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O00443 (P3C2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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 alpha

Short name=PI3K-C2-alpha
Short name=PtdIns-3-kinase C2 subunit alpha
EC=2.7.1.154
Alternative name(s):
Phosphoinositide 3-kinase-C2-alpha
Gene names
Name:PIK3C2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1686 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Ref.1 Ref.5 Ref.6 Ref.8 Ref.10 Ref.11 Ref.17

Catalytic activity

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

Cofactor

Calcium or magnesium. Manganese cannot be used. Ref.1 Ref.6

Enzyme regulation

Activated by insulin By similarity. Only slightly inhibited by wortmannin and LY294002. Activated by clathrin. Ref.1 Ref.5 Ref.8

Subunit structure

Part of a complex with ERBB2 and EGFR. Interacts with clathrin trimers. Ref.6 Ref.8 Ref.11

Subcellular location

Cell membrane. Golgi apparatus. Cytoplasmic vesicleclathrin-coated vesicle. Nucleus. Cytoplasm. Note: According to Ref.5 and Ref.8, it is found in the cell membrane, the Golgi apparatus and in clathrin-coated vesicles. According to Ref.23 it inserts preferentially into membranes containing PtdIns(4,5)P2. According to Ref.7, it is nuclear and cytoplasmic. Associated with RNA-containing structures. According to Ref.9, it is mainly cytoplasmic. Ref.5 Ref.7 Ref.8 Ref.9 Ref.23

Tissue specificity

Expressed in columnar and transitional epithelia, mononuclear cells, smooth muscle cells, and endothelial cells lining capillaries and small venules (at protein level). Ubiquitously expressed, with highest levels in heart, placenta and ovary, and lowest levels in the kidney. Detected at low levels in islets of Langerhans from type 2 diabetes mellitus individuals. Ref.1 Ref.9 Ref.20

Post-translational modification

Phosphorylated upon insulin stimulation; which may lead to enzyme activation By similarity. Phosphorylated on Ser-259 during mitosis and upon UV irradiation; which does not change enzymatic activity but leads to proteasomal degradation. Ser-259 phosphorylation may be mediated by CDK1 or JNK, depending on the physiological state of the cell. Ref.7 Ref.10

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.

Biophysicochemical properties

Kinetic parameters:

In the absence of the carrier phosphatidylserine, enzymatic kinetics toward PtdIns4P are non-linear.

KM=122 µM for PtdIns (in the absence of phosphatidylserine) Ref.1

KM=64 µM for PtdIns (in the presence of phosphatidylserine)

KM=25 µM for PtdIns4P (in the presence of phosphatidylserine)

KM=15 µM for ATP (with PtdIns as substrate) (in the absence of phosphatidylserine)

KM=32 µM for ATP (with PtdIns as substrate) (in the presence of phosphatidylserine)

KM=54 µM for ATP (with PtdIns4P as substrate) (in the presence of phosphatidylserine)

Vmax=990 pmol/min/mg enzyme with PtdIns as substrate (in the absence of phosphatidylserine)

Vmax=200 pmol/min/mg enzyme with PtdIns as substrate (in the presence of phosphatidylserine)

Vmax=240 pmol/min/mg enzyme with PtdIns4P as substrate (in the presence of phosphatidylserine)

Vmax=6800 pmol/min/mg enzyme toward ATP with PtdIns as substrate (in the absence of phosphatidylserine)

Vmax=805 pmol/min/mg enzyme toward ATP with PtdIns as substrate (in the presence of phosphatidylserine)

Vmax=880 pmol/min/mg enzyme toward ATP with PtdIns4P as substrate (in the presence of phosphatidylserine)

Ontologies

Keywords
   Biological processEndocytosis
Exocytosis
   Cellular componentCell membrane
Cytoplasm
Cytoplasmic vesicle
Golgi apparatus
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processclathrin coat assembly

