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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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). Interacts with NYAP1, NYAP2 and MYO16. 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
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 insulin receptor signaling pathway Traceable author statement. Source: Reactome leukocyte migration Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome phosphatidylinositol-3-phosphate biosynthetic process Inferred from sequence or structural similarity. Source: GOC phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome regulation of phosphatidylinositol 3-kinase activity Inferred from electronic annotation. Source: GOC regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome phosphatidylinositol 3-kinase complex Inferred from electronic annotation. Source: InterPro
Molecular_function	phosphatidylinositol 3-kinase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GRB2	P62993	4	EBI-346930,EBI-401755
PIK3CB	P42338	3	EBI-346930,EBI-2609540

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

464

1

Phosphotyrosine Ref.12

Modified residue

605

1

Phosphotyrosine Ref.11

Natural variations

Natural variant

234

1

S → R. Ref.1 Ref.2 Ref.4
Corresponds to variant rs2241088 [ dbSNP | Ensembl ].

VAR_030679

Natural variant

313

1

S → P. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1011320 [ dbSNP | Ensembl ].

VAR_030680

Secondary structure

1

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728

Helix Strand Turn

Details...

Beta strand

5 – 11

7

Beta strand

30 – 34

5

Helix

35 – 40

6

Helix

47 – 49

3

Helix

51 – 54

4

Beta strand

56 – 61

6

Turn

62 – 64

3

Beta strand

67 – 71

5

Helix

72 – 74

3

Beta strand

75 – 81

7

Helix

114 – 117

4

Helix

126 – 138

13

Helix

144 – 146

3

Helix

162 – 164

3

Helix

167 – 180

14

Beta strand

181 – 183

3

Helix

188 – 199

12

Helix

206 – 209

4

Turn

211 – 213

3

Helix

216 – 235

20

Helix

239 – 255

17

Helix

279 – 293

15

Helix

439 – 512

74

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FLT4.
[8]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPRJ.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-605, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[12]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-464, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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] [Europe PMC] [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_005027.3.

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. 33 interactions.

MINT

MINT-1210047.

STRING

9606.ENSP00000222254.

PTM databases

PhosphoSite

O00459.

Proteomic databases

PaxDb

O00459.

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.

HGNC

HGNC:8980. PIK3R2.

MIM

603157. gene.

neXtProt

NX_O00459.

PharmGKB

PA33313.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG263689.

HOGENOM

HOG000008438.

HOVERGEN

HBG082100.

InParanoid

O00459.

KO

K02649.

OMA

SDVDQWD.

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_111217. Metabolism.
REACT_116125. Disease.
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

Gene3D

1.10.555.10. 1 hit.
3.30.505.10. 2 hits.

InterPro

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

PANTHER

PTHR10155. PTHR10155. 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

BindingDB

O00459.

ChEMBL

CHEMBL4437.

ChiTaRS

PIK3R2. human.

EvolutionaryTrace

O00459.

GenomeRNAi

5296.

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:	April 3, 2013
This is version 133 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.