LRP3_HUMAN
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 03-AUG-2022, entry version 173.
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 BioGRID; 110217; 48.
DR ELM; O75074; -.
DR IntAct; O75074; 3.
DR MINT; O75074; -.
DR STRING; 9606.ENSP00000253193; -.
DR GlyGen; O75074; 3 sites.
DR iPTMnet; O75074; -.
DR PhosphoSitePlus; O75074; -.
DR BioMuta; LRP3; -.
DR jPOST; O75074; -.
DR MassIVE; O75074; -.
DR PaxDb; O75074; -.
DR PeptideAtlas; O75074; -.
DR PRIDE; O75074; -.
DR ProteomicsDB; 49739; -.
DR Antibodypedia; 29007; 170 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 CTD; 4037; -.
DR DisGeNET; 4037; -.
DR GeneCards; LRP3; -.
DR HGNC; HGNC:6695; LRP3.
DR HPA; ENSG00000130881; Low tissue specificity.
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; KACREPL; -.
DR OrthoDB; 135036at2759; -.
DR PhylomeDB; O75074; -.
DR TreeFam; TF332149; -.
DR PathwayCommons; O75074; -.
DR SignaLink; O75074; -.
DR BioGRID-ORCS; 4037; 24 hits in 1073 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 101 other tissues.
DR ExpressionAtlas; O75074; baseline and differential.
DR Genevisible; O75074; HS.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of 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; 2.60.120.290; -; 2.
DR Gene3D; 4.10.400.10; -; 4.
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; 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
