LRP1 (Homo sapiens)

Description [+]

Synonyms: LRP1, CD91
Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
Short gene description: Prolow-density lipoprotein receptor-related protein 1 Precursor (LRP)(Alpha-2-macroglobulin receptor)(A2MR)(Apolipoprotein E receptor)(APOER)(CD91 antigen) [Contains Low-density lipoprotein receptor-related protein 1 85 kDa subunit(LRP-85);Low-density lipoprotein receptor-related protein 1 515 kDa subunit(LRP-515);Low-density lipoprotein receptor-related protein 1 intracellular domain(LRPICD)] [Source:UniProtKB/Swiss-Prot;Acc:Q07954]
Family: other
Process: apoptosis,
Pathways: apoptotic cell clearance,
Criteria: manually curated
Curator comment: Null
Mouse ortholog(s): Lrp1
WIKI: LRP1-H_sapiens

References [+]

Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte.
Gardai SJ, McPhillips KA, Frasch SC, Janssen WJ, Starefeldt A, Murphy-Ullrich JE, Bratton DL, Oldenborg PA, Michalak M, Henson PM
Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where don't eat me signals are rendered inactive and eat me signals, including calreticulin and phosphatidylserine, congregate together and signal for removal. Cell. 2005 Oct 21;123(2):321-34.

Apoptosis: controlled demolition at the cellular level.
Taylor RC, Cullen SP, Martin SJ
Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses. Much of what happens during the demolition phase of apoptosis is orchestrated by members of the caspase family of cysteine proteases. These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules. Nat Rev Mol Cell Biol. 2008 Mar;9(3):231-41.

Structure & Sequence [+]

Pfam domains: (Pfam is a large collection of protein families.)

Source	Domain Name	Start	End
PFAM A	Ldl_recept_a	25	64
PFAM A	Ldl_recept_a	70	108
PFAM A	EGF_CA	150	188
PFAM A	Ldl_recept_b	614	658
PFAM A	Ldl_recept_b	660	709
PFAM A	Ldl_recept_a	852	890
PFAM A	Ldl_recept_a	893	931
PFAM A	Ldl_recept_a	934	971
PFAM A	Ldl_recept_a	974	1011
PFAM A	Ldl_recept_a	1013	1051
PFAM A	Ldl_recept_a	1060	1097
PFAM A	Ldl_recept_a	1102	1140
PFAM A	Ldl_recept_a	1143	1185
PFAM A	Ldl_recept_b	1356	1397
PFAM A	Ldl_recept_b	1399	1444
PFAM A	Ldl_recept_b	1627	1668
PFAM A	Ldl_recept_b	1977	2018
PFAM A	Ldl_recept_b	2020	2062
PFAM A	Ldl_recept_b	2344	2387
PFAM A	Ldl_recept_b	2389	2429
PFAM A	Ldl_recept_a	2522	2561
PFAM A	Ldl_recept_a	2564	2600
PFAM A	Ldl_recept_a	2603	2639
PFAM A	Ldl_recept_a	2657	2688
PFAM A	Ldl_recept_a	2694	2730
PFAM A	Ldl_recept_a	2732	2769
PFAM A	Ldl_recept_a	2772	2812
PFAM A	Ldl_recept_a	2816	2853
PFAM A	Ldl_recept_a	2856	2897
PFAM A	Ldl_recept_a	2902	2939
PFAM A	EGF_CA	2982	3021
PFAM A	Ldl_recept_b	3069	3112
PFAM A	Ldl_recept_b	3114	3155
PFAM A	Ldl_recept_b	3157	3199
PFAM A	Ldl_recept_b	3201	3241
PFAM A	Ldl_recept_a	3332	3369
PFAM A	Ldl_recept_a	3372	3408
PFAM A	Ldl_recept_a	3411	3448
PFAM A	Ldl_recept_a	3451	3489
PFAM A	Ldl_recept_a	3492	3531
PFAM A	Ldl_recept_a	3534	3570
PFAM A	Ldl_recept_a	3573	3609
PFAM A	Ldl_recept_a	3611	3647
PFAM A	Ldl_recept_a	3652	3690
PFAM A	Ldl_recept_a	3694	3731
PFAM A	Ldl_recept_a	3739	3776
PFAM A	Ldl_recept_b	3970	4011
PFAM A	Ldl_recept_b	4013	4055
PFAM A	Ldl_recept_b	4057	4099

Protein sequence [+]

LRP1 | Homo sapiens | 9606 | length:4544

MLTPPLLLLLPLLSALVAAAIDAPKTCSPKQFACRDQITCISKGWRCDGERDCPDGSDEA
PEICPQSKAQRCQPNEHNCLGTELCVPMSRLCNGVQDCMDGSDEGPHCRELQGNCSRLGC
QHHCVPTLDGPTCYCNSSFQLQADGKTCKDFDECSVYGTCSQLCTNTDGSFICGCVEGYL
LQPDNRSCKAKNEPVDRPPVLLIANSQNILATYLSGAQVSTITPTSTRQTTAMDFSYANE
TVCWVHVGDSAAQTQLKCARMPGLKGFVDEHTINISLSLHHVEQMAIDWLTGNFYFVDDI
DDRIFVCNRNGDTCVTLLDLELYNPKGIALDPAMGKVFFTDYGQIPKVERCDMDGQNRTK
LVDSKIVFPHGITLDLVSRLVYWADAYLDYIEVVDYEGKGRQTIIQGILIEHLYGLTVFE
NYLYATNSDNANAQQKTSVIRVNRFNSTEYQVVTRVDKGGALHIYHQRRQPRVRSHACEN
DQYGKPGGCSDICLLANSHKARTCRCRSGFSLGSDGKSCKKPEHELFLVYGKGRPGIIRG
MDMGAKVPDEHMIPIENLMNPRALDFHAETGFIYFADTTSYLIGRQKIDGTERETILKDG
IHNVEGVAVDWMGDNLYWTDDGPKKTISVARLEKAAQTRKTLIEGKMTHPRAIVVDPLNG
WMYWTDWEEDPKDSRRGRLERAWMDGSHRDIFVTSKTVLWPNGLSLDIPAGRLYWVDAFY
DRIETILLNGTDRKIVYEGPELNHAFGLCHHGNYLFWTEYRSGSVYRLERGVGGAPPTVT
LLRSERPPIFEIRMYDAQQQQVGTNKCRVNNGGCSSLCLATPGSRQCACAEDQVLDADGV
TCLANPSYVPPPQCQPGEFACANSRCIQERWKCDGDNDCLDNSDEAPALCHQHTCPSDRF
KCENNRCIPNRWLCDGDNDCGNSEDESNATCSARTCPPNQFSCASGRCIPISWTCDLDDD
CGDRSDESASCAYPTCFPLTQFTCNNGRCININWRCDNDNDCGDNSDEAGCSHSCSSTQF
KCNSGRCIPEHWTCDGDNDCGDYSDETHANCTNQATRPPGGCHTDEFQCRLDGLCIPLRW
RCDGDTDCMDSSDEKSCEGVTHVCDPSVKFGCKDSARCISKAWVCDGDNDCEDNSDEENC
ESLACRPPSHPCANNTSVCLPPDKLCDGNDDCGDGSDEGELCDQCSLNNGGCSHNCSVAP
GEGIVCSCPLGMELGPDNHTCQIQSYCAKHLKCSQKCDQNKFSVKCSCYEGWVLEPDGES
CRSLDPFKPFIIFSNRHEIRRIDLHKGDYSVLVPGLRNTIALDFHLSQSALYWTDVVEDK
IYRGKLLDNGALTSFEVVIQYGLATPEGLAVDWIAGNIYWVESNLDQIEVAKLDGTLRTT
LLAGDIEHPRAIALDPRDGILFWTDWDASLPRIEAASMSGAGRRTVHRETGSGGWPNGLT
VDYLEKRILWIDARSDAIYSARYDGSGHMEVLRGHEFLSHPFAVTLYGGEVYWTDWRTNT
LAKANKWTGHNVTVVQRTNTQPFDLQVYHPSRQPMAPNPCEANGGQGPCSHLCLINYNRT
VSCACPHLMKLHKDNTTCYEFKKFLLYARQMEIRGVDLDAPYYNYIISFTVPDIDNVTVL
DYDAREQRVYWSDVRTQAIKRAFINGTGVETVVSADLPNAHGLAVDWVSRNLFWTSYDTN
KKQINVARLDGSFKNAVVQGLEQPHGLVVHPLRGKLYWTDGDNISMANMDGSNRTLLFSG
QKGPVGLAIDFPESKLYWISSGNHTINRCNLDGSGLEVIDAMRSQLGKATALAIMGDKLW
WADQVSEKMGTCSKADGSGSVVLRNSTTLVMHMKVYDESIQLDHKGTNPCSVNNGDCSQL
CLPTSETTRSCMCTAGYSLRSGQQACEGVGSFLLYSVHEGIRGIPLDPNDKSDALVPVSG
TSLAVGIDFHAENDTIYWVDMGLSTISRAKRDQTWREDVVTNGIGRVEGIAVDWIAGNIY
WTDQGFDVIEVARLNGSFRYVVISQGLDKPRAITVHPEKGYLFWTEWGQYPRIERSRLDG
TERVVLVNVSISWPNGISVDYQDGKLYWCDARTDKIERIDLETGENREVVLSSNNMDMFS
VSVFEDFIYWSDRTHANGSIKRGSKDNATDSVPLRTGIGVQLKDIKVFNRDRQKGTNVCA
VANGGCQQLCLYRGRGQRACACAHGMLAEDGASCREYAGYLLYSERTILKSIHLSDERNL
NAPVQPFEDPEHMKNVIALAFDYRAGTSPGTPNRIFFSDIHFGNIQQINDDGSRRITIVE
NVGSVEGLAYHRGWDTLYWTSYTTSTITRHTVDQTRPGAFERETVITMSGDDHPRAFVLD
ECQNLMFWTNWNEQHPSIMRAALSGANVLTLIEKDIRTPNGLAIDHRAEKLYFSDATLDK
IERCEYDGSHRYVILKSEPVHPFGLAVYGEHIFWTDWVRRAVQRANKHVGSNMKLLRVDI
PQQPMGIIAVANDTNSCELSPCRINNGGCQDLCLLTHQGHVNCSCRGGRILQDDLTCRAV
NSSCRAQDEFECANGECINFSLTCDGVPHCKDKSDEKPSYCNSRRCKKTFRQCSNGRCVS
NMLWCNGADDCGDGSDEIPCNKTACGVGEFRCRDGTCIGNSSRCNQFVDCEDASDEMNCS
ATDCSSYFRLGVKGVLFQPCERTSLCYAPSWVCDGANDCGDYSDERDCPGVKRPRCPLNY
FACPSGRCIPMSWTCDKEDDCEHGEDETHCNKFCSEAQFECQNHRCISKQWLCDGSDDCG
DGSDEAAHCEGKTCGPSSFSCPGTHVCVPERWLCDGDKDCADGADESIAAGCLYNSTCDD
REFMCQNRQCIPKHFVCDHDRDCADGSDESPECEYPTCGPSEFRCANGRCLSSRQWECDG
ENDCHDQSDEAPKNPHCTSQEHKCNASSQFLCSSGRCVAEALLCNGQDDCGDSSDERGCH
INECLSRKLSGCSQDCEDLKIGFKCRCRPGFRLKDDGRTCADVDECSTTFPCSQRCINTH
GSYKCLCVEGYAPRGGDPHSCKAVTDEEPFLIFANRYYLRKLNLDGSNYTLLKQGLNNAV
ALDFDYREQMIYWTDVTTQGSMIRRMHLNGSNVQVLHRTGLSNPDGLAVDWVGGNLYWCD
KGRDTIEVSKLNGAYRTVLVSSGLREPRALVVDVQNGYLYWTDWGDHSLIGRIGMDGSSR
SVIVDTKITWPNGLTLDYVTERIYWADAREDYIEFASLDGSNRHVVLSQDIPHIFALTLF
EDYVYWTDWETKSINRAHKTTGTNKTLLISTLHRPMDLHVFHALRQPDVPNHPCKVNNGG
CSNLCLLSPGGGHKCACPTNFYLGSDGRTCVSNCTASQFVCKNDKCIPFWWKCDTEDDCG
DHSDEPPDCPEFKCRPGQFQCSTGICTNPAFICDGDNDCQDNSDEANCDIHVCLPSQFKC
TNTNRCIPGIFRCNGQDNCGDGEDERDCPEVTCAPNQFQCSITKRCIPRVWVCDRDNDCV
DGSDEPANCTQMTCGVDEFRCKDSGRCIPARWKCDGEDDCGDGSDEPKEECDERTCEPYQ
FRCKNNRCVPGRWQCDYDNDCGDNSDEESCTPRPCSESEFSCANGRCIAGRWKCDGDHDC
ADGSDEKDCTPRCDMDQFQCKSGHCIPLRWRCDADADCMDGSDEEACGTGVRTCPLDEFQ
CNNTLCKPLAWKCDGEDDCGDNSDENPEECARFVCPPNRPFRCKNDRVCLWIGRQCDGTD
NCGDGTDEEDCEPPTAHTTHCKDKKEFLCRNQRCLSSSLRCNMFDDCGDGSDEEDCSIDP
KLTSCATNASICGDEARCVRTEKAAYCACRSGFHTVPGQPGCQDINECLRFGTCSQLCNN
TKGGHLCSCARNFMKTHNTCKAEGSEYQVLYIADDNEIRSLFPGHPHSAYEQAFQGDESV
RIDAMDVHVKAGRVYWTNWHTGTISYRSLPPAAPPTTSNRHRRQIDRGVTHLNISGLKMP
RGIAIDWVAGNVYWTDSGRDVIEVAQMKGENRKTLISGMIDEPHAIVVDPLRGTMYWSDW
GNHPKIETAAMDGTLRETLVQDNIQWPTGLAVDYHNERLYWADAKLSVIGSIRLNGTDPI
VAADSKRGLSHPFSIDVFEDYIYGVTYINNRVFKIHKFGHSPLVNLTGGLSHASDVVLYH
QHKQPEVTNPCDRKKCEWLCLLSPSGPVCTCPNGKRLDNGTCVPVPSPTPPPDAPRPGTC
NLQCFNGGSCFLNARRQPKCRCQPRYTGDKCELDQCWEHCRNGGTCAASPSGMPTCRCPT
GFTGPKCTQQVCAGYCANNSTCTVNQGNQPQCRCLPGFLGDRCQYRQCSGYCENFGTCQM
AADGSRQCRCTAYFEGSRCEVNKCSRCLEGACVVNKQSGDVTCNCTDGRVAPSCLTCVGH
CSNGGSCTMNSKMMPECQCPPHMTGPRCEEHVFSQQQPGHIASILIPLLLLLLLVLVAGV
VFWYKRRVQGAKGFQHQRMTNGAMNVEIGNPTYKMYEGGEPDDVGGLLDADFALDPDKPT
NFTNPVYATLYMGGHGSRHSLASTDEKRELLGRGPEDEIGDPLA

