Mineralocorticoid receptor genetics: A scoping review

Table 7 Interactions of mineralocorticoid receptors in non-aldosterone-bound states

Protein name	Type	Cellular compartment	Functional role
Hsp90	Chaperone	Cytoplasm	Maintaining MR in an appropriate conformation for ligand binding[107]
Hsp70, Hsp40, Hip(p48)	Chaperone and co-chaperone	Cytoplasm	Stabilize unliganded MR and assist in early complex assembly before Hsp90 recruitment[108-111]
Hop (p60), p23	Co-chaperone	Cytoplasm	Link Hsp70 and Hsp90 during MR complex assembly and stabilize the receptor-chaperone complex[108-111]
BAG-1	Co-chaperone (Hsp70-interacting protein)	Cytoplasm	Modulates MR transcriptional activity[112,113]
FKBP51, FKBP52, PP5	Immunophilins/TPR co-chaperones	Cytoplasm	Regulate receptor transport: FKBP51 impairs nuclear translocation; FKBP52 and PP5 facilitate dynein/dynactin-mediated retrograde transport toward the nucleus[108,111,114]
CyP40	Immunophilin	Cytoplasm and nucleus	TPR-domain co-chaperone that associates with HSP90 complexes; contributes to receptor-HSP90 assembly and may modulate receptor function through regulation of HSP90 ATPase activity[108,111,115]
XAP2/ARA9, WISp39	Immunophilin-like co-chaperones	Cytoplasm	Stabilization and assembly of the HSP90-MR complex[111]
Actin	Chaperone	Cytoplasm	Ligand-dependent nuclear translocation[109]
SRC-1, SRC-2, PGC1-α	Co-regulators (common co- activators)	Nucleus	Interact with LBD and RNA Pol II; enhance transcription through LxxLL motifs[116-119]
CBP/p300	Co-regulator (activator)	Nucleus	Interacts NTD and LBD, induces chromatin remodeling and histone acetylation[118-120]
ELL	Co-regulator (activator)	Nucleus	Potentiates MR activity while repressing GR[121]
HDAC3–4, HDAC5	Co-regulators (modulators)	Nucleus	Modulate MR acetylation and transcriptional activity[122]
RNA Helicase A	Co-regulator (activator)	Nucleus	Recruits CBP and enhances aldosterone-dependent MR transcription[123]
NCoR, SMRT, DAXX	Co-regulators (repressors)	Nucleus	Bind MR and repress its transcriptional function[118,124,125]
PIAS1	Co-regulator (repressor)	Nucleus	SUMOylates MR, repressing its transcriptional activity[71,121]
Rac1 (small GTPase)	Signal transducer	Cytoplasm	Activates MR in a ligand-independent manner (notably in kidney and heart)[87,126]
CHIP	E3 ubiquitin ligase	Cytoplasm	Promotes MR polyubiquitination and proteasomal degradation[127]

MR: Mineralocorticoid receptor; DBD: DNA-binding domain; LBD: Ligand-binding domain; NTD: N-terminal domain; GR: Glucocorticoid; CBP: CREB-binding protein; TPR: Tetratricopeptide repeat.