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FLASH GENE

Symbol

HMGCR

contributors: mct/ - updated : 28-01-2020

HGNC name	3-hydroxy-3-methylglutaryl-Coenzyme A reductase
HGNC id	5006

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	LGMDR28 muscular dystrophy, limb-girdle, autosomal recessive 28
Location	5q13.3      Physical location : 74.632.992 - 74.657.924
Synonym name	HMG CoA reductase
	3-hydroxy-3-methylglutaryl CoA reductase (NADPH)
Synonym symbol(s)	EVI19, LDLCQ3, HMGR
EC.number	1.1.1.88, 1.1.1.34

DNA

TYPE	functioning gene
STRUCTURE	25.78 kb     20 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	two sterol-regulatory elements (SREs) in close proximity in both the human HMGCR and SQLE promoters, as well as one NF-Y site in HMGCR and two in SQLE

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000859 20 - 4589 NP_000850 - 888 - 2019 30483734 NM_001130996 19 - 4430 NP_001124468 - 835 - 2019 30483734 NM_001364187 20 - 4507 NP_001351116 - 888 - 2019 30483734

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 Nervous brain       highly Reproductive male system       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES		Hydrophobic
STRUCTURE

motifs/domains	a N terminal hydrophobic membrane-bound domain
	a five spanning transmembrane sterol sensing domain (SSD), TM2-6
	a flexible linker domain
	a catalytic domain

HOMOLOGY

intraspecies

homolog to NPC1L1

Homologene

FAMILY	Patched family
	HMG-CoA reductase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,peroxisome
	intracellular,cytoplasm,organelle,endoplasmic reticulum

basic FUNCTION	catalyzing a rate-limiting step in cholesterol biosynthesis (conversion of HMG-CoA to mevalonate)
	membrane-bound enzyme, catalyzing a rate-limiting step in sterol and isoprenoid biosynthesis and being the primary target of hypocholesterolemic drug therapy
	oncogenic roles of HMGCR in glioblastoma cells
	promotes protein prenylation and therefore is indispensible for T-cell survival

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

lipid/lipoprotein

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	is a critical regulator of MYC phosphorylation, activation, and tumorigenic properties
	ubiquitin ligase (E3) AMFR has been implicated in the sterol-regulated degradation of HMGCR and INSIG1 through ER-associated degradation (ERAD)
	HNRNPA1 regulates HMGCR alternative splicing and modulates cellular cholesterol metabolism
	MARCHF6 controls abundance of both SQLE and HMGCR, establishing it as a major regulator of flux through the cholesterol synthesis pathway
	TSH could regulate the phosphorylation of HMGCR via AMPK, which established a potential mechanism for hypercholesterolemia involved in a direct action of the TSH in the liver
	HMGCR is a target gene of SREBF2 and luteolin modulates HMGCR transcription by decreasing the expression and nuclear translocation of SREBF2
	FAF2 is an essential determinant of metabolically stimulated degradation of HMGCR and of cholesterol biosynthesis in multiple cell types
	HSP90AA1 interacted with HMGCR, the rate&
	8209;limiting enzyme of mevalonate pathway, and regulated its protein expression level by inhibiting protein degradation
	stabilization of HMGCR by UBIAD1 increases cholesterol biosynthesis and eventually causes cholesterol accumulation in the cornea

cell & other

REGULATION

inhibited by

maybe degradated by the p97 subunit of 265 proteasome (see PSMD2)

Other

regulated by phosphorylation/dephosphorylation and by a negative feedback mechanism mediated by sterols (cholesterol) and non sterol metabolites derived from mevalonate

ASSOCIATED DISORDERS

corresponding disease(s)

LGMDR28

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in gastric cancer and promotes the growth and migration of the cancer cells

Susceptibility

to Alzheimer disease (AD)

Variant & Polymorphism SNP	HMGCR (rs3846662) plays a vital role in AD pathology mainly by influencing brain structure and glucose metabolism during AD progression

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive stomach is a promising therapeutic targetin gastric cancer

ANIMAL & CELL MODELS