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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

IRS1 Gene

protein-coding GIFtS: 70
GCID: GC02M227563

insulin receptor substrate 1

Explore 93 diseases affiliated with
IRS1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Insulin Receptor Substrate 1¹ ²
HIRS-1¹ ²
IRS-1² ³

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for IRS1:

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)

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

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.1 NT_005403.17

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for IRS1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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 Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

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

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

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)¹

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

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P35568

IRS1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_005535.1

ENSEMBL proteins:

ENSP00000304895

Reactome Protein details: P35568
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant IRS1 Protein
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
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	GenScript Custom Purified and Recombinant Proteins Services for IRS1
	Novus Biologicals IRS1 Protein Novus Biologicals IRS1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for IRS1

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	ISS	--
GO:0005737	cytoplasm	ISS	--
GO:0005792	microsome	--	--
GO:0005829	cytosol	TAS	--
GO:0005886	plasma membrane	TAS	--

IRS1 for ontologies About GeneDecksing

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 (see all 5): IRS1 OriGene Custom Antibody Services for IRS1
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	Novus Biologicals IRS1 Antibodies
	Abcam antibodies for IRS1
	Uscn Antibodies for IRS1
	ThermoFisher Antibody for IRS1

Assay Products for IRS1:

	EMD Millipore Kits and Assays for the Analysis of IRS1
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	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
	Uscn ELISAs and CLIAs for IRS1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

IRS1 for domains About GeneDecksing

3 InterPro domains/families:

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 families:

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

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

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)

Genatlas biochemistry entry for IRS1:

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

miRNA Products:		miRTarBase miRNAs that target IRS1: hsa-mir-126 (MIRT004355), hsa-mir-145 (MIRT000731)

		OriGene 3'-UTR Clone: IRS1 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat IRS1
		8/119 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for IRS1 (see all 7) OriGene shRNA RFP: IRS1 OriGene siRNA: IRS1
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat IRS1

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for IRS1

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for IRS1 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, 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
		Search LifeMap BioReagents cell lines for IRS1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IRS1

Gene Ontology (GO): 5/12 molecular function terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004871	signal transducer activity	IEA	--
GO:0005010	insulin-like growth factor-activated receptor activity	--	--
GO:0005068	transmembrane receptor protein tyrosine kinase adaptor activity	ISS	--
GO:0005080	protein kinase C binding	ISS	--
GO:0005158	insulin receptor binding	IPI	7493946

IRS1 for ontologies About GeneDecksing

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

Animal Models:
Mouse knock-outs for IRS1: Irs1^tm1Tka Irs1^tm1Jos
14 MGI mutant phenotypes (inferred from 8 alleles) (MGI details for Irs1):

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

IRS1 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/60 super-pathways (see all 60) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Development_CNTF receptor signaling

8/13 pathways (see all 13)
Transcription Receptor-mediated HIF regulation	0.43	Development Growth hormone signaling via PI3K/AKT and MAPK cascades	0.34
Transcription_Receptor-mediated HIF regulation	0.43	Translation _Regulation of EIF4F activity	0.32
Regulation of lipid metabolism_Insulin signaling-generic cascades	0.35	Translation Regulation activity of EIF4F	0.32
Translation_Insulin regulation of translation	0.35	Translation _Regulation of EIF2 activity	0.25

Signaling by FGFR

8/12 pathways (see all 12)
Signaling by FGFR	1.00	DAP12 signaling	0.83
Downstream signaling of activated FGFR	0.92	Signaling by EGFR in Cancer	0.83
Signaling by FGFR in disease	0.91	DAP12 interactions	0.76
Signaling by ERBB2	0.89	Signaling by PDGF	0.72

IL-9 Signaling Pathways

8/12 pathways (see all 12)
IL-9 Signaling Pathways	1.00	IL-4 Signaling Pathways	0.80
IL-21 Signaling Pathways	0.90	IL-9 Signaling Pathway	0.42
IL-7 Signaling Pathways	0.90	Immune response_IL-9 signaling pathway	0.42
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways	0.90	Immune response IL-9 signaling pathway	0.42

PIP3 activates AKT signaling

8/10 pathways (see all 10)
PI-3K cascade	1.00	PI3K/AKT activation	0.97
PIP3 activates AKT signaling	1.00	GAB1 signalosome	0.96
PI3K/AKT Signaling in Cancer	1.00	Constitutive PI3K/AKT Signaling in Cancer	0.88
PI3K events in ERBB2 signaling	1.00	Signaling by SCF-KIT	0.72

IRS-related events

IRS-related events	1.00	Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	0.90
IRS-mediated signalling	0.98	IGF1R signaling cascade	0.90
Insulin receptor signalling cascade	0.94	PI3K Cascade	0.84
IRS-related events triggered by IGF1R	0.93	Signaling by Insulin receptor	0.74

Pathway sources
See GeneCards unified pathways
Show all pathways

5/22 EMD Millipore Pathways for IRS1 (see all 22)

	Immune response IL-9 signaling pathway
	Development Ligand-independent activation of ESR1 and ESR2
	Development EGFR signaling via PIP3
	Transcription PPAR Pathway
	Development Growth hormone signaling via PI3K/AKT and MAPK cascades

5/8 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

5/19 Downloadable PowerPoint Slides of QIAGEN 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

5/22 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

5/26 BioSystems Pathways for IRS1 (see all 26)

	EPO Receptor Signaling
	Adipogenesis
	AGE/RAGE pathway
	Integrated Breast Cancer Pathway
	Oncostatin M Signaling Pathway

5/42 Reactome Pathways for IRS1 (see all 42)

	Signaling by EGFR in Cancer
	Downstream signal transduction
	IRS-mediated signalling
	Signal Transduction
	Signaling by PDGF

1 PharmGKB Pathway for IRS1

Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics

5 Kegg Pathways (Kegg details for IRS1):

	Neurotrophin signaling pathway
	Insulin signaling pathway
	Adipocytokine signaling pathway
	Type II diabetes mellitus
	Aldosterone-regulated sodium reabsorption

IRS1 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for IRS1

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

5/168 Interacting proteins for IRS1 (P35568^{2, 3} ENSP00000304895⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 168)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PIK3R1	P27986²^,³, ENSP00000274335⁴	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
YWHAE	P62258²^,³, ENSP00000264335⁴	MINT-16662 MINT-8005105 MINT-8005168 MINT-8005150 MINT-16661 MINT-8005175 I2D: score=7 STRING: ENSP00000264335
PTPN11	Q06124²^,³, ENSP00000340944⁴	MINT-8035069 MINT-8032601 MINT-8037305 I2D: score=5 STRING: ENSP00000340944
ERBB2	P04626²^,³, ENSP00000269571⁴	MINT-74553 MINT-74552 I2D: score=2 STRING: ENSP00000269571
SFN	P31947²^,³, ENSP00000340989⁴	MINT-3975430 I2D: score=2 STRING: ENSP00000340989

About this table

Gene Ontology (GO): 5/33 biological process terms (GO ID links to tree view) (see all 33): 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:0007169	transmembrane receptor protein tyrosine kinase signaling pathway	--	--
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 HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

IRS1 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

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

10/87 Novoseek 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)

Search CenterWatch for drugs/clinical trials and news about IRS1

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

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:		OriGene 3'-UTR Clone: IRS1 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat IRS1
		8/119 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for IRS1 (see all 7) OriGene shRNA RFP: IRS1 OriGene siRNA: IRS1
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat IRS1

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for IRS1 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, 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 genome-wide validated SYBR primer pairs in human, mouse, rat for IRS1 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat IRS1
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat IRS1
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat IRS1

Additional cDNA sequence:

BC053895.1 S62539.1

6 DOTS entries:

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

24/115 AceView cDNA sequences (see all 115):

AI681976 N34594 CA390441 BG187732 BM982252 AA694085 AL039246 BU541406

AA069842 BF732525 AI160216 BX479667 BX281773 NM_005544 D17048 AI358832

BG207239 BQ433020 AI580782 BU154427 CB053406 BM469043 S62539 CB306477

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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

IRS1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TATTGTAAAC

About this image

IRS1 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

PureStem™ myogenic progenitor Z11 (Embryonic Progenitor Cell)

Heart, Myocardium, Smooth Muscle

PureStem™ progenitor EN2 (Embryonic Progenitor Cell)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See IRS1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for IRS1

SOURCE GeneReport for Unigene cluster: Hs.471508

SABiosciences Expression via Pathway-Focused 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 genome-wide validated SYBR primer pairs in human, mouse, rat for IRS1 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat IRS1
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat IRS1
		QIAGEN 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)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for IRS1 gene from 5/17 species (see all 17) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	IRS1¹	insulin receptor substrate 1	92.81(n) 91.36(a)		429262 NM_001031570.1 NP_001026741.1
lizard (Anolis carolinensis)	Reptilia	IRS1⁶	--	66(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	61.71(n) 65.51(a)		559281 XM_682610.5 XP_687702.4
fruit fly (Drosophila melanogaster)	Insecta	chico⁶	chico	18(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)
About This Section

Paralogs for IRS1 gene

IRS2² IRS4²

1 SIMAP similar gene for IRS1 using alignment to 1 protein entry: IRS1_HUMAN:

IRS2

IRS1 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568

Polymorphism: 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
				--	--	--		--	--
rs104893642^1,2	C	pathogenic	227918388(-)	`CCACAC/GGGATG`	2	T R	mis¹		0	--	--	--	--
rs1801278^1,2	C,F,H,	other	227919476(-)	`CTCCCA/C/G/T GGGCT`	4	R G W	mis¹ ese³		19		EA MN NA CA NS WA EU	9510
rs12620057^1,2	C,F,A,H,	--	219440766(+)	`atataC/Tacaca`	1	--	ut3¹		1		NA	4
rs75174566^1,2	F,	--	219440903(+)	`ACACAC/TGTCAC`	1	--	ut3¹		1		EA	120
rs113836440^1,2	C,	--	219440984(+)	`CACAAACAC/- ACACA`	1	--	ut3¹		1		CSA	2
rs73083604^1,2	C,F,	--	219441127(+)	`TTCCCA/GTTCCT`	1	--	ut3¹		4		WA CSA	123
rs17208239^1,2	C,F,H,	--	219441256(+)	`ATGGGG/TTCATT`	1	--	ut3¹		24		NA NS EA	2266
rs77510690^1,2		--	219441383(+)	`TTTCCA/GACTTT`	1	--	ut3¹		0	--	--	--	--
rs80213278^1,2	F,	--	219442155(+)	`CTTTAT/CGCTTT`	1	--	ut3¹		1		WA	118
rs113073045^1,2		--	219442924(+)	`ATAGAG/CAGATA`	1	--	ut3¹		1		CSA	2

HapMap Linkage Disequilibrium report for IRS1 (227596033 - 227664475 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for IRS1
2 CNVs: 78995 90313
1 Indel: 78996
Human Gene Mutation Database (HGMD): IRS1

5/8 SABiosciences Cancer Mutation 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

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat 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, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

IRS1 for disorders           About GeneDecksing

OMIM gene information: 147545
OMIM disorders: 125853
UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568

Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM)

[MIM:125853]

20/93 diseases for IRS1 (see all 93): About MalaCards

insulin resistance diabetes mellitus, noninsulin-dependent estrogen-receptor negative breast cancer silver-russell syndrome

retinol binding protein maturity-onset diabetes of the young carbohydrate metabolic disorder polycystic ovary syndrome

diabetes mellitus familial combined hyperlipidemia precocious puberty primitive neuroectodermal tumor

non-hodgkin lymphoma type 2 diabetes mellitus lipoatrophic diabetes coronary heart disease

glucose intolerance tuberous sclerosis herpes simplex sleep apnea

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

Diabetes mellitus Hyperglycemia Hyperinsulinism Polycystic ovary syndrome

10/64 Novoseek 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 9 sources (see all 1352):
(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. (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. (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. (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. (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. (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. (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. (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. (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....Forsti A. (2004)
Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls. (PubMed id 16037106)^{1, 4, 9} Villuendas G....San Millan J.L. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
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(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, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

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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insulin receptor substrate 1

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IRS1 Gene

insulin receptor substrate 1

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