ID   LRP3_HUMAN              Reviewed;         770 AA.
AC   O75074; B3KQD6; B4DKF2;
DT   13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT   20-DEC-2005, sequence version 2.
DT   24-JAN-2024, entry version 181.
DE   RecName: Full=Low-density lipoprotein receptor-related protein 3;
DE            Short=LRP-3;
DE   AltName: Full=105 kDa low-density lipoprotein receptor-related protein;
DE            Short=hLRp105;
DE   Flags: Precursor;
GN   Name=LRP3;
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], TISSUE SPECIFICITY, AND VARIANT ALA-708.
RX   PubMed=9693042; DOI=10.1006/geno.1998.5339;
RA   Ishii H., Kim D.-H., Fujita T., Endo Y., Saeki S., Yamamoto T.T.;
RT   "cDNA cloning of a new low-density lipoprotein receptor-related protein and
RT   mapping of its gene (LRP3) to chromosome bands 19q12-q13. 2.";
RL   Genomics 51:132-135(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-708.
RC   TISSUE=Muscle;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-770, AND VARIANT ALA-708.
RC   TISSUE=Thalamus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 10-770, AND VARIANT ALA-708.
RX   PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA   Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA   Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA   Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA   Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA   Isogai T.;
RT   "Signal sequence and keyword trap in silico for selection of full-length
RT   human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT   libraries.";
RL   DNA Res. 12:117-126(2005).
CC   -!- FUNCTION: Probable receptor, which may be involved in the
CC       internalization of lipophilic molecules and/or signal transduction. Its
CC       precise role is however unclear, since it does not bind to very low
CC       density lipoprotein (VLDL) or to LRPAP1 in vitro.
CC   -!- SUBUNIT: Binds GGA1 and GGA2. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}. Membrane, coated pit {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in skeletal
CC       muscle and ovary. Expressed at intermediate level in heart, brain,
CC       liver, pancreas, prostate and small intestine. Weakly expressed in
CC       testis, colon and leukocyte. {ECO:0000269|PubMed:9693042}.
CC   -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAG51998.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=BAG59164.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB009462; BAA32330.1; -; mRNA.
DR   EMBL; BC007408; AAH07408.1; -; mRNA.
DR   EMBL; AK074751; BAG51998.1; ALT_INIT; mRNA.
DR   EMBL; AK296536; BAG59164.1; ALT_INIT; mRNA.
DR   CCDS; CCDS12430.1; -.
DR   PIR; T00204; T00204.
DR   RefSeq; NP_002324.2; NM_002333.3.
DR   AlphaFoldDB; O75074; -.
DR   SMR; O75074; -.
DR   BioGRID; 110217; 49.
DR   ELM; O75074; -.
DR   IntAct; O75074; 3.
DR   MINT; O75074; -.
DR   STRING; 9606.ENSP00000253193; -.
DR   GlyCosmos; O75074; 3 sites, No reported glycans.
DR   GlyGen; O75074; 3 sites.
DR   iPTMnet; O75074; -.
DR   PhosphoSitePlus; O75074; -.
DR   BioMuta; LRP3; -.
DR   jPOST; O75074; -.
DR   MassIVE; O75074; -.
DR   PaxDb; 9606-ENSP00000253193; -.
DR   PeptideAtlas; O75074; -.
DR   ProteomicsDB; 49739; -.
DR   Antibodypedia; 29007; 179 antibodies from 28 providers.
DR   DNASU; 4037; -.
DR   Ensembl; ENST00000253193.9; ENSP00000253193.6; ENSG00000130881.14.
DR   GeneID; 4037; -.
DR   KEGG; hsa:4037; -.
DR   MANE-Select; ENST00000253193.9; ENSP00000253193.6; NM_002333.4; NP_002324.2.
DR   UCSC; uc010edh.4; human.
DR   AGR; HGNC:6695; -.
DR   CTD; 4037; -.
DR   DisGeNET; 4037; -.
DR   GeneCards; LRP3; -.
DR   HGNC; HGNC:6695; LRP3.
DR   HPA; ENSG00000130881; Tissue enhanced (brain).
DR   MIM; 603159; gene.
DR   neXtProt; NX_O75074; -.
DR   OpenTargets; ENSG00000130881; -.
DR   PharmGKB; PA30453; -.
DR   VEuPathDB; HostDB:ENSG00000130881; -.
DR   eggNOG; KOG1215; Eukaryota.
DR   GeneTree; ENSGT00940000160021; -.
DR   HOGENOM; CLU_013747_1_0_1; -.
DR   InParanoid; O75074; -.
DR   OMA; NFDLMES; -.
DR   OrthoDB; 2916406at2759; -.
DR   PhylomeDB; O75074; -.
DR   TreeFam; TF332149; -.
DR   PathwayCommons; O75074; -.
DR   SignaLink; O75074; -.
DR   BioGRID-ORCS; 4037; 24 hits in 1149 CRISPR screens.
DR   ChiTaRS; LRP3; human.
DR   GeneWiki; LRP3; -.
DR   GenomeRNAi; 4037; -.
DR   Pharos; O75074; Tbio.
DR   PRO; PR:O75074; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; O75074; Protein.
DR   Bgee; ENSG00000130881; Expressed in putamen and 103 other cell types or tissues.
DR   ExpressionAtlas; O75074; baseline and differential.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:ARUK-UCL.
DR   GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:ARUK-UCL.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; TAS:ProtInc.
DR   GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR   CDD; cd00041; CUB; 2.
DR   CDD; cd00112; LDLa; 4.
DR   Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 4.
DR   Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 2.
DR   InterPro; IPR000859; CUB_dom.
DR   InterPro; IPR036055; LDL_receptor-like_sf.
DR   InterPro; IPR023415; LDLR_class-A_CS.
DR   InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR   InterPro; IPR035914; Sperma_CUB_dom_sf.
DR   PANTHER; PTHR24270; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED; 1.
DR   PANTHER; PTHR24270:SF22; LOW-DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 3; 1.
DR   Pfam; PF00431; CUB; 2.
DR   Pfam; PF00057; Ldl_recept_a; 3.
DR   PRINTS; PR00261; LDLRECEPTOR.
DR   SMART; SM00042; CUB; 2.
DR   SMART; SM00192; LDLa; 5.
DR   SUPFAM; SSF57424; LDL receptor-like module; 4.
DR   SUPFAM; SSF49854; Spermadhesin, CUB domain; 2.
DR   PROSITE; PS01180; CUB; 2.
DR   PROSITE; PS01209; LDLRA_1; 3.
DR   PROSITE; PS50068; LDLRA_2; 4.
DR   Genevisible; O75074; HS.
PE   2: Evidence at transcript level;
KW   Coated pit; Disulfide bond; Endocytosis; Glycoprotein; Membrane; Receptor;
KW   Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..36
FT                   /evidence="ECO:0000255"
FT   CHAIN           37..770
FT                   /note="Low-density lipoprotein receptor-related protein 3"
FT                   /id="PRO_0000017323"
FT   TOPO_DOM        37..496
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        497..517
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        518..770
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          43..159
FT                   /note="CUB 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT   DOMAIN          165..201
FT                   /note="LDL-receptor class A 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT   DOMAIN          211..250
FT                   /note="LDL-receptor class A 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT   DOMAIN          254..365
FT                   /note="CUB 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT   DOMAIN          415..453
FT                   /note="LDL-receptor class A 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT   DOMAIN          454..490
FT                   /note="LDL-receptor class A 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT   REGION          635..770
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        672..689
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        691..706
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        725..739
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        359
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        43..72
FT                   /evidence="ECO:0000250"
FT   DISULFID        99..120
FT                   /evidence="ECO:0000250"
FT   DISULFID        166..178
FT                   /evidence="ECO:0000250"
FT   DISULFID        173..191
FT                   /evidence="ECO:0000250"
FT   DISULFID        185..200
FT                   /evidence="ECO:0000250"
FT   DISULFID        212..227
FT                   /evidence="ECO:0000250"
FT   DISULFID        219..240
FT                   /evidence="ECO:0000250"
FT   DISULFID        234..249
FT                   /evidence="ECO:0000250"
FT   DISULFID        254..282
FT                   /evidence="ECO:0000250"
FT   DISULFID        416..430
FT                   /evidence="ECO:0000250"
FT   DISULFID        423..443
FT                   /evidence="ECO:0000250"
FT   DISULFID        437..452
FT                   /evidence="ECO:0000250"
FT   DISULFID        455..467
FT                   /evidence="ECO:0000250"
FT   DISULFID        462..480
FT                   /evidence="ECO:0000250"
FT   DISULFID        474..489
FT                   /evidence="ECO:0000250"
FT   VARIANT         213
FT                   /note="P -> L (in dbSNP:rs3745978)"
FT                   /id="VAR_049764"
FT   VARIANT         708
FT                   /note="V -> A (in dbSNP:rs3745974)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16303743,
FT                   ECO:0000269|PubMed:9693042"
FT                   /id="VAR_018171"
FT   CONFLICT        85
FT                   /note="T -> I (in Ref. 4; BAG51998)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        458
FT                   /note="G -> D (in Ref. 4; BAG51998)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   770 AA;  82884 MW;  5175EDCB7A7D22EE CRC64;
     MEKRAAAGLE GAPGARAQLA VVCLVNIFLT GRLSSAVPAL AACSGKLEQH TERRGVIYSP
     AWPLNYPPGT NCSWYIQGDR GDMITISFRN FDVEESHQCS LDWLLLGPAA PPRQEAFRLC
     GSAIPPAFIS ARDHVWIFFH SDASSSGQAQ GFRLSYIRGK LGQASCQADE FRCDNGKCLP
     GPWQCNTVDE CGDGSDEGNC SAPASEPPGS LCPGGTFPCS GARSTRCLPV ERRCDGLQDC
     GDGSDEAGCP DLACGRRLGS FYGSFASPDL FGAARGPSDL HCTWLVDTQD SRRVLLQLEL
     RLGYDDYVQV YEGLGERGDR LLQTLSYRSN HRPVSLEAAQ GRLTVAYHAR ARSAGHGFNA
     TYQVKGYCLP WEQPCGSSSD SDGGSLGDQG CFSEPQRCDG WWHCASGRDE QGCPACPPDQ
     YPCEGGSGLC YTPADRCNNQ KSCPDGADEK NCFSCQPGTF HCGTNLCIFE TWRCDGQEDC
     QDGSDEHGCL AAVPRKVITA ALIGSLVCGL LLVIALGCAF KLYSLRTQEY RAFETQMTRL
     EAEFVRREAP PSYGQLIAQG LIPPVEDFPV YSASQASVLQ NLRTAMRRQM RRHASRRGPS
     RRRLGRLWNR LFHRPRAPRG QIPLLTAARP SQTVLGDGFL QPAPGAAPDP PAPLMDTGST
     RAAGDRPPSA PGRAPEVGPS GPPLPSGLRD PECRPVDKDR KVCREPLVDG PAPADAPREP
     CSAQDPHPQV STASSTLGPH SPEPLGVCRN PPPPCSPMLE ASDDEALLVC
//