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Protein

Phosphatidylinositol 3-kinase regulatory subunit alpha

Gene

PIK3R1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Biological processHost-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-112399 IRS-mediated signalling
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 family interactions
R-HSA-388841 Costimulation by the CD28 family
R-HSA-389357 CD28 dependent PI3K/Akt signaling
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, Interleukin-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-6785807 Interleukin-4 and Interleukin-13 signaling
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-9028335 Activated NTRK2 signals through PI3K
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-9603381 Activated NTRK3 signals through PI3K
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiP27986
SIGNORiP27986

Protein family/group databases

MoonDBiP27986 Predicted

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

EuPathDBiHostDB:ENSG00000145675.14
HGNCiHGNC:8979 PIK3R1
MIMi171833 gene
neXtProtiNX_P27986

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

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 dbSNP:rs397514047EnsemblClinVar.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 dbSNP:rs397515453EnsemblClinVar.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
DB05210 SF1126

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
ProteomicsDBi54429
54430 [P27986-2]
54431 [P27986-3]
54432 [P27986-4]

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 Expressed in 248 organ(s), highest expression level in caput epididymis
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. 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 FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467).By similarity28 Publications
(Microbial infection) 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.1 Publication
(Microbial infection) Interacts with HCV NS5A.1 Publication
(Microbial infection) Interacts with herpes simplex virus 1 UL46; this interaction activates the PI3K/AKT pathway.1 Publication
(Microbial infection) Interacts with herpes simplex virus 1 UL46 and varicella virus ORF12; this interaction activates the PI3K/AKT pathway.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
P0DOJ92EBI-79464,EBI-16746307From Mus musculus polyomavirus 1.
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
ERBB3P2186041EBI-79464,EBI-720706
ESR1P033727EBI-79464,EBI-78473
FASLGP480232EBI-79464,EBI-495538
FGFR1P113625EBI-79464,EBI-1028277
FLT1P179482EBI-79464,EBI-1026718
FLT3P368882EBI-79464,EBI-3946257
GAB1Q1348033EBI-79464,EBI-517684
GRB10Q133222EBI-79464,EBI-80275
GRB2P629934EBI-79464,EBI-401755
HTTP428587EBI-79464,EBI-466029
ICOSQ9Y6W83EBI-79464,EBI-3922712
IGF1RP080694EBI-79464,EBI-475981
INSRP062133EBI-79464,EBI-475899
IRS1P3556812EBI-79464,EBI-517592
Irs1P355702EBI-79464,EBI-520230From Rattus norvegicus.
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
NSP034966EBI-79464,EBI-2547442From Influenza A virus (strain A/Puerto Rico/8/1934 H1N1).
Nyap1Q6PFX74EBI-79464,EBI-7447489From Mus musculus.
Nyap2Q8BM65-43EBI-79464,EBI-7447598From a different organism.
PDGFRBP0961919EBI-79464,EBI-641237
PIK3CAP4233622EBI-79464,EBI-2116585
PIK3CBP423383EBI-79464,EBI-2609540
PIK3CDO003296EBI-79464,EBI-718309
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
SIK2Q9H0K17EBI-79464,EBI-1181664
SIRT1Q96EB63EBI-79464,EBI-1802965
SOS1Q078893EBI-79464,EBI-297487
SRCP129317EBI-79464,EBI-621482
SSTR2P308745EBI-79464,EBI-6266898
TGOLN2O434932EBI-79464,EBI-1752146
TIRAPP587533EBI-79464,EBI-528644
TLR3O154552EBI-79464,EBI-6116630
TPSAB1Q156612EBI-79464,EBI-1761369
TPX2Q9ULW02EBI-79464,EBI-1037322
VAV3Q9UKW42EBI-79464,EBI-297568
VP3Q991523EBI-79464,EBI-1776808From Chicken anemia virus (isolate Germany Cuxhaven-1).
ZDHHC17Q8IUH52EBI-9090282,EBI-524753

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111313, 180 interactors
CORUMiP27986
DIPiDIP-119N
IntActiP27986, 242 interactors
MINTiP27986
STRINGi9606.ENSP00000274335

Chemistry databases

BindingDBiP27986

Structurei

Secondary structure

1724
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

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

Family and domain databases

CDDicd09930 SH2_cSH2_p85_like, 1 hit
cd09942 SH2_nSH2_p85_like, 1 hit
cd11910 SH3_PI3K_p85alpha, 1 hit
Gene3Di1.10.555.10, 1 hit
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR032498 PI3K_P85_iSH2
IPR035591 PI3K_p85alpha_SH3
IPR035020 PI3kinase_P85_cSH2
IPR035022 PI3kinase_P85_nSH2
IPR001720 PI3kinase_P85_p55
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10155 PTHR10155, 1 hit
PfamiView protein in Pfam
PF16454 PI3K_P85_iSH2, 1 hit
PF00620 RhoGAP, 1 hit
PF00017 SH2, 2 hits
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00324 RhoGAP, 1 hit
SM00252 SH2, 2 hits
SM00326 SH3, 1 hit
SUPFAMiSSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50238 RHOGAP, 1 hit
PS50001 SH2, 2 hits
PS50002 SH3, 1 hit

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

This entry has 5 described isoforms and 6 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YBC2H0YBC2_HUMAN
Phosphatidylinositol 3-kinase regul...
PIK3R1
189Annotation score:
E5RJY0E5RJY0_HUMAN
Phosphatidylinositol 3-kinase regul...
PIK3R1
137Annotation score:
E5RGI8E5RGI8_HUMAN
Phosphatidylinositol 3-kinase regul...
PIK3R1
117Annotation score:
E5RHI0E5RHI0_HUMAN
Phosphatidylinositol 3-kinase regul...
PIK3R1
102Annotation score:
H0YB27H0YB27_HUMAN
Phosphatidylinositol 3-kinase regul...
PIK3R1
131Annotation score:
E5RK66E5RK66_HUMAN
Phosphatidylinositol 3-kinase regul...
PIK3R1
38Annotation score:

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 dbSNP:rs3730089EnsemblClinVar.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 dbSNP:rs748784250Ensembl.1
Natural variantiVAR_029562451E → K1 PublicationCorresponds to variant dbSNP:rs17852841Ensembl.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 dbSNP:rs397514047EnsemblClinVar.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 dbSNP:rs397515453EnsemblClinVar.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

Similar proteinsi

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[»]
5GJIX-ray0.90A325-430[»]
5ITDX-ray3.02B307-617[»]
5M6UX-ray2.85B1-724[»]
5SW8X-ray3.30B322-600[»]
5SWGX-ray3.11B322-600[»]
5SWOX-ray3.50B322-600[»]
5SWPX-ray3.41B322-600[»]
5SWRX-ray3.31B322-600[»]
5SWTX-ray3.49B322-600[»]
5SX8X-ray3.47B322-600[»]
5SX9X-ray3.52B322-600[»]
5SXAX-ray3.35B322-600[»]
5SXBX-ray3.30B322-600[»]
5SXCX-ray3.55B322-600[»]
5SXDX-ray3.50B322-600[»]
5SXEX-ray3.51B322-600[»]
5SXFX-ray3.46B322-600[»]
5SXIX-ray3.40B322-600[»]
5SXJX-ray3.42B322-600[»]
5SXKX-ray3.55B322-600[»]
5UBTX-ray2.83B432-599[»]
5UK8X-ray2.50B306-593[»]
5UKJX-ray2.80B306-593[»]
5UL1X-ray3.00B306-593[»]
5VLRX-ray2.80B431-600[»]
5XGHX-ray2.97B322-598[»]
5XGIX-ray2.56B322-598[»]
5XGJX-ray2.97B322-599[»]
ProteinModelPortaliP27986
SMRiP27986
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111313, 180 interactors
CORUMiP27986
DIPiDIP-119N
IntActiP27986, 242 interactors
MINTiP27986
STRINGi9606.ENSP00000274335

Chemistry databases

BindingDBiP27986
ChEMBLiCHEMBL2506
DrugBankiDB01064 Isoprenaline
DB05210 SF1126

Protein family/group databases

MoonDBiP27986 Predicted

PTM databases

iPTMnetiP27986
PhosphoSitePlusiP27986

Polymorphism and mutation databases

BioMutaiPIK3R1
DMDMi118572681

Proteomic databases

EPDiP27986
MaxQBiP27986
PaxDbiP27986
PeptideAtlasiP27986
PRIDEiP27986
ProteomicsDBi54429
54430 [P27986-2]
54431 [P27986-3]
54432 [P27986-4]

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
EuPathDBiHostDB:ENSG00000145675.14
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
OMAiLNGYNET
OrthoDBiEOG091G0C3Z
PhylomeDBiP27986
TreeFamiTF102033

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000145675-MONOMER
BRENDAi2.7.1.153 2681
ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-112399 IRS-mediated signalling
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 family interactions
R-HSA-388841 Costimulation by the CD28 family
R-HSA-389357 CD28 dependent PI3K/Akt signaling
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, Interleukin-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-6785807 Interleukin-4 and Interleukin-13 signaling
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-9028335 Activated NTRK2 signals through PI3K
R-HSA-912526 Interleukin receptor SHC signaling
R-HSA-912631 Regulation of signaling by CBL
R-HSA-9603381 Activated NTRK3 signals through PI3K
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiP27986
SIGNORiP27986

Miscellaneous databases

ChiTaRSiPIK3R1 human
EvolutionaryTraceiP27986
GeneWikiiPIK3R1
GenomeRNAii5295
PROiPR:P27986
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145675 Expressed in 248 organ(s), highest expression level in caput epididymis
CleanExiHS_PIK3R1
ExpressionAtlasiP27986 baseline and differential
GenevisibleiP27986 HS

Family and domain databases

CDDicd09930 SH2_cSH2_p85_like, 1 hit
cd09942 SH2_nSH2_p85_like, 1 hit
cd11910 SH3_PI3K_p85alpha, 1 hit
Gene3Di1.10.555.10, 1 hit
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR032498 PI3K_P85_iSH2
IPR035591 PI3K_p85alpha_SH3
IPR035020 PI3kinase_P85_cSH2
IPR035022 PI3kinase_P85_nSH2
IPR001720 PI3kinase_P85_p55
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10155 PTHR10155, 1 hit
PfamiView protein in Pfam
PF16454 PI3K_P85_iSH2, 1 hit
PF00620 RhoGAP, 1 hit
PF00017 SH2, 2 hits
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00324 RhoGAP, 1 hit
SM00252 SH2, 2 hits
SM00326 SH3, 1 hit
SUPFAMiSSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50238 RHOGAP, 1 hit
PS50001 SH2, 2 hits
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiP85A_HUMAN
AccessioniPrimary (citable) accession number: P27986
Secondary accession number(s): B3KT19
, D3DWA0, E7EX19, Q15747, Q4VBZ7, Q53EM6, Q8IXA2, Q8N1C5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: November 28, 2006
Last modified: September 12, 2018
This is version 225 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health

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