Phosphatidylinositol 3-kinase regulatory subunit alpha

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Reviewed, UniProtKB/Swiss-Prot P27986 (P85A_HUMAN)

Last modified February 9, 2010. Version 131. History...

Clusters with 100%, 90%, 50% identity |

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Phosphatidylinositol 3-kinase regulatory subunit alpha
      Short name=PtdIns-3-kinase regulatory subunit alpha
      Short name=PI3-kinase regulatory subunit alpha
      Short name=PI3K regulatory subunit alpha
Alternative name(s):
    Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
      Short name=PtdIns-3-kinase regulatory subunit p85-alpha
      Short name=PI3-kinase subunit p85-alpha

Gene names

Name:	PIK3R1
Synonyms:	GRB1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	724 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	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.
Subunit structure	Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunits. Interacts with phosphorylated TOM1L1. Interacts with phosphorylated LIME1 upon TCR and/or BCR activation. Interacts with SOCS7. Interacts with RUFY3 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. Ref.2 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19
Tissue specificity	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). Ref.2
Domain	The SH3 domain mediates the binding to CBLB, and to HIV-1 Nef.
Post-translational modification	Polyubiquitinated in T-cells by CBLB; which does not promote proteasomal degradation but impairs association with CD28 and CD3Z upon T-cell activation.
Involvement in disease	Defects in PIK3R1 are a cause of severe insulin resistance.
Sequence similarities	Belongs to the PI3K p85 subunit family. Contains 1 Rho-GAP domain. Contains 2 SH2 domains. Contains 1 SH3 domain.

