LRP1

Protein identityUniProt · HPA

UniProt accession

Q07954

Gene

LRP1

Ensembl

ENSG00000123384

Chromosome

12

Canonical length

4544 aa

Protein class

Candidate cardiovascular disease genes, CD markers, Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Nucleoli,Plasma membrane,Cytosol

Secretome location

Intracellular and membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

4544 residues, UniProt reviewed canonical sequence.

>Q07954|LRP1
     1  MLTPPLLLLL PLLSALVAAA IDAPKTCSPK QFACRDQITC ISKGWRCDGE RDCPDGSDEA
    61  PEICPQSKAQ RCQPNEHNCL GTELCVPMSR LCNGVQDCMD GSDEGPHCRE LQGNCSRLGC
   121  QHHCVPTLDG PTCYCNSSFQ LQADGKTCKD FDECSVYGTC SQLCTNTDGS FICGCVEGYL
   181  LQPDNRSCKA KNEPVDRPPV LLIANSQNIL ATYLSGAQVS TITPTSTRQT TAMDFSYANE
   241  TVCWVHVGDS AAQTQLKCAR MPGLKGFVDE HTINISLSLH HVEQMAIDWL TGNFYFVDDI
   301  DDRIFVCNRN GDTCVTLLDL ELYNPKGIAL DPAMGKVFFT DYGQIPKVER CDMDGQNRTK
   361  LVDSKIVFPH GITLDLVSRL VYWADAYLDY IEVVDYEGKG RQTIIQGILI EHLYGLTVFE
   421  NYLYATNSDN ANAQQKTSVI RVNRFNSTEY QVVTRVDKGG ALHIYHQRRQ PRVRSHACEN
   481  DQYGKPGGCS DICLLANSHK ARTCRCRSGF SLGSDGKSCK KPEHELFLVY GKGRPGIIRG
   541  MDMGAKVPDE HMIPIENLMN PRALDFHAET GFIYFADTTS YLIGRQKIDG TERETILKDG
   601  IHNVEGVAVD WMGDNLYWTD DGPKKTISVA RLEKAAQTRK TLIEGKMTHP RAIVVDPLNG
   661  WMYWTDWEED PKDSRRGRLE RAWMDGSHRD IFVTSKTVLW PNGLSLDIPA GRLYWVDAFY
   721  DRIETILLNG TDRKIVYEGP ELNHAFGLCH HGNYLFWTEY RSGSVYRLER GVGGAPPTVT
   781  LLRSERPPIF EIRMYDAQQQ QVGTNKCRVN NGGCSSLCLA TPGSRQCACA EDQVLDADGV
   841  TCLANPSYVP PPQCQPGEFA CANSRCIQER WKCDGDNDCL DNSDEAPALC HQHTCPSDRF
   901  KCENNRCIPN RWLCDGDNDC GNSEDESNAT CSARTCPPNQ FSCASGRCIP ISWTCDLDDD
   961  CGDRSDESAS CAYPTCFPLT QFTCNNGRCI NINWRCDNDN DCGDNSDEAG CSHSCSSTQF
  1021  KCNSGRCIPE HWTCDGDNDC GDYSDETHAN CTNQATRPPG GCHTDEFQCR LDGLCIPLRW
  1081  RCDGDTDCMD SSDEKSCEGV THVCDPSVKF GCKDSARCIS KAWVCDGDND CEDNSDEENC
  1141  ESLACRPPSH PCANNTSVCL PPDKLCDGND DCGDGSDEGE LCDQCSLNNG GCSHNCSVAP
  1201  GEGIVCSCPL GMELGPDNHT CQIQSYCAKH LKCSQKCDQN KFSVKCSCYE GWVLEPDGES
  1261  CRSLDPFKPF IIFSNRHEIR RIDLHKGDYS VLVPGLRNTI ALDFHLSQSA LYWTDVVEDK
  1321  IYRGKLLDNG ALTSFEVVIQ YGLATPEGLA VDWIAGNIYW VESNLDQIEV AKLDGTLRTT
  1381  LLAGDIEHPR AIALDPRDGI LFWTDWDASL PRIEAASMSG AGRRTVHRET GSGGWPNGLT
  1441  VDYLEKRILW IDARSDAIYS ARYDGSGHME VLRGHEFLSH PFAVTLYGGE VYWTDWRTNT
  1501  LAKANKWTGH NVTVVQRTNT QPFDLQVYHP SRQPMAPNPC EANGGQGPCS HLCLINYNRT
  1561  VSCACPHLMK LHKDNTTCYE FKKFLLYARQ MEIRGVDLDA PYYNYIISFT VPDIDNVTVL
  1621  DYDAREQRVY WSDVRTQAIK RAFINGTGVE TVVSADLPNA HGLAVDWVSR NLFWTSYDTN
  1681  KKQINVARLD GSFKNAVVQG LEQPHGLVVH PLRGKLYWTD GDNISMANMD GSNRTLLFSG
  1741  QKGPVGLAID FPESKLYWIS SGNHTINRCN LDGSGLEVID AMRSQLGKAT ALAIMGDKLW
  1801  WADQVSEKMG TCSKADGSGS VVLRNSTTLV MHMKVYDESI QLDHKGTNPC SVNNGDCSQL
  1861  CLPTSETTRS CMCTAGYSLR SGQQACEGVG SFLLYSVHEG IRGIPLDPND KSDALVPVSG
  1921  TSLAVGIDFH AENDTIYWVD MGLSTISRAK RDQTWREDVV TNGIGRVEGI AVDWIAGNIY
  1981  WTDQGFDVIE VARLNGSFRY VVISQGLDKP RAITVHPEKG YLFWTEWGQY PRIERSRLDG
  2041  TERVVLVNVS ISWPNGISVD YQDGKLYWCD ARTDKIERID LETGENREVV LSSNNMDMFS
  2101  VSVFEDFIYW SDRTHANGSI KRGSKDNATD SVPLRTGIGV QLKDIKVFNR DRQKGTNVCA
  2161  VANGGCQQLC LYRGRGQRAC ACAHGMLAED GASCREYAGY LLYSERTILK SIHLSDERNL
  2221  NAPVQPFEDP EHMKNVIALA FDYRAGTSPG TPNRIFFSDI HFGNIQQIND DGSRRITIVE
  2281  NVGSVEGLAY HRGWDTLYWT SYTTSTITRH TVDQTRPGAF ERETVITMSG DDHPRAFVLD
  2341  ECQNLMFWTN WNEQHPSIMR AALSGANVLT LIEKDIRTPN GLAIDHRAEK LYFSDATLDK
  2401  IERCEYDGSH RYVILKSEPV HPFGLAVYGE HIFWTDWVRR AVQRANKHVG SNMKLLRVDI
  2461  PQQPMGIIAV ANDTNSCELS PCRINNGGCQ DLCLLTHQGH VNCSCRGGRI LQDDLTCRAV
  2521  NSSCRAQDEF ECANGECINF SLTCDGVPHC KDKSDEKPSY CNSRRCKKTF RQCSNGRCVS
  2581  NMLWCNGADD CGDGSDEIPC NKTACGVGEF RCRDGTCIGN SSRCNQFVDC EDASDEMNCS
  2641  ATDCSSYFRL GVKGVLFQPC ERTSLCYAPS WVCDGANDCG DYSDERDCPG VKRPRCPLNY
  2701  FACPSGRCIP MSWTCDKEDD CEHGEDETHC NKFCSEAQFE CQNHRCISKQ WLCDGSDDCG
  2761  DGSDEAAHCE GKTCGPSSFS CPGTHVCVPE RWLCDGDKDC ADGADESIAA GCLYNSTCDD
  2821  REFMCQNRQC IPKHFVCDHD RDCADGSDES PECEYPTCGP SEFRCANGRC LSSRQWECDG
  2881  ENDCHDQSDE APKNPHCTSQ EHKCNASSQF LCSSGRCVAE ALLCNGQDDC GDSSDERGCH
  2941  INECLSRKLS GCSQDCEDLK IGFKCRCRPG FRLKDDGRTC ADVDECSTTF PCSQRCINTH
  3001  GSYKCLCVEG YAPRGGDPHS CKAVTDEEPF LIFANRYYLR KLNLDGSNYT LLKQGLNNAV
  3061  ALDFDYREQM IYWTDVTTQG SMIRRMHLNG SNVQVLHRTG LSNPDGLAVD WVGGNLYWCD
  3121  KGRDTIEVSK LNGAYRTVLV SSGLREPRAL VVDVQNGYLY WTDWGDHSLI GRIGMDGSSR
  3181  SVIVDTKITW PNGLTLDYVT ERIYWADARE DYIEFASLDG SNRHVVLSQD IPHIFALTLF
  3241  EDYVYWTDWE TKSINRAHKT TGTNKTLLIS TLHRPMDLHV FHALRQPDVP NHPCKVNNGG
  3301  CSNLCLLSPG GGHKCACPTN FYLGSDGRTC VSNCTASQFV CKNDKCIPFW WKCDTEDDCG
  3361  DHSDEPPDCP EFKCRPGQFQ CSTGICTNPA FICDGDNDCQ DNSDEANCDI HVCLPSQFKC
  3421  TNTNRCIPGI FRCNGQDNCG DGEDERDCPE VTCAPNQFQC SITKRCIPRV WVCDRDNDCV
  3481  DGSDEPANCT QMTCGVDEFR CKDSGRCIPA RWKCDGEDDC GDGSDEPKEE CDERTCEPYQ
  3541  FRCKNNRCVP GRWQCDYDND CGDNSDEESC TPRPCSESEF SCANGRCIAG RWKCDGDHDC
  3601  ADGSDEKDCT PRCDMDQFQC KSGHCIPLRW RCDADADCMD GSDEEACGTG VRTCPLDEFQ
  3661  CNNTLCKPLA WKCDGEDDCG DNSDENPEEC ARFVCPPNRP FRCKNDRVCL WIGRQCDGTD
  3721  NCGDGTDEED CEPPTAHTTH CKDKKEFLCR NQRCLSSSLR CNMFDDCGDG SDEEDCSIDP
  3781  KLTSCATNAS ICGDEARCVR TEKAAYCACR SGFHTVPGQP GCQDINECLR FGTCSQLCNN
  3841  TKGGHLCSCA RNFMKTHNTC KAEGSEYQVL YIADDNEIRS LFPGHPHSAY EQAFQGDESV
  3901  RIDAMDVHVK AGRVYWTNWH TGTISYRSLP PAAPPTTSNR HRRQIDRGVT HLNISGLKMP
  3961  RGIAIDWVAG NVYWTDSGRD VIEVAQMKGE NRKTLISGMI DEPHAIVVDP LRGTMYWSDW
  4021  GNHPKIETAA MDGTLRETLV QDNIQWPTGL AVDYHNERLY WADAKLSVIG SIRLNGTDPI
  4081  VAADSKRGLS HPFSIDVFED YIYGVTYINN RVFKIHKFGH SPLVNLTGGL SHASDVVLYH
  4141  QHKQPEVTNP CDRKKCEWLC LLSPSGPVCT CPNGKRLDNG TCVPVPSPTP PPDAPRPGTC
  4201  NLQCFNGGSC FLNARRQPKC RCQPRYTGDK CELDQCWEHC RNGGTCAASP SGMPTCRCPT
  4261  GFTGPKCTQQ VCAGYCANNS TCTVNQGNQP QCRCLPGFLG DRCQYRQCSG YCENFGTCQM
  4321  AADGSRQCRC TAYFEGSRCE VNKCSRCLEG ACVVNKQSGD VTCNCTDGRV APSCLTCVGH
  4381  CSNGGSCTMN SKMMPECQCP PHMTGPRCEE HVFSQQQPGH IASILIPLLL LLLLVLVAGV
  4441  VFWYKRRVQG AKGFQHQRMT NGAMNVEIGN PTYKMYEGGE PDDVGGLLDA DFALDPDKPT
  4501  NFTNPVYATL YMGGHGSRHS LASTDEKREL LGRGPEDEIG DPLA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LRP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0

Highest tissue expression

102 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LRP1.

Disease | AllUniProt

Conditions LRP1 is implicated in, by any mechanism.

• Keratosis pilaris atrophicans (KPA) MIM:604093
• Developmental dysplasia of the hip 3 (DDH3) MIM:620690

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 772 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental dysplasia of the hip 3
• Atrophoderma vermiculatum
• Keratosis pilaris
• Global developmental delay

ReferencesPubMed · IEDB

Publications for LRP1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.06

gnomAD pLI

1

gnomAD missense Z

8.25

DepMap mean gene effect

-0.18

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid-beta clearance
• amyloid-beta clearance by cellular catabolic process
• amyloid-beta clearance by transcytosis
• aorta morphogenesis
• apoptotic cell clearance
• astrocyte activation involved in immune response
• cellular response to amyloid-beta
• enzyme-linked receptor protein signaling pathway
• lipid metabolic process
• lipoprotein transport
• lysosomal transport
• negative regulation of gene expression
• negative regulation of platelet-derived growth factor receptor-beta signaling pathway
• negative regulation of SMAD protein signal transduction
• negative regulation of smooth muscle cell migration
• negative regulation of Wnt signaling pathway
• phagocytosis
• positive regulation of amyloid-beta clearance
• positive regulation of cholesterol efflux
• positive regulation of endocytosis
• positive regulation of lipid transport
• positive regulation of lysosomal protein catabolic process
• positive regulation of protein localization to plasma membrane
• positive regulation of reverse cholesterol transport
• receptor internalization
• receptor-mediated endocytosis
• regulation of actin cytoskeleton organization
• regulation of extracellular matrix disassembly
• regulation of extracellular matrix organization
• retinoid metabolic process
• transcytosis
• transport across blood-brain barrier
• positive regulation of transcytosis

Molecular functions

• amyloid-beta binding
• apolipoprotein binding
• calcium ion binding
• cargo receptor activity
• clathrin heavy chain binding
• heparan sulfate proteoglycan binding
• lipoprotein particle receptor binding
• low-density lipoprotein particle receptor activity
• protein-containing complex binding
• RNA binding
• scavenger receptor activity
• signaling receptor activity
• alpha-2 macroglobulin receptor activity
• apolipoprotein receptor activity

Cellular components

• basolateral plasma membrane
• clathrin-coated pit
• cytosol
• early endosome
• endocytic vesicle membrane
• focal adhesion
• lysosomal membrane
• membrane
• microtubule organizing center
• nucleolus
• plasma membrane
• plasma membrane protein complex
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• LDLR class B repeat
• EGF-type aspartate/asparagine hydroxylation site
• EGF-like domain
• EGF-like calcium-binding domain
• Low-density lipoprotein (LDL) receptor class A repeat
• Growth factor receptor cysteine-rich domain superfamily
• Six-bladed beta-propeller, TolB-like
• EGF-like calcium-binding, conserved site
• Low-density lipoprotein (LDL) receptor class A, conserved site
• Complement Clr-like EGF domain
• LDL receptor-like superfamily
• NOTCH1, EGF-like calcium-binding domain
• Low-density lipoprotein receptor-related
• Low-density lipoprotein receptor domain class A
• Low-density lipoprotein receptor repeat class B
• Calcium-binding EGF domain
• Complement Clr-like EGF-like
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Acetylation
• Calcium
• Cell membrane
• Coated pit
• Cytoplasm
• Cytoskeleton
• Developmental protein
• Disulfide bond
• EGF-like domain
• Endocytosis
• Glycoprotein
• Golgi apparatus
• Host-virus interaction
• Membrane
• Metal-binding
• Nucleus
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of LRP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ADGRG6
• CUBN
• DAB1
• GULP1
• IGFBP3
• LRPAP1
• MAFB
• MDK
• PDGF
• PDGFB
• SHC1
• SNX17
• SERPINE1
• MAPT
• PLAU
• PID1
• APBB1
• EGFR