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Set Analyses:

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IRS1 Gene

protein-coding GIFtS: 69
GCID: GC02M227563

Insulin Receptor Substrate 1

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Insulin Receptor Substrate 1¹ ²
IRS-1² ³
HIRS-1²

External Ids:	HGNC: 6125¹	Entrez Gene: 3667²	Ensembl: ENSG00000169047⁷	OMIM: 147545⁵	UniProtKB: P35568³

Export aliases for IRS1 gene to outside databases

Previous GC identifers: GC02M225622 GC02M226321 GC02M227802 GC02M227425 GC02M227308 GC02M219439

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for IRS1 Gene:

This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene

are associated with type II diabetes and susceptibility to insulin resistance. (provided by RefSeq, Nov 2009)

GeneCards Summary for IRS1 Gene:

IRS1 (insulin receptor substrate 1) is a protein-coding gene. Diseases associated with IRS1 include lipoatrophic diabetes, and insulin resistance. GO annotations related to this gene include protein kinase C binding and phospholipid binding. An important paralog of this gene is IRS2.

UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568

Function: May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin

receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol

3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit

(By similarity)

Gene Wiki entry for IRS1 Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000002.12 NT_005403.18 NC_018913.2

Regulatory elements:

Regulatory transcription factor binding sites in the IRS1 gene promoter:
c-Fos CREB AP-1 ATF-2 deltaCREB STAT3 c-Jun c-Ets-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: IRS1 promoter sequence

Search Chromatin IP Primers for IRS1

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat IRS1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q36 Ensembl cytogenetic band: 2q36.3 HGNC cytogenetic band: 2q36

IRS1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
IRS1 gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02M227563: view genomic region (about GC identifiers)

Start:	227,596,033 bp from pter	End:	227,664,475 bp from pter
Size:	68,443 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568 (See protein sequence)

Recommended Name: Insulin receptor substrate 1

Size: 1242 amino acids; 131591 Da

Subunit: Interacts with UBTF and PIK3CA (By similarity). Interacts (via phosphorylated YXXM motifs) with PIK3R1

(By similarity). Interacts with ROCK1 and FER (By similarity). Interacts (via PH domain) with PHIP (By

similarity). Interacts with GRB2 (By similarity). Interacts with SOCS7. Interacts (via IRS-type PTB domain) with

IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif). Interacts with ALK. Interacts with EIF2AK2/PKR (By

similarity)

4 PDB 3D structures from and Proteopedia for IRS1:

1IRS (3D)

1K3A (3D)

1QQG (3D)

2Z8C (3D)

Explore the universe of human proteins at neXtProt for IRS1: NX_P35568

Explore proteomics data for IRS1 at MOPED

Post-translational modifications:

Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin

action through disruption of IRS1 interaction with the insulin receptor (By similarity). Phosphorylation of

Tyr-896 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307,

Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1¹

Modification sites at neXtProt

Modification sites at PhosphoSitePlus

See IRS1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_005535.1

ENSEMBL proteins:

ENSP00000304895

Reactome Protein details: P35568

IRS1 Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant IRS1 Protein
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	Novus Biologicals IRS1 Protein Novus Biologicals IRS1 Lysate
	Browse Sino Biological Recombinant Proteins Browse Sino Biological Cell Lysates
	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for IRS1

IRS1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of IRS1
	R&D Systems Antibodies for IRS1
	Cell Signaling Technology (CST) Antibodies for IRS1
	OriGene Antibodies for IRS1 OriGene Custom Antibody Services for IRS1
	Novus Biologicals IRS1 Antibodies
	Abcam antibodies for IRS1
	Cloud-Clone Corp. Antibodies for IRS1
	ThermoFisher Antibodies for IRS1
	LSBio Antibodies in human, mouse, rat for IRS1

IRS1 Assay Products:

	EMD Millipore Kits and Assays for the Analysis of IRS1
	OriGene Custom Assay Services for IRS1
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for IRS1
	Cell Signaling Technology (CST) Sandwich ELISA Kits for IRS1
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for IRS1 Cloud-Clone Corp. CLIAs for IRS1

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

PLEKH: Pleckstrin homology (PH) domain containing

3 InterPro protein domains:

IPR002404 Insln_rcpt_S1

IPR001849 Pleckstrin_homology

IPR011993 PH_like_dom

Graphical View of Domain Structure for InterPro Entry P35568

ProtoNet protein and cluster: P35568

2 Blocks protein domains:

IPB001849 Pleckstrin-like

IPB002404 Insulin receptor substrate-1 PTB domain signature

UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568

Similarity: Contains 1 IRS-type PTB domain

Similarity: Contains 1 PH domain

IRS1 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: IRS1_HUMAN, P35568

Function: May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin

receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol

3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit

insulin receptor,substrate 1,overexpressed in skeletal muscle,and adipocytes (polymorphism associated to

susceptibility to NIDDM),located in the low density microsome fraction,tyrosine phosphorylated in response to

insulin stimulation,interacting with several proteins containing SH2 domains,such as PIKRs,GRB2

Gene Ontology (GO): Selected molecular function terms (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004871	signal transducer activity	IEA	--
GO:0005068	transmembrane receptor protein tyrosine kinase adaptor activity	ISS	--
GO:0005080	protein kinase C binding	ISS	--
GO:0005158	insulin receptor binding	IPI	7493946
GO:0005159	insulin-like growth factor receptor binding	IPI	7541045

IRS1 for ontologies About GeneDecksing

Phenotypes:
5 GenomeRNAi human phenotypes for IRS1:

Decreased Salmonella enterica	Decreased focal adhesion (FA)	Decreased nuclei size in G2M	Increased cell death HMECs cel
Increased gamma-H2AX phosphory

14 MGI mutant phenotypes (inferred from 8 alleles) (MGI details for Irs1):

adipose tissue	cardiovascular system	cellular	endocrine/exocrine gland	growth/size/body
hearing/vestibular/ear	hematopoietic system	homeostasis/metabolism	immune system	limbs/digits/tail
liver/biliary system	mortality/aging	muscle	skeleton

IRS1 for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-outs for IRS1: Irs1^tm1Tka Irs1^tm1Jos

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for IRS1

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for IRS1

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for IRS1

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for IRS1

miRNA Products:		miRTarBase miRNAs that target IRS1: hsa-mir-126-3p (MIRT004355), hsa-mir-148a-3p (MIRT006859), hsa-mir-152-3p (MIRT006860), hsa-mir-145-5p (MIRT000731), hsa-mir-7-5p (MIRT003807)

		Block miRNA regulation of human, mouse, rat IRS1 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate IRS1 (see all 119):
		hsa-miR-576-3p hsa-miR-548j hsa-miR-26a-2* hsa-miR-15a hsa-miR-128 hsa-miR-30d hsa-miR-550a* hsa-miR-30a

		SwitchGear 3'UTR luciferase reporter plasmid: IRS1 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for IRS1
		Predesigned siRNA for gene silencing in human, mouse, rat IRS1

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for IRS1

Clone Products:		OriGene clones in human, mouse for IRS1 (see all 7) OriGene ORF clones in mouse, rat for IRS1 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: IRS1 (NM_005544)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for IRS1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IRS1

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for IRS1
		Browse ESI BIO Cell Lines and PureStem Progenitors for IRS1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IRS1

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from COMPARTMENTS:

Compartment	Confidence
cytosol	4
nucleus	4
plasma membrane	4
cytoskeleton	2
endoplasmic reticulum	2
extracellular	2
mitochondrion	2
peroxisome	2

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Gene Ontology (GO): Selected cellular component terms (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	ISS	--
GO:0005737	cytoplasm	ISS	--
GO:0005829	cytosol	TAS	--
GO:0005886	plasma membrane	TAS	--
GO:0005899	insulin receptor complex	ISS	--

IRS1 for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for IRS1 About (see all 63)

See pathways by source

SuperPath

Selected contained pathways About (see all per SuperPath)

IL-9 Signaling Pathways

IL-9 Signaling Pathways	0.90	IL-4 Signaling Pathways	0.84
IL-7 Signaling Pathways	0.90	IL-9 Signaling Pathway	0.42
IL-21 Signaling Pathways	0.90	Immune response IL 9 signaling pathway	0.42
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways	0.90	IL-7 Signaling Pathway	0.40

Development IGF 1 receptor signaling

	Development IGF RI signaling	0.49			Development IGF 1 receptor signaling	0.48
	Signal transduction AKT signaling	0.49			Immune response IL 4 signaling pathway	0.39

Type II diabetes mellitus

	Type II diabetes mellitus	0.38			Type II diabetes mellitus	0.35
	Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics	0.38

Translation Insulin regulation of translation

Translation Insulin regulation of translation	0.59	Transcription PPAR Pathway	0.34
Regulation of lipid metabolism Insulin signaling generic cascades	0.59	Development Growth hormone signaling via PI3K AKT and MAPK cascades	0.34
Transcription Receptor mediated HIF regulation	0.51	mTOR signaling pathway	0.34
Translation Regulation activity of EIF2	0.47	Insulin signaling pathway	0.32

Prolactin Signaling Pathway

	Development Prolactin receptor signaling	0.39			Leptin signaling pathway	0.35
	Prolactin Signaling Pathway	0.39

Pathways by source See SuperPaths
Show all pathways

Selected R&D Systems Pathways for IRS1 (see all 8)

	IL-21 Signaling Pathways
	IL-2 Signaling Pathways
	IL-4 Signaling Pathways
	Adipocytokines & Insulin Signaling
	IL-7 Signaling Pathways

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for IRS1 (see all 19)

	IL-4 Pathway
	Molecular Mechanisms of Cancer
	Interferon Pathway
	JNK Pathway
	mTOR Pathway

2 Cell Signaling Technology (CST) Pathways for IRS1

	Tyrosine Kinases / Adaptors
	Glucose / Energy Metabolism

Selected GeneGo (Thomson Reuters) Pathways for IRS1 (see all 22)

	Apoptosis and survival Caspase cascade
	Signal transduction AKT signaling
	Immune response IL-9 signaling pathway
	Transcription PPAR Pathway
	Translation Insulin regulation of translation

Selected BioSystems Pathways for IRS1 (see all 27)

	Adipogenesis
	Insulin Signaling
	DNA damage response (only ATM dependent)
	EPO Receptor Signaling
	Integrated Breast Cancer Pathway

Selected Reactome Pathways for IRS1 (see all 10)

	PI3K Cascade
	PI3K/AKT activation
	Signal attenuation
	SOS-mediated signalling
	Constitutive PI3K/AKT Signaling in Cancer

1 PharmGKB Pathway for IRS1

Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics

Selected Kegg Pathways (Kegg details for IRS1) (see all 10):

	FoxO signaling pathway
	mTOR signaling pathway
	PI3K-Akt signaling pathway
	Neurotrophin signaling pathway
	Insulin signaling pathway

IRS1 for pathways About GeneDecksing

Pathway & Disease-focused RT² Profiler PCR Arrays including IRS1 (see all 10):

mTOR Signaling in human mouse rat

Insulin Signaling Pathway in human mouse rat

Liver Cancer in human mouse rat

Diabetes in human mouse rat

Adipogenesis in human mouse rat

Interactions:

GeneGlobe Interaction Network for IRS1

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for IRS1 (P35568^{1, 2, 3} ENSP00000304895⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 212)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PIK3R1	P27986¹^,²^,³, ENSP00000274335⁴	EBI-517592,EBI-79464 MINT-8036617 MINT-8028908 MINT-8036602 MINT-8033089 MINT-8036587 MINT-8033340 MINT-8036572 MINT-8028923 MINT-8033074 MINT-68735 I2D: score=10 STRING: ENSP00000274335
PTPN11	Q06124¹^,²^,³, ENSP00000340944⁴	EBI-517592,EBI-297779 MINT-8035069 MINT-8032601 MINT-8037305 I2D: score=5 STRING: ENSP00000340944
ERBB2	P04626¹^,²^,³, ENSP00000269571⁴	EBI-517592,EBI-641062 MINT-74553 MINT-74552 I2D: score=2 STRING: ENSP00000269571
YWHAE	P62258²^,³, ENSP00000264335⁴	MINT-16662 MINT-8005105 MINT-8005168 MINT-8005150 MINT-16661 MINT-8005175 I2D: score=7 STRING: ENSP00000264335
SFN	P31947²^,³, ENSP00000340989⁴	MINT-3975430 I2D: score=2 STRING: ENSP00000340989

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Gene Ontology (GO): Selected biological process terms (see all 32): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002053	positive regulation of mesenchymal cell proliferation	IEA	--
GO:0007165	signal transduction	TAS	1311924
GO:0007173	epidermal growth factor receptor signaling pathway	TAS	--
GO:0008284	positive regulation of cell proliferation	NAS	17925406
GO:0008286	insulin receptor signaling pathway	TAS	--

IRS1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for IRS1

1 DrugBank Compound for IRS1 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
[4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID	--	--	target	--	10592235

Selected Novoseek inferred chemical compound relationships for IRS1 gene (see all 87) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
phosphatidylinositol	90.7	672	8385139 (7), 1332046 (6), 9242642 (5), 1380456 (5) (see all 99)
tyrosine	87.3	1172	1334490 (5), 7592659 (5), 15130378 (5), 15240096 (5) (see all 99)
glucose	78.9	352	15001544 (5), 16556765 (5), 15581362 (4), 10764799 (4) (see all 99)
phosphotyrosine	77.5	75	7520748 (3), 8383963 (3), 9312143 (3), 14668342 (3) (see all 42)
glycogen	76.2	93	8037748 (3), 17279354 (2), 10416561 (2), 11325523 (2) (see all 61)
wortmannin	75	32	8660383 (4), 8649395 (2), 8674815 (2), 9761740 (2) (see all 22)
serine	72.9	441	12351658 (6), 7818531 (5), 14556646 (5), 10488146 (5) (see all 99)
ag 1024	70.2	6	17454144 (1), 18762365 (1), 14767998 (1)
rapamycin	68.6	92	17908691 (4), 18264722 (4), 10847581 (4), 11438661 (3) (see all 39)
2-deoxyglucose	67.2	13	7507665 (1), 8960823 (1), 11438661 (1), 16269459 (1) (see all 11)

IRS1 for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for IRS1 gene:

NM_005544.2

Unigene Cluster for IRS1:

Insulin receptor substrate 1

Hs.471508 [show with all ESTs]

Unigene Representative Sequence: NM_005544

2 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000305123(uc002voh.4) ENST00000498335

miRNA Products:		Block miRNA regulation of human, mouse, rat IRS1 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate IRS1 (see all 119):
		hsa-miR-576-3p hsa-miR-548j hsa-miR-26a-2* hsa-miR-15a hsa-miR-128 hsa-miR-30d hsa-miR-550a* hsa-miR-30a

		SwitchGear 3'UTR luciferase reporter plasmid: IRS1 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for IRS1
		Predesigned siRNA for gene silencing in human, mouse, rat IRS1

Clone Products:		OriGene clones in human, mouse for IRS1 (see all 7) OriGene ORF clones in mouse, rat for IRS1 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: IRS1 (NM_005544)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for IRS1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IRS1

Primer Products:		OriGene qPCR primer pairs and template standards for IRS1 OriGene qSTAR qPCR primer pairs in human, mouse for IRS1
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat IRS1
		QuantiTect SYBR Green Assays in human, mouse, rat IRS1
		QuantiFast Probe-based Assays in human, mouse, rat IRS1

Additional mRNA sequence:

BC053895.1 S62539.1

6 DOTS entries:

DT.112047 DT.40220008 DT.447217 DT.40112397 DT.100716681 DT.97786529

Selected AceView cDNA sequences (see all 115):

AI358832 AL043318 CB053406 AA860695 N34594 BQ433020 BG207239 AL039246

AI580782 AA694085 BM982252 NM_005544 CA425762 BG187732 AI681976 CB306477

S62539 AI160216 BU154427 D17048 BQ771873 AI752714 AA069842 BU541406

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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IRS1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: TATTGTAAAC

About this image

IRS1 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 3) fully expand


Blood (Cardiovascular System) fully expand to see all 3 entries
Mature B-Cells Peripheral Blood

Thymus (Hematopoietic System)
Double Positive Thymocytes Thymus

Thyroid (Endocrine System)

IRS1 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

IRS1 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.471508

Pathway & Disease-focused RT² Profiler PCR Arrays including IRS1 (see all 10):

mTOR Signaling in human mouse rat

Insulin Signaling Pathway in human mouse rat

Liver Cancer in human mouse rat

Diabetes in human mouse rat

Adipogenesis in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for IRS1 OriGene qSTAR qPCR primer pairs in human, mouse for IRS1
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat IRS1
		QuantiTect SYBR Green Assays in human, mouse, rat IRS1
		QuantiFast Probe-based Assays in human, mouse, rat IRS1

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IRS1

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for IRS1 gene from Selected species (see all 13) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Irs1^{1 , 5}	insulin receptor substrate 1^{1, 5}	85.37(n)¹ 89.17(a)¹		1 (42.00 cM)⁵ 16367¹ NM_010570.4¹ NP_034700.2¹ 82233101⁵
chicken (Gallus gallus)	Aves	IRS1¹	insulin receptor substrate 1	74.2(n) 79.78(a)		101749888 XM_004951101.1 XP_004951158.1
lizard (Anolis carolinensis)	Reptilia	IRS1⁶	insulin receptor substrate 1	63(a)	1 ↔ 1	3(23742830-23746420)
African clawed frog (Xenopus laevis)	Amphibia	Xl.957²	Xenopus laevis insulin receptor substrate-1-like protein more	78.78(n)		U27842.1
zebrafish (Danio rerio)	Actinopterygii	irs1¹	insulin receptor substrate 1	61.99(n) 65.38(a)		559281 XM_005157774.1 XP_005157831.1
fruit fly (Drosophila melanogaster)	Insecta	chico⁶	chico	21(a)	1 → many	2L(10242512-10247078)

ENSEMBL Gene Tree for IRS1 (if available)
TreeFam Gene Tree for IRS1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for IRS1 gene

IRS2² IRS4²

1 SIMAP similar gene for IRS1 using alignment to 4 protein entries: IRS1_HUMAN (see all proteins):

IRS2

IRS1 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Polymorphic Variants from UniProtKB/Swiss-Prot

IRS1_HUMAN, P35568: The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose

transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The

polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant.

Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with

non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic

abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic

impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric

oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes

to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971

polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K,

producing global insulin resistance

SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_005303⁴		Diabetes mellitus, non-insulin-dependent (NIDDM)⁴	--	see VAR_005303	2	C Y	mis⁴		0	--	--	--	--
VAR_005302⁴		Diabetes mellitus, non-insulin-dependent (NIDDM)⁴	--	see VAR_005302	2	S Y	mis⁴		0	--	--	--	--
rs104893642^1,2	C	pathogenic¹	227032835(-)	`CCACAC/G/TGGATG`	2	T R	mis¹		0	--	--	--	--
rs1801278^1,2,,4	C,F,H	other¹	227031747(-)	`CTCCCA/C/G/T GGGCT`	2	R G	mis¹ ese³		19		EA MN NA CA NS WA EU	9510
rs138435065^1,2	C	--	219459551(+)	`CGGGT-/ATTTTT`	1	--	int¹		0	--	--	--	--
rs34319959^1,2	C	--	219489040(+)	`AGATTACAA/- ACAGT`	1	--	int¹		1		CSA	2
rs72174828^1,2	C	--	219489042(+)	`GATTA-/ACAA CAGTC`	1	--	int¹		0	--	--	--	--
rs3054795^1,2	C	--	219489043(+)	`TTACA-/AACA GTCTT`	1	--	int¹		0	--	--	--	--
rs202109179^1,2		--	219494936(+)	`AAAAA-/ACAAAAA`	1	--	int¹		0	--	--	--	--
rs200340976^1,2	C	--	219495078(+)	`AGTCT-/AAAAAAA`	1	--	int¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for IRS1 (227596033 - 227664475 bp)

Structural Variations
Database of Genomic Variants (DGV) 3 variations for IRS1: About this table

Variant ID	Type	Subtype	PubMed ID
nsv875921	CNV	Loss	21882294
nsv3190	CNV	Loss	18451855
nsv821910	CNV	Gain	20364138

Human Gene Mutation Database (HGMD): IRS1

Selected Site Specific Mutation Identification with PCR Assays for IRS1 (see all 8):

Cosmic Id	AA Change
39670	p.Y47C
35437	p.R1140H
48440	p.V154L
87724	p.P679L
48441	p.E147D

SeqTarget long-range PCR primers for resequencing IRS1

DNA2.0 Custom Variant and Variant Library Synthesis for IRS1

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 147545
OMIM disorders: 125853
UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568

Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose

homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese

body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance,

hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes,

kidneys, nerves, and blood vessels. Note=The gene represented in this entry may be involved in disease

pathogenesis

Selected diseases for IRS1 (see all 86):
About MalaCards

lipoatrophic diabetes insulin resistance coronary artery disease carbohydrate metabolic disorder

type 2 diabetes mellitus diabetes mellitus, noninsulin-dependent polycystic ovary syndrome ossification of the posterior longitudinal ligament of the spine

silver-russell syndrome gestational diabetes estrogen-receptor negative breast cancer familial combined hyperlipidemia

21-hydroxylase deficiency hyperinsulinism precocious puberty diabetes mellitus

hyperandrogenism hypertriglyceridemia tuberous sclerosis glucose intolerance

4 diseases from the University of Copenhagen DISEASES database for IRS1:

Diabetes mellitus Hyperglycemia Hyperinsulinism Polycystic ovary syndrome

IRS1 for disorders About GeneDecksing

Congresses - knowledge worth sharing:
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

Selected Novoseek inferred disease relationships for IRS1 gene (see all 64) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
insulin resistance	89.1	293	16896943 (4), 12176670 (4), 12358865 (3), 15634339 (3) (see all 99)
insulin sensitivity	79.2	40	19801385 (2), 15356080 (2), 10591678 (2), 10707551 (1) (see all 30)
niddm	67.8	159	8739921 (6), 8104271 (5), 9032113 (5), 11038788 (4) (see all 44)
hyperinsulinemia	64.6	25	10480621 (2), 10416561 (1), 15855318 (1), 17416760 (1) (see all 18)
obesity	61.5	65	11317670 (4), 15636429 (3), 9812905 (3), 8960833 (3) (see all 28)
polycystic ovary syndrome	58	32	15705377 (3), 15130378 (3), 11522686 (2), 15474880 (2) (see all 13)
hyperglycemia	49.8	6	15855318 (1), 8617880 (1), 20207740 (1), 17184177 (1) (see all 5)
syndrome x	42.2	2	10842657 (1)
breast cancer	41.9	114	19261680 (5), 16882697 (5), 15917419 (5), 16151579 (4) (see all 46)
diabetes gestational	41	10	10973656 (3), 17631765 (2), 17046546 (2), 11832353 (1)

Genetic Association Database (GAD): IRS1
Human Genome Epidemiology (HuGE) Navigator: IRS1 (138 documents)

Export disorders for IRS1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for IRS1 gene, integrated from 10 sources (see all 1396):
(articles sorted by number of sources associating them with IRS1)

Utopia: connect your pdf to the dynamic
world of online information

A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling. (PubMed id 12679424)^{1, 2, 4, 9} Esposito D.L....Cama A. (J. Clin. Endocrinol. Metab. 2003)
The Arg(972) variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients. (PubMed id 12843189)^{1, 2, 4, 9} Marini M.A.... Sesti G. (J. Clin. Endocrinol. Metab. 2003)
Aminoacid polymorphisms of insulin receptor substrate-1 in non- insulin-dependent diabetes mellitus. (PubMed id 8104271)^{1, 2, 4, 9} Almind K....Pedersen O. (Lancet 1993)
Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. (PubMed id 7559478)^{1, 2, 9} He W.... Gustafson T.A. (J. Biol. Chem. 1995)
S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. (PubMed id 18952604)^{1, 2, 9} Zhang J.... Ye J. (J. Biol. Chem. 2008)
Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation. (PubMed id 15590636)^{1, 2, 9} McGettrick A.J.... Kahn C.R. (J. Biol. Chem. 2005)
The role of insulin receptor substrate-1 gene (IRS1) in type 2 diabetes in Pima Indians. (PubMed id 14633864)^{1, 4, 9} Kovacs P....Baier L.J. (Diabetes 2003)
The G972R variant of the insulin receptor substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance. (PubMed id 11317670)^{1, 4, 9} Baroni M.G....Di Mario U. (Diabetologia 2001)
The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer. (PubMed id 15308584)^{1, 4, 9} Wagner K....FAPrsti A. (Carcinogenesis 2004)
No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia. (PubMed id 20012307)^{1, 4, 9} Marioli D.J....Georgopoulos N.A. (Arch. Gynecol. Obstet. 2010)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 3667	HGNC: 6125	AceView: IRS1	Ensembl:ENSG00000169047	euGenes: HUgn3667
ECgene: IRS1	Kegg: 3667	H-InvDB: IRS1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for IRS1	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for IRS1	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for IRS1 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for IRS1 gene:
Search GeneIP for patents involving IRS1

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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IRS1 Gene

Insulin Receptor Substrate 1

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IRS1 Gene

Insulin Receptor Substrate 1

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