P42338 (PK3CB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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
Synonyms:	PIK3C1

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	1070 AA.
Sequence status	Complete.
Protein existence	Evidence 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.6 Ref.7 Ref.9 Ref.11
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. Part of a complex with PIK3R1 and PTEN. Binding to PTEN may antagonize the lipid kinase activity under normal growth conditions. Part of a complex involved in autophagosome formation composed of PIK3C3 and PIK3R4 By similarity. Interacts with BECN1, ATG14 and RAB5A By similarity. Ref.8 Ref.11
Subcellular location	Cytoplasm. Nucleus. Note: Interaction with PIK3R2 is required for nuclear localization and export. Ref.11
Tissue specificity	Expressed ubiquitously.
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.
Post-translational modification	Phosphorylation at Ser-1070 down-regulates lipid kinase activity.
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 process	Autophagy Cell adhesion Endocytosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement Ref.12. Source: UniProtKB T cell receptor signaling pathway Traceable author statement. Source: Reactome activation of MAPK activity Traceable author statement PubMed 10570282. Source: ProtInc autophagy Inferred from electronic annotation. Source: UniProtKB-KW cellular calcium ion homeostasis Inferred from electronic annotation. Source: Compara chemotaxis Traceable author statement PubMed 10570282. Source: ProtInc embryonic cleavage Inferred from electronic annotation. Source: Compara endocytosis Inferred from electronic annotation. Source: UniProtKB-KW homophilic cell adhesion Inferred from electronic annotation. Source: Compara 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-kinase cascade Traceable author statement Ref.12. Source: UniProtKB platelet aggregation Traceable author statement Ref.13. Source: UniProtKB positive regulation of autophagy Traceable author statement Ref.12. Source: UniProtKB regulation of cell-matrix adhesion Inferred from electronic annotation. Source: Compara regulation of clathrin-mediated endocytosis Traceable author statement Ref.12. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	nucleus 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_function	1-phosphatidylinositol-3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome 1-phosphatidylinositol-4-phosphate 3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol-4,5-bisphosphate 3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PIK3R2	O00459	3	EBI-2609540,EBI-346930

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1070	1070	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform		PRO_0000088787
Regions
	Domain	26 – 115	90	PI3K-ABD
	Domain	194 – 285	92	PI3K-RBD
	Domain	327 – 496	170	C2 PI3K-type
	Domain	524 – 701	178	PIK helical
	Domain	800 – 1067	268	PI3K/PI4K
	Motif	410 – 418	9	Nuclear localization signal Ref.11
Amino acid modifications
	Modified residue	1070	1	Phosphoserine; by autocatalysis Ref.5
Natural variations
	Natural variant	672	1	Q → H. Corresponds to variant rs2230462 [ dbSNP | Ensembl ].		VAR_050530
Experimental info
	Mutagenesis	342	1	K → N: Enhanced inhibition by PIK3R1 leading to reduced lipid kinase activity and reduced oncogenicity. Does not modify regulation by GPCRs. Ref.9
	Mutagenesis	805	1	K → R: Loss of lipid kinase activity. May not affect insulin signaling and cell proliferation. Partially affects oncogene-induced trasformation. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	P42338 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 81135FE93452C00E	FASTA	1,070	122,762
	10 20 30 40 50 60 MCFSFIMPPA MADILDIWAV DSQIASDGSI PVDFLLPTGI YIQLEVPREA TISYIKQMLW 70 80 90 100 110 120 KQVHNYPMFN LLMDIDSYMF ACVNQTAVYE ELEDETRRLC DVRPFLPVLK LVTRSCDPGE 130 140 150 160 170 180 KLDSKIGVLI GKGLHEFDSL KDPEVNEFRR KMRKFSEEKI LSLVGLSWMD WLKQTYPPEH 190 200 210 220 230 240 EPSIPENLED KLYGGKLIVA VHFENCQDVF SFQVSPNMNP IKVNELAIQK RLTIHGKEDE 250 260 270 280 290 300 VSPYDYVLQV SGRVEYVFGD HPLIQFQYIR NCVMNRALPH FILVECCKIK KMYEQEMIAI 310 320 330 340 350 360 EAAINRNSSN LPLPLPPKKT RIISHVWENN NPFQIVLVKG NKLNTEETVK VHVRAGLFHG 370 380 390 400 410 420 TELLCKTIVS SEVSGKNDHI WNEPLEFDIN ICDLPRMARL CFAVYAVLDK VKTKKSTKTI 430 440 450 460 470 480 NPSKYQTIRK AGKVHYPVAW VNTMVFDFKG QLRTGDIILH SWSSFPDELE EMLNPMGTVQ 490 500 510 520 530 540 TNPYTENATA LHVKFPENKK QPYYYPPFDK IIEKAAEIAS SDSANVSSRG GKKFLPVLKE 550 560 570 580 590 600 ILDRDPLSQL CENEMDLIWT LRQDCREIFP QSLPKLLLSI KWNKLEDVAQ LQALLQIWPK 610 620 630 640 650 660 LPPREALELL DFNYPDQYVR EYAVGCLRQM SDEELSQYLL QLVQVLKYEP FLDCALSRFL 670 680 690 700 710 720 LERALGNRRI GQFLFWHLRS EVHIPAVSVQ FGVILEAYCR GSVGHMKVLS KQVEALNKLK 730 740 750 760 770 780 TLNSLIKLNA VKLNRAKGKE AMHTCLKQSA YREALSDLQS PLNPCVILSE LYVEKCKYMD 790 800 810 820 830 840 SKMKPLWLVY NNKVFGEDSV GVIFKNGDDL RQDMLTLQML RLMDLLWKEA GLDLRMLPYG 850 860 870 880 890 900 CLATGDRSGL IEVVSTSETI ADIQLNSSNV AAAAAFNKDA LLNWLKEYNS GDDLDRAIEE 910 920 930 940 950 960 FTLSCAGYCV ASYVLGIGDR HSDNIMVKKT GQLFHIDFGH ILGNFKSKFG IKRERVPFIL 970 980 990 1000 1010 1020 TYDFIHVIQQ GKTGNTEKFG RFRQCCEDAY LILRRHGNLF ITLFALMLTA GLPELTSVKD 1030 1040 1050 1060 1070 IQYLKDSLAL GKSEEEALKQ FKQKFDEALR ESWTTKVNWM AHTVRKDYRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85." Hu P., Mondino A., Skolnik E.Y., Schlessinger J. Mol. Cell. Biol. 13:7677-7688(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Gene encoding the catalytic subunit p110beta of human phosphatidylinositol 3-kinase: cloning, genomic structure, and screening for variants in patients with type 2 diabetes." Kossila M., Sinkovic M., Karkkainen P., Laukkanen M.O., Miettinen R., Rissanen J., Kekalainen P., Kuusisto J., Yla-Herttuala S., Laakso M. Diabetes 49:1740-1743(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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].
[5]	"Identification and characterization of the autophosphorylation sites of phosphoinositide 3-kinase isoforms beta and gamma." Czupalla C., Culo M., Muller E.C., Brock C., Reusch H.P., Spicher K., Krause E., Nurnberg B. J. Biol. Chem. 278:11536-11545(2003) [PubMed] [Europe PMC] [Abstract] Cited for: AUTOPHOSPHORYLATION AT SER-1070.
[6]	"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, MUTAGENESIS OF LYS-805.
[7]	"PTEN-deficient cancers depend on PIK3CB." Wee S., Wiederschain D., Maira S.-M., Loo A., Miller C., deBeaumont R., Stegmeier F., Yao Y.-M., Lengauer C. Proc. Natl. Acad. Sci. U.S.A. 105:13057-13062(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ONCOGENIC SIGNALING.
[8]	"p85 Associates with unphosphorylated PTEN and the PTEN-associated complex." Rabinovsky R., Pochanard P., McNear C., Brachmann S.M., Duke-Cohan J.S., Garraway L.A., Sellers W.R. Mol. Cell. Biol. 29:5377-5388(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH PIK3R1 AND PTEN.
[9]	"A biochemical mechanism for the oncogenic potential of the p110beta catalytic subunit of phosphoinositide 3-kinase." Dbouk H.A., Pang H., Fiser A., Backer J.M. Proc. Natl. Acad. Sci. U.S.A. 107:19897-19902(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-342.
[10]	"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].
[11]	"Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival." Kumar A., Redondo-Munoz J., Perez-Garcia V., Cortes I., Chagoyen M., Carrera A.C. Mol. Cell. Biol. 31:2122-2133(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PIK3R2, SUBCELLULAR LOCATION, MOTIF NUCLEAR LOCALIZATION SIGNAL.
[12]	"A beta version of life: p110beta takes center stage." Dbouk H.A., Backer J.M. Oncotarget 1:729-733(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[13]	"Regulation and roles of PI3Kbeta, a major actor in platelet signaling and functions." Gratacap M.-P., Guillermet-Guibert J., Martin V., Chicanne G., Tronchere H., Gaits-Iacovoni F., Payrastre B. Adv. Enzyme Regul. 51:106-116(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	S67334 mRNA. Translation: AAB29081.1. AJ297549 , AJ297550, AJ297551, AJ297552, AJ297553, AJ297554, AJ297555, AJ297556, AJ297557, AJ297558, AJ297559, AJ297560 Genomic DNA. Translation: CAC21449.1. CH471052 Genomic DNA. Translation: EAW79053.1. CH471052 Genomic DNA. Translation: EAW79055.1. BC114432 mRNA. Translation: AAI14433.1.
IPI	IPI00031388.
PIR	A54600.
RefSeq	NP_006210.1. NM_006219.2.
UniGene	Hs.239818.
3D structure databases
ProteinModelPortal	P42338.
SMR	P42338. Positions 533-1069.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-44775N.
IntAct	P42338. 8 interactions.
STRING	9606.ENSP00000289153.
PTM databases
PhosphoSite	P42338.
Polymorphism databases
DMDM	1171955.
Proteomic databases
PaxDb	P42338.
PeptideAtlas	P42338.
PRIDE	P42338.
Protocols and materials databases
DNASU	5291.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000289153; ENSP00000289153; ENSG00000051382. ENST00000477593; ENSP00000418143; ENSG00000051382.
GeneID	5291.
KEGG	hsa:5291.
UCSC	uc011bmq.2. human.
Organism-specific databases
CTD	5291.
GeneCards	GC03M138372.
HGNC	HGNC:8976. PIK3CB.
HPA	CAB031938.
MIM	602925. gene.
neXtProt	NX_P42338.
PharmGKB	PA33309.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5032.
HOGENOM	HOG000252911.
HOVERGEN	HBG052721.
InParanoid	P42338.
KO	K00922.
OMA	AMHTCLK.
OrthoDB	EOG4ZPDTJ.
PhylomeDB	P42338.
Enzyme and pathway databases
BioCyc	MetaCyc:HS00644-MONOMER.
Pathway_Interaction_DB	pi3kcipathway. Class I PI3K signaling events. lysophospholipid_pathway. LPA receptor mediated 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.
UniPathway	UPA00220.
Gene expression databases
ArrayExpress	P42338.
Bgee	P42338.
CleanEx	HS_PIK3CB.
Genevestigator	P42338.
GermOnline	ENSG00000051382. Homo sapiens.
Family and domain databases
Gene3D	1.10.1070.11. 1 hit. 1.25.40.70. 1 hit.
InterPro	IPR016024. ARM-type_fold. IPR008973. C2_Ca/lipid-bd_dom_CaLB. 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. [Graphical view]
PANTHER	PTHR10048. PTHR10048. 1 hit.
Pfam	PF00454. 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]
SMART	SM00142. PI3K_C2. 1 hit. SM00143. PI3K_p85B. 1 hit. SM00144. PI3K_rbd. 1 hit. SM00145. PI3Ka. 1 hit. SM00146. PI3Kc. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit. SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS00915. 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]
ProtoNet	Search...
Other
BindingDB	P42338.
ChEMBL	CHEMBL3145.
GenomeRNAi	5291.
NextBio	20446.
SOURCE	Search...

Entry information

Entry name

PK3CB_HUMAN

Accession

Primary (citable) accession number: P42338
Secondary accession number(s): D3DNF0, Q24JU2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 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.