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FLASH GENE

Symbol

INSR

contributors: mct - updated : 22-01-2018

HGNC name	insulin receptor
HGNC id	6091

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_000208 22 - 9059 154 1382 expressed predominantly in fetal cells and the early embryo, including the trophoblast and inner cell mass of the blastocyst 2010 20519504 differ by a 12-AA insertion in the hormone-binding domain of the receptor due to alternative splicing of exon 11 IR-A IR isoform lacking exon 11 (IR-A) binds both insulin and insulin-like growth factor-II NM_001079817 21 - 9023 NP_001073285 153 1370 predominantly in the insulin-sensitive tissues liver, muscle, adipocytes, and kidney 2010 20519504 IR-B IR isoform lacking exon 11 (IR-A) binds both insulin and insulin-like growth factor-II, whereas the exon 11+ isoform (IR-B) only binds insulin

EXPRESSION

Rna function	insulin receptor mRNA contains a functional internal ribosome entry segment
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       highly Homo sapiens Reproductive female system ovary     highly Respiratory lung       highly Visual eye retina       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens Nervous peripherous       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Visual rod photoreceptor Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	precursor of two subunits alpha (ligand binding) and beta including the tyrosine kinase domain
	19 predicted N-linked glycosylation sites in each monomer
	furin-like repeats
	fibronectin type 3 domain
	tyrosine kinase catalytic domain

secondary structure

two alpha and two beta chains linked by disulfide bonds

isoforms

Precursor

precursor is post-translationally cleaved into two chains (alpha and beta) that are covalently linked

HOMOLOGY

interspecies

homolog to murine Insr

intraspecies

homolog to IG1R

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family
	insulin receptor subfamily

CATEGORY

signaling hormone , receptor membrane tyrosine kinase

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

basic FUNCTION	binding insulin and having a tyrosine-protein kinase activity
	potentially having a neuroprotective role in rod photoreceptor cell function
	INSR signaling in osteoblasts controls osteoblast development and osteocalcin expression by suppressing the RUNX2 inhibitor TWIST2
	plays a key role in both metabolic and growth signaling pathways
	dysregulation of its alternative splicing may have important consequences for insulin and insulin-like growth factor-II sensitivity and responsiveness
	GLS, NCALD and INSR are involved in nutrient signaling pathways and energy homeostasis suggesting a role in celiac disease pathogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

carbohydrate

signaling

INSR signaling pathways can regulate actin and tubulin cytoskeletal organization in photoreceptors

a component

INTERACTION

DNA

RNA

small molecule

protein	binds specifically to MBNL1 (strong MBNL1 binding to a GGCUUU motif in INSR gene)
	LMBRD1 plays an imperative role in mediating and regulating the endocytosis of the INSR
	a putative defect in POU2F1 and/or POU2F2, by affecting HMGA1 expression, may cause INSR dysfunction, leading to defects of the INSR signaling pathway
	GRB14 interacts with insulin receptor (INSR) through the between PH and SH2 (BPS) domain
	APPL1 is a critical molecule that promotes IRS1/2-INSR interaction
	IRS1 is recruited to interact with the INSRR-catalyzed phospho-tyrosine CAV2, which facilitates IRS1 association with and activation by INSR to initiate IRS1-mediated downstream signaling
	ATIC, which is a rate-limiting enzyme in the de novo purine biosynthesis pathway, and PTPLAD1 are associated with insulin receptor (INSR) internalization
	SORL1 acts as a sorting factor for the insulin receptor (IR) that redirects internalized receptor molecules from endosomes to the plasma membrane, thereby enhancing IR surface expression
	MAD2L1BP blocks the MAD2L1-BUB1B interaction and prevents spontaneous clathrin-mediated INSR endocytosis
	MARCHF1 is a negative regulator of INSR
	interaction between BRD7 and INSR

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

INSRDA , LPCN , HHF5 , RMS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         splicing abnormalities in muscle of myotonic dystrophy 1 and 2 (DM1, DM2) constitutional     --other   haploinsufficiency for INSR and CHN2 associated with severe insulin resistance and intrauterine growth deficiency

Susceptibility

to typical migraine (MAWMA) to colorectal cancer (CRC) to type 2 diabetes (T2DM)

Variant & Polymorphism SNP	INSR A-603G promoter SNP, which is located within a known Sp1-binding site, was associated with the risk of CRC, with carriers of the G allele having a decreased risk
	variant genotypes rs1366600CC and TC/CC in the insulin receptor (INSR) gene were associated with T2DM

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS