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   13-FEB-2019, entry version 155.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   protein and mapping of its gene (LRP3) to chromosome bands 19q12-q13.
RT   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
RT   project: 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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-
RT   length human cDNAs encoding secretion or membrane proteins from oligo-
RT   capped cDNA 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
CC       transduction. Its precise role is however unclear, since it does
CC       not bind to very low density lipoprotein (VLDL) or to LRPAP1 in
CC       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
CC       {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   UniGene; Hs.515340; -.
DR   ProteinModelPortal; O75074; -.
DR   BioGrid; 110217; 2.
DR   ELM; O75074; -.
DR   IntAct; O75074; 3.
DR   MINT; O75074; -.
DR   STRING; 9606.ENSP00000253193; -.
DR   iPTMnet; O75074; -.
DR   PhosphoSitePlus; O75074; -.
DR   BioMuta; LRP3; -.
DR   jPOST; O75074; -.
DR   PaxDb; O75074; -.
DR   PeptideAtlas; O75074; -.
DR   PRIDE; O75074; -.
DR   ProteomicsDB; 49739; -.
DR   DNASU; 4037; -.
DR   Ensembl; ENST00000253193; ENSP00000253193; ENSG00000130881.
DR   GeneID; 4037; -.
DR   KEGG; hsa:4037; -.
DR   UCSC; uc010edh.4; human.
DR   CTD; 4037; -.
DR   EuPathDB; HostDB:ENSG00000130881.13; -.
DR   GeneCards; LRP3; -.
DR   H-InvDB; HIX0014999; -.
DR   HGNC; HGNC:6695; LRP3.
DR   MIM; 603159; gene.
DR   neXtProt; NX_O75074; -.
DR   OpenTargets; ENSG00000130881; -.
DR   PharmGKB; PA30453; -.
DR   eggNOG; KOG1215; Eukaryota.
DR   eggNOG; ENOG410XP34; LUCA.
DR   GeneTree; ENSGT00940000160021; -.
DR   HOGENOM; HOG000013017; -.
DR   HOVERGEN; HBG049162; -.
DR   InParanoid; O75074; -.
DR   KO; K20050; -.
DR   OMA; SLDWLML; -.
DR   OrthoDB; 135036at2759; -.
DR   PhylomeDB; O75074; -.
DR   TreeFam; TF332149; -.
DR   ChiTaRS; LRP3; human.
DR   GeneWiki; LRP3; -.
DR   GenomeRNAi; 4037; -.
DR   PRO; PR:O75074; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000130881; Expressed in 92 organ(s), highest expression level in putamen.
DR   ExpressionAtlas; O75074; baseline and differential.
DR   Genevisible; O75074; HS.
DR   GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR   GO; GO:0006898; P:receptor-mediated endocytosis; TAS:ProtInc.
DR   CDD; cd00041; CUB; 2.
DR   CDD; cd00112; LDLa; 4.
DR   Gene3D; 2.60.120.290; -; 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   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; SSF49854; SSF49854; 2.
DR   SUPFAM; SSF57424; SSF57424; 4.
DR   PROSITE; PS01180; CUB; 2.
DR   PROSITE; PS01209; LDLRA_1; 3.
DR   PROSITE; PS50068; LDLRA_2; 4.
PE   2: Evidence at transcript level;
KW   Coated pit; Complete proteome; Disulfide bond; Endocytosis;
KW   Glycoprotein; Membrane; Polymorphism; Receptor; Reference proteome;
KW   Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL        1     36       {ECO:0000255}.
FT   CHAIN        37    770       Low-density lipoprotein receptor-related
FT                                protein 3.
FT                                /FTId=PRO_0000017323.
FT   TOPO_DOM     37    496       Extracellular. {ECO:0000255}.
FT   TRANSMEM    497    517       Helical. {ECO:0000255}.
FT   TOPO_DOM    518    770       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       43    159       CUB 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN      165    201       LDL-receptor class A 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      211    250       LDL-receptor class A 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      254    365       CUB 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00059}.
FT   DOMAIN      415    453       LDL-receptor class A 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN      454    490       LDL-receptor class A 4.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   COMPBIAS    751    754       Poly-Pro.
FT   CARBOHYD     71     71       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    199    199       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    359    359       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     43     72       {ECO:0000250}.
FT   DISULFID     99    120       {ECO:0000250}.
FT   DISULFID    166    178       {ECO:0000250}.
FT   DISULFID    173    191       {ECO:0000250}.
FT   DISULFID    185    200       {ECO:0000250}.
FT   DISULFID    212    227       {ECO:0000250}.
FT   DISULFID    219    240       {ECO:0000250}.
FT   DISULFID    234    249       {ECO:0000250}.
FT   DISULFID    254    282       {ECO:0000250}.
FT   DISULFID    416    430       {ECO:0000250}.
FT   DISULFID    423    443       {ECO:0000250}.
FT   DISULFID    437    452       {ECO:0000250}.
FT   DISULFID    455    467       {ECO:0000250}.
FT   DISULFID    462    480       {ECO:0000250}.
FT   DISULFID    474    489       {ECO:0000250}.
FT   VARIANT     213    213       P -> L (in dbSNP:rs3745978).
FT                                /FTId=VAR_049764.
FT   VARIANT     708    708       V -> A (in dbSNP:rs3745974).
FT                                {ECO:0000269|PubMed:14702039,
FT                                ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:16303743,
FT                                ECO:0000269|PubMed:9693042}.
FT                                /FTId=VAR_018171.
FT   CONFLICT     85     85       T -> I (in Ref. 4; BAG51998).
FT                                {ECO:0000305}.
FT   CONFLICT    458    458       G -> D (in Ref. 4; BAG51998).
FT                                {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
//