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FLASH GENE

Symbol

INSIG2

contributors: mct - updated : 30-12-207

HGNC name	insulin induced gene 2
HGNC id	20452

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	2q14.2      Physical location : 118.846.049 - 118.867.596
Synonym name	INSIG2 membrane protein
	insulin-induced gene 2 protein
Synonym symbol(s)	LOC51141, MGC26273, INSIG-2

DNA

TYPE	functioning gene
STRUCTURE	21.55 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site
text structure	an Ets-consensus motif in the proximal region of the promoter, binding phosphorylated ELK4 (Fernández-Alvarez 2010)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016133 6 - 2592 NP_057217 24.8 225 - 2002 12242332

EXPRESSION

Type

widely

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 Endocrine parathyroid       highly nervous brain diencephalon       Nervous nerve       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial secretory glandular endocrine

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

six transmembrane helices

HOMOLOGY

interspecies	homolog to murine Insig2 (96.9pc)
	homolog to rattus Insig2 (96.4pc)

intraspecies

homolog to INSIG1

Homologene

FAMILY

INSIG family

CATEGORY

regulatory

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

basic FUNCTION	negative regulator of cholesterol synthesis
	involved in adipocyte metabolism and body weight regulation
	in the presence of sterols, INSIG2 regulates lipid synthesis by blocking the proteolytic activation of SREBPs by SCAP and causing SREBPs to be retained in the ER (Yabe 2002)
	essential role of INSIG1, INSIG2 proteins in the sterol homeostasis of enterocytes

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

lipid/lipoprotein

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	with SCAP (to block export of sterol regulatory element-binding proteins)
	sterol-induced ubiquitination and proteasomal degradation of reductase is dictated by the complex interplay of at least four proteins: INSIG1, INSIG2, AMFR, and RNF139
	gluconeogenic enzyme PCK1 phosphorylates INSIG1/INSIG2 for lipogenesis

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   . cholesterol metabolic aberrations, induced through disruption of either DHCR7 or INSIG1 and INSIG2 , result in osteoblast differentiation abnormalities

Susceptibility

to severe obesity to metabolic syndrome

Variant & Polymorphism SNP	significantly associated with obesity
	common INSIG2 variant rs9308762 was associated with poorer metabolic control and a greater sensitivity of trigylcerides to a modern dietary pattern

Candidate gene	putative positive prognostic biomarker for colon cancer prognosis
Marker
Therapy target

ANIMAL & CELL MODELS