Traceable author statement Ref.21. Source: UniProtKB

endocytosis

Inferred from mutant phenotype Ref.17. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Traceable author statement Ref.21. Source: UniProtKB

exocytosis

Traceable author statement Ref.21. Source: UniProtKB

insulin receptor signaling pathway

Traceable author statement Ref.21. Source: UniProtKB

phosphatidylinositol biosynthetic process

Traceable author statement. Source: Reactome

phosphatidylinositol-mediated signaling

Inferred from electronic annotation. Source: InterPro

phospholipid metabolic process

Traceable author statement. Source: Reactome

platelet-derived growth factor receptor signaling pathway

Traceable author statement Ref.21. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

vascular smooth muscle contraction

Traceable author statement Ref.21. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

clathrin-coated vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay Ref.17. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

phosphatidylinositol 3-kinase complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from direct assay Ref.17. Source: UniProtKB

vesicle

Inferred from direct assay Ref.17. Source: UniProtKB

   Molecular_function1-phosphatidylinositol-3-kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

1-phosphatidylinositol-4-phosphate 3-kinase activity

Traceable author statement. Source: Reactome

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatidylinositol 3-kinase activity

Traceable author statement Ref.21. Source: UniProtKB

phosphatidylinositol binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.14
Chain2 – 16861685Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha
PRO_0000088795

Regions

Domain421 – 50989PI3K-RBD
Domain682 – 841160C2 PI3K-type
Domain861 – 1037177PIK helical
Domain1133 – 1397265PI3K/PI4K
Domain1422 – 1538117PX
Domain1559 – 1662104C2
Region2 – 142141Interaction with clathrin; sufficient to induce clathrin assemby
Region1488 – 14936Interaction with PtdIns(4,5)P2-containing membranes
Motif1608 – 161912Nuclear localization signal Ref.7

Sites

Site2441Not phosphorylated
Site2491Not phosphorylated
Site2511Not phosphorylated
Site2541Not phosphorylated
Site2621Not phosphorylated
Site2661Not phosphorylated

Amino acid modifications

Modified residue21N-acetylalanine Ref.14
Modified residue601Phosphoserine Ref.13
Modified residue1081Phosphoserine Ref.12 Ref.13 Ref.18
Modified residue2591Phosphoserine Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.18 Ref.22
Modified residue3271Phosphoserine Ref.22
Modified residue3381Phosphoserine Ref.13

Natural variations

Natural variant14151T → A.
Corresponds to variant rs11604561 [ dbSNP | Ensembl ].
VAR_023333

Experimental info

Mutagenesis103 – 1075LLLDD → AAAAA: Reduces clathrin binding. Ref.8
Mutagenesis2541S → A: No effect on phosphorylation in vitro. Ref.10
Mutagenesis2591S → A, D or E: Abolishes phosphorylation, no change in activity. Ref.10
Mutagenesis2591S → A: Protects from proteolysis. Ref.10
Mutagenesis2621S → A: No effect on phosphorylation in vitro. Ref.10
Mutagenesis2661S → A: No effect on phosphorylation in vitro. Ref.10
Mutagenesis12501D → A: Abolishes lipid kinase activity. Affects clathrin distribution when combined with a truncation encompassing the region of clathrin interaction. Ref.11
Mutagenesis14881R → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 7-fold. Ref.23
Mutagenesis14901V → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 7-fold. Ref.23
Mutagenesis14911L → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 5-fold. Ref.23
Mutagenesis14931R → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 23-fold. Ref.23
Mutagenesis15031R → A: Abolishes interaction with PtdIns(4,5)P2-containing membranes. Ref.23
Sequence conflict51S → F in CAA73797. Ref.1
Sequence conflict151S → F in CAA73797. Ref.1
Sequence conflict7961F → C in CAA73797. Ref.1
Sequence conflict7991K → R in CAA73797. Ref.1
Sequence conflict9221V → G in CAA73797. Ref.1
Sequence conflict11291M → L in CAA73797. Ref.1
Sequence conflict14501R → W in CAA73797. Ref.1
Sequence conflict14641D → V in CAA73797. Ref.1

Secondary structure

....................... 1686
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O00443 [UniParc].

