLLFW SDWGHHPRIE RASMDGSMRT VIVQDKIFWP CGLTIDYPNR LLYFMDSYLD
YMDFCDYNGH HRRQVIASDL IIRHPYALTL FEDSVYWTDR ATRRVMRANK WHGGNQSVVM
YNIQWPLGIV AVHPSKQPNS VNPCAFSRCS HLCLLSSQGP HFYSCVCPSG WSLSPDLLNC
LRDDQPFLIT VRQHIIFGIS LNPEVKSNDA MVPIAGIQNG LDVEFDDAEQ YIYWVENPGE
IHRVKTDGTN RTVFASISMV GPSMNLALDW ISRNLYSTNP RTQSIEVLTL HGDIRYRKTL
IANDGTALGV GFPIGITVDP ARGKLYWSDQ GTDSGVPAKI ASANMDGTSV KTLFTGNLEH
LECVTLDIEE QKLYWAVTGR GVIERGNVDG TDRMILVHQL SHPWGIAVHD SFLYYTDEQY
EVIERVDKAT GANKIVLRDN VPNLRGLQVY HRRNAAESSN GCSNNMNACQ QICLPVPGGL
FSCACATGFK LNPDNRSCSP YNSFIVVSML SAIRGFSLEL SDHSETMVPV AGQGRNALHV
DVDVSSGFIY WCDFSSSVAS DNAIRRIKPD GSSLMNIVTH GIGENGVRGI AVDWVAGNLY
FTNAFVSETL IEVLRINTTY RRVLLKVTVD MPRHIVVDPK NRYLFWADYG QRPKIERSFL
DCTNRTVLVS EGIVTPRGLA VDRSDGYVYW VDDSLDIIAR IRINGENSEV IRYGSRYPTP
YGITVFENSI IWVDRNLKKI FQASKEPENT EPPTVIRDNI NWLRDVTIFD KQVQPRSPAE
VNNNPCLENN GGCSHLCFAL PGLHTPKCDC AFGTLQSDGK NCAISTENFL IFALSNSLRS
LHLDPENHSP PFQTINVERT VMSLDYDSVS DRIYFTQNLA SGVGQISYAT LSSGIHTPTV
IASGIGTADG IAFDWITRRI YYSDYLNQMI NSMAEDGSNR TVIARVPKPR AIVLDPCQGY
LYWADWDTHA KIERATLGGN FRVPIVNSSL VMPSGLTLDY EEDLLYWVDA SLQRIERSTL
TGVDREVIVN AAVHAFGLTL YGQYIYWTDL YTQRIYRANK YDGSGQIAMT TNLLSQPRGI
NTVVKNQKQQ CNNPCEQFNG GCSHICAPGP NGAECQCPHE GNWYLANNRK HCIVDNGERC
GASSFTCSNG RCISEEWKCD NDNDCGDGSD EMESVCALHT CSPTAFTCAN GRCVQYSYRC
DYYNDCGDGS DEAGCLFRDC NATTEFMCNN RRCIPREFIC NGVDNCHDNN TSDEKNCPDR
TCQSGYTKCH NSNICIPRVY LCDGDNDCGD NSDENPTYCT THTCSSSEFQ CASGRCIPQH
WYCDQETDCF DASDEPASCG HSERTCLADE FKCDGGRCIP SEWICDGDND CGDMSDEDKR
HQCQNQNCSD SEFLCVNDRP PDRRCIPQSW VCDGDVDCTD GYDENQNCTR RTCSENEFTC
GYGLCIPKIF RCDRHNDCGD YSDERGCLYQ TCQQNQFTCQ NGRCISKTFV CDEDNDCGDG
SDELMHLCHT PEPTCPPHEF KCDNGRCIEM MKLCNHLDDC LDNSDEKGCG INECHDPSIS
GCDHNCTDTL TSFYCSCRPG YKLMSDKRTC VDIDECTEMP FVCSQKCENV IGSYICKCAP
GYLREPDGKT CRQNSNIEPY LIFSNRYYLR NLTIDGYFYS LILEGLDNVV ALDFDRVEKR
LYWIDTQRQV IERMFLNKTN KETIINHRLP AAESLAVDWV SRKLYWLDAR LDGLFVSDLN
GGHRRMLAQH CVDANNTFCF DNPRGLALHP QYGYLYWADW GHRAYIGRVG MDGTNKSVII
STKLEWPNGI TIDYTNDLLY WADAHLGYIE YSDLEGHHRH TVYDGALPHP FAITIFEDTI
YWTDWNTRTV EKGNKYDGSN RQTLVNTTHR PFDIHVYHPY RQPIVSNPCG TNNGGCSHLC
LIKPGGKGFT CECPDDFRTL QLSGSTYCMP MCSSTQFLCA NNEKCIPIWW KCDGQKDCSD
GSDELALCPQ RFCRLGQFQC SDGNCTSPQT LCNAHQNCPD GSDEDRLLCE NHHCDSNEWQ
CANKRCIPES WQCDTFNDCE DNSDEDSSHC ASRTCRPGQF RCANGRCIPQ AWKCDVDNDC
GDHSDEPIEE CMSSAHLCDN FTEFSCKTNY RCIPKWAVCN GVDDCRDNSD EQGCEERTCH
PVGDFRCKNH HCIPLRWQCD GQNDCGDNSD EENCAPRECT ESEFRCVNQQ CIPSRWICDH
YNDCGDNSDE RDCEMRTCHP EYFQCTSGHC VHSELKCDGS ADCLDASDEA DCPTRFPDGA
YCQATMFECK NHVCIPPYWK CDGDDDCGDG SDEELHLCLD VPCNSPNRFR CDNNRCIYSH
EVCNGVDDCG DGTDETEEHC RKPTPKPCTE YEYKCGNGHC IPHDNVCDDA DDCGDWSDEL
GCNKGKERTC AENICEQNCT QLNEGGFICS CTAGFETNVF DRTSCLDINE CEQFGTCPQH
CRNTKGSYEC VCADGFTSMS DRPGKRCAAE GSSPLLLLPD NVRIRKYNLS SERFSEYLQD
EEYIQAVDYD WDPKDIGLSV VYYTVRGEGS RFGAIKRAYI PNFESGRNNL VQEVDLKLKY
VMQPDGIAVD WVGRHIYWSD VKNKRIEVAK LDGRYRKWLI STDLDQPAAI AVNPKLGLMF
WTDWGKEPKI ESAWMNGEDR NILVFEDLGW PTGLSIDYLN NDRIYWSDFK EDVIETIKYD
GTDRRVIAKE AMNPYSLDIF EDQLYWISKE KGEVWKQNKF GQGKKEKTLV VNPWLTQVRI
FHQLRYNKSV PNLCKQICSH LCLLRPGGYS CACPQGSSFI EGSTTECDAA IELPINLPPP
CRCMHGGNCY FDETDLPKCK CPSGYTGKYC EMAFSKGISP GTTAVAVLLT ILLIVVIGAL
AIAGFFHYRR TGSLLPALPK LPSLSSLVKP SENGNGVTFR SGADLNMDIG VSGFGPETAI
DRSMAMSEDF VMEMGKQPII FENPMYSARD SAVKVVQPIQ VTVSENVDNK NYGSPINPSE
IVPETNPTSP AADGTQVTKW NLFKRKSKQT TNFENPIYAQ MENEQKESVA ATPPPSPSLP
AKPKPPSRRD PTPTYSATED TFKDTANLVK EDSEV
