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O00750 (P3C2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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-phosphate 3-kinase C2 domain-containing subunit beta

Short name=PI3K-C2-beta
Short name=PtdIns-3-kinase C2 subunit beta
EC=2.7.1.154
Alternative name(s):
C2-PI3K
Phosphoinositide 3-kinase-C2-beta
Gene names
Name:PIK3C2B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1634 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns. Does not phosphorylate PtdIns(4,5)P2. May be involved in EGF and PDGF signaling cascades. Ref.4

Catalytic activity

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

Cofactor

Calcium, magnesium, or manganese. Ref.4

Enzyme regulation

Activated by GRB2. Ref.5

Subunit structure

Part of a complex with ERBB2 and EGFR. Part of a complex with phosphorylated EGFR and GRB2. Interacts with phosphorylated EGFR and PDGFR, maybe indirectly. Interacts with GRB2 and SHC1. Ref.4 Ref.5

Subcellular location

Microsome. Cell membrane. Cytoplasmcytosol. Nucleus. Endoplasmic reticulum. Note: Found mostly in the microsome, but also in the plasma membrane and cytosol. Nuclear in testis. Ref.6

Tissue specificity

Expressed in columnar and transitional epithelia, mononuclear cells, and ganglion cells (at protein level). Widely expressed, with highest levels in thymus and placenta and lowest in peripheral blood, skeletal muscle and kidney. Ref.1 Ref.6

Sequence similarities

Belongs to the PI3/PI4-kinase family.

Contains 1 C2 domain.

Contains 1 C2 PI3K-type domain.

Contains 1 PI3K-RBD domain.

Contains 1 PI3K/PI4K domain.

Contains 1 PIK helical domain.

Contains 1 PX (phox homology) domain.

Caution

It is uncertain whether Met-1 or Met-26 is the initiator.

Sequence caution

The sequence CAA74194.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Endoplasmic reticulum
Membrane
Microsome
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processphosphatidylinositol biosynthetic process

Traceable author statement. Source: Reactome

phosphatidylinositol-3-phosphate biosynthetic process

Inferred from Biological aspect of Ancestor. Source: GOC

phosphatidylinositol-mediated signaling

Inferred from electronic annotation. Source: InterPro

phospholipid metabolic process

Traceable author statement. Source: Reactome

protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

endocytic vesicle

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

phosphatidylinositol 3-kinase complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_function1-phosphatidylinositol-3-kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

1-phosphatidylinositol-4-phosphate 3-kinase activity

Non-traceable author statement Ref.2. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

lipid kinase activity

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.4PubMed 17474147PubMed 21706016PubMed 22128329. Source: IntAct

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 16341634Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
PRO_0000088798

Regions

Domain375 – 46389PI3K-RBD
Domain635 – 786152C2 PI3K-type
Domain805 – 981177PIK helical
Domain1079 – 1343265PI3K/PI4K
Domain1365 – 1481117PX
Domain1517 – 160892C2
Region2 – 298297Interaction with GRB2
Compositional bias156 – 1627Pro-rich
Compositional bias169 – 1746Pro-rich

Experimental info

Sequence conflict61G → D in CAA72168. Ref.1
Sequence conflict631P → S in CAA74194. Ref.2
Sequence conflict751R → W in CAA74194. Ref.2
Sequence conflict991Q → L in CAA74194. Ref.2
Sequence conflict2461A → V in CAA72168. Ref.1
Sequence conflict2781K → E in CAA74194. Ref.2
Sequence conflict5671P → S in CAA74194. Ref.2
Sequence conflict664 – 6652EL → DM in CAA72168. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O00750 [UniParc].

Last modified August 30, 2005. Version 2.
Checksum: CA817BA77C12E833

FASTA1,634184,768
        10         20         30         40         50         60 
MSSTQGNGEH WKSLESVGIS RKELAMAEAL QMEYDALSRL RHDKEENRAK QNADPSLISW 

        70         80         90        100        110        120 
DEPGVDFYSK PAGRRTDLKL LRGLSGSDPT LNYNSLSPQE GPPNHSTSQG PQPGSDPWPK 

       130        140        150        160        170        180 
GSLSGDYLYI FDGSDGGVSS SPGPGDIEGS CKKLSPPPLP PRASIWDTPP LPPRKGSPSS 

       190        200        210        220        230        240 
SKISQPSDIN TFSLVEQLPG KLLEHRILEE EEVLGGGGQG RLLGSVDYDG INDAITRLNL 