Last modified July 10, 2007. Version 2.
Checksum: 904AA5470F80DAC6

FASTA1,686190,680
        10         20         30         40         50         60 
MAQISSNSGF KECPSSHPEP TRAKDVDKEE ALQMEAEALA KLQKDRQVTD NQRGFELSSS 

        70         80         90        100        110        120 
TRKKAQVYNK QDYDLMVFPE SDSQKRALDI DVEKLTQAEL EKLLLDDSFE TKKTPVLPVT 

       130        140        150        160        170        180 
PILSPSFSAQ LYFRPTIQRG QWPPGLPGPS TYALPSIYPS TYSKQAAFQN GFNPRMPTFP 

       190        200        210        220        230        240 
STEPIYLSLP GQSPYFSYPL TPATPFHPQG SLPIYRPVVS TDMAKLFDKI ASTSEFLKNG 

       250        260        270        280        290        300 
KARTDLEITD SKVSNLQVSP KSEDISKFDW LDLDPLSKPK VDNVEVLDHE EEKNVSSLLA 

       310        320        330        340        350        360 
KDPWDAVLLE ERSTANCHLE RKVNGKSLSV ATVTRSQSLN IRTTQLAKAQ GHISQKDPNG 

       370        380        390        400        410        420 
TSSLPTGSSL LQEVEVQNEE MAAFCRSITK LKTKFPYTNH RTNPGYLLSP VTAQRNICGE 

       430        440        450        460        470        480 
NASVKVSIDI EGFQLPVTFT CDVSSTVEII IMQALCWVHD DLNQVDVGSY VLKVCGQEEV 

       490        500        510        520        530        540 
LQNNHCLGSH EHIQNCRKWD TEIRLQLLTF SAMCQNLART AEDDETPVDL NKHLYQIEKP 

       550        560        570        580        590        600 
CKEAMTRHPV EELLDSYHNQ VELALQIENQ HRAVDQVIKA VRKICSALDG VETLAITESV 

       610        620        630        640        650        660 
KKLKRAVNLP RSKTADVTSL FGGEDTSRSS TRGSLNPENP VQVSINQLTA AIYDLLRLHA 

       670        680        690        700        710        720 
NSGRSPTDCA QSSKSVKEAW TTTEQLQFTI FAAHGISSNW VSNYEKYYLI CSLSHNGKDL 

       730        740        750        760        770        780 
FKPIQSKKVG TYKNFFYLIK WDELIIFPIQ ISQLPLESVL HLTLFGILNQ SSGSSPDSNK 

       790        800        810        820        830        840 
QRKGPEALGK VSLPLFDFKR FLTCGTKLLY LWTSSHTNSV PGTVTKKGYV MERIVLQVDF 

       850        860        870        880        890        900 
PSPAFDIIYT TPQVDRSIIQ QHNLETLEND IKGKLLDILH KDSSLGLSKE DKAFLWEKRY 

       910        920        930        940        950        960 
YCFKHPNCLP KILASAPNWK WVNLAKTYSL LHQWPALYPL IALELLDSKF ADQEVRSLAV 

       970        980        990       1000       1010       1020 
TWIEAISDDE LTDLLPQFVQ ALKYEIYLNS SLVQFLLSRA LGNIQIAHNL YWLLKDALHD 

      1030       1040       1050       1060       1070       1080 
VQFSTRYEHV LGALLSVGGK RLREELLKQT KLVQLLGGVA EKVRQASGSA RQVVLQRSME 

      1090       1100       1110       1120       1130       1140 
RVQSFFQKNK CRLPLKPSLV AKELNIKSCS FFSSNAVPLK VTMVNADPMG EEINVMFKVG 

      1150       1160       1170       1180       1190       1200 
EDLRQDMLAL QMIKIMDKIW LKEGLDLRMV IFKCLSTGRD RGMVELVPAS DTLRKIQVEY 

