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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.
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-8853334. Signaling by FGFR3 fusions in cancer.
R-HSA-8853338. Signaling by FGFR3 point mutants in cancer.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti489 – 4891E → 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 Publication
Corresponds to variant rs397514047 [ dbSNP | Ensembl ].
VAR_070221
Natural varianti539 – 5391Missing 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 Publication
VAR_070222
Natural varianti649 – 6491R → W in SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling. 2 Publications
Corresponds to variant rs397515453 [ dbSNP | Ensembl ].
VAR_070223
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

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

Chemistry

ChEMBLiCHEMBL3559703.
DrugBankiDB01064. Isoprenaline.

Polymorphism and mutation databases

BioMutaiPIK3R1.
DMDMi118572681.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 724723Phosphatidylinositol 3-kinase regulatory subunit alphaPRO_0000080758Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserineCombined sources
Modified residuei154 – 1541PhosphoserineCombined sources
Modified residuei279 – 2791PhosphoserineCombined sources
Modified residuei467 – 4671PhosphotyrosineBy similarity
Modified residuei580 – 5801PhosphotyrosineCombined sources
Modified residuei608 – 6081PhosphoserineBy similarity

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.
PhosphoSiteiP27986.

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 interactions.
DIPiDIP-119N.
IntActiP27986. 221 interactions.
MINTiMINT-93751.
STRINGi9606.ENSP00000274335.

Chemistry

BindingDBiP27986.

Structurei

Secondary structure

1
724
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 107Combined sources
Beta strandi29 – 335Combined sources
Helixi34 – 407Combined sources
Turni43 – 453Combined sources
Helixi46 – 483Combined sources
Helixi50 – 534Combined sources
Beta strandi55 – 606Combined sources
Turni61 – 644Combined sources
Beta strandi65 – 706Combined sources
Helixi71 – 733Combined sources
Beta strandi74 – 818Combined sources
Turni100 – 1023Combined sources
Helixi118 – 1214Combined sources
Helixi130 – 14314Combined sources
Turni147 – 1504Combined sources
Helixi160 – 1645Combined sources
Beta strandi167 – 1704Combined sources
Helixi174 – 1763Combined sources
Helixi179 – 19113Combined sources
Beta strandi193 – 1953Combined sources
Helixi200 – 20910Combined sources
Helixi210 – 2123Combined sources
Helixi216 – 22712Combined sources
Helixi234 – 25219Combined sources
Helixi254 – 2574Combined sources
Helixi261 – 27313Combined sources
Helixi280 – 29516Combined sources
Helixi323 – 3253Combined sources
Helixi326 – 3294Combined sources
Beta strandi334 – 3374Combined sources
Helixi340 – 3478Combined sources
Beta strandi354 – 3596Combined sources
Helixi363 – 3653Combined sources
Beta strandi367 – 3748Combined sources
Beta strandi377 – 38610Combined sources
Beta strandi389 – 3957Combined sources
Beta strandi398 – 4003Combined sources
Helixi401 – 41010Combined sources
Helixi413 – 4153Combined sources
Helixi418 – 4203Combined sources
Turni430 – 4323Combined sources
Helixi433 – 4364Combined sources
Helixi442 – 51574Combined sources
Helixi518 – 58770Combined sources
Helixi591 – 5988Combined sources
Helixi617 – 6193Combined sources
Helixi621 – 6233Combined sources
Beta strandi625 – 6295Combined sources
Helixi631 – 6388Combined sources
Beta strandi645 – 6506Combined sources
Beta strandi652 – 6554Combined sources
Beta strandi657 – 6637Combined sources
Beta strandi666 – 67510Combined sources
Beta strandi678 – 6825Combined sources
Beta strandi688 – 6903Combined sources
Helixi691 – 70010Combined sources
Helixi703 – 7053Combined sources
Turni708 – 7103Combined sources
Beta strandi716 – 7194Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP27986.
SMRiP27986. Positions 3-85, 115-309, 322-724.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27986.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini3 – 7977SH3PROSITE-ProRule annotationAdd
BLAST
Domaini113 – 301189Rho-GAPPROSITE-ProRule annotationAdd
BLAST
Domaini333 – 42896SH2 1PROSITE-ProRule annotationAdd
BLAST
Domaini624 – 71895SH2 2PROSITE-ProRule annotationAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti330 – 3301D → N in M61906 (PubMed:1849461).Curated
Sequence conflicti460 – 4601S → G in BAG52931 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti326 – 3261M → I Does not affect insulin-stimulated lipid kinase activity. 3 Publications
Corresponds to variant rs3730089 [ dbSNP | Ensembl ].
VAR_010023
Natural varianti409 – 4091R → Q in a patient with severe insulin resistance; lower insulin-stimulated lipid kinase activity compared with wild-type. 1 Publication
Corresponds to variant rs748784250 [ dbSNP | Ensembl ].
VAR_010024
Natural varianti451 – 4511E → K.1 Publication
Corresponds to variant rs17852841 [ dbSNP | Ensembl ].
VAR_029562
Natural varianti489 – 4891E → 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 Publication
Corresponds to variant rs397514047 [ dbSNP | Ensembl ].
VAR_070221
Natural varianti539 – 5391Missing 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 Publication
VAR_070222
Natural varianti649 – 6491R → W in SHORTS; impairs interaction between PIK3R1 and IRS1 and reduces AKT1-mediated insulin signaling. 2 Publications
Corresponds to variant rs397515453 [ dbSNP | Ensembl ].
VAR_070223

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 363363Missing in isoform 5. 1 PublicationVSP_045903Add
BLAST
Alternative sequencei1 – 300300Missing in isoform 3. 1 PublicationVSP_021841Add
BLAST
Alternative sequencei1 – 270270Missing in isoform 2. 3 PublicationsVSP_021842Add
BLAST
Alternative sequencei271 – 30434MLFRF…ERQPA → MYNTVWNMEDLDLEYAKTDI NCGTDLMFYIEMDP in isoform 2. 3 PublicationsVSP_021843Add
BLAST
Alternative sequencei301 – 3066RQPAPA → MHNLQT in isoform 3. 1 PublicationVSP_021844
Alternative sequencei605 – 6051D → ENFLSCLPS in isoform 4. 1 PublicationVSP_021845

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]
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]
UniGeneiHs.132225.
Hs.604502.
Hs.734132.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP27986.
SMRiP27986. Positions 3-85, 115-309, 322-724.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111313. 156 interactions.
DIPiDIP-119N.
IntActiP27986. 221 interactions.
MINTiMINT-93751.
STRINGi9606.ENSP00000274335.

Chemistry

BindingDBiP27986.
ChEMBLiCHEMBL3559703.
DrugBankiDB01064. Isoprenaline.

PTM databases

iPTMnetiP27986.
PhosphoSiteiP27986.

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.
GeneCardsiPIK3R1.
HGNCiHGNC:8979. PIK3R1.
HPAiCAB004268.
HPA001216.
MalaCardsiPIK3R1.
MIMi171833. gene.
269880. phenotype.
615214. phenotype.
616005. phenotype.
neXtProtiNX_P27986.
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.
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-8853334. Signaling by FGFR3 fusions in cancer.
R-HSA-8853338. Signaling by FGFR3 point mutants in cancer.
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: September 7, 2016
This is version 203 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.