VLDLR_RAT
ID VLDLR_RAT Reviewed; 873 AA.
AC P98166;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 25-MAY-2022, entry version 152.
DE RecName: Full=Very low-density lipoprotein receptor;
DE Short=VLDL receptor;
DE Short=VLDL-R;
DE Flags: Precursor;
GN Name=Vldlr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7929362; DOI=10.1016/s0021-9258(18)47209-2;
RA Jokinen E.V., Landschulz K.T., Wyne K.L., Ho Y.K., Frykman P.K.,
RA Hobbs H.H.;
RT "Regulation of the very low density lipoprotein receptor by thyroid hormone
RT in rat skeletal muscle.";
RL J. Biol. Chem. 269:26411-26418(1994).
CC -!- FUNCTION: Multifunctional cell surface receptor that binds VLDL and
CC transports it into cells by endocytosis and therefore plays an
CC important role in energy metabolism. Binds also to a wide range of
CC other molecules including Reelin/RELN or apolipoprotein E/APOE-
CC containing ligands as well as clusterin/CLU. In the off-state of the
CC pathway, forms homooligomers or heterooligomers with LRP8. Upon binding
CC to ligands, homooligomers are rearranged to higher order receptor
CC clusters that transmit the extracellular RELN signal to intracellular
CC signaling processes by binding to DAB1 (By similarity). This
CC interaction results in phosphorylation of DAB1 leading to the ultimate
CC cell responses required for the correct positioning of newly generated
CC neurons. Later, mediates a stop signal for migrating neurons,
CC preventing them from entering the marginal zone (By similarity).
CC {ECO:0000250|UniProtKB:P98155, ECO:0000250|UniProtKB:P98156}.
CC -!- SUBUNIT: Homooligomer. Binds to the extracellular matrix protein
CC Reelin/RELN. Interacts with LRP8 (By similarity). Interacts with
CC LDLRAP1 (By similarity). Interacts with SNX17 (By similarity).
CC Interacts with DAB1. Interacts with PCSK9. Interacts with PAFAH1B3 and
CC PAFAH1B2, the catalytic complex of (PAF-AH (I)) heterotetrameric
CC enzyme; these interactions may modulate the Reelin pathway. Interacts
CC with STX5; this interaction mediates VLDLR translocation from the
CC endoplasmic reticulum to the plasma membrane. Interacts with CLU (By
CC similarity). {ECO:0000250|UniProtKB:P98155,
CC ECO:0000250|UniProtKB:P98156}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC Membrane, clathrin-coated pit; Single-pass type I membrane protein.
CC -!- TISSUE SPECIFICITY: Abundant in soleus, gastrocnemicus, heart muscle,
CC placenta, brain, lung and white fat. Less in aorta, ovary, kidney,
CC spleen, adrenal gland and thymus.
CC -!- PTM: Ubiquitinated at Lys-839 by MYLIP leading to degradation.
CC {ECO:0000250}.
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DR EMBL; L35767; AAA42341.1; -; mRNA.
DR AlphaFoldDB; P98166; -.
DR SMR; P98166; -.
DR STRING; 10116.ENSRNOP00000036229; -.
DR GlyGen; P98166; 3 sites.
DR jPOST; P98166; -.
DR PaxDb; P98166; -.
DR UCSC; RGD:3963; rat.
DR RGD; 3963; Vldlr.
DR eggNOG; KOG1215; Eukaryota.
DR InParanoid; P98166; -.
DR PhylomeDB; P98166; -.
DR Reactome; R-RNO-8866376; Reelin signalling pathway.
DR Reactome; R-RNO-8866427; VLDLR internalisation and degradation.
DR Reactome; R-RNO-8964046; VLDL clearance.
DR PRO; PR:P98166; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IEA:UniProtKB-KW.
DR GO; GO:0034185; F:apolipoprotein binding; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:RGD.
DR GO; GO:0038024; F:cargo receptor activity; ISO:RGD.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; TAS:RGD.
DR GO; GO:0038025; F:reelin receptor activity; ISO:RGD.
DR GO; GO:0034189; F:very-low-density lipoprotein particle binding; ISO:RGD.
DR GO; GO:0030229; F:very-low-density lipoprotein particle receptor activity; ISS:BHF-UCL.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:RGD.
DR GO; GO:0042149; P:cellular response to glucose starvation; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0021987; P:cerebral cortex development; IEP:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0048813; P:dendrite morphogenesis; ISO:RGD.
DR GO; GO:0034436; P:glycoprotein transport; ISO:RGD.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:1900006; P:positive regulation of dendrite development; ISO:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISO:RGD.
DR GO; GO:0038026; P:reelin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0021517; P:ventral spinal cord development; ISO:RGD.
DR GO; GO:0034447; P:very-low-density lipoprotein particle clearance; ISS:BHF-UCL.
DR CDD; cd00112; LDLa; 8.
DR Gene3D; 2.120.10.30; -; 1.
DR Gene3D; 4.10.400.10; -; 8.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
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; IPR032931; VLDLR.
DR PANTHER; PTHR24270:SF16; PTHR24270:SF16; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00057; Ldl_recept_a; 8.
DR Pfam; PF00058; Ldl_recept_b; 5.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 6.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00192; LDLa; 8.
DR SMART; SM00135; LY; 5.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57424; SSF57424; 8.
DR PROSITE; PS00010; ASX_HYDROXYL; 2.
DR PROSITE; PS01186; EGF_2; 3.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS01209; LDLRA_1; 8.
DR PROSITE; PS50068; LDLRA_2; 8.
DR PROSITE; PS51120; LDLRB; 5.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Coated pit; Disulfide bond; EGF-like domain;
KW Endocytosis; Glycoprotein; Isopeptide bond; Lipid metabolism;
KW Lipid transport; Membrane; Receptor; Reference proteome; Repeat; Signal;
KW Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation; VLDL.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..873
FT /note="Very low-density lipoprotein receptor"
FT /id="PRO_0000017346"
FT TOPO_DOM 28..797
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 798..819
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 820..873
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 31..69
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 70..110
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 111..151
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 152..190
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 191..231
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 237..275
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 276..314
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 316..355
FT /note="LDL-receptor class A 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 356..395
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 396..435
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 439..480
FT /note="LDL-receptor class B 1"
FT REPEAT 481..524
FT /note="LDL-receptor class B 2"
FT REPEAT 525..567
FT /note="LDL-receptor class B 3"
FT REPEAT 568..611
FT /note="LDL-receptor class B 4"
FT REPEAT 612..654
FT /note="LDL-receptor class B 5"
FT REPEAT 655..697
FT /note="LDL-receptor class B 6"
FT DOMAIN 702..750
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 751..790
FT /note="Clustered O-linked oligosaccharides"
FT MOTIF 832..837
FT /note="Endocytosis signal"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 781
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 33..45
FT /evidence="ECO:0000250"
FT DISULFID 40..58
FT /evidence="ECO:0000250"
FT DISULFID 52..67
FT /evidence="ECO:0000250"
FT DISULFID 72..84
FT /evidence="ECO:0000250"
FT DISULFID 79..97
FT /evidence="ECO:0000250"
FT DISULFID 91..108
FT /evidence="ECO:0000250"
FT DISULFID 113..127
FT /evidence="ECO:0000250"
FT DISULFID 120..140
FT /evidence="ECO:0000250"
FT DISULFID 134..149
FT /evidence="ECO:0000250"
FT DISULFID 154..166
FT /evidence="ECO:0000250"
FT DISULFID 161..179
FT /evidence="ECO:0000250"
FT DISULFID 173..188
FT /evidence="ECO:0000250"
FT DISULFID 193..205
FT /evidence="ECO:0000250"
FT DISULFID 200..218
FT /evidence="ECO:0000250"
FT DISULFID 212..229
FT /evidence="ECO:0000250"
FT DISULFID 239..251
FT /evidence="ECO:0000250"
FT DISULFID 246..264
FT /evidence="ECO:0000250"
FT DISULFID 258..273
FT /evidence="ECO:0000250"
FT DISULFID 278..290
FT /evidence="ECO:0000250"
FT DISULFID 285..303
FT /evidence="ECO:0000250"
FT DISULFID 297..312
FT /evidence="ECO:0000250"
FT DISULFID 318..331
FT /evidence="ECO:0000250"
FT DISULFID 326..344
FT /evidence="ECO:0000250"
FT DISULFID 338..355
FT /evidence="ECO:0000250"
FT DISULFID 360..371
FT /evidence="ECO:0000250"
FT DISULFID 367..380
FT /evidence="ECO:0000250"
FT DISULFID 382..394
FT /evidence="ECO:0000250"
FT DISULFID 400..410
FT /evidence="ECO:0000250"
FT DISULFID 406..419
FT /evidence="ECO:0000250"
FT DISULFID 421..434
FT /evidence="ECO:0000250"
FT DISULFID 706..719
FT /evidence="ECO:0000250"
FT DISULFID 715..734
FT /evidence="ECO:0000250"
FT DISULFID 736..749
FT /evidence="ECO:0000250"
FT CROSSLNK 839
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P98155"
SQ SEQUENCE 873 AA; 96542 MW; E521D08314F2726B CRC64;
MGTSARWALW LLLALCWAPR DSGATASGKK AKCDSSQFQC TNGRCITLLW KCDGDEDCTD
GSDEKNCVKK TCAESDFVCK NGQCVPNRWQ CDGDPDCEDG SDESPEQCHM RTCRINEISC
GARSTQCIPE SWRCDGENDC DNGEDEENCG NITCSADEFT CSSGRCVSRN FVCNGQDDCD
DGSDELDCAP PTCGAHEFQC RTSSCIPLSW VCDDDADCSD QSDESLEQCG RQPVIHTKCP
TSEIQCGSGE CIHKKWRCDG DPDCKDGSDE VNCPSRTCRP DQFECEDGSC IHGSRQCNGI
RDCVDGSDEV NCKNVNQCLG PGKFKCRSGE CIDITKVCDQ EQDCRDWSDE PLKECHINEC
LVNNGGCSHI CKDLVIGYEC DCAAGFELID RKTCGDIDEC QNPGICSQIC INLKGGYKCE
CSRGYQMDLA TGVCKAVGKE PSLIFTNRRD IRKIGLERKE YIQLVEQLRN TVALDADIAA
QKLFWADLSQ KAIFSASIDD KVGRHFKMID NVYNPAAIAV DWVYKTIYWT DAASKTISVA
TLDGTKRKFL FNSDLREPAS IAVDPLSGFV YWSDWGEPAK IEKAGMNGFD RRPLVTEDIQ
WPNGITLDLV KSRLYWLDSK LHMLSSVDLN GQDRRIVLKS LEFLAHPLAL TIFEDRVYWI
DGENEAVYGA NKFTGSELAT LVNNLNDAQD IIIYHELVQP SGKNWCEEDM ENGGCEYLCL
PAPQINDHSP KYTCSCPNGY NLEENGRECQ STSTPVTYSE TKDVNTTDIL RTSGLVPGGI
NVTTAVSEVS VPPKGTSAAW AILPLLLLVM AAVGGYLMWR NWQHKNMKSM NFDNPVYLKT
TEEDLSIDIG RHSASVGHTY PAISVVSTDD DLA