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Ontologies

Keywords
Biological process	Host-virus interaction
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat SH2 domain SH3 domain
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	growth hormone receptor signaling pathway Inferred from direct assay. Source: UniProtKB insulin receptor signaling pathway Ref.6 Inferred from physical interaction. Source: UniProtKB insulin-like growth factor receptor signaling pathway Ref.7 Inferred from physical interaction. Source: UniProtKB interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW phosphoinositide 3-kinase cascade Inferred from direct assay. Source: UniProtKB phosphoinositide phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of establishment of protein localization in plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of glucose import Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	1-phosphatidylinositol-4-phosphate 3-kinase, class IA complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ErbB-3 class receptor binding Inferred from direct assay. Source: UniProtKB insulin binding Inferred from direct assay. Source: UniProtKB insulin receptor binding Ref.6 Ref.8 Inferred from physical interaction. Source: UniProtKB insulin receptor substrate binding Inferred from sequence or structural similarity. Source: UniProtKB insulin-like growth factor receptor binding Ref.7 Inferred from physical interaction. Source: UniProtKB phosphatidylinositol binding Non-traceable author statement. Source: UniProtKB phosphoinositide 3-kinase regulator activity Inferred from sequence or structural similarity. Source: UniProtKB protein phosphatase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABCG5	Q9H222	1	EBI-79464,EBI-1761423
ABL1	P00519	1	EBI-79464,EBI-375543
ABL2	P42684	1	EBI-79464,EBI-1102694
AIRE	O43918	1	EBI-79464,EBI-1753081
AKAP2	Q9Y2D5	1	EBI-79464,EBI-1754555
AKAP6	Q13023	1	EBI-79464,EBI-1056102
ALS2CR12	Q96Q35	1	EBI-79464,EBI-1755548
APOL5	Q9BWW9	1	EBI-79464,EBI-1753592
ARHGEF11	O15085	1	EBI-79464,EBI-311099
ASAP1	Q9ULH1	1	EBI-79464,EBI-346622
ASAP2	O43150	1	EBI-79464,EBI-310968
BRCA1	P38398	1	EBI-79464,EBI-349905
BRD4	O60885	1	EBI-79464,EBI-723869
BRPF3	Q9ULD4	1	EBI-79464,EBI-1753470
CAST	P20810	1	EBI-79464,EBI-1268770
CDC27	P30260	1	EBI-79464,EBI-994813
CHAF1A	Q13111	1	EBI-79464,EBI-1020839
CKAP5	Q14008	1	EBI-79464,EBI-310585
COBRA1	Q8WX92	1	EBI-79464,EBI-347721
CSDC2	Q9Y534	1	EBI-79464,EBI-1763657
CSDE1	O75534	1	EBI-79464,EBI-719186
CSF2RA	P15509	1	EBI-79464,EBI-1763264
DAB2	P98082	1	EBI-79464,EBI-1171238
DAG1	Q14118	1	EBI-79464,EBI-1755945
DARS	P14868	1	EBI-79464,EBI-358730
DLGAP1	O14490	1	EBI-79464,EBI-1753207
DLGAP2	Q9P1A6	1	EBI-79464,EBI-1753397
DLGAP3	O95886	1	EBI-79464,EBI-1752541
DLGAP4	Q9Y2H0	1	EBI-79464,EBI-722139
DLX4	Q92988	1	EBI-79464,EBI-1752755
DOCK3	Q8IZD9	1	EBI-79464,EBI-1752361
DTNBP1	Q96EV8	1	EBI-79464,EBI-465804
DUSP15	Q9H1R2	1	EBI-79464,EBI-1752795
ECT2	Q9H8V3	1	EBI-79464,EBI-1054039
EFS	O43281	1	EBI-79464,EBI-718488
ELK3	P41970	1	EBI-79464,EBI-1758534
EPX	P11678	1	EBI-79464,EBI-1761505
ERBB3	P21860	3	EBI-79464,EBI-720706
EXTL3	O43909	1	EBI-79464,EBI-1754679
FANCA	O15360	1	EBI-79464,EBI-81570
FASLG	P48023	1	EBI-79464,EBI-495538
FLNA	P21333	1	EBI-79464,EBI-350432
FLNB	O75369	1	EBI-79464,EBI-352089
FLNC	Q14315	1	EBI-79464,EBI-489954
FOXH1	O75593	1	EBI-79464,EBI-1759806
Gab1	Q9QYY0	1	EBI-79464,EBI-644784	From a different organism.
GABBR1	Q9UBS5	1	EBI-79464,EBI-724156
GABRA3	P34903	1	EBI-79464,EBI-1763805
GHR	P10912	1	EBI-79464,EBI-286316
GLTSCR1	Q9NZM4	1	EBI-79464,EBI-1754943
HCK	P08631	1	EBI-79464,EBI-346340
ID4	P47928	1	EBI-79464,EBI-1754719
JAK2	O60674	1	EBI-79464,EBI-518647
KIF13A	Q9H1H9	1	EBI-79464,EBI-1759129
LIG3	P49916	1	EBI-79464,EBI-1753381
MAP4	P27816	1	EBI-79464,EBI-715255
MAP4K1	Q92918	1	EBI-79464,EBI-881
MEPE	Q9NQ76	1	EBI-79464,EBI-1753293
MYLK	Q15746	1	EBI-79464,EBI-968482
MYRIP	Q8NFW9	1	EBI-79464,EBI-1759414
NR5A1	Q13285	1	EBI-79464,EBI-874629
PDIA2	Q13087	1	EBI-79464,EBI-1752525
PEBP1	P30086	1	EBI-79464,EBI-716384
PHACTR2	O75167	1	EBI-79464,EBI-1754409
PIK3C2B	O00750	1	EBI-79464,EBI-641107
PIK3CA	P32871	1	EBI-79464,EBI-1373130	From a different organism.
PLCG2	P16885	1	EBI-79464,EBI-617403
POLR1B	Q9H9Y6	1	EBI-79464,EBI-355441
PPFIA3	O75145	1	EBI-79464,EBI-1763225
PTPN4	P29074	1	EBI-79464,EBI-710431
RAPGEF1	Q13905	1	EBI-79464,EBI-976876
RPL13	P26373	1	EBI-79464,EBI-356849
RRAS	P10301	1	EBI-79464,EBI-968703
SCG2	P13521	1	EBI-79464,EBI-947132
SH3KBP1	Q96B97	1	EBI-79464,EBI-346595
SHANK2	Q9UPX8	1	EBI-79464,EBI-1570571
SHANK3	Q9BYB0	1	EBI-79464,EBI-1752330
SLC23A1	Q9UHI7	1	EBI-79464,EBI-1759386
SLC24A1	O60721	1	EBI-79464,EBI-1753504
SNX17	Q15036	1	EBI-79464,EBI-1752620
SNX8	Q9Y5X2	1	EBI-79464,EBI-1752557
SOS1	Q07889	1	EBI-79464,EBI-297487
SOS2	Q07890	1	EBI-79464,EBI-298181
SPEN	Q96T58	1	EBI-79464,EBI-765739
SUV39H2	Q9H5I1	1	EBI-79464,EBI-723127
SYNJ2	O15056	1	EBI-79464,EBI-310513
TGDS	O95455	1	EBI-79464,EBI-1761487
TGOLN2	O43493	1	EBI-79464,EBI-1752146
TPSAB1	P15157	1	EBI-79464,EBI-1762849
TPSAB1	Q15661	1	EBI-79464,EBI-1761369
TPSB2	P20231	1	EBI-79464,EBI-1761383
TPX2	Q9ULW0	1	EBI-79464,EBI-1037322
TULP4	Q9NRJ4	1	EBI-79464,EBI-1753487
VPS13A	Q96RL7	1	EBI-79464,EBI-1752583
ZC4H2	Q9NQZ6	1	EBI-79464,EBI-747993

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Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P27986-1) 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.

Isoform 2 (identifier: P27986-2) Also known as: AS53; The sequence of this isoform differs from the canonical sequence as follows: 1-270: Missing. 271-304: MLFRFSAASSDNTENLIKVIEILISTEWNERQPA → MYNTVWNMEDLDLEYAKTDINCGTDLMFYIEMDP

Isoform 3 (identifier: P27986-3) Also known as: p46; The sequence of this isoform differs from the canonical sequence as follows: 1-300: Missing. 301-306: RQPAPA → MHNLQT

Isoform 4 (identifier: P27986-4) Also known as: p85I; The sequence of this isoform differs from the canonical sequence as follows: 605-605: D → ENFLSCLPS

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 724

724

Phosphatidylinositol 3-kinase regulatory subunit alpha

PRO_0000080758

Regions

Domain

3 – 79

SH3

Domain

113 – 301

189

Rho-GAP

Domain

333 – 428

SH2 1

Domain

624 – 718

SH2 2

Amino acid modifications

Modified residue

152

Phosphothreonine

Modified residue

154

Phosphoserine

Modified residue

452

Phosphotyrosine Ref.21 Ref.23

Modified residue

467

Phosphotyrosine Ref.21 Ref.23

Modified residue

508

Phosphotyrosine Ref.23

Modified residue

530

N6-acetyllysine Ref.25

Modified residue

556

Phosphotyrosine Ref.21 Ref.23

Modified residue

580

Phosphotyrosine Ref.21 Ref.23

Modified residue

607

Phosphotyrosine Ref.20

Modified residue

679

Phosphotyrosine Ref.23

Natural variations

Alternative sequence

1 – 300

300

Missing in isoform 3.

VSP_021841

Alternative sequence

1 – 270

270

Missing in isoform 2.

VSP_021842

Alternative sequence

271 – 304

MLFRF…ERQPA → MYNTVWNMEDLDLEYAKTDI NCGTDLMFYIEMDP in isoform 2.

VSP_021843

Alternative sequence

301 – 306

RQPAPA → MHNLQT in isoform 3.

VSP_021844

Alternative sequence

605

D → ENFLSCLPS in isoform 4.

VSP_021845

Natural variant

326

M → I: dbSNP rs3730089. Ref.4 Ref.33 Ref.34

VAR_010023

Natural variant

409

R → Q in severe insulin resistance; reduction of insulin-stimulated activity. Ref.34

VAR_010024

Natural variant

451

E → K: dbSNP rs17852841. Ref.5

VAR_029562

Experimental info

Sequence conflict

330

D → N in M61906. Ref.1

Secondary structure

724

Helix Strand Turn

Details...

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: B9DAD8416C33140F Show »	FASTA	724	83,598
10 20 30 40 50 60 MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP EEIGWLNGYN 70 80 90 100 110 120 ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG SSKTEADVEQ QALTLPDLAE 130 140 150 160 170 180 QFAPPDIAPP LLIKLVEAIE KKGLECSTLY RTQSSSNLAE LRQLLDCDTP SVDLEMIDVH 190 200 210 220 230 240 VLADAFKRYL LDLPNPVIPA AVYSEMISLA PEVQSSEEYI QLLKKLIRSP SIPHQYWLTL 250 260 270 280 290 300 QYLLKHFFKL SQTSSKNLLN ARVLSEIFSP MLFRFSAASS DNTENLIKVI EILISTEWNE 310 320 330 340 350 360 RQPAPALPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA 370 380 390 400 410 420 STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFSS VVELINHYRN ESLAQYNPKL 430 440 450 460 470 480 DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK 490 500 510 520 530 540 RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNEKE IQRIMHNYDK LKSRISEIID 550 560 570 580 590 600 SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN 610 620 630 640 650 660 ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS 670 680 690 700 710 720 VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA QQRR « Hide
Isoform 2 (AS53). Checksum: 33BB0F88AA47CB3F Show »	FASTA	454	53,486
10 20 30 40 50 60 MYNTVWNMED LDLEYAKTDI NCGTDLMFYI EMDPPALPPK PPKPTTVANN GMNNNMSLQD 70 80 90 100 110 120 AEWYWGDISR EEVNEKLRDT ADGTFLVRDA STKMHGDYTL TLRKGGNNKL IKIFHRDGKY 130 140 150 160 170 180 GFSDPLTFSS VVELINHYRN ESLAQYNPKL DVKLLYPVSK YQQDQVVKED NIEAVGKKLH 190 200 210 220 230 240 EYNTQFQEKS REYDRLYEEY TRTSQEIQMK RTAIEAFNET IKIFEEQCQT QERYSKEYIE 250 260 270 280 290 300 KFKREGNEKE IQRIMHNYDK LKSRISEIID SRRRLEEDLK KQAAEYREID KRMNSIKPDL 310 320 330 340 350 360 IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN 370 380 390 400 410 420 RNKAENLLRG KRDGTFLVRE SSKQGCYACS VVVDGEVKHC VINKTATGYG FAEPYNLYSS 430 440 450 LKELVLHYQH TSLVQHNDSL NVTLAYPVYA QQRR « Hide
Isoform 3 (p46). Checksum: EF2D6D4D668C62D8 Show »	FASTA	424	49,965
10 20 30 40 50 60 MHNLQTLPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA 70 80 90 100 110 120 STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFSS VVELINHYRN ESLAQYNPKL 130 140 150 160 170 180 DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK 190 200 210 220 230 240 RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNEKE IQRIMHNYDK LKSRISEIID 250 260 270 280 290 300 SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN 310 320 330 340 350 360 ENTEDQYSLV EDDEDLPHHD EKTWNVGSSN RNKAENLLRG KRDGTFLVRE SSKQGCYACS 370 380 390 400 410 420 VVVDGEVKHC VINKTATGYG FAEPYNLYSS LKELVLHYQH TSLVQHNDSL NVTLAYPVYA QQRR « Hide
Isoform 4 (p85I). Checksum: F4820A783035803A Show »	FASTA	732	84,474
10 20 30 40 50 60 MSAEGYQYRA LYDYKKEREE DIDLHLGDIL TVNKGSLVAL GFSDGQEARP EEIGWLNGYN 70 80 90 100 110 120 ETTGERGDFP GTYVEYIGRK KISPPTPKPR PPRPLPVAPG SSKTEADVEQ QALTLPDLAE 130 140 150 160 170 180 QFAPPDIAPP LLIKLVEAIE KKGLECSTLY RTQSSSNLAE LRQLLDCDTP SVDLEMIDVH 190 200 210 220 230 240 VLADAFKRYL LDLPNPVIPA AVYSEMISLA PEVQSSEEYI QLLKKLIRSP SIPHQYWLTL 250 260 270 280 290 300 QYLLKHFFKL SQTSSKNLLN ARVLSEIFSP MLFRFSAASS DNTENLIKVI EILISTEWNE 310 320 330 340 350 360 RQPAPALPPK PPKPTTVANN GMNNNMSLQD AEWYWGDISR EEVNEKLRDT ADGTFLVRDA 370 380 390 400 410 420 STKMHGDYTL TLRKGGNNKL IKIFHRDGKY GFSDPLTFSS VVELINHYRN ESLAQYNPKL 430 440 450 460 470 480 DVKLLYPVSK YQQDQVVKED NIEAVGKKLH EYNTQFQEKS REYDRLYEEY TRTSQEIQMK 490 500 510 520 530 540 RTAIEAFNET IKIFEEQCQT QERYSKEYIE KFKREGNEKE IQRIMHNYDK LKSRISEIID 550 560 570 580 590 600 SRRRLEEDLK KQAAEYREID KRMNSIKPDL IQLRKTRDQY LMWLTQKGVR QKKLNEWLGN 610 620 630 640 650 660 ENTEENFLSC LPSQYSLVED DEDLPHHDEK TWNVGSSNRN KAENLLRGKR DGTFLVRESS 670 680 690 700 710 720 KQGCYACSVV VDGEVKHCVI NKTATGYGFA EPYNLYSSLK ELVLHYQHTS LVQHNDSLNV 730 TLAYPVYAQQ RR « Hide

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases." Skolnik E.Y., Margolis B., Mohammadi M., Lowenstein E., Fischer R., Drepps A., Ullrich A., Schlessinger J. Cell 65:83-90(1991) [PubMed: 1849461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain." Antonetti D.A., Algenstaedt P., Kahn C.R. Mol. Cell. Biol. 16:2195-2203(1996) [PubMed: 8628286] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), INTERACTION WITH IRS1, TISSUE SPECIFICITY. Tissue: Skeletal muscle.
[3]	Udelhoven M., Kotzka J., Knebel B., Klein E., Krone W., Mueller-Wieland D. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). Tissue: Skeletal muscle.
[4]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-326. Tissue: Brain.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LYS-451. Tissue: Placenta and Skeletal muscle.
[6]	"Direct activation of the phosphatidylinositol 3'-kinase by the insulin receptor." Van Horn D.J., Myers M.G. Jr., Backer J.M. J. Biol. Chem. 269:29-32(1994) [PubMed: 8276809] [Abstract] Cited for: INTERACTION WITH INSR.
[7]	"Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor." Craparo A., O'Neill T.J., Gustafson T.A. J. Biol. Chem. 270:15639-15643(1995) [PubMed: 7541045] [Abstract] Cited for: INTERACTION WITH IGF1R.
[8]	"Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain." Gustafson T.A., He W., Craparo A., Schaub C.D., O'Neill T.J. Mol. Cell. Biol. 15:2500-2508(1995) [PubMed: 7537849] [Abstract] Cited for: INTERACTION WITH INSR.
[9]	"LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation." Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E. Cell 92:83-92(1998) [PubMed: 9489702] [Abstract] Cited for: INTERACTION WITH LAT.
[10]	"Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells." Fantin V.R., Sparling J.D., Slot J.W., Keller S.R., Lienhard G.E., Lavan B.E. J. Biol. Chem. 273:10726-10732(1998) [PubMed: 9553137] [Abstract] Cited for: INTERACTION WITH IRS4.
[11]	"T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane." Bruyns E., Marie-Cardine A., Kirchgessner H., Sagolla K., Shevchenko A., Mann M., Autschbach F., Bensussan A., Meuer S., Schraven B. J. Exp. Med. 188:561-575(1998) [PubMed: 9687533] [Abstract] Cited for: INTERACTION WITH TRAT1.
[12]	"KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties." Chang C., Dietrich J., Harpur A.G., Lindquist J.A., Haude A., Loke Y.W., King A., Colonna M., Trowsdale J., Wilson M.J. J. Immunol. 163:4651-4654(1999) [PubMed: 10528161] [Abstract] Cited for: INTERACTION WITH HCST.
[13]	"cbl-b inhibits epidermal growth factor receptor signaling." Ettenberg S.A., Keane M.M., Nau M.M., Frankel M., Wang L.-M., Pierce J.H., Lipkowitz S. Oncogene 18:1855-1866(1999) [PubMed: 10086340] [Abstract] Cited for: INTERACTION WITH CBLB.
[14]	"Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells." Fang D., Wang H.-Y., Fang N., Altman Y., Elly C., Liu Y.-C. J. Biol. Chem. 276:4872-4878(2001) [PubMed: 11087752] [Abstract] Cited for: INTERACTION WITH CBLB, UBIQUITINATION.
[15]	"Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells." Fang D., Liu Y.-C. Nat. Immunol. 2:870-875(2001) [PubMed: 11526404] [Abstract] Cited for: INTERACTION WITH CD3Z AND CD28, UBIQUITINATION.
[16]	"Insulin receptor substrate 4 associates with the protein IRAS." Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E. J. Biol. Chem. 277:19439-19447(2002) [PubMed: 11912194] [Abstract] Cited for: INTERACTION WITH NISCH.
[17]	"Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling." Zhu M., Janssen E., Leung K., Zhang W. J. Biol. Chem. 277:46151-46158(2002) [PubMed: 12359715] [Abstract] Cited for: INTERACTION WITH LAX1.
[18]	"Interaction between Nef and phosphatidylinositol-3-kinase leads to activation of p21-activated kinase and increased production of HIV." Linnemann T., Zheng Y.-H., Mandic R., Peterlin B.M. Virology 294:246-255(2002) [PubMed: 12009866] [Abstract] Cited for: INTERACTION WITH HIV-1 NEF.
[19]	"Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase." He Y., Nakao H., Tan S.-L., Polyak S.J., Neddermann P., Vijaysri S., Jacobs B.L., Katze M.G. J. Virol. 76:9207-9217(2002) [PubMed: 12186904] [Abstract] Cited for: INTERACTION WITH HCV NS5A.
[20]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-607, MASS SPECTROMETRY. Tissue: Epithelium.
[21]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-452; TYR-467; TYR-556 AND TYR-580, MASS SPECTROMETRY. Tissue: Lung.
[22]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[23]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-452; TYR-467; TYR-508; TYR-556; TYR-580 AND TYR-679, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[24]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-152; SER-154; TYR-452 AND TYR-580, MASS SPECTROMETRY.
[25]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-530, MASS SPECTROMETRY.
[26]	"Crystal structure of P13K SH3 domain at 2.0-A resolution." Liang J., Chen J.K., Schreiber S.L., Clardy J. J. Mol. Biol. 257:632-643(1996) [PubMed: 8648629] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-85.
[27]	"Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes." Nolte R.T., Eck M.J., Schlessinger J., Shoelson S.E., Harrison S.C. Nat. Struct. Biol. 3:364-373(1996) [PubMed: 8599763] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 324-434.
[28]	"Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit." Musacchio A., Cantley L.C., Harrison S.C. Proc. Natl. Acad. Sci. U.S.A. 93:14373-14378(1996) [PubMed: 8962058] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 115-298.
[29]	"NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex." Pauptit R.A., Dennis C.A., Derbyshire D.J., Breeze A.L., Weston S.A., Rowsell S., Murshudov G.N. Acta Crystallogr. D 57:1397-1404(2001) [PubMed: 11567151] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 617-724 IN COMPLEX WITH PDGFRB.
[30]	"Structure of the PI3K SH3 domain and analysis of the SH3 family." Koyama S., Yu H., Dalgarno D.C., Shin T.B., Zydowsky L.D., Schreiber S.L. Cell 72:945-952(1993) [PubMed: 7681364] [Abstract] Cited for: STRUCTURE BY NMR OF 1-79.
[31]	"Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase." Renzoni D.A., Pugh D.J., Siligardi G., Das P., Morton C.J., Rossi C., Waterfield M.D., Campbell I.D., Ladbury J.E. Biochemistry 35:15646-15653(1996) [PubMed: 8961927] [Abstract] Cited for: STRUCTURE BY NMR OF 91-104.
[32]	"Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase." Breeze A.L., Kara B.V., Barratt D.G., Anderson M., Smith J.C., Luke R.W., Best J.R., Cartlidge S.A. EMBO J. 15:3579-3589(1996) [PubMed: 8670861] [Abstract] Cited for: STRUCTURE BY NMR OF 617-724.
[33]	"Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index." Hansen T., Andersen C.B., Echwald S.M., Urhammer S.A., Clausen J.O., Vestergaard H., Owens D., Hansen L., Pedersen O. Diabetes 46:494-501(1997) [PubMed: 9032108] [Abstract] Cited for: VARIANT ILE-326.
[34]	"Natural variants of human p85 alpha phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity." Baynes K.C.R., Beeton C.A., Panayotou G., Stein R., Soos M., Hansen T., Simpson H., O'Rahilly S., Shepherd P.R., Whitehead J.P. Diabetologia 43:321-331(2000) [PubMed: 10768093] [Abstract] Cited for: VARIANT SEVERE INSULIN RESISTANCE GLN-409, VARIANT ILE-326.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M61906 mRNA. No translation available.
U49349 mRNA. Translation: AAB04140.1.
AF279367 mRNA. Translation: AAO15359.1.
AK223613 mRNA. Translation: BAD97333.1.
BC030815 mRNA. Translation: AAH30815.1.
BC094795 mRNA. Translation: AAH94795.1.

IPI

IPI00021448.
IPI00295788.
IPI00333040.
IPI00807573.

PIR

A38748.

RefSeq

NP_852556.2.
NP_852664.1.
NP_852665.1.

UniGene

Hs.132225
Hs.604502

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A0N	NMR	-	A	91-104	[»]
1AZG	NMR	-	A	91-104	[»]
1H9O	X-ray	1.79	A	617-724	[»]
1PBW	X-ray	2.00	A/B	105-319	[»]
1PHT	X-ray	2.00	A	1-85	[»]
1PIC	NMR	-	A	617-724	[»]
1PKS	NMR	-	A	1-79	[»]
1PKT	NMR	-	A	1-79	[»]
2IUG	X-ray	1.89	A	321-440	[»]
2IUH	X-ray	2.00	A	321-440	[»]
2IUI	X-ray	2.40	A/B	321-440	[»]
2RD0	X-ray	3.05	B	322-600	[»]
2V1Y	X-ray	2.40	B	431-600	[»]
3HHM	X-ray	2.80	B	322-694	[»]
3HIZ	X-ray	3.30	B	322-694	[»]

SMR

P27986. Positions 89-295.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-119N.

IntAct

P27986. 102 interactions.

STRING

P27986.

PTM databases

PhosphoSite

P27986.

Proteomic databases

PRIDE

P27986.

Genome annotation databases

Ensembl

ENST00000274335; ENSP00000274335; ENSG00000145675; Homo sapiens. [Genome view]

GeneID

5295.

KEGG

hsa:5295.

UCSC

uc003jva.1. human.
uc003jvc.1. human.
uc003jvd.1. human.

Organism-specific databases

CTD

5295.

GeneCards

GC05P067558.

HGNC

HGNC:8979. PIK3R1.

HPA

CAB004268.
HPA001216.

MIM

171833. gene.

PharmGKB

PA33312.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13282.

HOVERGEN

P27986.

OMA

DLEMIDV.

OrthoDB

EOG9HDWCT.

PhylomeDB

P27986.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000145675-MONOMER.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
arf6cyclingpathway. Arf6 signaling events.
nfkappabatypicalpathway. Atypical NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
pi3kcipathway. Class I PI3K signaling events.
epha2_fwdpathway. EPHA2 forward signaling.
ephbfwdpathway. EPHB forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
epopathway. EPO signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
ifngpathway. IFN-gamma pathway.
igf1_pathway. IGF1 pathway.
il1pathway. IL1-mediated signaling events.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il2_stat5pathway. IL2 signaling events mediated by STAT5.
il2_1pathway. IL2-mediated signaling events.
il23pathway. IL23-mediated signaling events.
il4_2pathway. IL4-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
insulin_pathway. Insulin Pathway.
avb3_integrin_pathway. Integrins in angiogenesis.
lysophospholipid_pathway. LPA receptor mediated events.
mtor_4pathway. mTOR signaling pathway.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
avb3_opn_pathway. Osteopontin-mediated events.
p75ntrpathway. p75(NTR)-mediated signaling.
a4b1_paxdep_pathway. Paxillin-dependent events mediated by a4b1.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
pdgfrapathway. PDGFR-alpha signaling pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
reelinpathway. Reelin signaling pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
ret_pathway. Signaling events regulated by Ret tyrosine kinase.
trail_pathway. TRAIL signaling pathway.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
vegfr1_pathway. VEGFR1 specific signals.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_11061. Signalling by NGF.
REACT_14797. Signaling by GPCR.
REACT_16888. Signaling by PDGF.
REACT_498. Signaling by Insulin receptor.
REACT_604. Hemostasis.
REACT_6900. Signaling in Immune system.
REACT_9417. Signaling by EGFR.

Gene expression databases

ArrayExpress

P27986.

Bgee

P27986.

CleanEx

HS_PIK3R1.

Genevestigator

P27986.

GermOnline

ENSG00000145675. Homo sapiens.

Family and domain databases

InterPro

IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP.
IPR000980. SH2.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Gene3D

G3DSA:1.10.555.10. RhoGAP. 1 hit.

PANTHER

PTHR10155. PI3kinase_P85. 1 hit.

Pfam

PF00620. RhoGAP. 1 hit.
PF00017. SH2. 2 hits.
PF07653. SH3_2. 1 hit.
[Graphical view]

PRINTS

PR00678. PI3KINASEP85.
PR00401. SH2DOMAIN.

SMART

SM00324. RhoGAP. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]

PROSITE

PS50238. RHOGAP. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01064. Isoproterenol.

NextBio

20462.

SOURCE

Search...

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Entry information

Entry name

P85A_HUMAN

Accession

Primary (citable) accession number: P27986
Secondary accession number(s): Q15747

Q8N1C5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	November 28, 2006
Last modified:	February 9, 2010
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents