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FLASH GENE

Symbol

PGRMC1

contributors: mct/npt - updated : 24-12-2015

HGNC name	progesterone receptor membrane component 1
HGNC id	16090

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006667 3 - 1931 NP_006658 21.7 195 - 2001 11697142 NM_001282621 2 - 1772 NP_001269550 - 143 - 2001 11697142

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Reproductive female system ovary corpus luteum       female system ovary ovarian follicle       female system uterus       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining endometrium     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial cell Homo sapiens Reproductive granulosa cell Reproductive lutein cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	smooth muscle of placenta, vasculature capillar of trophoblast

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	short extracellular N-terminus
	an intracellular domain containing a heme binding motif
	a putative transmembrane domain
	a highly conserved stretch of 58AA
	a cytochrome b5 domain

HOMOLOGY

interspecies	homolog to murine Pgrmc1
	homolog to rattus 25Dx
	homolog to Drosophila Cg9066

intraspecies

homolog to PGRMC2

Homologene

FAMILY	cytochrome b5 family
	MAPR subfamily

CATEGORY

receptor membrane

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,microsome
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus,nucleolus
text	localized to the plasma membrane, cytoplasm and nuclear membranes
	is distributed to the spindle apparatus as well as to the centrosomes at metaphase
	higher molecular mass forms of PGRMC1 localize to the nucleus
	PGRMC1 and SERBP1 colocalized in the cytoplasmic fractions of nondecidualized and decidualized endometrial stromal cells (ESCs)

basic FUNCTION	receptor for progesterone
	with SERBP1 complex functions in events important to early pregnancy including cellular differentiation, modulation of apoptosis and steroidogenesis
	required for CYP7B1 function and interindividual variation in PGRMC1 function may impact multiple biochemical pathways and drug metabolism
	mediating the anti-apoptotic action of progesterone in ovarian cells, being important regulator of the cytochrome P450 enzymes, and critical for ovarian function and maintained fertility (Mansouri 2008)
	function through a protein kinase G-dependent mechanism (Mansouri 2008)
	in granulosa/luteal (GL) cells PGRMC1 functions as a receptor through which progesterone activates a signal cascade that prevents apoptosis
	role for PGRMC1 in promoting cancer-associated phenotypes
	may mediate the non-genomic action of Progesterone and the relaxation effect on human myometrium during pregnancy
	novel role for progesterone and PGRMC1 in regulating spindle microtubule stability during ovarian cell mitosis
	plays a prominent role in the growth and chemoresistance of human endometrial tumors
	role for PGRMC1 in regulating heme synthesis via interactions with FECH

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component	complexing with SERBP1
	part of a progesterone binding complex (component of the membrane complex that functions as a receptor for progesterone (P4)) (Mansouri 2008)

INTERACTION

DNA

RNA

small molecule	other,
	steroid (like progesterone)

protein	interacting with SERBP1 (binding partner of PGRMC1)
	stably binds CYP51A1 (loss of PGRMC1 reduces activity of CYP51A1, blocking cholesterol synthesis and increasing production of toxic sterol intermediates)
	PGRMC1 negatively modulates the drug-metabolizing activities of CYP2B6 through direct interaction
	direct interaction between PGRMC1 and SUMO1, and this interaction is increased by progesterone
	progesterone-induced BDNF release was dependent on the expression of PGRMC1
	binds to key components of the autophagy machinery (MAP1LC3B) and is required for the degradative activity of autophagy
	PGRMC1 may regulate FECH activity by controlling heme release

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional germinal mutation       could mediate premature ovarian failure through altered apoptosis and thereby cause a more rapid loss of ovarian follicles (Mansouri 2008)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	ABHD5, PGRMC1 and FDFT1 are novel markers for sebaceous carcinoma and can reliably distinguish sebaceous neoplasms from non-sebaceous tumors, specifically basal cell carcinoma (BCC) with clear cell features
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer potential therapeutic target for future hormone-based drug development for the treatment of such degenerative diseases as Alzheimer disease as well as other diseases wherein neurotrophin dysregulation is noted cancer lung   targeting PGRMC1 with a small molecule in lung and breast cancer

ANIMAL & CELL MODELS