O00443 (P3C2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	1686 AA.
Sequence status	Complete.
Protein existence	Evidence 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.16
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 vesicle › clathrin-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.22 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.22
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.19
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 process	Endocytosis Exocytosis
Cellular component	Cell membrane Cytoplasm Cytoplasmic vesicle Golgi apparatus Membrane Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	clathrin coat assembly Traceable author statement Ref.20. Source: UniProtKB endocytosis Inferred from mutant phenotype Ref.16. Source: UniProtKB epidermal growth factor receptor signaling pathway Traceable author statement Ref.20. Source: UniProtKB exocytosis Traceable author statement Ref.20. Source: UniProtKB insulin receptor signaling pathway Traceable author statement Ref.20. Source: UniProtKB phosphatidylinositol-mediated signaling Inferred from electronic annotation. Source: InterPro platelet-derived growth factor receptor signaling pathway Traceable author statement Ref.20. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome vascular smooth muscle contraction Traceable author statement Ref.20. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell clathrin-coated vesicle 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 direct assay Ref.16. Source: UniProtKB vesicle Inferred from direct assay Ref.16. Source: UniProtKB
Molecular_function	1-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 binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1686

1686

Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha

PRO_0000088795

Regions

Domain

421 – 509

89

PI3K-RBD

Domain

682 – 841

160

C2 PI3K-type

Domain

861 – 1037

177

PIK helical

Domain

1133 – 1397

265

PI3K/PI4K

Domain

1422 – 1538

117

PX

Domain

1559 – 1662

104

C2

Region

1 – 142

142

Interaction with clathrin; sufficient to induce clathrin assemby

Region

1488 – 1493

6

Interaction with PtdIns(4,5)P2-containing membranes

Motif

1608 – 1619

12

Nuclear localization signal Ref.7

Sites

Site

244

1

Not phosphorylated

Site

249

1

Not phosphorylated

Site

251

1

Not phosphorylated

Site

254

1

Not phosphorylated

Site

262

1

Not phosphorylated

Site

266

1

Not phosphorylated

Amino acid modifications

Modified residue

60

1

Phosphoserine Ref.13

Modified residue

108

1

Phosphoserine Ref.12 Ref.13 Ref.17

Modified residue

259

1

Phosphoserine Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.21

Modified residue

327

1

Phosphoserine Ref.21

Modified residue

338

1

Phosphoserine Ref.13

Natural variations

Natural variant

1415

1

T → A.
Corresponds to variant rs11604561 [ dbSNP | Ensembl ].

VAR_023333

Experimental info

Mutagenesis

103 – 107

5

LLLDD → AAAAA: Reduces clathrin binding. Ref.8

Mutagenesis

254

1

S → A: No effect on phosphorylation in vitro. Ref.10

Mutagenesis

259

1

S → A, D or E: Abolishes phosphorylation, no change in activity. Ref.10

Mutagenesis

259

1

S → A: Protects from proteolysis. Ref.10

Mutagenesis

262

1

S → A: No effect on phosphorylation in vitro. Ref.10

Mutagenesis

266

1

S → A: No effect on phosphorylation in vitro. Ref.10

Mutagenesis

1250

1

D → A: Abolishes lipid kinase activity. Affects clathrin distribution when combined with a truncation encompassing the region of clathrin interaction. Ref.11

Mutagenesis

1488

1

R → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 7-fold. Ref.22

Mutagenesis

1490

1

V → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 7-fold. Ref.22

Mutagenesis

1491

1

L → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 5-fold. Ref.22

Mutagenesis

1493

1

R → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 23-fold. Ref.22

Mutagenesis

1503

1

R → A: Abolishes interaction with PtdIns(4,5)P2-containing membranes. Ref.22

Sequence conflict

5

1

S → F in CAA73797. Ref.1

Sequence conflict

15

1

S → F in CAA73797. Ref.1

Sequence conflict

796

1

F → C in CAA73797. Ref.1

Sequence conflict

799

1

K → R in CAA73797. Ref.1

Sequence conflict

922

1

V → G in CAA73797. Ref.1

Sequence conflict

1129

1

M → L in CAA73797. Ref.1

Sequence conflict

1450

1

R → W in CAA73797. Ref.1

Sequence conflict

1464

1

D → V in CAA73797. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1686

Helix Strand Turn

Details...

Helix

1418 – 1421

4

Beta strand

1422 – 1433

12

Beta strand

1437 – 1440

4

Beta strand

1443 – 1450

8

Beta strand

1457 – 1462

6

Helix

1463 – 1476

14

Helix

1479 – 1481

3

Beta strand

1491 – 1495

5

Helix

1498 – 1515

18

Helix

1519 – 1522

4

Helix

1525 – 1530

6

Turn

1535 – 1537

3

Sequences

	Sequence		Length	Mass (Da)
	O00443 [UniParc]. Last modified July 10, 2007. Version 2. Checksum: 904AA5470F80DAC6	FASTA	1,686	190,680
	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

References

	« Hide 'large scale' referencesShow '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. , 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, 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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, MASS SPECTROMETRY.
[15]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[16]	"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.
[17]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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].
[19]	"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.
[20]	"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.
[21]	"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, MASS SPECTROMETRY.
[22]	"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.
[23]	"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.

IPI

IPI00002580.

PIR

PC4345.

RefSeq

NP_002636.2. NM_002645.2.

UniGene

Hs.175343.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AR5	X-ray	1.80	A	1421-1532	[»]
2IWL	X-ray	2.60	X	1405-1544	[»]
2REA	X-ray	2.50	A	1421-1532	[»]
2RED	X-ray	2.10	A	1421-1532	[»]

ProteinModelPortal

O00443.

ModBase

Search...

Protein-protein interaction databases

IntAct

O00443. 14 interactions.

MINT

MINT-2794824.

STRING

9606.ENSP00000265970.

PTM databases

PhosphoSite

O00443.

Proteomic databases

PaxDb

O00443.

PRIDE

O00443.

Protocols and materials databases

DNASU

5286.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000265970; ENSP00000265970; ENSG00000011405.

GeneID

5286.

KEGG

hsa:5286.

UCSC

uc001mmq.4. human.

Organism-specific databases

CTD

5286.

GeneCards

GC11M017099.

HGNC

HGNC:8971. PIK3C2A.

HPA

HPA037641.
HPA037642.

MIM

603601. gene.

neXtProt

NX_O00443.

PharmGKB

PA33304.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5032.

HOGENOM

HOG000006920.

HOVERGEN

HBG082099.

InParanoid

O00443.

KO

K00923.

OMA

PRMPTFP.

OrthoDB

EOG4933H0.

PhylomeDB

O00443.

Enzyme and pathway databases

BioCyc

MetaCyc:HS00315-MONOMER.

BRENDA

2.7.1.154. 2681.

Pathway_Interaction_DB

avb3_integrin_pathway. Integrins in angiogenesis.

Reactome

REACT_111217. Metabolism.
REACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpress

O00443.

Bgee

O00443.

CleanEx

HS_PIK3C2A.

Genevestigator

O00443.

GermOnline

ENSG00000011405. Homo sapiens.

Family and domain databases

Gene3D

1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
3.30.1520.10. 1 hit.

InterPro

IPR016024. ARM-type_fold.
IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
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.
[Graphical view]

PANTHER

PTHR10048. PTHR10048. 1 hit.

Pfam

PF00168. 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]

SMART

SM00239. 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]

SUPFAM

SSF48371. ARM-type_fold. 1 hit.
SSF49562. C2_CaLB. 2 hits.
SSF56112. Kinase_like. 1 hit.
SSF64268. PX. 1 hit.

PROSITE

PS50004. 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]

ProtoNet

Search...

Other

BindingDB

O00443.

ChEMBL

CHEMBL1075102.

ChiTaRS

PIK3C2A. human.

DrugBank

DB00144. Phosphatidylserine.

EvolutionaryTrace

O00443.

GenomeRNAi

5286.

NextBio

20426.

SOURCE

Search...

Entry information

Entry name

P3C2A_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 118 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.