9.B.433. The Progesterone Receptor Membrane-associated Component (PGRMC) Family PGRMC2 is required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan. It may serve as a universal non-classical progesterone receptor in the uterus. An intracellular heme chaperone is required for delivery of labile, or signaling heme to the nucleus. It plays a role in adipocyte function and systemic glucose homeostasis (Parker et al. 2017). It forms a complex with the dopamine transporter (TC# 2.A.22.1.3). Progesterone receptor membrane component 1 facilitates Ca²⁺ signal amplification between endosomes and the endoplasmic reticulum (Gunaratne et al. 2023).
References:
Gunaratne, G.S., S. Kumar, Y. Lin-Moshier, J.T. Slama, E. Brailiou, S. Patel, T.F. Walseth, and J.S. Marchant. (2023). Progesterone receptor membrane component 1 facilitates Ca signal amplification between endosomes and the endoplasmic reticulum. J. Biol. Chem. 105378. [Epub: Ahead of Print]
Parker, C.G., A. Galmozzi, Y. Wang, B.E. Correia, K. Sasaki, C.M. Joslyn, A.S. Kim, C.L. Cavallaro, R.M. Lawrence, S.R. Johnson, I. Narvaiza, E. Saez, and B.F. Cravatt. (2017). Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell 168: 527-541.e29.
Piel, R.B., 3rd, M.T. Shiferaw, A.A. Vashisht, J.R. Marcero, J.L. Praissman, J.D. Phillips, J.A. Wohlschlegel, and A.E. Medlock. (2016). A Novel Role for Progesterone Receptor Membrane Component 1 (PGRMC1): A Partner and Regulator of Ferrochelatase. Biochemistry 55: 5204-5217.
Piniella, D., E. Martínez-Blanco, D. Bartolomé-Martín, A.B. Sanz-Martos, and F. Zafra. (2021). Identification by proximity labeling of novel lipidic and proteinaceous potential partners of the dopamine transporter. Cell Mol Life Sci. [Epub: Ahead of Print]
Ryu, C.S., K. Klein, and U.M. Zanger. (2017). Membrane Associated Progesterone Receptors: Promiscuous Proteins with Pleiotropic Functions - Focus on Interactions with Cytochromes P450. Front Pharmacol 8: 159.
Examples:
TC#	Name	Organismal Type	Example
9.B.433.1.1	The progesterone receptor membrane component 2, PGRMC2 of 223 aas and1 TMS near the N-terminus. (see family description; it forms a complex with the dopamine transporter (TC#2.A.22.1.3) (Piniella et al. 2021).		PGRMC2 of Homo sapiens

9.B.433.1.2	Membrane-associated progesterone-binding protein 4 isoform X2of 239 aas and 1 TM		PGR of Spinacia oleracea

9.B.433.1.3	Uncharacterized protein of 239 aas and 1 TMS		UP of Tribonema minus

9.B.433.1.4	Neuferricin-like protein of 540 aa		Neuferricin-like protein of Porphyridium purpureum

9.B.433.1.5	PGRMC1 (Membrane-associated progesterone receptor component 1) of 195 aas and one N-terminal TMS. It is a component of a progesterone-binding protein complex (Ryu et al. 2017). It has several reported cellular functions (heme homeostasis, interaction with CYPs), and is required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan. It is also an intracellular heme chaperone, regulating heme synthesis via interactions with FECH. It acts as a heme donor for at least some hemoproteins (Piel et al. 2016). It facilitates Ca²⁺ signal amplification between endosomes and the endoplasmic reticulum (Gunaratne et al. 2023). It is a TPC1 (TC # 1.A.1.11.25) interactor.		PGRMC1 of Homo sapiens

Examples:
TC#	Name	Organismal Type	Example
9.B.433.2.1	Membrane steroid-binding protein 2 of 194 aas and 1 N-terminal TMS.		Steroid binding protein of Drosophila eugracilis