CDB25:0003741 HSP90AA1 — LRP1

Experimentally validated in Human, Mouse; Orthology-inferred in Human, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep, Mouse

Title

Journal:; Year Published:

Abstract

CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin.

Immunity, 2001; PubMed, Mus Musculus Hsp90aa1 — Mus Musculus Lrp1

ABSTRACT: Complexes of the heat shock protein gp96 and antigenic peptides are taken up by antigen-presenting cells and presented by MHC class I molecules. In order to explain the unusual efficiency of this process, the uptake of gp96 had been postulated to occur through a receptor, identified recently as CD91. We show here that complexes of peptides with heat shock proteins hsp90, calreticulin, and hsp70 are also taken up by macrophages and dendritic cells and re-presented by MHC class I molecules. All heat shock proteins utilize the CD91 receptor, even though some of the proteins have no homology with each other. Postuptake processing of gp96-chaperoned peptides requires proteasomes and the transporters associated with antigen processing, utilizing the classical endogenous antigen presentation pathway.

Extracellular Hsp90α and clusterin synergistically promote breast cancer epithelial-to-mesenchymal transition and metastasis via LRP1.

Journal of cell science, 2019; PubMed, Homo sapiens HSP90AA1 — Homo sapiens LRP1

ABSTRACT: Extracellular heat shock protein 90 alpha (eHsp90α, also known as HSP90AA1) has been widely reported to promote tumor cell motility and tumor metastasis in various types of cancer. Several extracellular proteins and membrane receptors have been identified as interacting proteins of eHsp90α and mediate its pro-metastasis function. However, the regulatory mechanism of eHsp90α activity remains largely unknown. Here, we report that clusterin, a protein newly demonstrated to interact with eHsp90α, modulates eHsp90α signaling. We found that clusterin potentiated the effects of eHsp90α on activation of the AKT, ERK and NF-κB protein families, epithelial-to-mesenchymal transition (EMT) and migration in breast cancer cells. Furthermore, in vivo investigations demonstrated similar synergistic effects of eHsp90α and clusterin on tumor metastasis. Notably, the effects of eHsp90α and clusterin were mediated by low-density lipoprotein receptor-related protein 1 (LRP1). Proximity ligation assay and co-immunoprecipitation experiments demonstrated that clusterin participated in eHsp90α-LRP1 complex formation, which enhanced the binding affinity of eHsp90α to LRP1. Collectively, our data establish a role of clusterin as a newly discovered modulator of eHsp90α, and unravel detailed molecular mechanisms underlying the synergistic metastasis-promoting effects of clusterin and eHsp90α.

Basic Information on HSP90AA1

Ligand Name: heat shock protein 90 alpha family class A member 1

Other Symbols: HSPC1, HSPCA, HSPCAL4, Hsp89, Hsp90, FLJ31884, HSP90N

Ligand Location: cell membrane based on uniprot

HGNC Gene Symbol Report: HSP90AA1

GeneCards: HSP90AA1

HGNC Gene Group: Heat shock proteins

Functional Annotations for HSP90AA1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for HSP90AA1

Basic Information on LRP1

Receptor Name: LDL receptor related protein 1

Other Symbols: APR, A2MR, LRP, CD91, LRP1A, APOER, IGFBP3R1, IGFBP-3R

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: LRP1

GeneCards: LRP1

HGNC Gene Group: MicroRNA host genes, CD molecules, Low density lipoprotein receptors

Functional Annotations for LRP1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for LRP1

A2M — LRP1 ・ APOE — LRP1 ・ APP — LRP1 ・ C1QB — LRP1 ・ C3 — LRP1 ・ C4BPA — LRP1 ・ CALR — LRP1 ・ CCN2 — LRP1 ・ F8 — LRP1 ・ F9 — LRP1 ・ FCN2 — LRP1 ・ HSP90B1 — LRP1 ・ LIPC — LRP1 ・ LPL — LRP1 ・ LRPAP1 — LRP1 ・ LTF — LRP1 ・ MDK — LRP1 ・ MMP13 — LRP1 ・ MMP9 — LRP1 ・ PDGFB — LRP1 ・ PLAT — LRP1 ・ PLAU — LRP1 ・ PSAP — LRP1 ・ SERPINA1 — LRP1 ・ SERPINC1 — LRP1 ・ SERPINE1 — LRP1 ・ SERPINE2 — LRP1 ・ SERPING1 — LRP1 ・ TFPI — LRP1 ・ THBS1 — LRP1 ・ ADAMTS1 — LRP1 ・ APOC3 — LRP1 ・ C1QA — LRP1 ・ CCN1 — LRP1 ・ CEMIP — LRP1 ・ HGFAC — LRP1 ・ HMGB1 — LRP1 ・ HMGB2 — LRP1 ・ HPX — LRP1 ・ HSPA1A — LRP1 ・ HSPA4 — LRP1 ・ IGFBP7 — LRP1 ・ LIF — LRP1 ・ MBL2 — LRP1 ・ MMP1 — LRP1 ・ PF4 — LRP1 ・ PLAUR — LRP1 ・ SERPIND1 — LRP1 ・ SFTPA1 — LRP1 ・ SFTPD — LRP1 ・ SLIT2 — LRP1 ・ SPARC — LRP1 ・ TIMP1 — LRP1 ・ TIMP3 — LRP1 ・ TNFAIP6 — LRP1 ・ VWF — LRP1