BLAST at NCBI | WU-BLAST2 at EBI

Evolution [+]

Name	Relationship	Species
A_aegypti_AAEL007041-PA	orthology	Aedes
A_gambiae_AGAP012372-PA	orthology	Anopheles
LRP1	orthology	Chimpanzee
NA	orthology	Ciona
XR_027983.2	orthology	Cow
LRP1	orthology	Dog
CG33087	orthology	Fly
LRP1 (2 of 2)	orthology	Fugu
O73809_FUGRU	orthology	Fugu
LRP1 (2 of 2)	orthology	Gasterosteus
LRP1 (1 of 2)	orthology	Gasterosteus
LRP1	orthology	Gorilla
LRP1	orthology	Horse
A_carolinensis_ENSACAP00000006105	orthology	Lyzard
LRP1	orthology	Macaca
LRP1 (1 of 2)	orthology	Medaka
LRP1 (2 of 2)	orthology	Medaka
LRP1	orthology	Monodelphis
Lrp1	orthology	Mouse
LRP1	orthology	Orangutan
LRP1	orthology	Rabbit
Q5I0H1_RAT	orthology	Rat
LRP1 (2 of 2)	orthology	Tetraodon
LRP1 (1 of 2)	orthology	Tetraodon
NP_491270.2	orthology	Worm
LRP1	orthology	Zebra finch
LRP1 (2 of 2)	orthology	Zebrafish
B0V3M2_DANRE	orthology	Zebrafish
A_aegypti_AAEL009869-PA	paralogy	Aedes
A_aegypti_AAEL014222-PA	paralogy	Aedes
A_aegypti_AAEL007657-PA	paralogy	Aedes
A_aegypti_AAEL010712-PA	paralogy	Aedes
A_gambiae_AGAP000037-PA	paralogy	Anopheles
A_gambiae_AGAP000331-PA	paralogy	Anopheles
A_gambiae_AGAP000427-PA	paralogy	Anopheles
IPI00598221.2	paralogy	Chicken
IPI00586700.2	paralogy	Chicken
LRP2	paralogy	Chicken
LRP1B	paralogy	Chimpanzee
LRP2	paralogy	Chimpanzee
LRP4	paralogy	Chimpanzee
NA	paralogy	Ciona
NA	paralogy	Ciona
NP_001071311.1	paralogy	Cow
IPI00906523.1	paralogy	Cow
IPI00696767.4	paralogy	Cow
LRP4	paralogy	Dog
LRP2	paralogy	Dog
CG8909	paralogy	Fly
CG34352	paralogy	Fly
yl	paralogy	Fly
T_rubripes_ENSTRUP00000014683	paralogy	Fugu
LRP2	paralogy	Fugu
LRP4	paralogy	Fugu
T_rubripes_ENSTRUP00000015259	paralogy	Fugu
LRP2	paralogy	Gasterosteus
G_aculeatus_ENSGACP00000009126	paralogy	Gasterosteus
LRP1B	paralogy	Gasterosteus
LRP2	paralogy	Gorilla
LRP4	paralogy	Gorilla
LRP1B	paralogy	Gorilla
LRP4	paralogy	Horse
LRP2	paralogy	Horse
LRP2	paralogy	Human
LRP1B	paralogy	Human
LRP4	paralogy	Human
LRP4	paralogy	Lyzard
LRP2	paralogy	Lyzard
A_carolinensis_ENSACAP00000003402	paralogy	Lyzard
LRP4	paralogy	Macaca
LRP1B	paralogy	Macaca
LRP2	paralogy	Macaca
O_latipes_ENSORLP00000006788	paralogy	Medaka
LRP2	paralogy	Medaka
O_latipes_ENSORLP00000022869	paralogy	Medaka
LRP4	paralogy	Monodelphis
LRP2	paralogy	Monodelphis
LRP1B	paralogy	Monodelphis
Lrp2	paralogy	Mouse
Lrp1b	paralogy	Mouse
Lrp4	paralogy	Mouse
LRP2	paralogy	Orangutan
Q5NVF0_PONPY	paralogy	Orangutan
LRP4	paralogy	Orangutan
O_anatinus_ENSOANP00000012723	paralogy	Ornithorhynchus
LRP2	paralogy	Ornithorhynchus
LRP1B	paralogy	Rabbit
LRP4	paralogy	Rabbit
LRP2	paralogy	Rabbit
LRP2_RAT	paralogy	Rat
LRP4_RAT	paralogy	Rat
T_nigroviridis_ENSTNIP00000022105	paralogy	Tetraodon
LRP2	paralogy	Tetraodon
LRP4	paralogy	Tetraodon
LRP1B	paralogy	Tetraodon
lrp-1	paralogy	Worm
C_elegans_F47B3.8	paralogy	Worm
LRP2	paralogy	Xenopus
LRP2	paralogy	Zebra finch
LRP1B	paralogy	Zebra finch
LRP4	paralogy	Zebra finch
B0S7C7_DANRE	paralogy	Zebrafish
si:dkeyp-122a9.3	paralogy	Zebrafish

Gene Ontology [+]

GO id	Name	Ontology type	Evidence
GO:0007596	blood coagulation	biological_proccess	IEA
GO:0006629	lipid metabolic process	biological_proccess	TAS
GO:0008283	cell proliferation	biological_proccess	TAS
GO:0006897	endocytosis	biological_proccess	IEA
GO:0007275	multicellular organismal development	biological_proccess	IEA
GO:0006898	receptor-mediated endocytosis	biological_proccess	IEA
GO:0007205	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway	biological_proccess	IEA
GO:0007568	aging	biological_proccess	IEA
GO:0008283	cell proliferation	biological_proccess	IEA
GO:0042157	lipoprotein metabolic process	biological_proccess	IEA
GO:0045768	positive regulation of anti-apoptosis	biological_proccess	IEA
GO:0030178	negative regulation of Wnt receptor signaling pathway	biological_proccess	IEA
GO:0043277	apoptotic cell clearance	biological_proccess	IEA
GO:0004888	transmembrane receptor activity	mollecular_function	IEA
GO:0005509	calcium ion binding	mollecular_function	IEA
GO:0070325	lipoprotein receptor binding	mollecular_function	IC
GO:0034185	apolipoprotein binding	mollecular_function	IPI
GO:0004872	receptor activity	mollecular_function	TAS
GO:0005319	lipid transporter activity	mollecular_function	TAS
GO:0005509	calcium ion binding	mollecular_function	TAS
GO:0008034	lipoprotein binding	mollecular_function	TAS
GO:0005515	protein binding	mollecular_function	IEA
GO:0002020	protease binding	mollecular_function	IEA
GO:0016020	membrane	cell_component	IEA
GO:0005624	membrane fraction	cell_component	TAS
GO:0005887	integral to plasma membrane	cell_component	TAS
GO:0005634	nucleus	cell_component	IEA
GO:0005737	cytoplasm	cell_component	IEA
GO:0005886	plasma membrane	cell_component	IEA
GO:0005905	coated pit	cell_component	IEA
GO:0005768	endosome	cell_component	IEA
GO:0030136	clathrin-coated vesicle	cell_component	IEA
GO:0030425	dendrite	cell_component	IEA
GO:0043025	cell soma	cell_component	IEA
GO:0005624	membrane fraction	cell_component	IEA

Check GO Evidence Codes here

Information from other databases [+]