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O00443

- P3C2A_HUMAN

UniProt

O00443 - P3C2A_HUMAN

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Protein

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

Gene

PIK3C2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.7 Publications

Catalytic activityi

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

Cofactori

Calcium or magnesium. Manganese cannot be used.2 Publications

Enzyme regulationi

Activated by insulin By similarity. Only slightly inhibited by wortmannin and LY294002. Activated by clathrin.By similarity3 Publications

Kineticsi

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

  1. KM=122 µM for PtdIns (in the absence of phosphatidylserine)1 Publication
  2. KM=64 µM for PtdIns (in the presence of phosphatidylserine)1 Publication
  3. KM=25 µM for PtdIns4P (in the presence of phosphatidylserine)1 Publication
  4. KM=15 µM for ATP (with PtdIns as substrate) (in the absence of phosphatidylserine)1 Publication
  5. KM=32 µM for ATP (with PtdIns as substrate) (in the presence of phosphatidylserine)1 Publication
  6. KM=54 µM for ATP (with PtdIns4P as substrate) (in the presence of phosphatidylserine)1 Publication

Vmax=990 pmol/min/mg enzyme with PtdIns as substrate (in the absence of phosphatidylserine)1 Publication

Vmax=200 pmol/min/mg enzyme with PtdIns as substrate (in the presence of phosphatidylserine)1 Publication

Vmax=240 pmol/min/mg enzyme with PtdIns4P as substrate (in the presence of phosphatidylserine)1 Publication

Vmax=6800 pmol/min/mg enzyme toward ATP with PtdIns as substrate (in the absence of phosphatidylserine)1 Publication

Vmax=805 pmol/min/mg enzyme toward ATP with PtdIns as substrate (in the presence of phosphatidylserine)1 Publication

Vmax=880 pmol/min/mg enzyme toward ATP with PtdIns4P as substrate (in the presence of phosphatidylserine)1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei244 – 2441Not phosphorylated
Sitei249 – 2491Not phosphorylated
Sitei251 – 2511Not phosphorylated
Sitei254 – 2541Not phosphorylated
Sitei262 – 2621Not phosphorylated
Sitei266 – 2661Not phosphorylated

GO - Molecular functioni

  1. 1-phosphatidylinositol-3-kinase activity Source: RefGenome
  2. 1-phosphatidylinositol-4-phosphate 3-kinase activity Source: Reactome
  3. ATP binding Source: UniProtKB-KW
  4. phosphatidylinositol 3-kinase activity Source: UniProtKB
  5. phosphatidylinositol binding Source: InterPro

GO - Biological processi

  1. clathrin coat assembly Source: UniProtKB
  2. endocytosis Source: UniProtKB
  3. epidermal growth factor receptor signaling pathway Source: UniProtKB
  4. exocytosis Source: UniProtKB
  5. insulin receptor signaling pathway Source: UniProtKB
  6. phosphatidylinositol biosynthetic process Source: Reactome
  7. phosphatidylinositol-mediated signaling Source: InterPro
  8. phospholipid metabolic process Source: Reactome
  9. platelet-derived growth factor receptor signaling pathway Source: UniProtKB
  10. small molecule metabolic process Source: Reactome
  11. vascular smooth muscle contraction Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Endocytosis, Exocytosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00315-MONOMER.
BRENDAi2.7.1.154. 2681.
ReactomeiREACT_120756. Synthesis of PIPs at the early endosome membrane.
REACT_120836. Synthesis of PIPs at the Golgi membrane.
REACT_120918. Synthesis of PIPs at the late endosome membrane.
REACT_121025. Synthesis of PIPs at the plasma membrane.
REACT_19400. Golgi Associated Vesicle Biogenesis.

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (EC:2.7.1.154)
Short name:
PI3K-C2-alpha
Short name:
PtdIns-3-kinase C2 subunit alpha
Alternative name(s):
Phosphoinositide 3-kinase-C2-alpha
Gene namesi
Name:PIK3C2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:8971. PIK3C2A.

Subcellular locationi

Cell membrane. Golgi apparatus. Cytoplasmic vesicleclathrin-coated vesicle. Nucleus. Cytoplasm
Note: According to PubMed:10766823 and PubMed:11239472, it is found in the cell membrane, the Golgi apparatus and in clathrin-coated vesicles. According to PubMed:17038310 it inserts preferentially into membranes containing PtdIns(4,5)P2. According to PubMed:11606566, it is nuclear and cytoplasmic. Associated with RNA-containing structures. According to PubMed:14563213, it is mainly cytoplasmic.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoplasmic vesicle Source: UniProtKB-KW
  3. cytosol Source: Reactome
  4. extracellular vesicular exosome Source: UniProt
  5. Golgi apparatus Source: UniProtKB-KW
  6. membrane Source: UniProtKB
  7. nucleus Source: UniProtKB-KW
  8. phosphatidylinositol 3-kinase complex Source: RefGenome
  9. plasma membrane Source: UniProtKB
  10. vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Golgi apparatus, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi103 – 1075LLLDD → AAAAA: Reduces clathrin binding. 1 Publication
Mutagenesisi254 – 2541S → A: No effect on phosphorylation in vitro. 1 Publication
Mutagenesisi259 – 2591S → A, D or E: Abolishes phosphorylation, no change in activity. 1 Publication
Mutagenesisi259 – 2591S → A: Protects from proteolysis. 1 Publication
Mutagenesisi262 – 2621S → A: No effect on phosphorylation in vitro. 1 Publication
Mutagenesisi266 – 2661S → A: No effect on phosphorylation in vitro. 1 Publication
Mutagenesisi1250 – 12501D → A: Abolishes lipid kinase activity. Affects clathrin distribution when combined with a truncation encompassing the region of clathrin interaction. 1 Publication
Mutagenesisi1488 – 14881R → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 7-fold. 1 Publication
Mutagenesisi1490 – 14901V → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 7-fold. 1 Publication
Mutagenesisi1491 – 14911L → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 5-fold. 1 Publication
Mutagenesisi1493 – 14931R → A: Reduces affinity for PtdIns(4,5)P2-containing membranes 23-fold. 1 Publication
Mutagenesisi1503 – 15031R → A: Abolishes interaction with PtdIns(4,5)P2-containing membranes. 1 Publication

Organism-specific databases

PharmGKBiPA33304.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 16861685Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alphaPRO_0000088795Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei60 – 601Phosphoserine1 Publication
Modified residuei108 – 1081Phosphoserine3 Publications
Modified residuei259 – 2591Phosphoserine7 Publications
Modified residuei327 – 3271Phosphoserine1 Publication
Modified residuei338 – 3381Phosphoserine1 Publication

Post-translational modificationi

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.By similarity8 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO00443.
PaxDbiO00443.
PRIDEiO00443.

PTM databases

PhosphoSiteiO00443.

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiO00443.
CleanExiHS_PIK3C2A.
ExpressionAtlasiO00443. baseline and differential.
GenevestigatoriO00443.

Organism-specific databases

HPAiHPA037641.
HPA037642.

Interactioni

Subunit structurei

Part of a complex with ERBB2 and EGFR. Interacts with clathrin trimers.3 Publications

Protein-protein interaction databases

BioGridi111304. 25 interactions.
IntActiO00443. 16 interactions.
MINTiMINT-2794824.
STRINGi9606.ENSP00000265970.

Structurei

Secondary structure

1
1686
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi1418 – 14214Combined sources
Beta strandi1422 – 143312Combined sources
Beta strandi1437 – 14404Combined sources
Beta strandi1443 – 14508Combined sources
Beta strandi1457 – 14626Combined sources
Helixi1463 – 147614Combined sources
Helixi1479 – 14813Combined sources
Beta strandi1491 – 14955Combined sources
Helixi1498 – 151518Combined sources
Helixi1519 – 15224Combined sources
Helixi1525 – 15306Combined sources
Turni1535 – 15373Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2AR5X-ray1.80A1421-1532[»]
2IWLX-ray2.60X1405-1544[»]
2REAX-ray2.50A1421-1532[»]
2REDX-ray2.10A1421-1532[»]
ProteinModelPortaliO00443.
SMRiO00443. Positions 666-1391, 1421-1532, 1561-1682.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00443.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini421 – 50989PI3K-RBDPROSITE-ProRule annotationAdd
BLAST
Domaini682 – 841160C2 PI3K-typePROSITE-ProRule annotationAdd
BLAST
Domaini861 – 1037177PIK helicalPROSITE-ProRule annotationAdd
BLAST
Domaini1133 – 1397265PI3K/PI4KPROSITE-ProRule annotationAdd
BLAST
Domaini1422 – 1538117PXPROSITE-ProRule annotationAdd
BLAST
Domaini1559 – 1662104C2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 142141Interaction with clathrin; sufficient to induce clathrin assembyAdd
BLAST
Regioni1488 – 14936Interaction with PtdIns(4,5)P2-containing membranes

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1608 – 161912Nuclear localization signal1 PublicationAdd
BLAST

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation
Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 1 C2 PI3K-type domain.PROSITE-ProRule annotation
Contains 1 PI3K-RBD domain.PROSITE-ProRule annotation
Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
Contains 1 PIK helical domain.PROSITE-ProRule annotation
Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5032.
GeneTreeiENSGT00760000119110.
HOGENOMiHOG000006920.
HOVERGENiHBG082099.
InParanoidiO00443.
KOiK00923.
OMAiKCRLPLN.
OrthoDBiEOG71CFK4.
PhylomeDBiO00443.
TreeFamiTF102031.

Family and domain databases

Gene3Di1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 2 hits.
3.30.1520.10. 1 hit.
InterProiIPR016024. 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]
PANTHERiPTHR10048. PTHR10048. 1 hit.
PfamiPF00168. 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]
SMARTiSM00239. 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]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 2 hits.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEiPS50004. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O00443-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAQISSNSGF KECPSSHPEP TRAKDVDKEE ALQMEAEALA KLQKDRQVTD
60 70 80 90 100
NQRGFELSSS TRKKAQVYNK QDYDLMVFPE SDSQKRALDI DVEKLTQAEL
110 120 130 140 150
EKLLLDDSFE TKKTPVLPVT PILSPSFSAQ LYFRPTIQRG QWPPGLPGPS
160 170 180 190 200
TYALPSIYPS TYSKQAAFQN GFNPRMPTFP STEPIYLSLP GQSPYFSYPL
210 220 230 240 250
TPATPFHPQG SLPIYRPVVS TDMAKLFDKI ASTSEFLKNG KARTDLEITD
260 270 280 290 300
SKVSNLQVSP KSEDISKFDW LDLDPLSKPK VDNVEVLDHE EEKNVSSLLA
310 320 330 340 350
KDPWDAVLLE ERSTANCHLE RKVNGKSLSV ATVTRSQSLN IRTTQLAKAQ
360 370 380 390 400
GHISQKDPNG TSSLPTGSSL LQEVEVQNEE MAAFCRSITK LKTKFPYTNH
410 420 430 440 450
RTNPGYLLSP VTAQRNICGE NASVKVSIDI EGFQLPVTFT CDVSSTVEII
460 470 480 490 500
IMQALCWVHD DLNQVDVGSY VLKVCGQEEV LQNNHCLGSH EHIQNCRKWD
510 520 530 540 550
TEIRLQLLTF SAMCQNLART AEDDETPVDL NKHLYQIEKP CKEAMTRHPV
560 570 580 590 600
EELLDSYHNQ VELALQIENQ HRAVDQVIKA VRKICSALDG VETLAITESV
610 620 630 640 650
KKLKRAVNLP RSKTADVTSL FGGEDTSRSS TRGSLNPENP VQVSINQLTA
660 670 680 690 700
AIYDLLRLHA NSGRSPTDCA QSSKSVKEAW TTTEQLQFTI FAAHGISSNW
710 720 730 740 750
VSNYEKYYLI CSLSHNGKDL FKPIQSKKVG TYKNFFYLIK WDELIIFPIQ
760 770 780 790 800
ISQLPLESVL HLTLFGILNQ SSGSSPDSNK QRKGPEALGK VSLPLFDFKR
810 820 830 840 850
FLTCGTKLLY LWTSSHTNSV PGTVTKKGYV MERIVLQVDF PSPAFDIIYT
860 870 880 890 900
TPQVDRSIIQ QHNLETLEND IKGKLLDILH KDSSLGLSKE DKAFLWEKRY
910 920 930 940 950
YCFKHPNCLP KILASAPNWK WVNLAKTYSL LHQWPALYPL IALELLDSKF
960 970 980 990 1000
ADQEVRSLAV TWIEAISDDE LTDLLPQFVQ ALKYEIYLNS SLVQFLLSRA
1010 1020 1030 1040 1050
LGNIQIAHNL YWLLKDALHD VQFSTRYEHV LGALLSVGGK RLREELLKQT
1060 1070 1080 1090 1100
KLVQLLGGVA EKVRQASGSA RQVVLQRSME RVQSFFQKNK CRLPLKPSLV
1110 1120 1130 1140 1150
AKELNIKSCS FFSSNAVPLK VTMVNADPMG EEINVMFKVG EDLRQDMLAL
1160 1170 1180 1190 1200
QMIKIMDKIW LKEGLDLRMV IFKCLSTGRD RGMVELVPAS DTLRKIQVEY
1210 1220 1230 1240 1250
GVTGSFKDKP LAEWLRKYNP SEEEYEKASE NFIYSCAGCC VATYVLGICD
1260 1270 1280 1290 1300
RHNDNIMLRS TGHMFHIDFG KFLGHAQMFG SFKRDRAPFV LTSDMAYVIN
1310 1320 1330 1340 1350
GGEKPTIRFQ LFVDLCCQAY NLIRKQTNLF LNLLSLMIPS GLPELTSIQD
1360 1370 1380 1390 1400
LKYVRDALQP QTTDAEATIF FTRLIESSLG SIATKFNFFI HNLAQLRFSG
1410 1420 1430 1440 1450
LPSNDEPILS FSPKTYSFRQ DGRIKEVSVF TYHKKYNPDK HYIYVVRILR
1460 1470 1480 1490 1500
EGQIEPSFVF RTFDEFQELH NKLSIIFPLW KLPGFPNRMV LGRTHIKDVA
1510 1520 1530 1540 1550
AKRKIELNSY LQSLMNASTD VAECDLVCTF FHPLLRDEKA EGIARSADAG
1560 1570 1580 1590 1600
SFSPTPGQIG GAVKLSISYR NGTLFIMVMH IKDLVTEDGA DPNPYVKTYL
1610 1620 1630 1640 1650
LPDNHKTSKR KTKISRKTRN PTFNEMLVYS GYSKETLRQR ELQLSVLSAE
1660 1670 1680
SLRENFFLGG VTLPLKDFNL SKETVKWYQL TAATYL
Length:1,686
Mass (Da):190,680
Last modified:July 10, 2007 - v2
Checksum:i904AA5470F80DAC6
GO
Isoform 2 (identifier: O00443-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     484-1686: Missing.

Note: No experimental confirmation available.

Show »
Length:483
Mass (Da):53,742
Checksum:iB63EDBEA18725E91
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 51S → F in CAA73797. (PubMed:9337861)Curated
Sequence conflicti15 – 151S → F in CAA73797. (PubMed:9337861)Curated
Sequence conflicti483 – 4831N → K in BAG65126. (PubMed:14702039)Curated
Sequence conflicti796 – 7961F → C in CAA73797. (PubMed:9337861)Curated
Sequence conflicti799 – 7991K → R in CAA73797. (PubMed:9337861)Curated
Sequence conflicti922 – 9221V → G in CAA73797. (PubMed:9337861)Curated
Sequence conflicti1129 – 11291M → L in CAA73797. (PubMed:9337861)Curated
Sequence conflicti1450 – 14501R → W in CAA73797. (PubMed:9337861)Curated
Sequence conflicti1464 – 14641D → V in CAA73797. (PubMed:9337861)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1415 – 14151T → A.
Corresponds to variant rs11604561 [ dbSNP | Ensembl ].
VAR_023333

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei484 – 16861203Missing in isoform 2. 1 PublicationVSP_056158Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y13367 mRNA. Translation: CAA73797.1.
AK304262 mRNA. Translation: BAG65126.1.
EU332862 Genomic DNA. Translation: ABY87551.1.
AC107956 Genomic DNA. No translation available.
AC116533 Genomic DNA. No translation available.
AC126389 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68447.1.
BC113658 mRNA. Translation: AAI13659.1.
CCDSiCCDS7824.1. [O00443-1]
PIRiPC4345.
RefSeqiNP_002636.2. NM_002645.2.
XP_005253034.1. XM_005252977.1.
XP_005253035.1. XM_005252978.2.
XP_005253036.1. XM_005252979.2.
UniGeneiHs.175343.

Genome annotation databases

EnsembliENST00000265970; ENSP00000265970; ENSG00000011405. [O00443-1]
ENST00000533645; ENSP00000436244; ENSG00000011405.
GeneIDi5286.
KEGGihsa:5286.
UCSCiuc001mmq.4. human. [O00443-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y13367 mRNA. Translation: CAA73797.1 .
AK304262 mRNA. Translation: BAG65126.1 .
EU332862 Genomic DNA. Translation: ABY87551.1 .
AC107956 Genomic DNA. No translation available.
AC116533 Genomic DNA. No translation available.
AC126389 Genomic DNA. No translation available.
CH471064 Genomic DNA. Translation: EAW68447.1 .
BC113658 mRNA. Translation: AAI13659.1 .
CCDSi CCDS7824.1. [O00443-1 ]
PIRi PC4345.
RefSeqi NP_002636.2. NM_002645.2.
XP_005253034.1. XM_005252977.1.
XP_005253035.1. XM_005252978.2.
XP_005253036.1. XM_005252979.2.
UniGenei Hs.175343.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali O00443.
SMRi O00443. Positions 666-1391, 1421-1532, 1561-1682.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111304. 25 interactions.
IntActi O00443. 16 interactions.
MINTi MINT-2794824.
STRINGi 9606.ENSP00000265970.

Chemistry

BindingDBi O00443.
ChEMBLi CHEMBL1075102.

PTM databases

PhosphoSitei O00443.

Proteomic databases

MaxQBi O00443.
PaxDbi O00443.
PRIDEi O00443.

Protocols and materials databases

DNASUi 5286.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000265970 ; ENSP00000265970 ; ENSG00000011405 . [O00443-1 ]
ENST00000533645 ; ENSP00000436244 ; ENSG00000011405 .
GeneIDi 5286.
KEGGi hsa:5286.
UCSCi uc001mmq.4. human. [O00443-1 ]

Organism-specific databases

CTDi 5286.
GeneCardsi GC11M017099.
HGNCi HGNC:8971. PIK3C2A.
HPAi HPA037641.
HPA037642.
MIMi 603601. gene.
neXtProti NX_O00443.
PharmGKBi PA33304.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5032.
GeneTreei ENSGT00760000119110.
HOGENOMi HOG000006920.
HOVERGENi HBG082099.
InParanoidi O00443.
KOi K00923.
OMAi KCRLPLN.
OrthoDBi EOG71CFK4.
PhylomeDBi O00443.
TreeFami TF102031.

Enzyme and pathway databases

BioCyci MetaCyc:HS00315-MONOMER.
BRENDAi 2.7.1.154. 2681.
Reactomei REACT_120756. Synthesis of PIPs at the early endosome membrane.
REACT_120836. Synthesis of PIPs at the Golgi membrane.
REACT_120918. Synthesis of PIPs at the late endosome membrane.
REACT_121025. Synthesis of PIPs at the plasma membrane.
REACT_19400. Golgi Associated Vesicle Biogenesis.

Miscellaneous databases

ChiTaRSi PIK3C2A. human.
EvolutionaryTracei O00443.
GeneWikii PIK3C2A.
GenomeRNAii 5286.
NextBioi 20426.
PROi O00443.
SOURCEi Search...

Gene expression databases

Bgeei O00443.
CleanExi HS_PIK3C2A.
ExpressionAtlasi O00443. baseline and differential.
Genevestigatori O00443.

Family and domain databases

Gene3Di 1.10.1070.11. 1 hit.
1.25.40.70. 1 hit.
2.60.40.150. 2 hits.
3.30.1520.10. 1 hit.
InterProi IPR016024. 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 ]
PANTHERi PTHR10048. PTHR10048. 1 hit.
Pfami 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 ]
SMARTi 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 ]
SUPFAMi SSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 2 hits.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEi 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 ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 1), FUNCTION, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Trachea.
  3. NHLBI resequencing and genotyping service (RS&G)
    Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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] (ISOFORM 1).
    Tissue: Lung.
  7. "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.
  8. "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.
  9. "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.
  10. "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.
  11. "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.
  12. "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.
  13. "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.
  14. "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.
  15. 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.
  16. "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].
  17. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  18. "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.
  19. "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.
  20. "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.
  21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. Cited for: TISSUE SPECIFICITY.
  23. "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.
  24. "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].
  25. "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.
  26. "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.

Entry informationi

Entry nameiP3C2A_HUMAN
AccessioniPrimary (citable) accession number: O00443
Secondary accession number(s): B0LPH2, B4E2G4, Q14CQ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: July 10, 2007
Last modified: October 29, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

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