Human Gene LRP1 (ENST00000338962.8) from GENCODE V44
  Description: Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission. (from UniProt Q07954)
RefSeq Summary (NM_002332): This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients. [provided by RefSeq, Oct 2015].
Gencode Transcript: ENST00000338962.8
Gencode Gene: ENSG00000123384.14
Transcript (Including UTRs)
   Position: hg38 chr12:57,128,716-57,150,059 Size: 21,344 Total Exon Count: 7 Strand: +
Coding Region
   Position: hg38 chr12:57,128,965-57,149,018 Size: 20,054 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 09:09:47

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr12:57,128,716-57,150,059)mRNA (may differ from genome)Protein (292 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Prolow-density lipoprotein receptor-related protein 1; Short=LRP-1; AltName: Full=Alpha-2-macroglobulin receptor; Short=A2MR; AltName: Full=Apolipoprotein E receptor; Short=APOER; AltName: CD_antigen=CD91; Contains: RecName: Full=Low-density lipoprotein receptor-related protein 1 85 kDa subunit; Short=LRP-85; Contains: RecName: Full=Low-density lipoprotein receptor-related protein 1 515 kDa subunit; Short=LRP-515; Contains: RecName: Full=Low-density lipoprotein receptor-related protein 1 intracellular domain; Short=LRPICD; Flags: Precursor;
FUNCTION: Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Required for early embryonic development. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission.
FUNCTION: Functions as a receptor for Pseudomonas aeruginosa exotoxin A.
SUBUNIT: Heterodimer of an 85-kDa membrane-bound carboxyl subunit and a non-covalently attached 515-kDa N-terminal subunit. Intracellular domain interacts with MAFB (By similarity). Found in a complex with PID1/PCLI1, LRP1 and CUBNI. Interacts with SNX17, PID1/PCLI1, PDGF and CUBN. The intracellular domain interacts with SHC1, GULP1 and DAB1. Interacts with LRPAP1. Can weakly interact (via NPXY motif) with DAB2 (via PID domain); the interaction is enhanced by tyrosine phosphorylation of the NPXY motif. Interacts with bacterial exotoxins.
INTERACTION: Q63722:Jag1 (xeno); NbExp=4; IntAct=EBI-1046087, EBI-4567800; Q03350:Thbs2 (xeno); NbExp=2; IntAct=EBI-1046087, EBI-4567830;
SUBCELLULAR LOCATION: Low-density lipoprotein receptor-related protein 1 85 kDa subunit: Cell membrane; Single-pass type I membrane protein. Membrane, coated pit.
SUBCELLULAR LOCATION: Low-density lipoprotein receptor-related protein 1 515 kDa subunit: Cell membrane; Peripheral membrane protein; Extracellular side. Membrane, coated pit.
SUBCELLULAR LOCATION: Low-density lipoprotein receptor-related protein 1 intracellular domain: Cytoplasm. Nucleus. Note=After cleavage, the intracellular domain (LRPICD) is detected both in the cytoplasm and in the nucleus.
TISSUE SPECIFICITY: Most abundant in liver, brain and lung.
PTM: Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515 kDa large extracellular domain (LRP-515) that remains non- covalently associated. Gamma-secretase-dependent cleavage of LRP- 85 releases the intracellular domain from the membrane.
PTM: The N-terminus is blocked.
PTM: Phosphorylated on serine and threonine residues.
PTM: Phosphorylated on tyrosine residues upon stimulation with PDGF. Tyrosine phosphorylation promotes interaction with SHC1.
SIMILARITY: Belongs to the LDLR family.
SIMILARITY: Contains 22 EGF-like domains.
SIMILARITY: Contains 31 LDL-receptor class A domains.
SIMILARITY: Contains 34 LDL-receptor class B repeats.

-  Primer design for this transcript

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: LRP1
Diseases sorted by gene-association score: keratosis pilaris atrophicans* (1291), atrophoderma vermiculata* (750), burnett schwartz berberian syndrome* (400), keratosis follicularis spinulosa decalvans* (261), alzheimer disease (16), keratosis (15), cerebral amyloid angiopathy (10), liposarcoma (8), myxoid liposarcoma (8)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 149.51 RPKM in Cells - Cultured fibroblasts
Total median expression: 2022.06 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -103.64249-0.416 Picture PostScript Text
3' UTR -377.901041-0.363 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011042 - 6-blade_b-propeller_TolB-like
IPR000742 - EG-like_dom
IPR001881 - EGF-like_Ca-bd
IPR013032 - EGF-like_CS
IPR000152 - EGF-type_Asp/Asn_hydroxyl_site
IPR018097 - EGF_Ca-bd_CS
IPR009030 - Growth_fac_rcpt
IPR023415 - LDLR_class-A_CS
IPR000033 - LDLR_classB_rpt
IPR002172 - LDrepeatLR_classA_rpt

Pfam Domains:
PF07645 - Calcium-binding EGF domain
PF00057 - Low-density lipoprotein receptor domain class A
PF00058 - Low-density lipoprotein receptor repeat class B

Protein Data Bank (PDB) 3-D Structure
MuPIT help

ModBase Predicted Comparative 3D Structure on Q07954
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0002020 protease binding
GO:0003723 RNA binding
GO:0005041 low-density lipoprotein receptor activity
GO:0005044 scavenger receptor activity
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0016964 alpha-2 macroglobulin receptor activity
GO:0030226 apolipoprotein receptor activity
GO:0032050 clathrin heavy chain binding
GO:0034185 apolipoprotein binding
GO:0038023 signaling receptor activity
GO:0042954 lipoprotein transporter activity
GO:0043395 heparan sulfate proteoglycan binding
GO:0044877 macromolecular complex binding
GO:0046872 metal ion binding
GO:0070325 lipoprotein particle receptor binding

Biological Process:
GO:0001523 retinoid metabolic process
GO:0002265 astrocyte activation involved in immune response
GO:0006629 lipid metabolic process
GO:0006897 endocytosis
GO:0006898 receptor-mediated endocytosis
GO:0006909 phagocytosis
GO:0007205 protein kinase C-activating G-protein coupled receptor signaling pathway
GO:0007275 multicellular organism development
GO:0007568 aging
GO:0008283 cell proliferation
GO:0010715 regulation of extracellular matrix disassembly
GO:0010875 positive regulation of cholesterol efflux
GO:0010942 positive regulation of cell death
GO:0010977 negative regulation of neuron projection development
GO:0014912 negative regulation of smooth muscle cell migration
GO:0021987 cerebral cortex development
GO:0030178 negative regulation of Wnt signaling pathway
GO:0031623 receptor internalization
GO:0032092 positive regulation of protein binding
GO:0032370 positive regulation of lipid transport
GO:0032374 regulation of cholesterol transport
GO:0032429 regulation of phospholipase A2 activity
GO:0032956 regulation of actin cytoskeleton organization
GO:0035909 aorta morphogenesis
GO:0042157 lipoprotein metabolic process
GO:0042953 lipoprotein transport
GO:0043277 apoptotic cell clearance
GO:0043524 negative regulation of neuron apoptotic process
GO:0045056 transcytosis
GO:0045732 positive regulation of protein catabolic process
GO:0045807 positive regulation of endocytosis
GO:0051222 positive regulation of protein transport
GO:0051246 regulation of protein metabolic process
GO:0097242 beta-amyloid clearance
GO:1900223 positive regulation of beta-amyloid clearance
GO:1903078 positive regulation of protein localization to plasma membrane
GO:1904646 cellular response to beta-amyloid
GO:1905167 positive regulation of lysosomal protein catabolic process
GO:2000587 negative regulation of platelet-derived growth factor receptor-beta signaling pathway

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0005769 early endosome
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0005905 clathrin-coated pit
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0030136 clathrin-coated vesicle
GO:0030425 dendrite
GO:0030666 endocytic vesicle membrane
GO:0043025 neuronal cell body
GO:0043235 receptor complex
GO:0098797 plasma membrane protein complex

-  Descriptions from all associated GenBank mRNAs
  LF208941 - JP 2014500723-A/16444: Polycomb-Associated Non-Coding RNAs.
MA444518 - JP 2018138019-A/16444: Polycomb-Associated Non-Coding RNAs.
BC052593 - Homo sapiens low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor), mRNA (cDNA clone IMAGE:6575284), complete cds.
BC072015 - Homo sapiens low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor), mRNA (cDNA clone IMAGE:6384902), complete cds.
HZ466381 - JP 2015532642-A/5: MicroRNAs that Suppress Human Melanoma.
LP722496 - Sequence 9 from Patent EP2882496.
MA622446 - JP 2018140982-A/5: MicroRNAs that Suppress Human Melanoma.
X13916 - Human mRNA for LDL-receptor related protein.
BC045107 - Homo sapiens low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor), mRNA (cDNA clone IMAGE:4859182), complete cds.
BC021204 - Homo sapiens low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor), mRNA (cDNA clone IMAGE:4110815), complete cds.
KJ901558 - Synthetic construct Homo sapiens clone ccsbBroadEn_10952 LRP1 gene, encodes complete protein.
AB209498 - Homo sapiens mRNA for low density lipoprotein-related protein 1 variant protein.
LF208943 - JP 2014500723-A/16446: Polycomb-Associated Non-Coding RNAs.
MA444520 - JP 2018138019-A/16446: Polycomb-Associated Non-Coding RNAs.
MP557060 - Sequence 9 from Patent EP3626309.
LF324390 - JP 2014500723-A/131893: Polycomb-Associated Non-Coding RNAs.
MA559967 - JP 2018138019-A/131893: Polycomb-Associated Non-Coding RNAs.
JD054668 - Sequence 35692 from Patent EP1572962.
JD123098 - Sequence 104122 from Patent EP1572962.
LF324388 - JP 2014500723-A/131891: Polycomb-Associated Non-Coding RNAs.
MA559965 - JP 2018138019-A/131891: Polycomb-Associated Non-Coding RNAs.
JD082676 - Sequence 63700 from Patent EP1572962.
JD488666 - Sequence 469690 from Patent EP1572962.
CU692248 - Synthetic construct Homo sapiens gateway clone IMAGE:100023062 5' read LRP1 mRNA.
LF324386 - JP 2014500723-A/131889: Polycomb-Associated Non-Coding RNAs.
MA559963 - JP 2018138019-A/131889: Polycomb-Associated Non-Coding RNAs.
LF324376 - JP 2014500723-A/131879: Polycomb-Associated Non-Coding RNAs.
MA559953 - JP 2018138019-A/131879: Polycomb-Associated Non-Coding RNAs.
LF324374 - JP 2014500723-A/131877: Polycomb-Associated Non-Coding RNAs.
MA559951 - JP 2018138019-A/131877: Polycomb-Associated Non-Coding RNAs.
LF324370 - JP 2014500723-A/131873: Polycomb-Associated Non-Coding RNAs.
MA559947 - JP 2018138019-A/131873: Polycomb-Associated Non-Coding RNAs.
LF324368 - JP 2014500723-A/131871: Polycomb-Associated Non-Coding RNAs.
MA559945 - JP 2018138019-A/131871: Polycomb-Associated Non-Coding RNAs.
LF324366 - JP 2014500723-A/131869: Polycomb-Associated Non-Coding RNAs.
MA559943 - JP 2018138019-A/131869: Polycomb-Associated Non-Coding RNAs.
LF324365 - JP 2014500723-A/131868: Polycomb-Associated Non-Coding RNAs.
MA559942 - JP 2018138019-A/131868: Polycomb-Associated Non-Coding RNAs.
LF324364 - JP 2014500723-A/131867: Polycomb-Associated Non-Coding RNAs.
MA559941 - JP 2018138019-A/131867: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05010 - Alzheimer's disease

Reactome (by CSHL, EBI, and GO)

Protein Q07954 (Reactome details) participates in the following event(s):

R-HSA-2168897 LRP1 (CD91) binds Hemopexin:heme
R-HSA-2404131 LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
R-HSA-2168880 Scavenging of heme from plasma
R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656 Vesicle-mediated transport
R-HSA-975634 Retinoid metabolism and transport
R-HSA-2187338 Visual phototransduction
R-HSA-6806667 Metabolism of fat-soluble vitamins
R-HSA-418594 G alpha (i) signalling events
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-388396 GPCR downstream signalling
R-HSA-1430728 Metabolism
R-HSA-372790 Signaling by GPCR
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A2MR, APR, BC045107, ENST00000338962.1, ENST00000338962.2, ENST00000338962.3, ENST00000338962.4, ENST00000338962.5, ENST00000338962.6, ENST00000338962.7, LRP1_HUMAN, Q07954, Q2PP12, Q8IVG8, uc010sre.1, uc010sre.2, uc010sre.3
UCSC ID: ENST00000338962.8
RefSeq Accession: NM_002332
Protein: Q07954 (aka LRP1_HUMAN)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.