       250        260        270        280        290        300 
KSTYDAEMLR DATRGWKEGR GPLDFSKDTS GKPVARSKTM PPQVPPRTYA SRYGNRKNAT 

       310        320        330        340        350        360 
PGKNRRISAA PVGSRPHTVA NGHELFEVSE ERDEEVAAFC HMLDILRSGS DIQDYFLTGY 

       370        380        390        400        410        420 
VWSAVTPSPE HLGDEVNLKV TVLCDRLQEA LTFTCNCSST VDLLIYQTLC YTHDDLRNVD 

       430        440        450        460        470        480 
VGDFVLKPCG LEEFLQNKHA LGSHEYIQYC RKFDIDIRLQ LMEQKVVRSD LARTVNDDQS 

       490        500        510        520        530        540 
PSTLNYLVHL QERPVKQTIS RQALSLLFDT YHNEVDAFLL ADGDFPLKAD RVVQSVKAIC 

       550        560        570        580        590        600 
NALAAVETPE ITSALNQLPP CPSRMQPKIQ KDPSVLAVRE NREKVVEALT AAILDLVELY 

       610        620        630        640        650        660 
CNTFNADFQT AVPGSRKHDL VQEACHFARS LAFTVYATHR IPIIWATSYE DFYLSCSLSH 

       670        680        690        700        710        720 
GGKELCSPLQ TRRAHFSKYL FHLIVWDQQI CFPVQVNRLP RETLLCATLY ALPIPPPGSS 

       730        740        750        760        770        780 
SEANKQRRVP EALGWVTTPL FNFRQVLTCG RKLLGLWPAT QENPSARWSA PNFHQPDSVI 

       790        800        810        820        830        840 
LQIDFPTSAF DIKFTSPPGD KFSPRYEFGS LREEDQRKLK DIMQKESLYW LTDADKKRLW 

       850        860        870        880        890        900 
EKRYYCHSEV SSLPLVLASA PSWEWACLPD IYVLLKQWTH MNHQDALGLL HATFPDQEVR 

       910        920        930        940        950        960 
RMAVQWIGSL SDAELLDYLP QLVQALKYEC YLDSPLVRFL LKRAVSDLRV THYFFWLLKD 

       970        980        990       1000       1010       1020 
GLKDSQFSIR YQYLLAALLC CCGKGLREEF NRQCWLVNAL AKLAQQVREA APSARQGILR 

      1030       1040       1050       1060       1070       1080 
TGLEEVKQFF ALNGSCRLPL SPSLLVKGIV PRDCSYFNSN AVPLKLSFQN VDPLGENIRV 

      1090       1100       1110       1120       1130       1140 
IFKCGDDLRQ DMLTLQMIRI MSKIWVQEGL DMRMVIFRCF STGRGRGMVE MIPNAETLRK 

      1150       1160       1170       1180       1190       1200 
IQVEHGVTGS FKDRPLADWL QKHNPGEDEY EKAVENFIYS CAGCCVATYV LGICDRHNDN 

      1210       1220       1230       1240       1250       1260 
IMLKTTGHMF HIDFGRFLGH AQMFGNIKRD RAPFVFTSDM AYVINGGDKP SSRFHDFVDL 

      1270       1280       1290       1300       1310       1320 
CCQAYNLIRK HTHLFLNLLG LMLSCGIPEL SDLEDLKYVY DALRPQDTEA NATTYFTRLI 

      1330       1340       1350       1360       1370       1380 
ESSLGSVATK LNFFIHNLAQ MKFTGSDDRL TLSFASRTHT LKSSGRISDV FLCRHEKIFH 

      1390       1400       1410       1420       1430       1440 
PNKGYIYVVK VMRENTHEAT YIQRTFEEFQ ELHNKLRLLF PSSHLPSFPS RFVIGRSRGE 

      1450       1460       1470       1480       1490       1500 
AVAERRREEL NGYIWHLIHA PPEVAECDLV YTFFHPLPRD EKAMGTSPAP KSSDGTWARP 

      1510       1520       1530       1540       1550       1560 
VGKVGGEVKL SISYKNNKLF IMVMHIRGLQ LLQDGNDPDP YVKIYLLPDP QKTTKRKTKV 

      1570       1580       1590       1600       1610       1620 
ARKTCNPTYN EMLVYDGIPK GDLQQRELQL SVLSEQGFWE NVLLGEVNIR LRELDLAQEK 

      1630 
TGWFALGSRS HGTL 

« Hide

References

« Hide 'large scale' references
[1]"Identification and cDNA cloning of a novel mammalian C2 domain-containing phosphoinositide 3-kinase, HsC2-PI3K."
Brown R.A., Ho L.K.F., Weber-Hall S.J., Shipley J.M., Fry M.J.
Biochem. Biophys. Res. Commun. 233:537-544(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Mammary gland.
[2]"Human phosphoinositide 3-kinase C2beta, the role of calcium and the C2 domain in enzyme activity."
Arcaro A., Volinia S., Zvelebil M.J., Stein R.C., Watton S.J., Layton M.J., Gout I., Ahmadi K., Downward J., Waterfield M.D.
J. Biol. Chem. 273:33082-33090(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
Tissue: Monocyte.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors."
Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., Domin J.
Mol. Cell. Biol. 20:3817-3830(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH ERBB2 AND EGFR, INTERACTION WITH EGFR AND PDGFR, COFACTOR, FUNCTION.
[5]"Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2."
Wheeler M., Domin J.
Mol. Cell. Biol. 21:6660-6667(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH GRB2 AND EGFR, INTERACTION WITH SHC1 AND GRB2, ENZYME REGULATION.
[6]"Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation."
El Sheikh S.S., Domin J., Tomtitchong P., Abel P., Stamp G., Lalani E.-N.
BMC Clin. Pathol. 3:4-4(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[7]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y11312 mRNA. Translation: CAA72168.1.
Y13892 mRNA. Translation: CAA74194.1. Different initiation.
AL606489 Genomic DNA. Translation: CAI16572.1.
CCDSCCDS1446.1.
PIRJC5500.
PC4346.
RefSeqNP_002637.3. NM_002646.3.
XP_005245314.1. XM_005245257.1.
XP_006711447.1. XM_006711384.1.
UniGeneHs.497487.

3D structure databases

ProteinModelPortalO00750.
SMRO00750. Positions 640-1321, 1365-1475, 1506-1626.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111305. 11 interactions.
IntActO00750. 9 interactions.
MINTMINT-2794980.
STRING9606.ENSP00000356155.

Chemistry

BindingDBO00750.
ChEMBLCHEMBL5554.
GuidetoPHARMACOLOGY2151.

PTM databases

PhosphoSiteO00750.

Proteomic databases

MaxQBO00750.
PaxDbO00750.
PeptideAtlasO00750.
PRIDEO00750.

Protocols and materials databases

DNASU5287.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367187; ENSP00000356155; ENSG00000133056.
GeneID5287.
KEGGhsa:5287.
UCSCuc001haw.3. human.

Organism-specific databases

CTD5287.
GeneCardsGC01M204391.
HGNCHGNC:8972. PIK3C2B.
HPAHPA030515.
MIM602838. gene.
neXtProtNX_O00750.
PharmGKBPA33305.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5032.
HOVERGENHBG082099.
InParanoidO00750.
KOK00923.
OMAIHLQERP.
OrthoDBEOG71CFK4.
PhylomeDBO00750.
TreeFamTF102031.

Enzyme and pathway databases

BRENDA2.7.1.137. 2681.
ReactomeREACT_111217. Metabolism.
SignaLinkO00750.

Gene expression databases

ArrayExpressO00750.
BgeeO00750.
CleanExHS_PIK3C2B.
GenevestigatorO00750.

Family and domain databases

Gene3D1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 2 hits.
3.30.1520.10. 1 hit.
InterProIPR016024. ARM-type_fold.
IPR000008. C2_dom.
IPR011009. Kinase-like_dom.
IPR001683. Phox.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
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.
PfamPF00168. C2. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
PF00792. PI3K_C2. 1 hit.
PF00794. PI3K_rbd. 1 hit.
PF00613. PI3Ka. 1 hit.
PF00787. PX. 1 hit.
[Graphical view]
SMARTSM00239. C2. 1 hit.
SM00142. PI3K_C2. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
SM00312. PX. 1 hit.
[Graphical view]
SUPFAMSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 2 hits.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEPS50004. C2. 1 hit.
PS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
PS51547. PI3K_C2. 1 hit.
PS51546. PI3K_RBD. 1 hit.
PS51545. PIK_HELICAL. 1 hit.
PS50195. PX. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPIK3C2B. human.
GeneWikiPIK3C2B.
GenomeRNAi5287.
NextBio20430.
PROO00750.
SOURCESearch...

Entry information

Entry nameP3C2B_HUMAN
AccessionPrimary (citable) accession number: O00750
Secondary accession number(s): O95666, Q5SW99
Entry history
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: August 30, 2005
Last modified: July 9, 2014
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

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

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM