Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10513)
Regulator Name Low-density lipoprotein receptor-related protein 6 (LRP6)
Gene Name LRP6
Gene ID 4040
Regulator Type Protein coding
Uniprot ID O75581
Sequence
MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVF
SHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIE
VSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSE
IYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWT
DWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMS
PVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIR
HAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWT
DTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSD
RVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTL
LGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCS
HLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTG
VKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLY
WADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDG
SERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQ
YQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHC
SHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILP
IHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLS
IDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERS
PKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLE
DSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQ
EYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGE
IDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEK
NCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGV
IVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMS
RGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTM
EFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDL
NYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS

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Family LDLR family
Function
Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalosomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity).

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HGNC ID
HGNC:6698
KEGG ID hsa:4040
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
LRP6 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 HL-1 cells Normal Mus musculus CVCL_0303
In Vivo Model
C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min.

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Response regulation CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction.
Acute myocardial infarction [ICD-11: BA41]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Low-density lipoprotein receptor-related protein 6 (LRP6) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
 HL-1 cells Normal Mus musculus CVCL_0303
In Vivo Model
C57BL/6J male mice of SPF grade, 8-10 weeks old, were used. The day before operation, the mice in the MI + ferrostatin-1 (Fer-1) group were injected a dose of 1 mg/kg ferroptosis inhibitor Fer-1 (SML0583-5MG, Sigma-Aldrich, USA). Fer-1 was dissolved in dimethyl sulfoxide (DMSO), then diluted in sterile saline. The sham group and the MI + NS group were injected with the same dose of saline (NS). The mice were anesthetized by 3% pentobarbital sodium via intraperitoneal injection, and the MI model was established by ligating the anterior descending branch of the left coronary artery (LAD) for 30 min.

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Response regulation CircRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of myocardial infarction.
References
Ref 1 Effect and Mechanism of LRP6 on Cardiac Myocyte Ferroptosis in Myocardial Infarction. Oxid Med Cell Longev. 2021 Oct 19;2021:8963987. doi: 10.1155/2021/8963987. eCollection 2021.