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Protein

Phosphatidylinositol 3-kinase regulatory subunit alpha

Gene

PIK3R1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (PubMed:17626883, PubMed:19805105, PubMed:7518429). Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348923).4 Publications

GO - Molecular functioni

  • 1-phosphatidylinositol-3-kinase activity Source: Reactome
  • 1-phosphatidylinositol-3-kinase regulator activity Source: GO_Central
  • ErbB-3 class receptor binding Source: UniProtKB
  • insulin binding Source: UniProtKB
  • insulin-like growth factor receptor binding Source: UniProtKB
  • insulin receptor binding Source: UniProtKB
  • insulin receptor substrate binding Source: BHF-UCL
  • neurotrophin TRKA receptor binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: BHF-UCL
  • phosphatidylinositol 3-kinase regulator activity Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: Reactome
  • protein phosphatase binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Host-virus interaction, Protein transport, Stress response, Transport

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000145675-MONOMER.
ZFISH:ENSG00000145675-MONOMER.
BRENDAi2.7.1.153. 2681.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-114604. GPVI-mediated activation cascade.
R-HSA-1236382. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
R-HSA-1250342. PI3K events in ERBB4 signaling.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1266695. Interleukin-7 signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1660499. Synthesis of PIPs at the plasma membrane.
R-HSA-180292. GAB1 signalosome.
R-HSA-1839117. Signaling by cytosolic FGFR1 fusion mutants.
R-HSA-186763. Downstream signal transduction.
R-HSA-1963642. PI3K events in ERBB2 signaling.
R-HSA-198203. PI3K/AKT activation.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2029485. Role of phospholipids in phagocytosis.
R-HSA-210993. Tie2 Signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-2424491. DAP12 signaling.
R-HSA-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-HSA-373753. Nephrin interactions.
R-HSA-388841. Costimulation by the CD28 family.
R-HSA-389357. CD28 dependent PI3K/Akt signaling.
R-HSA-392451. G beta:gamma signalling through PI3Kgamma.
R-HSA-416476. G alpha (q) signalling events.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-430116. GP1b-IX-V activation signalling.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-512988. Interleukin-3, 5 and GM-CSF signaling.
R-HSA-5637810. Constitutive Signaling by EGFRvIII.
R-HSA-5654689. PI-3K cascade:FGFR1.
R-HSA-5654695. PI-3K cascade:FGFR2.
R-HSA-5654710. PI-3K cascade:FGFR3.
R-HSA-5654720. PI-3K cascade:FGFR4.
R-HSA-5655253. Signaling by FGFR2 in disease.
R-HSA-5655291. Signaling by FGFR4 in disease.
R-HSA-5655302. Signaling by FGFR1 in disease.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8851907. MET activates PI3K/AKT signaling.
R-HSA-8853334. Signaling by FGFR3 fusions in cancer.
R-HSA-8853338. Signaling by FGFR3 point mutants in cancer.
R-HSA-8853659. RET signaling.
R-HSA-912526. Interleukin receptor SHC signaling.
R-HSA-912631. Regulation of signaling by CBL.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLinkiP27986.
SIGNORiP27986.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 3-kinase regulatory subunit alpha
Short name:
PI3-kinase regulatory subunit alpha
Short name:
PI3K regulatory subunit alpha
Short name:
PtdIns-3-kinase regulatory subunit alpha
Alternative name(s):
Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
Short name:
PI3-kinase subunit p85-alpha
Short name:
PtdIns-3-kinase regulatory subunit p85-alpha
Gene namesi
Name:PIK3R1
Synonyms:GRB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:8979. PIK3R1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Agammaglobulinemia 7, autosomal recessive (AGM7)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
See also OMIM:615214
SHORT syndrome (SHORTS)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare, multisystem disease characterized by short stature, anomalies of the anterior chamber of the eye, characteristic facial features such as triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella, partial lipodystrophy, hernias, hyperextensibility, and delayed dentition. The clinical phenotype can include insulin resistance, nephrocalcinosis, and hearing deficits. Developmental milestones and cognition are normal.
See also OMIM:269880
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070221489E → K in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 PublicationCorresponds to variant rs397514047dbSNPEnsembl.1
Natural variantiVAR_070222539Missing in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 Publication1
Natural variantiVAR_070223649R → W in SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling. 2 PublicationsCorresponds to variant rs397515453dbSNPEnsembl.1
Immunodeficiency 36 (IMD36)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by impaired B-cell function, hypogammaglobulinemia and recurrent infections.
See also OMIM:616005