      1210       1220       1230       1240       1250       1260 
GVTGSFKDKP LAEWLRKYNP SEEEYEKASE NFIYSCAGCC VATYVLGICD RHNDNIMLRS 

      1270       1280       1290       1300       1310       1320 
TGHMFHIDFG KFLGHAQMFG SFKRDRAPFV LTSDMAYVIN GGEKPTIRFQ LFVDLCCQAY 

      1330       1340       1350       1360       1370       1380 
NLIRKQTNLF LNLLSLMIPS GLPELTSIQD LKYVRDALQP QTTDAEATIF FTRLIESSLG 

      1390       1400       1410       1420       1430       1440 
SIATKFNFFI HNLAQLRFSG LPSNDEPILS FSPKTYSFRQ DGRIKEVSVF TYHKKYNPDK 

      1450       1460       1470       1480       1490       1500 
HYIYVVRILR EGQIEPSFVF RTFDEFQELH NKLSIIFPLW KLPGFPNRMV LGRTHIKDVA 

      1510       1520       1530       1540       1550       1560 
AKRKIELNSY LQSLMNASTD VAECDLVCTF FHPLLRDEKA EGIARSADAG SFSPTPGQIG 

      1570       1580       1590       1600       1610       1620 
GAVKLSISYR NGTLFIMVMH IKDLVTEDGA DPNPYVKTYL LPDNHKTSKR KTKISRKTRN 

      1630       1640       1650       1660       1670       1680 
PTFNEMLVYS GYSKETLRQR ELQLSVLSAE SLRENFFLGG VTLPLKDFNL SKETVKWYQL 


TAATYL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of a human phosphoinositide 3-kinase with a C2 domain which displays reduced sensitivity to the inhibitor wortmannin."
Domin J., Pages F., Volinia S., Rittenhouse S.E., Zvelebil M.J., Stein R.C., Waterfield M.D.
Biochem. J. 326:139-147(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[2]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
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. expand/collapse author list , 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].
Tissue: Lung.
[5]"The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles."
Domin J., Gaidarov I., Smith M.E.K., Keen J.H., Waterfield M.D.
J. Biol. Chem. 275:11943-11950(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION.
[6]"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: FUNCTION, COFACTOR, IDENTIFICATION IN A COMPLEX WITH ERBB2 AND EGFR.
[7]"Phosphatidylinositol 3-kinase c2alpha contains a nuclear localization sequence and associates with nuclear speckles."
Didichenko S.A., Thelen M.
J. Biol. Chem. 276:48135-48142(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, PHOSPHORYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
[8]"The class II phosphoinositide 3-kinase C2alpha is activated by clathrin and regulates clathrin-mediated membrane trafficking."
Gaidarov I., Smith M.E.K., Domin J., Keen J.H.
Mol. Cell 7:443-449(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, INTERACTION WITH CLATHRIN, MUTAGENESIS OF 103-LEU--ASP-107.
[9]"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[10]"Mitotic and stress-induced phosphorylation of HsPI3K-C2alpha targets the protein for degradation."
Didichenko S.A., Fragoso C.M., Thelen M.
J. Biol. Chem. 278:26055-26064(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-259, MUTAGENESIS OF SER-254; SER-259; SER-262 AND SER-266, IDENTIFICATION BY MASS SPECTROMETRY.
[11]"Individual phosphoinositide 3-kinase C2alpha domain activities independently regulate clathrin function."
Gaidarov I., Zhao Y., Keen J.H.
J. Biol. Chem. 280:40766-40772(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ASSEMBLY AND CELLULAR DISTRIBUTION OF CLATHRIN, INTERACTION WITH CLATHRIN, MUTAGENESIS OF ASP-1250, REGION.
[12]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108 AND SER-259, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60; SER-108; SER-259 AND SER-338, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[15]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"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 SER-259, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[17]"PI3KC2alpha, a class II PI3K, is required for dynamin-independent internalization pathways."
Krag C., Malmberg E.K., Salcini A.E.
J. Cell Sci. 123:4240-4250(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DYNAMIN-INDEPENDENT ENDOCYTOSIS.
[18]"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 SER-108 AND SER-259, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[19]"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].
[20]"Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells."
Dominguez V., Raimondi C., Somanath S., Bugliani M., Loder M.K., Edling C.E., Divecha N., da Silva-Xavier G., Marselli L., Persaud S.J., Turner M.D., Rutter G.A., Marchetti P., Falasca M., Maffucci T.
J. Biol. Chem. 286:4216-4225(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[21]"Role of class II phosphoinositide 3-kinase in cell signalling."
Falasca M., Maffucci T.
Biochem. Soc. Trans. 35:211-214(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[22]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-327, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Structural and membrane binding analysis of the Phox homology domain of phosphoinositide 3-kinase-C2alpha."
Stahelin R.V., Karathanassis D., Bruzik K.S., Waterfield M.D., Bravo J., Williams R.L., Cho W.
J. Biol. Chem. 281:39396-39406(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1405-1544, PHOSPHOINOSITIDE BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-1488; VAL-1490; LEU-1491; ARG-1493 AND ARG-1503.
[24]"Ligand-binding specificity of PI3kinase C2alpha PX domain."
Parkinson G.N., Vines D., Driscoll P.C., Djordjevic S.
Submitted (OCT-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1421-1532.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y13367 mRNA. Translation: CAA73797.1.
EU332862 Genomic DNA. Translation: ABY87551.1.
CH471064 Genomic DNA. Translation: EAW68447.1.
BC113658 mRNA. Translation: AAI13659.1.
CCDSCCDS7824.1.
PIRPC4345.
RefSeqNP_002636.2. NM_002645.2.
XP_005253034.1. XM_005252977.1.
XP_005253035.1. XM_005252978.2.
XP_005253036.1. XM_005252979.2.
UniGeneHs.175343.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AR5X-ray1.80A1421-1532[»]
2IWLX-ray2.60X1405-1544[»]
2REAX-ray2.50A1421-1532[»]
2REDX-ray2.10A1421-1532[»]
ProteinModelPortalO00443.
SMRO00443. Positions 666-1391, 1421-1532, 1561-1682.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111304. 19 interactions.
IntActO00443. 16 interactions.
MINTMINT-2794824.
STRING9606.ENSP00000265970.

Chemistry

BindingDBO00443.
ChEMBLCHEMBL1075102.
DrugBankDB00144. Phosphatidylserine.

PTM databases

PhosphoSiteO00443.

Proteomic databases

MaxQBO00443.
PaxDbO00443.
PRIDEO00443.

Protocols and materials databases

DNASU5286.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265970; ENSP00000265970; ENSG00000011405.
GeneID5286.
KEGGhsa:5286.
UCSCuc001mmq.4. human.

Organism-specific databases

CTD5286.
GeneCardsGC11M017099.
HGNCHGNC:8971. PIK3C2A.
HPAHPA037641.
HPA037642.
MIM603601. gene.
neXtProtNX_O00443.
PharmGKBPA33304.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5032.
HOGENOMHOG000006920.
HOVERGENHBG082099.
InParanoidO00443.
KOK00923.
OMAKCRLPLN.
OrthoDBEOG71CFK4.
PhylomeDBO00443.
TreeFamTF102031.

Enzyme and pathway databases

BioCycMetaCyc:HS00315-MONOMER.
BRENDA2.7.1.154. 2681.
ReactomeREACT_111217. Metabolism.
REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpressO00443.
BgeeO00443.
CleanExHS_PIK3C2A.
GenevestigatorO00443.

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. 2 hits.
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

ChiTaRSPIK3C2A. human.
EvolutionaryTraceO00443.
GeneWikiPIK3C2A.
GenomeRNAi5286.
NextBio20426.
PROO00443.
SOURCESearch...

Entry information

Entry nameP3C2A_HUMAN
AccessionPrimary (citable) accession number: O00443
Secondary accession number(s): B0LPH2, Q14CQ9
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: July 10, 2007
Last modified: July 9, 2014
This is version 130 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM