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Protein

Insulin receptor substrate 1

Gene

chico

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity). May mediate the control of various cellular processes by insulin-like peptides. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains. Involved in control of cell proliferation, cell size, and body and organ growth throughout development. Also has a role in a signaling pathway controlling the physiological response required to endure periods of low nutrient conditions. Insulin/insulin-like growth factor (IGF) signaling pathway has a role in regulating aging and is necessary in the ovary for vitellogenic maturation.By similarity4 Publications

Miscellaneous

'Chico' means 'small boy' in Spanish.Curated

GO - Molecular functioni

  • insulin-like growth factor receptor binding Source: FlyBase
  • insulin receptor binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • signal transducer activity Source: GO_Central

GO - Biological processi

  • aging Source: FlyBase
  • determination of adult lifespan Source: FlyBase
  • entry into reproductive diapause Source: FlyBase
  • germ-line stem-cell niche homeostasis Source: FlyBase
  • glucose homeostasis Source: FlyBase
  • growth of a germarium-derived egg chamber Source: FlyBase
  • insulin-like growth factor receptor signaling pathway Source: UniProtKB
  • insulin receptor signaling pathway Source: FlyBase
  • lipid metabolic process Source: FlyBase
  • long-term synaptic potentiation Source: FlyBase
  • male germ-line stem cell asymmetric division Source: FlyBase
  • multicellular organism aging Source: UniProtKB
  • multicellular organism growth Source: FlyBase
  • olfactory learning Source: FlyBase
  • phosphatidylinositol phosphorylation Source: Reactome
  • positive regulation of cell proliferation Source: FlyBase
  • positive regulation of cell size Source: FlyBase
  • positive regulation of immune response Source: FlyBase
  • positive regulation of multicellular organism growth Source: FlyBase
  • positive regulation of organ growth Source: FlyBase
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: FlyBase
  • primary spermatocyte growth Source: FlyBase
  • protein kinase B signaling Source: FlyBase
  • regulation of activin receptor signaling pathway Source: FlyBase
  • regulation of lipid metabolic process Source: GO_Central
  • regulation of organ growth Source: FlyBase
  • regulation of tube length, open tracheal system Source: FlyBase
  • response to anoxia Source: FlyBase
  • response to starvation Source: FlyBase
  • vitellogenesis Source: UniProtKB

Keywordsi

Biological processDifferentiation, Growth regulation, Oogenesis

Enzyme and pathway databases

ReactomeiR-DME-109704 PI3K Cascade
R-DME-110478 Insulin signaling pathway
R-DME-112412 SOS-mediated signalling
R-DME-1257604 PIP3 activates AKT signaling
R-DME-198203 PI3K/AKT activation
R-DME-5673001 RAF/MAP kinase cascade
R-DME-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-DME-74749 Signal attenuation
SignaLinkiQ9XTN2

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin receptor substrate 1
Short name:
dIRS
Alternative name(s):
Protein chico
Gene namesi
Name:chico
Synonyms:IRS
ORF Names:CG5686
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraHolometabolaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2L

Organism-specific databases

FlyBaseiFBgn0024248 chico

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Disruption phenotypei

Female sterile. Extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000842351 – 968Insulin receptor substrate 1Add BLAST968

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei286Phosphoserine1 Publication1
Modified residuei287Phosphoserine1 Publication1
Modified residuei342Phosphoserine1 Publication1
Modified residuei411Phosphotyrosine; by INSRBy similarity1
Modified residuei555Phosphoserine1 Publication1
Modified residuei911Phosphotyrosine; by INSRBy similarity1
Modified residuei932Phosphoserine1 Publication1
Modified residuei935Phosphoserine1 Publication1
Modified residuei948Phosphotyrosine; by INSRBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9XTN2
PRIDEiQ9XTN2

PTM databases

iPTMnetiQ9XTN2

Expressioni

Developmental stagei

Expressed during G1, S and G2 phase of the cell cycle.1 Publication

Gene expression databases

BgeeiFBgn0024248
ExpressionAtlasiQ9XTN2 differential
GenevisibleiQ9XTN2 DM

Interactioni

Subunit structurei

Bindings to phosphatidylinositol 3-kinase and SHP2.

Binary interactionsi

Show more details

GO - Molecular functioni

  • insulin-like growth factor receptor binding Source: FlyBase
  • insulin receptor binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi72865, 37 interactors
DIPiDIP-23631N
IntActiQ9XTN2, 8 interactors
STRINGi7227.FBpp0079677

Structurei

3D structure databases

ProteinModelPortaliQ9XTN2
SMRiQ9XTN2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 109PHPROSITE-ProRule annotationCuratedAdd BLAST102
Domaini122 – 236IRS-type PTBPROSITE-ProRule annotationAdd BLAST115

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi411 – 414YXXM motif 14
Motifi641 – 644YXXM motif 24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi855 – 858Poly-Ser4
Compositional biasi870 – 873Poly-Ala4
Compositional biasi956 – 963Poly-Ser8

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IXEK Eukaryota
ENOG410Z9EP LUCA
GeneTreeiENSGT00530000063420
InParanoidiQ9XTN2
KOiK16172
OMAiSKIPRCD
OrthoDBiEOG091G02EF
PhylomeDBiQ9XTN2

Family and domain databases

CDDicd01204 PTB_IRS, 1 hit
Gene3Di2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR002404 IRS_PTB
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PfamiView protein in Pfam
PF02174 IRS, 1 hit
PRINTSiPR00628 INSULINRSI
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00310 PTBI, 1 hit
PROSITEiView protein in PROSITE
PS51064 IRS_PTB, 1 hit
PS50003 PH_DOMAIN, 1 hit

Sequencei

Sequence statusi: Complete.

Q9XTN2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASISDDGMA LSGYLKKLKT MKKKFFVLYE ETSTSAARLE YYDTEKKFLQ
60 70 80 90 100
RAEPKRVIYL KNCFNINRRL DTKHRFVIVL SSRDGGFGIV LENENDLRKW
110 120 130 140 150
LDKLLVLQRN IANSNGTAHS PYDHVWQVVI QKKGISEKVG ITGTYHCCLT
160 170 180 190 200
SKSLTFVCIG PEKTPNGEDR VASIEILLTT IRRCGHASPQ CIFYVELGRQ
210 220 230 240 250
SVLGSGDLWM ETDNAAIATN MHNTILSAMS AKTESNTNLI NVYQNRPDLS
260 270 280 290 300
HEPMRKRSSS ANEASKPINV NVIQNSQNSL ELRSCSSPHN YGFGRERCDS
310 320 330 340 350
LPTRNGTLSE SSNQTYFGSN HGLRSNTISG IRPHSTNKHS NSPTFTMPLR
360 370 380 390 400
CSESEESSIS VDESDDNGSF SHYRLNTRSS ETAIPEENID DFASAELFSK
410 420 430 440 450
VTEQNVSDEN YIPMNPVNPT DAIHEKEKAD MQRLEDASLH FNFPEHASEK
460 470 480 490 500
LAKDFDLDSD NQCCRPIRAY SIGNKVEHLK FNKRLGHLND TGQNPNRVRA
510 520 530 540 550
YSVGSKSKIP RCDLQRVVLV EDNKHEFTAN RSQSSITKEG TSYGSSANRQ
560 570 580 590 600
KKSTSAPLLS LKNQINSDRM SDLMEIDFSQ ATNLEKQKFI KNNEIPKYIE
610 620 630 640 650
NVFPKAPRTD SSSLTLHATS QKDIFNGTKL NNTAITSEDG YLEMKPVGNG
660 670 680 690 700
YTPSSNCLPM KVEKLKLSDY QTAPPLTATA APVHDLNKIS TYNISAEKWR
710 720 730 740 750
EQPSRSEEKK SNSPLNDNTF SSKPTNVEST SKSHDVHSAN QIDCEKVCAQ
760 770 780 790 800
SSDKLNNHLA DKIVENNNLD IGGHEEKKLV HSISSEDYTQ IKDKSNDFTK
810 820 830 840 850
FNEAGYKILQ IKSDSSLISS KLYQKGIHKD NLERSQRLTE SVNTIPDNAT
860 870 880 890 900
ATAVSSSSLT KFNINSAKPA AAADSRSTGT DPSTPQNILQ IKDLNFPSRS
910 920 930 940 950
SSRISQPELH YASLDLPHCS GQNPAKYLKR GSRESPPVSA CPEDGNTYAK
960
IDFDQSDSSS SSSNIFNT
Length:968
Mass (Da):107,832
Last modified:November 1, 1999 - v1
Checksum:i04E9856F37F7A4CF
GO

Sequence cautioni

The sequence AAD55429 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti29Y → C in strain: S108. 1 Publication1
Natural varianti165P → T in strain: FSP2, FSP15, FSP16, FSP19, FSP23, FSP29, RR8, RR11, RR17, RR18, RR35, RR52, S76, SL5_131, SL5_29, T28 and T39. 1 Publication1
Natural varianti334Missing in strain: S108. 1 Publication1
Natural varianti429A → V in strain: FSP19, RR33 and S108. 1 Publication1
Natural varianti452A → T in strain: RR33, S108, T28 and T39. 1 Publication1
Natural varianti664K → R in strain: FSP2, FSP3, FSP15, FSP19, FSP23, FSP25, FSP29, RR8, RR11, RR17, RR18, RR33, RR35, RR52, S76, S107, S108, T9, T15, T28, T39 and T41. 1 Publication1
Natural varianti675P → S in strain: S103. 1 Publication1
Natural varianti676L → I in strain: FSP3, FSP15, FSP19, FSP23, FSP25, RR8, RR11, RR17, RR33, RR35, RR52, S76, S97, S107, S108, T9, T28, T39 and T41. 1 Publication1
Natural varianti721S → G in strain: FSP2, FSP3, FSP15, FSP23, FSP25, FSP29, RR8, RR11, RR17, RR18, RR33, RR35, RR52, S108, T9, T15, T28, T39 and T41. 1 Publication1
Natural varianti722S → L in strain: FSP2, FSP3, FSP15, FSP16, FSP19, FSP23, FSP25, FSP29, RR8, RR11, RR17, RR18, RR33, RR35, RR52, S76, S97, S103, S107, S108, SL5_131, SL5_29, T9, T15, T28, T39 and T41. 1 Publication1
Natural varianti744C → S in strain: FSP3, FSP15, FSP16, FSP23, FSP25, FSP29, RR8, RR11, RR17, RR33, RR35, RR52, S108, T9, T15, T28, T39 and T41. 1 Publication1
Natural varianti758Missing in strain: FSP2, FSP3, FSP15, FSP16, FSP23, FSP25. FSP29, RR8, RR11, RR17, RR18, RR35, RR52, S97, S103, S108, SL5_131, SL5_29, T9, T15 and T41. 1 Publication1
Natural varianti808I → M in strain: RR8 and T41. 1 Publication1
Natural varianti851A → V in strain: FSP19. 1 Publication1
Natural varianti873A → T in strain: FSP16. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF154826 mRNA Translation: AAD40880.1
AF092046 mRNA Translation: AAD43005.1
GQ927177 Genomic DNA Translation: ACY01718.1
GQ927178 Genomic DNA Translation: ACY01719.1
GQ927179 Genomic DNA Translation: ACY01720.1
GQ927180 Genomic DNA Translation: ACY01721.1
GQ927181 Genomic DNA Translation: ACY01722.1
GQ927182 Genomic DNA Translation: ACY01723.1
GQ927183 Genomic DNA Translation: ACY01724.1
GQ927184 Genomic DNA Translation: ACY01725.1
GQ927185 Genomic DNA Translation: ACY01726.1
GQ927186 Genomic DNA Translation: ACY01727.1
GQ927187 Genomic DNA Translation: ACY01728.1
GQ927188 Genomic DNA Translation: ACY01729.1
GQ927189 Genomic DNA Translation: ACY01730.1
GQ927190 Genomic DNA Translation: ACY01731.1
GQ927191 Genomic DNA Translation: ACY01732.1
GQ927192 Genomic DNA Translation: ACY01733.1
GQ927193 Genomic DNA Translation: ACY01734.1
GQ927194 Genomic DNA Translation: ACY01735.1
GQ927195 Genomic DNA Translation: ACY01736.1
GQ927196 Genomic DNA Translation: ACY01737.1
GQ927197 Genomic DNA Translation: ACY01738.1
GQ927198 Genomic DNA Translation: ACY01739.1
GQ927199 Genomic DNA Translation: ACY01740.1
GQ927200 Genomic DNA Translation: ACY01741.1
GQ927201 Genomic DNA Translation: ACY01742.1
GQ927202 Genomic DNA Translation: ACY01743.1
GQ927203 Genomic DNA Translation: ACY01744.1
AE014134 Genomic DNA Translation: AAF52882.1
BT016137 mRNA Translation: AAV37022.1
AF181643 mRNA Translation: AAD55429.1 Different initiation.
RefSeqiNP_001188772.1, NM_001201843.2
NP_001260316.1, NM_001273387.1
NP_723540.1, NM_164899.3
UniGeneiDm.3017

Genome annotation databases

EnsemblMetazoaiFBtr0080088; FBpp0079677; FBgn0024248
FBtr0303904; FBpp0292907; FBgn0024248
FBtr0333412; FBpp0305604; FBgn0024248
GeneIDi64880
KEGGidme:Dmel_CG5686
UCSCiCG5686-RA d. melanogaster

Similar proteinsi

Entry informationi

Entry nameiIRS1_DROME
AccessioniPrimary (citable) accession number: Q9XTN2
Secondary accession number(s): D0UY43
, D0UY45, D0UY46, D0UY47, D0UY49, D0UY50, D0UY51, D0UY52, D0UY54, D0UY55, D0UY61, D0UY62, D0UY64, D0UY65, D0UY66, D0UY67, D0UY68, Q5U0V5, Q9U4G2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2003
Last sequence update: November 1, 1999
Last modified: April 25, 2018
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health