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi5295.
MalaCardsiPIK3R1.
MIMi269880. phenotype.
615214. phenotype.
616005. phenotype.
OpenTargetsiENSG00000145675.
Orphaneti397596. Activated PIK3-delta syndrome.
33110. Autosomal agammaglobulinemia.
3163. SHORT syndrome.
PharmGKBiPA33312.

Chemistry databases

ChEMBLiCHEMBL2506.
DrugBankiDB01064. Isoprenaline.

Polymorphism and mutation databases

BioMutaiPIK3R1.
DMDMi118572681.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000807582 – 724Phosphatidylinositol 3-kinase regulatory subunit alphaAdd BLAST723

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei154PhosphoserineCombined sources1
Modified residuei279PhosphoserineCombined sources1
Modified residuei467PhosphotyrosineBy similarity1
Modified residuei580PhosphotyrosineCombined sources1
Modified residuei608PhosphoserineBy similarity1

Post-translational modificationi

Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation.2 Publications
Phosphorylated. Tyrosine phosphorylated in response to signaling by FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated by CSF1R. Phosphorylated by ERBB4. Phosphorylated on tyrosine residues by TEK/TIE2. Dephosphorylated by PTPRJ. Phosphorylated by PIK3CA at Ser-608; phosphorylation is stimulated by insulin and PDGF. The relevance of phosphorylation by PIK3CA is however unclear (By similarity). Phosphorylated in response to KIT and KITLG/SCF. Phosphorylated by FGR.By similarity2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP27986.
MaxQBiP27986.
PaxDbiP27986.
PeptideAtlasiP27986.
PRIDEiP27986.

PTM databases

iPTMnetiP27986.
PhosphoSitePlusiP27986.

Expressioni

Tissue specificityi

Isoform 2 is expressed in skeletal muscle and brain, and at lower levels in kidney and cardiac muscle. Isoform 2 and isoform 4 are present in skeletal muscle (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000145675.
CleanExiHS_PIK3R1.
ExpressionAtlasiP27986. baseline and differential.
GenevisibleiP27986. HS.

Organism-specific databases

HPAiCAB004268.
HPA001216.

Interactioni

Subunit structurei

Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with PIK3R2; the interaction is dissociated in an insulin-dependent manner (By similarity). Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner (PubMed:20348923). Heterodimer of a regulatory subunit PIK3R1 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with FER. Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated). Interacts with PTK2/FAK1 (By similarity). Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR and/or BCR activation. Interacts with SOCS7. Interacts with RUFY3. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with LYN (via SH3 domain); this enhances enzyme activity (By similarity). Interacts with phosphorylated LAT, LAX1 and TRAT1 upon TCR activation. Interacts with CBLB. Interacts with HIV-1 Nef to activate the Nef associated p21-activated kinase (PAK). This interaction depends on the C-terminus of both proteins and leads to increased production of HIV. Interacts with HCV NS5A. The SH2 domains interact with the YTHM motif of phosphorylated INSR in vitro. Also interacts with tyrosine-phosphorylated IGF1R in vitro. Interacts with CD28 and CD3Z upon T-cell activation. Interacts with IRS1 and phosphorylated IRS4, as well as with NISCH and HCST. Interacts with FASLG, KIT and BCR. Interacts with AXL, FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated). Interacts with FGR and HCK. Interacts with PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts with ERBB4 (phosphorylated). Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with herpes simplex virus 1 UL46 and varicella virus ORF12; these interactions activate the PI3K/AKT pathway. Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467).By similarity31 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABI1Q8IZP08EBI-79464,EBI-375446
ABL2P426842EBI-79464,EBI-1102694
ARP102755EBI-79464,EBI-608057
CBLP226815EBI-79464,EBI-518228
CD28P107478EBI-79464,EBI-4314301
CHAF1AQ131112EBI-79464,EBI-1020839
CMIPQ8IY222EBI-79464,EBI-7689652
CRKP461082EBI-79464,EBI-886
CRKLP461092EBI-79464,EBI-910
CTLA4P164103EBI-79464,EBI-1030991
DLGAP4Q9Y2H02EBI-79464,EBI-722139
EGFRP005335EBI-79464,EBI-297353
ELK3P419702EBI-79464,EBI-1758534
ERBB2P0462611EBI-79464,EBI-641062
ERBB3P2186040EBI-79464,EBI-720706
ESR1P033726EBI-79464,EBI-78473
FASLGP480232EBI-79464,EBI-495538
FGFR1P113625EBI-79464,EBI-1028277
FLT1P179482EBI-79464,EBI-1026718
FLT3P368882EBI-79464,EBI-3946257
GAB1Q1348033EBI-79464,EBI-517684
GRB2P629934EBI-79464,EBI-401755
HTTP428587EBI-79464,EBI-466029
IGF1RP080694EBI-79464,EBI-475981
INSRP062133EBI-79464,EBI-475899
IRS1P3556812EBI-79464,EBI-517592
Irs1P355702EBI-79464,EBI-520230From a different organism.
IRS2Q9Y4H23EBI-79464,EBI-1049582
KITP1072119EBI-79464,EBI-1379503
LAPTM4BQ86VI4-32EBI-79464,EBI-3267286
LATO435614EBI-79464,EBI-1222766
MAP4K1Q929182EBI-79464,EBI-881
MAPK8P459836EBI-79464,EBI-286483
METP085816EBI-79464,EBI-1039152
NELFBQ8WX922EBI-79464,EBI-347721
NSP034965EBI-79464,EBI-2547442From a different organism.
Nyap1Q6PFX74EBI-79464,EBI-7447489From a different organism.
Nyap2Q8BM65-43EBI-79464,EBI-7447598From a different organism.
PDGFRBP0961919EBI-79464,EBI-641237
PIK3CAP4233614EBI-79464,EBI-2116585
PIK3CBP423383EBI-9090282,EBI-2609540
PLCG2P168852EBI-79464,EBI-617403
PXNP490232EBI-79464,EBI-702209
RAPGEF1Q139052EBI-79464,EBI-976876
RPL13P263732EBI-79464,EBI-356849
RXRAP197938EBI-79464,EBI-78598
SH2D2AQ9NP313EBI-9090282,EBI-490630
SHANK2Q9UPX82EBI-79464,EBI-1570571
SHC1P293533EBI-79464,EBI-78835
SIRT1Q96EB63EBI-79464,EBI-1802965
SOS1Q078893EBI-79464,EBI-297487
SRCP129316EBI-79464,EBI-621482
SSTR2P308745EBI-79464,EBI-6266898
TIRAPP587533EBI-79464,EBI-528644
TLR3O154552EBI-79464,EBI-6116630
TPSAB1Q156612EBI-79464,EBI-1761369
TPX2Q9ULW02EBI-79464,EBI-1037322
VAV3Q9UKW42EBI-79464,EBI-297568
VP3Q991523EBI-79464,EBI-1776808From a different organism.
ZDHHC17Q8IUH52EBI-9090282,EBI-524753

GO - Molecular functioni

  • ErbB-3 class receptor binding Source: UniProtKB
  • insulin binding Source: UniProtKB
  • insulin-like growth factor receptor binding Source: UniProtKB
  • insulin receptor binding Source: UniProtKB
  • insulin receptor substrate binding Source: BHF-UCL
  • neurotrophin TRKA receptor binding Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: BHF-UCL
  • protein phosphatase binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase adaptor activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi111313. 156 interactors.
DIPiDIP-119N.
IntActiP27986. 224 interactors.
MINTiMINT-93751.
STRINGi9606.ENSP00000274335.

Chemistry databases

BindingDBiP27986.

Structurei

Secondary structure

1724
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 10Combined sources7
Beta strandi29 – 33Combined sources5
Helixi34 – 40Combined sources7
Turni43 – 45Combined sources3
Helixi46 – 48Combined sources3
Helixi50 – 53Combined sources4
Beta strandi55 – 60Combined sources6
Turni61 – 64Combined sources4
Beta strandi65 – 70Combined sources6
Helixi71 – 73Combined sources3
Beta strandi74 – 81Combined sources8
Turni100 – 102Combined sources3
Helixi118 – 121Combined sources4
Helixi130 – 143Combined sources14
Turni147 – 150Combined sources4
Helixi160 – 164Combined sources5
Beta strandi167 – 170Combined sources4
Helixi174 – 176Combined sources3
Helixi179 – 191Combined sources13
Beta strandi193 – 195Combined sources3
Helixi200 – 209Combined sources10
Helixi210 – 212Combined sources3
Helixi216 – 227Combined sources12
Helixi234 – 252Combined sources19
Helixi254 – 257Combined sources4
Helixi261 – 273Combined sources13
Helixi280 – 295Combined sources16
Helixi323 – 325Combined sources3
Helixi326 – 329Combined sources4
Beta strandi334 – 337Combined sources4
Helixi340 – 347Combined sources8
Beta strandi354 – 359Combined sources6
Helixi363 – 365Combined sources3
Beta strandi367 – 374Combined sources8
Beta strandi377 – 386Combined sources10
Beta strandi389 – 395Combined sources7
Beta strandi398 – 400Combined sources3
Helixi401 – 410Combined sources10
Helixi413 – 415Combined sources3
Helixi418 – 420Combined sources3
Turni430 – 432Combined sources3
Helixi433 – 436Combined sources4
Helixi442 – 515Combined sources74
Helixi518 – 587Combined sources70
Helixi591 – 598Combined sources8
Helixi617 – 619Combined sources3
Helixi621 – 623Combined sources3
Beta strandi625 – 629Combined sources5
Helixi631 – 638Combined sources8
Beta strandi645 – 650Combined sources6
Beta strandi652 – 655Combined sources4
Beta strandi657 – 663Combined sources7
Beta strandi666 – 675Combined sources10
Beta strandi678 – 682Combined sources5
Beta strandi688 – 690Combined sources3
Helixi691 – 698Combined sources8
Helixi703 – 705Combined sources3
Turni708 – 710Combined sources3
Beta strandi716 – 719Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A0NNMR-A91-104[»]
1AZGNMR-A91-104[»]
1H9OX-ray1.79A617-724[»]
1PBWX-ray2.00A/B105-319[»]
1PHTX-ray2.00A1-85[»]
1PICNMR-A617-724[»]
1PKSNMR-A1-79[»]
1PKTNMR-A1-79[»]
2IUGX-ray1.89A321-440[»]
2IUHX-ray2.00A321-440[»]
2IUIX-ray2.40A/B321-440[»]
2RD0X-ray3.05B322-600[»]
2V1YX-ray2.40B431-600[»]
3HHMX-ray2.80B322-694[»]
3HIZX-ray3.30B322-694[»]
3I5RX-ray1.70A1-83[»]
3I5SX-ray3.00A/B/C/D1-83[»]
4A55X-ray3.50B322-600[»]
4JPSX-ray2.20B307-593[»]
4L1BX-ray2.59B318-615[»]
4L23X-ray2.50B318-615[»]
4L2YX-ray2.80B318-615[»]
4OVUX-ray2.96B322-600[»]
4OVVX-ray3.50B322-600[»]
4WAFX-ray2.39B306-617[»]
4YKNX-ray2.90A318-615[»]
4ZOPX-ray2.62B307-590[»]
5AULX-ray1.10A614-720[»]
5FI4X-ray2.50B306-617[»]
5ITDX-ray3.02B307-617[»]
ProteinModelPortaliP27986.
SMRiP27986.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27986.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 79SH3PROSITE-ProRule annotationAdd BLAST77
Domaini113 – 301Rho-GAPPROSITE-ProRule annotationAdd BLAST189
Domaini333 – 428SH2 1PROSITE-ProRule annotationAdd BLAST96
Domaini624 – 718SH2 2PROSITE-ProRule annotationAdd BLAST95

Domaini

The SH3 domain mediates the binding to CBLB, and to HIV-1 Nef.

Sequence similaritiesi

Belongs to the PI3K p85 subunit family.Curated
Contains 1 Rho-GAP domain.PROSITE-ProRule annotation
Contains 2 SH2 domains.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG4637. Eukaryota.
ENOG410XP6R. LUCA.
GeneTreeiENSGT00390000010431.
HOGENOMiHOG000008438.
HOVERGENiHBG082100.
InParanoidiP27986.
KOiK02649.
OMAiPQYWLTL.
OrthoDBiEOG091G0C3Z.
PhylomeDBiP27986.
TreeFamiTF102033.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR032498. PI3K_P85_iSH2.
IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10155. PTHR10155. 1 hit.
PfamiPF16454. PI3K_P85_iSH2. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P27986-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP
60 70 80 90 100
EEIGWLNGYN ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG
110 120 130 140 150
SSKTEADVEQ QALTLPDLAE QFAPPDIAPP LLIKLVEAIE KKGLECSTLY
160 170 180 190 200
RTQSSSNLAE LRQLLDCDTP SVDLEMIDVH VLADAFKRYL LDLPNPVIPA
210 220 230 240 250
AVYSEMISLA PEVQSSEEYI QLLKKLIRSP SIPHQYWLTL QYLLKHFFKL
260 270 280 290 300
SQTSSKNLLN ARVLSEIFSP MLFRFSAASS DNTENLIKVI EILISTEWNE
310 320 330 340 350
RQPAPALPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT
360 370 380 390 400
ADGTFLVRDA STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFSS
410 420 430 440 450
VVELINHYRN ESLAQYNPKL DVKLLYPVSK YQQDQVVKED NIEAVGKKLH
460 470 480 490 500
EYNTQFQEKS REYDRLYEEY TRTSQEIQMK RTAIEAFNET IKIFEEQCQT
510 520 530 540 550
QERYSKEYIE KFKREGNEKE IQRIMHNYDK LKSRISEIID SRRRLEEDLK
560 570 580 590 600
KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN
610 620 630 640 650
ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE
660 670 680 690 700
SSKQGCYACS VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH
710 720
TSLVQHNDSL NVTLAYPVYA QQRR
Length:724
Mass (Da):83,598
Last modified:November 28, 2006 - v2
Checksum:iB9DAD8416C33140F
GO
Isoform 2 (identifier: P27986-2) [UniParc]FASTAAdd to basket
Also known as: AS53

The sequence of this isoform differs from the canonical sequence as follows:
     1-270: Missing.
     271-304: MLFRFSAASSDNTENLIKVIEILISTEWNERQPA → MYNTVWNMEDLDLEYAKTDINCGTDLMFYIEMDP

Show »
Length:454
Mass (Da):53,486
Checksum:i33BB0F88AA47CB3F
GO
Isoform 3 (identifier: P27986-3) [UniParc]FASTAAdd to basket
Also known as: p46

The sequence of this isoform differs from the canonical sequence as follows:
     1-300: Missing.
     301-306: RQPAPA → MHNLQT

Show »
Length:424
Mass (Da):49,965
Checksum:iEF2D6D4D668C62D8
GO
Isoform 4 (identifier: P27986-4) [UniParc]FASTAAdd to basket
Also known as: p85I

The sequence of this isoform differs from the canonical sequence as follows:
     605-605: D → ENFLSCLPS

Show »
Length:732
Mass (Da):84,474
Checksum:iF4820A783035803A
GO
Isoform 5 (identifier: P27986-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-363: Missing.

Note: No experimental confirmation available.
Show »
Length:361
Mass (Da):42,838
Checksum:i100325CF4D673C4B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti330D → N in M61906 (PubMed:1849461).Curated1
Sequence conflicti460S → G in BAG52931 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010023326M → I Does not affect insulin-stimulated lipid kinase activity. 3 PublicationsCorresponds to variant rs3730089dbSNPEnsembl.1
Natural variantiVAR_010024409R → Q in a patient with severe insulin resistance; lower insulin-stimulated lipid kinase activity compared with wild-type. 1 PublicationCorresponds to variant rs748784250dbSNPEnsembl.1
Natural variantiVAR_029562451E → K.1 PublicationCorresponds to variant rs17852841dbSNPEnsembl.1
Natural variantiVAR_070221489E → K in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 PublicationCorresponds to variant rs397514047dbSNPEnsembl.1
Natural variantiVAR_070222539Missing in SHORTS; there is 70 to 90% reduction in the effect of insulin on AKT1 activation, glycogen synthesis and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling. 1 Publication1
Natural variantiVAR_070223649R → W in SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling. 2 PublicationsCorresponds to variant rs397515453dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0459031 – 363Missing in isoform 5. 1 PublicationAdd BLAST363
Alternative sequenceiVSP_0218411 – 300Missing in isoform 3. 1 PublicationAdd BLAST300
Alternative sequenceiVSP_0218421 – 270Missing in isoform 2. 3 PublicationsAdd BLAST270
Alternative sequenceiVSP_021843271 – 304MLFRF…ERQPA → MYNTVWNMEDLDLEYAKTDI NCGTDLMFYIEMDP in isoform 2. 3 PublicationsAdd BLAST34
Alternative sequenceiVSP_021844301 – 306RQPAPA → MHNLQT in isoform 3. 1 Publication6
Alternative sequenceiVSP_021845605D → ENFLSCLPS in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61906 mRNA. No translation available.
U49349 mRNA. Translation: AAB04140.1.
AF279367 mRNA. Translation: AAO15359.1.
AK094785 mRNA. Translation: BAG52931.1.
AK223613 mRNA. Translation: BAD97333.1.
AC016564 Genomic DNA. No translation available.
AC104120 Genomic DNA. No translation available.
CH471137 Genomic DNA. Translation: EAW51312.1.
CH471137 Genomic DNA. Translation: EAW51313.1.
BC030815 mRNA. Translation: AAH30815.1.
BC094795 mRNA. Translation: AAH94795.1.
CCDSiCCDS3993.1. [P27986-1]
CCDS3994.1. [P27986-3]
CCDS3995.1. [P27986-2]
CCDS56374.1. [P27986-5]
PIRiA38748.
RefSeqiNP_001229395.1. NM_001242466.1. [P27986-5]
NP_852556.2. NM_181504.3. [P27986-2]
NP_852664.1. NM_181523.2. [P27986-1]
NP_852665.1. NM_181524.1. [P27986-3]
XP_005248599.1. XM_005248542.3. [P27986-1]
XP_016865074.1. XM_017009585.1. [P27986-1]
UniGeneiHs.132225.
Hs.604502.
Hs.734132.

Genome annotation databases

EnsembliENST00000320694; ENSP00000323512; ENSG00000145675. [P27986-3]
ENST00000336483; ENSP00000338554; ENSG00000145675. [P27986-2]
ENST00000521381; ENSP00000428056; ENSG00000145675. [P27986-1]
ENST00000521657; ENSP00000429277; ENSG00000145675. [P27986-1]
ENST00000523872; ENSP00000430098; ENSG00000145675. [P27986-5]
GeneIDi5295.
KEGGihsa:5295.
UCSCiuc003jva.4. human. [P27986-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M61906 mRNA. No translation available.
U49349 mRNA. Translation: AAB04140.1.
AF279367 mRNA. Translation: AAO15359.1.
AK094785 mRNA. Translation: BAG52931.1.
AK223613 mRNA. Translation: BAD97333.1.
AC016564 Genomic DNA. No translation available.
AC104120 Genomic DNA. No translation available.
CH471137 Genomic DNA. Translation: EAW51312.1.
CH471137 Genomic DNA. Translation: EAW51313.1.
BC030815 mRNA. Translation: AAH30815.1.
BC094795 mRNA. Translation: AAH94795.1.
CCDSiCCDS3993.1. [P27986-1]
CCDS3994.1. [P27986-3]
CCDS3995.1. [P27986-2]
CCDS56374.1. [P27986-5]
PIRiA38748.
RefSeqiNP_001229395.1. NM_001242466.1. [P27986-5]
NP_852556.2. NM_181504.3. [P27986-2]
NP_852664.1. NM_181523.2. [P27986-1]
NP_852665.1. NM_181524.1. [P27986-3]
XP_005248599.1. XM_005248542.3. [P27986-1]
XP_016865074.1. XM_017009585.1. [P27986-1]
UniGeneiHs.132225.
Hs.604502.
Hs.734132.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A0NNMR-A91-104[»]
1AZGNMR-A91-104[»]
1H9OX-ray1.79A617-724[»]
1PBWX-ray2.00A/B105-319[»]
1PHTX-ray2.00A1-85[»]
1PICNMR-A617-724[»]
1PKSNMR-A1-79[»]
1PKTNMR-A1-79[»]
2IUGX-ray1.89A321-440[»]
2IUHX-ray2.00A321-440[»]
2IUIX-ray2.40A/B321-440[»]
2RD0X-ray3.05B322-600[»]
2V1YX-ray2.40B431-600[»]
3HHMX-ray2.80B322-694[»]
3HIZX-ray3.30B322-694[»]
3I5RX-ray1.70A1-83[»]
3I5SX-ray3.00A/B/C/D1-83[»]
4A55X-ray3.50B322-600[»]
4JPSX-ray2.20B307-593[»]
4L1BX-ray2.59B318-615[»]
4L23X-ray2.50B318-615[»]
4L2YX-ray2.80B318-615[»]
4OVUX-ray2.96B322-600[»]
4OVVX-ray3.50B322-600[»]
4WAFX-ray2.39B306-617[»]
4YKNX-ray2.90A318-615[»]
4ZOPX-ray2.62B307-590[»]
5AULX-ray1.10A614-720[»]
5FI4X-ray2.50B306-617[»]
5ITDX-ray3.02B307-617[»]
ProteinModelPortaliP27986.
SMRiP27986.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111313. 156 interactors.
DIPiDIP-119N.
IntActiP27986. 224 interactors.
MINTiMINT-93751.
STRINGi9606.ENSP00000274335.

Chemistry databases

BindingDBiP27986.
ChEMBLiCHEMBL2506.
DrugBankiDB01064. Isoprenaline.

PTM databases

iPTMnetiP27986.
PhosphoSitePlusiP27986.

Polymorphism and mutation databases

BioMutaiPIK3R1.
DMDMi118572681.

Proteomic databases

EPDiP27986.
MaxQBiP27986.
PaxDbiP27986.
PeptideAtlasiP27986.
PRIDEiP27986.

Protocols and materials databases

DNASUi5295.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000320694; ENSP00000323512; ENSG00000145675. [P27986-3]
ENST00000336483; ENSP00000338554; ENSG00000145675. [P27986-2]
ENST00000521381; ENSP00000428056; ENSG00000145675. [P27986-1]
ENST00000521657; ENSP00000429277; ENSG00000145675. [P27986-1]
ENST00000523872; ENSP00000430098; ENSG00000145675. [P27986-5]
GeneIDi5295.
KEGGihsa:5295.
UCSCiuc003jva.4. human. [P27986-1]

Organism-specific databases

CTDi5295.
DisGeNETi5295.
GeneCardsiPIK3R1.
HGNCiHGNC:8979. PIK3R1.
HPAiCAB004268.
HPA001216.
MalaCardsiPIK3R1.
MIMi171833. gene.
269880. phenotype.
615214. phenotype.
616005. phenotype.
neXtProtiNX_P27986.
OpenTargetsiENSG00000145675.
Orphaneti397596. Activated PIK3-delta syndrome.
33110. Autosomal agammaglobulinemia.
3163. SHORT syndrome.
PharmGKBiPA33312.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4637. Eukaryota.
ENOG410XP6R. LUCA.
GeneTreeiENSGT00390000010431.
HOGENOMiHOG000008438.
HOVERGENiHBG082100.
InParanoidiP27986.
KOiK02649.
OMAiPQYWLTL.
OrthoDBiEOG091G0C3Z.
PhylomeDBiP27986.
TreeFamiTF102033.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000145675-MONOMER.
ZFISH:ENSG00000145675-MONOMER.
BRENDAi2.7.1.153. 2681.
ReactomeiR-HSA-109704. PI3K Cascade.
R-HSA-114604. GPVI-mediated activation cascade.
R-HSA-1236382. Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
R-HSA-1250342. PI3K events in ERBB4 signaling.
R-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1266695. Interleukin-7 signaling.
R-HSA-1433557. Signaling by SCF-KIT.
R-HSA-1660499. Synthesis of PIPs at the plasma membrane.
R-HSA-180292. GAB1 signalosome.
R-HSA-1839117. Signaling by cytosolic FGFR1 fusion mutants.
R-HSA-186763. Downstream signal transduction.
R-HSA-1963642. PI3K events in ERBB2 signaling.
R-HSA-198203. PI3K/AKT activation.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2029485. Role of phospholipids in phagocytosis.
R-HSA-210993. Tie2 Signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-2424491. DAP12 signaling.
R-HSA-2730905. Role of LAT2/NTAL/LAB on calcium mobilization.
R-HSA-373753. Nephrin interactions.
R-HSA-388841. Costimulation by the CD28 family.
R-HSA-389357. CD28 dependent PI3K/Akt signaling.
R-HSA-392451. G beta:gamma signalling through PI3Kgamma.
R-HSA-416476. G alpha (q) signalling events.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-430116. GP1b-IX-V activation signalling.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-512988. Interleukin-3, 5 and GM-CSF signaling.
R-HSA-5637810. Constitutive Signaling by EGFRvIII.
R-HSA-5654689. PI-3K cascade:FGFR1.
R-HSA-5654695. PI-3K cascade:FGFR2.
R-HSA-5654710. PI-3K cascade:FGFR3.
R-HSA-5654720. PI-3K cascade:FGFR4.
R-HSA-5655253. Signaling by FGFR2 in disease.
R-HSA-5655291. Signaling by FGFR4 in disease.
R-HSA-5655302. Signaling by FGFR1 in disease.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8851907. MET activates PI3K/AKT signaling.
R-HSA-8853334. Signaling by FGFR3 fusions in cancer.
R-HSA-8853338. Signaling by FGFR3 point mutants in cancer.
R-HSA-8853659. RET signaling.
R-HSA-912526. Interleukin receptor SHC signaling.
R-HSA-912631. Regulation of signaling by CBL.
R-HSA-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLinkiP27986.
SIGNORiP27986.

Miscellaneous databases

ChiTaRSiPIK3R1. human.
EvolutionaryTraceiP27986.
GeneWikiiPIK3R1.
GenomeRNAii5295.
PROiP27986.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145675.
CleanExiHS_PIK3R1.
ExpressionAtlasiP27986. baseline and differential.
GenevisibleiP27986. HS.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.30.505.10. 2 hits.
InterProiIPR032498. PI3K_P85_iSH2.
IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
PANTHERiPTHR10155. PTHR10155. 1 hit.
PfamiPF16454. PI3K_P85_iSH2. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
SMARTiSM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 2 hits.
PROSITEiPS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiP85A_HUMAN
AccessioniPrimary (citable) accession number: P27986
Secondary accession number(s): B3KT19
, D3DWA0, E7EX19, Q15747, Q4VBZ7, Q53EM6, Q8IXA2, Q8N1C5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: November 28, 2006
Last modified: November 30, 2016
This is version 206 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.