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Q8BTI9 (PK3CB_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform

Short name=PI3-kinase subunit beta
Short name=PI3K-beta
Short name=PI3Kbeta
Short name=PtdIns-3-kinase subunit beta
EC=2.7.1.153
Alternative name(s):
Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit beta
Short name=PtdIns-3-kinase subunit p110-beta
Short name=p110beta
Gene names
Name:Pik3cb
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1064 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8

Catalytic activity

ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.

Pathway

Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.

Subunit structure

Heterodimer of a catalytic subunit PIK3CB and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interaction with PIK3R2 is required for nuclear localization and nuclear export By similarity. Part of a complex with PIK3R1 and PTEN By similarity. Binding to PTEN may antagonize the lipid kinase activity under normal growth conditions By similarity. Part of a complex involved in autophagosome formation composed of PIK3C3 and PIK3R4. Interacts with BECN1, ATG14 and RAB5A. Ref.8

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: Interaction with PIK3R2 is required for nuclear localization and export.

Domain

The inhibitory interactions with PIK3R1 are mediated by the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1; the C2 PI3K-type domain, the PI3K helical domain, and the PI3K/PI4K kinase domain with the nSH2 (N-terminal SH2) region of PIK3R1; and the PI3K/PI4K kinase domain with the cSH2 (C-terminal SH2) region of PIK3R1. The inhibitory interaction between the PI3K-ABD domain and the C2 PI3K-type domain with the iSH2 (inter-SH2) region of PIK3R1 is weak. The nuclear localization signal (NLS) is required for its function in cell survival By similarity. Ref.9

Post-translational modification

Phosphorylation at Ser-1064 down-regulates lipid kinase activity By similarity.

Disruption phenotype

Mice have defects in autophagosome formation. Have normal bleeding time but are resistant to thrombosis after arterial injury. Mice fail to induce tumors in a model of prostate tumor formation induced by Pten loss. Ref.3 Ref.5 Ref.6 Ref.8

Sequence similarities

Belongs to the PI3/PI4-kinase family.

Contains 1 C2 PI3K-type domain.

Contains 1 PI3K-ABD domain.

Contains 1 PI3K-RBD domain.

Contains 1 PI3K/PI4K domain.

Contains 1 PIK helical domain.

Ontologies

Keywords
   Biological processAutophagy
Cell adhesion
Endocytosis
   Cellular componentCytoplasm
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processautophagy

Inferred from electronic annotation. Source: UniProtKB-KW

cellular calcium ion homeostasis

Inferred from mutant phenotype PubMed 15834429. Source: MGI

embryonic cleavage

Inferred from mutant phenotype PubMed 11919689. Source: MGI

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

homophilic cell adhesion

Inferred from mutant phenotype PubMed 15834429. Source: MGI

phosphatidylinositol-3-phosphate biosynthetic process

Inferred from mutant phenotype PubMed 15834429PubMed 16625210. Source: GOC

phosphatidylinositol-mediated signaling

Inferred from electronic annotation. Source: InterPro

platelet activation

Inferred from mutant phenotype PubMed 15834429. Source: MGI

regulation of cell-matrix adhesion

Inferred from mutant phenotype PubMed 15834429. Source: MGI

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

phosphatidylinositol 3-kinase complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_function1-phosphatidylinositol-3-kinase activity

Inferred from mutant phenotype PubMed 15834429PubMed 16625210. Source: MGI

1-phosphatidylinositol-4-phosphate 3-kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

insulin receptor substrate binding

Inferred from physical interaction PubMed 16625210. Source: MGI

phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 15102471. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Pik3r1P264504EBI-644672,EBI-641764

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10641064Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
PRO_0000088788

Regions

Domain20 – 10990PI3K-ABD
Domain188 – 27992PI3K-RBD
Domain323 – 490168C2 PI3K-type
Domain518 – 695178PIK helical
Domain794 – 1061268PI3K/PI4K
Motif404 – 4129Nuclear localization signal (NLS) By similarity

Amino acid modifications

Modified residue10641Phosphoserine; by autocatalysis By similarity

Experimental info

Sequence conflict1231L → R in BAC41102. Ref.1

Secondary structure

..................................................................................................................................................................... 1064
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8BTI9 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: EBDF0266BF0A2032

FASTA1,064121,711
        10         20         30         40         50         60 
MPPAMADNLD IWAVDSQIAS DGAISVDFLL PTGIYIQLEV PREATISYIK QMLWKQVHNY 

        70         80         90        100        110        120 
PMFNLLMDID SYMFACVNQT AVYEELEDET RRLCDVRPFL PVLKLVTRSC DPAEKLDSKI 

       130        140        150        160        170        180 
GVLIGKGLHE FDALKDPEVN EFRRKMRKFS EAKIQSLVGL SWIDWLKHTY PPEHEPSVLE 

       190        200        210        220        230        240 
NLEDKLYGGK LVVAVHFENS QDVFSFQVSP NLNPIKINEL AIQKRLTIRG KEDEASPCDY 

       250        260        270        280        290        300 
VLQVSGRVEY VFGDHPLIQF QYIRNCVMNR TLPHFILVEC CKIKKMYEQE MIAIEAAINR 

       310        320        330        340        350        360 
NSSNLPLPLP PKKTRVISHI WDNNNPFQIT LVKGNKLNTE ETVKVHVRAG LFHGTELLCK 

       370        380        390        400        410        420 
TVVSSEISGK NDHIWNEQLE FDINICDLPR MARLCFAVYA VLDKVKTKKS TKTINPSKYQ 

       430        440        450        460        470        480 
TIRKAGKVHY PVAWVNTMVF DFKGQLRSGD VILHSWSSFP DELEEMLNPM GTVQTNPYAE 

       490        500        510        520        530        540 
NATALHITFP ENKKQPCYYP PFDKIIEKAA ELASGDSANV SSRGGKKFLA VLKEILDRDP 

       550        560        570        580        590        600 
LSQLCENEMD LIWTLRQDCR ENFPQSLPKL LLSIKWNKLE DVAQLQALLQ IWPKLPPREA 

       610        620        630        640        650        660 
LELLDFNYPD QYVREYAVGC LRQMSDEELS QYLLQLVQVL KYEPFLDCAL SRFLLERALD 

       670        680        690        700        710        720 
NRRIGQFLFW HLRSEVHTPA VSVQFGVILE AYCRGSVGHM KVLSKQVEAL NKLKTLNSLI 

       730        740        750        760        770        780 
KLNAVKLSRA KGKEAMHTCL KQSAYREALS DLQSPLNPCV ILSELYVEKC KYMDSKMKPL 

       790        800        810        820        830        840 
WLVYSSRAFG EDSVGVIFKN GDDLRQDMLT LQMLRLMDLL WKEAGLDLRM LPYGCLATGD 

       850        860        870        880        890        900 
RSGLIEVVST SETIADIQLN SSNVAATAAF NKDALLNWLK EYNSGDDLDR AIEEFTLSCA 

       910        920        930        940        950        960 
GYCVASYVLG IGDRHSDNIM VKKTGQLFHI DFGHILGNFK SKFGIKRERV PFILTYDFIH 

       970        980        990       1000       1010       1020 
VIQQGKTGNT EKFGRFRQCC EDAYLILRRH GNLFITLFAL MLTAGLPELT SVKDIQYLKD 

      1030       1040       1050       1060 
SLALGKSEEE ALKQFKQKFD EALRESWTTK VNWMAHTVRK DYRS 

« Hide

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: NOD.
Tissue: Embryo.
[2]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis."
Jia S., Liu Z., Zhang S., Liu P., Zhang L., Lee S.H., Zhang J., Signoretti S., Loda M., Roberts T.M., Zhao J.J.
Nature 454:776-779(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]"The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma."
Guillermet-Guibert J., Bjorklof K., Salpekar A., Gonella C., Ramadani F., Bilancio A., Meek S., Smith A.J.H., Okkenhaug K., Vanhaesebroeck B.
Proc. Natl. Acad. Sci. U.S.A. 105:8292-8297(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Genetic evidence for a predominant role of PI3Kbeta catalytic activity in ITAM- and integrin-mediated signaling in platelets."
Canobbio I., Stefanini L., Cipolla L., Ciraolo E., Gruppi C., Balduini C., Hirsch E., Torti M.
Blood 114:2193-2196(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]"Deletion of the p110beta isoform of phosphoinositide 3-kinase in platelets reveals its central role in Akt activation and thrombus formation in vitro and in vivo."
Martin V., Guillermet-Guibert J., Chicanne G., Cabou C., Jandrot-Perrus M., Plantavid M., Vanhaesebroeck B., Payrastre B., Gratacap M.-P.
Blood 115:2008-2013(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[7]"Phosphoinositide 3-kinase p110 beta regulates integrin alpha IIb beta 3 avidity and the cellular transmission of contractile forces."
Schoenwaelder S.M., Ono A., Nesbitt W.S., Lim J., Jarman K., Jackson S.P.
J. Biol. Chem. 285:2886-2896(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy."
Dou Z., Chattopadhyay M., Pan J.-A., Guerriero J.L., Jiang Y.-P., Ballou L.M., Yue Z., Lin R.Z., Zong W.-X.
J. Cell Biol. 191:827-843(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH PIK3C3 AND PIK3R4, INTERACTION WITH BECN1; ATG14 AND RAB5A, DISRUPTION PHENOTYPE.
[9]"Structure of lipid kinase p110beta/p85beta elucidates an unusual SH2-domain-mediated inhibitory mechanism."
Zhang X., Vadas O., Perisic O., Anderson K.E., Clark J., Hawkins P.T., Stephens L.R., Williams R.L.
Mol. Cell 41:567-578(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) IN A COMPLEX WITH PIK3R2 AND GDC-0941, DOMAIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK090116 mRNA. Translation: BAC41102.1.
AK154106 mRNA. Translation: BAE32380.1.
CH466560 Genomic DNA. Translation: EDL20998.1.
CCDSCCDS23432.1.
RefSeqNP_083370.2. NM_029094.3.
UniGeneMm.213128.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2Y3AX-ray3.30A1-1064[»]
4BFRX-ray2.80A/B114-1064[»]
ProteinModelPortalQ8BTI9.
SMRQ8BTI9. Positions 117-1061.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid217006. 3 interactions.
DIPDIP-49395N.
IntActQ8BTI9. 6 interactions.

PTM databases

PhosphoSiteQ8BTI9.

Proteomic databases

MaxQBQ8BTI9.
PaxDbQ8BTI9.
PRIDEQ8BTI9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000035037; ENSMUSP00000035037; ENSMUSG00000032462.
GeneID74769.
KEGGmmu:74769.
UCSCuc009rdv.2. mouse.

Organism-specific databases

CTD5291.
MGIMGI:1922019. Pik3cb.

Phylogenomic databases

eggNOGCOG5032.
GeneTreeENSGT00620000087742.
HOGENOMHOG000252911.
HOVERGENHBG052721.
InParanoidQ3U4Q1.
KOK00922.
OMAAMHTCLK.
OrthoDBEOG70CR65.
TreeFamTF102031.

Enzyme and pathway databases

UniPathwayUPA00220.

Gene expression databases

ArrayExpressQ8BTI9.
BgeeQ8BTI9.
GenevestigatorQ8BTI9.

Family and domain databases

Gene3D1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 1 hit.
InterProIPR016024. ARM-type_fold.
IPR000008. C2_dom.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR003113. PI3K_adapt-bd_dom.
IPR002420. PI3K_C2_dom.
IPR000341. PI3K_Ras-bd_dom.
IPR015433. PI_Kinase.
IPR001263. PInositide-3_kin_accessory_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERPTHR10048. PTHR10048. 1 hit.
PfamPF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF02192. PI3K_p85B. 1 hit.
PF00794. PI3K_rbd. 1 hit.
PF00613. PI3Ka. 1 hit.
[Graphical view]
SMARTSM00142. PI3K_C2. 1 hit.
SM00143. PI3K_p85B. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
PS51544. PI3K_ABD. 1 hit.
PS51547. PI3K_C2. 1 hit.
PS51546. PI3K_RBD. 1 hit.
PS51545. PIK_HELICAL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio341596.
PROQ8BTI9.
SOURCESearch...

Entry information

Entry namePK3CB_MOUSE
AccessionPrimary (citable) accession number: Q8BTI9
Secondary accession number(s): Q3U4Q1
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot