O00459 (P85B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylinositol 3-kinase regulatory subunit beta
Short name=PI3-kinase regulatory subunit beta
Short name=PI3K regulatory subunit beta
Short name=PtdIns-3-kinase regulatory subunit beta

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

Gene names

Name:

PIK3R2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	728 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane.
Subunit structure	Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with AXL. Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated). Ref.5 Ref.6 Ref.7
Post-translational modification	Phosphorylated in response to signaling from activated receptor-type protein kinases. Dephosphorylated by PTPRJ. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Sequence similarities	Belongs to the PI3K p85 subunit family. Contains 1 Rho-GAP domain. Contains 2 SH2 domains. Contains 1 SH3 domain.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat SH2 domain SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell costimulation Traceable author statement. Source: Reactome T cell receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome insulin receptor signaling pathway Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome negative regulation of anti-apoptosis Inferred from sequence or structural similarity. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular component	phosphatidylinositol 3-kinase complex Inferred from electronic annotation. Source: InterPro
Molecular function	phosphatidylinositol 3-kinase regulator activity Inferred from electronic annotation. Source: InterPro phosphatidylinositol-4,5-bisphosphate 3-kinase activity Traceable author statement. Source: Reactome protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	4	EBI-346930,EBI-401755

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 728

728

Phosphatidylinositol 3-kinase regulatory subunit beta

PRO_0000080763

Regions

Domain

4 – 80

77

SH3

Domain

109 – 295

187

Rho-GAP

Domain

330 – 425

96

SH2 1

Domain

622 – 716

95

SH2 2

Amino acid modifications

Modified residue

262

1

Phosphoserine Ref.14

Modified residue

263

1

Phosphoserine Ref.14

Modified residue

365

1

Phosphotyrosine Ref.10

Modified residue

464

1

Phosphotyrosine Ref.8 Ref.9 Ref.10 Ref.11 Ref.13

Modified residue

467

1

Phosphotyrosine Ref.10

Modified residue

605

1

Phosphotyrosine Ref.11 Ref.15

Natural variations

Natural variant

234

1

S → R. [dbSNP:rs2241088] Ref.1 Ref.2 Ref.4

VAR_030679

Natural variant

313

1

S → P. [dbSNP:rs1011320] Ref.1 Ref.2 Ref.4

VAR_030680

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

728

Helix Strand Turn

Details...

Turn

439 – 441

3

Helix

445 – 493

49

Helix

497 – 511

15

Helix

515 – 583

69

Helix

588 – 594

7

Sequences

	Sequence		Length	Mass (Da)
	O00459 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: ADAC3E4B61F3F44A	FASTA	728	81,545
	10 20 30 40 50 60 MAGPEGFQYR ALYPFRRERP EDLELLPGDV LVVSRAALQA LGVAEGGERC PQSVGWMPGL 70 80 90 100 110 120 NERTRQRGDF PGTYVEFLGP VALARPGPRP RGPRPLPARP RDGAPEPGLT LPDLPEQFSP 130 140 150 160 170 180 PDVAPPLLVK LVEAIERTGL DSESHYRPEL PAPRTDWSLS DVDQWDTAAL ADGIKSFLLA 190 200 210 220 230 240 LPAPLVTPEA SAEARRALRE AAGPVGPALE PPTLPLHRAL TLRFLLQHLG RVASRAPALG 250 260 270 280 290 300 PAVRALGATF GPLLLRAPPP PSSPPPGGAP DGSEPSPDFP ALLVEKLLQE HLEEQEVAPP 310 320 330 340 350 360 ALPPKPPKAK PASTVLANGG SPPSLQDAEW YWGDISREEV NEKLRDTPDG TFLVRDASSK 370 380 390 400 410 420 IQGEYTLTLR KGGNNKLIKV FHRDGHYGFS EPLTFCSVVD LINHYRHESL AQYNAKLDTR 430 440 450 460 470 480 LLYPVSKYQQ DQIVKEDSVE AVGAQLKVYH QQYQDKSREY DQLYEEYTRT SQELQMKRTA 490 500 510 520 530 540 IEAFNETIKI FEEQGQTQEK CSKEYLERFR REGNEKEMQR ILLNSERLKS RIAEIHESRT 550 560 570 580 590 600 KLEQQLRAQA SDNREIDKRM NSLKPDLMQL RKIRDQYLVW LTQKGARQKK INEWLGIKNE 610 620 630 640 650 660 TEDQYALMED EDDLPHHEER TWYVGKINRT QAEEMLSGKR DGTFLIRESS QRGCYACSVV 670 680 690 700 710 720 VDGDTKHCVI YRTATGFGFA EPYNLYGSLK ELVLHYQHAS LVQHNDALTV TLAHPVRAPG PGPPPAAR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta." Volinia S., Patracchini P., Otsu M., Hiles I., Gout I., Calzolari E., Bernardi F., Rooke L., Waterfield M.D. Oncogene 7:789-793(1992) [PubMed: 1314371] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-234 AND PRO-313.
[2]	"An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta subunit and HUMORF8, a putative deubiquitinating enzyme." Janssen J.W.G., Schleithhoff L., Bartram C.R., Schulz A.S. Oncogene 16:1767-1772(1998) [PubMed: 9582025] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-234 AND PRO-313.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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], VARIANTS ARG-234 AND PRO-313. Tissue: Brain and Placenta.
[5]	"Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site." Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W. Oncogene 14:2619-2631(1997) [PubMed: 9178760] [Abstract] Cited for: INTERACTION WITH AXL.
[6]	"Tyrosine 1213 of Flt-1 is a major binding site of Nck and SHP-2." Igarashi K., Isohara T., Kato T., Shigeta K., Yamano T., Uno I. Biochem. Biophys. Res. Commun. 246:95-99(1998) [PubMed: 9600074] [Abstract] Cited for: INTERACTION WITH FLT1.
[7]	"Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress." Wang J.F., Zhang X., Groopman J.E. J. Biol. Chem. 279:27088-27097(2004) [PubMed: 15102829] [Abstract] Cited for: INTERACTION WITH FLT4.
[8]	"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-464, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[9]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-464, MASS SPECTROMETRY.
[10]	"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. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-365; TYR-464 AND TYR-467, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[11]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-464 AND TYR-605, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase." Tsuboi N., Utsunomiya T., Roberts R.L., Ito H., Takahashi K., Noda M., Takahashi T. Biochem. J. 413:193-200(2008) [PubMed: 18348712] [Abstract] Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRJ.
[13]	"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-464, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[14]	"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 SER-262 AND SER-263, MASS SPECTROMETRY.
[15]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-605, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X80907 mRNA. Translation: CAA56868.1.
AC007192 Genomic DNA. Translation: AAD22671.1.
BC070082 mRNA. Translation: AAH70082.1.
BC090249 mRNA. Translation: AAH90249.1.

IPI

IPI00011736.

PIR

H59435.

RefSeq

NP_005018.1. NM_005027.2.

UniGene

Hs.371344.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KT1	NMR	-	A	1-80	[»]
2XS6	X-ray	2.09	A	108-298	[»]
3MTT	X-ray	3.30	A	433-610	[»]
3O5Z	X-ray	2.01	A/B	1-85	[»]

ProteinModelPortal

O00459.

SMR

O00459. Positions 3-84, 109-294, 324-720.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00459. 21 interactions.

MINT

MINT-1210047.

STRING

O00459.

PTM databases

PhosphoSite

O00459.

Proteomic databases

PRIDE

O00459.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222254; ENSP00000222254; ENSG00000105647.

GeneID

5296.

KEGG

hsa:5296.

UCSC

uc002nia.1. human.

Organism-specific databases

CTD

5296.

GeneCards

GC19P018263.

H-InvDB

HIX0115622.

HGNC

HGNC:8980. PIK3R2.

MIM

603157. gene.

neXtProt

NX_O00459.

PharmGKB

PA33313.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15816.

HOGENOM

HBG506175.

HOVERGEN

HBG082100.

InParanoid

O00459.

OMA

DEDDLPH.

OrthoDB

EOG49GKG4.

PhylomeDB

O00459.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000105647-MONOMER.

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
trail_pathway. TRAIL signaling pathway.

Reactome

REACT_111102. Signal Transduction.
REACT_111155. Cell-Cell communication.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O00459.

Bgee

O00459.

CleanEx

HS_PIK3R2.

Genevestigator

O00459.

GermOnline

ENSG00000105647. Homo sapiens.

Family and domain databases

InterPro

IPR001720. PI3kinase_P85.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]

Gene3D

G3DSA:1.10.555.10. RhoGAP. 1 hit.
G3DSA:3.30.505.10. SH2. 2 hits.

KO

K02649.

PANTHER

PTHR10155. PI3kinase_P85. 1 hit.

Pfam

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

PRINTS

PR00678. PI3KINASEP85.
PR00401. SH2DOMAIN.

SMART

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

SUPFAM

SSF48350. Rho_GAP. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

NextBio

20470.

SOURCE

Search...

Entry information

Entry name

P85B_HUMAN

Accession

Primary (citable) accession number: O00459
Secondary accession number(s): Q5EAT5, Q9UPH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	January 11, 2011
Last modified:	January 25, 2012
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.