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Protein

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

Gene

Pik3c2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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.3 Publications

Catalytic activityi

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

Cofactori

Ca2+By similarity, Mg2+By similarityNote: Ca2+ or Mg2+. Mn2+ cannot be used.By similarity

Enzyme regulationi

Activated by clathrin (By similarity). Only slightly inhibited by wortmannin and LY294002. Activated by insulin.By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • autophagosome organization Source: MGI
  • cellular response to starvation Source: MGI
  • endocytosis Source: UniProtKB
  • exocytosis Source: UniProtKB-KW
  • negative regulation of zinc ion transmembrane transport Source: MGI
  • phosphatidylinositol-3-phosphate biosynthetic process Source: MGI
  • phosphatidylinositol-mediated signaling Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Endocytosis, Exocytosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.154. 3474.

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):
Cpk-m
Phosphoinositide 3-kinase-C2-alpha
p170
Gene namesi
Name:Pik3c2a
Synonyms:Cpk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1203729. Pik3c2a.

Subcellular locationi

  • Cell membrane By similarity
  • Golgi apparatus By similarity
  • Cytoplasmic vesicleclathrin-coated vesicle By similarity
  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: Inserts preferentially into membranes containing PtdIns(4,5)P2. Associated with RNA-containing structures.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Chronic renal failure and kidney lesions. Affects podocyte morphology and function.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000887962 – 1686Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alphaAdd BLAST1685

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei60PhosphoserineBy similarity1
Modified residuei261PhosphoserineBy similarity1
Modified residuei328PhosphoserineBy similarity1
Modified residuei339PhosphoserineBy similarity1
Modified residuei630PhosphoserineBy similarity1
Modified residuei1281PhosphoserineBy similarity1
Modified residuei1553PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on Ser-261 during mitosis and upon UV irradiation; which does not change enzymatic activity but leads to proteasomal degradation (By similarity). Phosphorylated upon insulin stimulation; which may lead to enzyme activation.By similarity1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ61194.
PaxDbiQ61194.
PeptideAtlasiQ61194.
PRIDEiQ61194.

PTM databases

iPTMnetiQ61194.
PhosphoSitePlusiQ61194.

Expressioni

Tissue specificityi

Detected in podocytes.1 Publication

Interactioni

Subunit structurei

Interacts with ERBB2 and EGFR. Interacts with clathrin trimers (By similarity).By similarity

Protein-protein interaction databases

BioGridi202158. 4 interactors.
IntActiQ61194. 1 interactor.
STRINGi10090.ENSMUSP00000126092.

Structurei

Secondary structure

11686
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1562 – 1570Combined sources9
Beta strandi1573 – 1582Combined sources10
Beta strandi1594 – 1602Combined sources9
Beta strandi1604 – 1606Combined sources3
Beta strandi1622 – 1631Combined sources10
Helixi1634 – 1637Combined sources4
Beta strandi1641 – 1648Combined sources8
Beta strandi1651 – 1653Combined sources3
Beta strandi1656 – 1664Combined sources9
Helixi1665 – 1667Combined sources3
Beta strandi1674 – 1679Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2B3RX-ray2.30A/B1561-1686[»]
ProteinModelPortaliQ61194.
SMRiQ61194.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61194.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini422 – 510PI3K-RBDPROSITE-ProRule annotationAdd BLAST89
Domaini682 – 841C2 PI3K-typePROSITE-ProRule annotationAdd BLAST160
Domaini861 – 1037PIK helicalPROSITE-ProRule annotationAdd BLAST177
Domaini1133 – 1395PI3K/PI4KPROSITE-ProRule annotationAdd BLAST263
Domaini1420 – 1536PXPROSITE-ProRule annotationAdd BLAST117
Domaini1557 – 1660C2PROSITE-ProRule annotationAdd BLAST104

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 142Interaction with clathrin; sufficient to induce clathrin assembyBy similarityAdd BLAST141
Regioni1488 – 1493Interaction with PtdIns(4,5)P2-containing membranesBy similarity6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1606 – 1617Nuclear localization signalBy similarityAdd BLAST12

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

eggNOGiKOG0905. Eukaryota.
COG5032. LUCA.
HOGENOMiHOG000006920.
HOVERGENiHBG082099.
InParanoidiQ61194.
KOiK00923.
PhylomeDBiQ61194.

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. 2 hits.
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. 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]
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. AlignAdd to basket

Isoform 1 (identifier: Q61194-1) [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
MAQISNNSEF KQCSSSHPEP IRTKDVNKAE ALQMEAEALA KLQKDRQMTD
60 70 80 90 100
SPRGFELSSS TRQRTQGFNK QDYDLMVFPE LDSQKRAVDI DVEKLTQAEL
110 120 130 140 150
EKILLDDNFE TRKPPALPVT PVLSPSFSTQ LYLRPSGQRG QWPPGLCGPS
160 170 180 190 200
TYTLPSTYPS AYSKQATFQN GFSPRMPTFP STESVYLRLP GQSPYFSYPL
210 220 230 240 250
TPATPFHPQG SLPVYRPLVS PDMAKLFEKI ASTSEFLKNG KARTDLEIAN
260 270 280 290 300
SKASVCNLQI SPKSEDINKF DWLDLDPLSK PKVDYVEVLE HEEEKKDPVL
310 320 330 340 350
LAEDPWDAVL LEERSPSCHL ERKVNGKSLS GATVTRSQSL IIRTAQFTKA
360 370 380 390 400
QGQVSQKDPN GTSSLPTGSS LLQEFEVQND EVAAFCQSIM KLKTKFPYTD
410 420 430 440 450
HCTNPGYLLS PVTVQRNMCG ENASVKVSIE IEGLQLPVTF TCDVSSTVEI
460 470 480 490 500
IIMQALCWVH DDLNQVDVGS YILKVCGQEE VLQNNHCLGS HEHIQNCRKW
510 520 530 540 550
DTEIKLQLLT LSAMCQNLAR TAEDDEAPVD LNKYLYQIEK PYKEVMTRHP
560 570 580 590 600
VEELLDSYHY QVELALQTEN QHRAVDQVIK AVRKICSALD GVETPSVTEA
610 620 630 640 650
VKKLKRAVNL PRNKSADVTS LSGSDTRKNS TKGSLNPENP VQVSMDHLTT
660 670 680 690 700
AIYDLLRLHA NSSRCSTACP RGSRNIKEAW TATEQLQFTV YAAHGISSNW
710 720 730 740 750
VSNYEKYYLI CSLSHNGKDL FKPIQSKKVG TYKNFFYLIK WDELIIFPIQ
760 770 780 790 800
ISQLPLESVL HLTLFGVLNQ SSGSSPDSNK QRKGPEALGK VSLTLFDFKR
810 820 830 840 850
FLTCGTKLLY LWTSSHTNSI PGAIPKKSYV MERIVLQVDF PSPAFDIIYT
860 870 880 890 900
SPQIDRNIIQ QDKLETLESD IKGKLLDIIH RDSSFGLSKE DKVFLWENRY
910 920 930 940 950
YCLKHPNCLP KILASAPNWK WANLAKTYSL LHQWPPLCPL AALELLDAKF
960 970 980 990 1000
ADQEVRSLAV SWMEAISDDE LADLLPQFVQ ALKYEIYLNS SLVRFLLSRA
1010 1020 1030 1040 1050
LGNIQIAHSL YWLLKDALHD THFGSRYEHV LGALLSVGGK GLREELSKQM
1060 1070 1080 1090 1100
KLVQLLGGVA EKVRQASGST RQVVLQKSME RVQSFFLRNK CRLPLKPSLV
1110 1120 1130 1140 1150
AKELNIKSCS FFSSNAMPLK VTMVNADPLG EEINVMFKVG EDLRQDMLAL
1160 1170 1180 1190 1200
QMIKIMDKIW LKEGLDLRMV IFRCLSTGRD 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
EGHLEPSFVF RTFDEFQELH NKLSIIFPLW KLPGFPNRMV LGRTHIKDVA
1510 1520 1530 1540 1550
AKRKIELNSY LQSLMNASTD VAECDLVCTF FHPLLRDEKA EGIARSAGAV
1560 1570 1580 1590 1600
PFSPTLGQIG GAVKLSVSYR NGTLFIMVMH IKDLVTEDGA DPNPYVKTYL
1610 1620 1630 1640 1650
LPDTHKTSKR KTKISRKTRN PTFNEMLVYS GYSKETLRQR ELQLSVLSAE
1660 1670 1680
SLRENFFLGG ITLPLKDFNL SKETVKWYQL TAATYL
Length:1,686
Mass (Da):190,758
Last modified:August 30, 2005 - v2
Checksum:iE390BA7D730F4F87
GO
Isoform 2 (identifier: Q61194-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     276-303: Missing.

Show »
Length:1,658
Mass (Da):187,526
Checksum:i4D18EBC1DDC2A57D
GO

Sequence cautioni

The sequence AAB07682 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti140G → V in AK049609 (PubMed:16141072).Curated1
Sequence conflicti668A → G in AAC52604 (PubMed:8662856).Curated1
Sequence conflicti954E → G in AAC52604 (PubMed:8662856).Curated1
Sequence conflicti1206 – 1208FKD → LR (PubMed:8663140).Curated3
Sequence conflicti1211 – 1212LA → TS (PubMed:8663140).Curated2
Sequence conflicti1218Y → N in AAB07682 (PubMed:8663140).Curated1
Sequence conflicti1325 – 1326KQ → T in AAB07682 (PubMed:8663140).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015254276 – 303Missing in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U52193 mRNA. Translation: AAC52604.1.
AK049609 mRNA. No translation available.
U55772 mRNA. Translation: AAB07682.1. Different initiation.
CCDSiCCDS52371.1. [Q61194-1]
PIRiT42642.
RefSeqiNP_035213.2. NM_011083.2.
UniGeneiMm.3810.

Genome annotation databases

GeneIDi18704.
KEGGimmu:18704.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U52193 mRNA. Translation: AAC52604.1.
AK049609 mRNA. No translation available.
U55772 mRNA. Translation: AAB07682.1. Different initiation.
CCDSiCCDS52371.1. [Q61194-1]
PIRiT42642.
RefSeqiNP_035213.2. NM_011083.2.
UniGeneiMm.3810.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2B3RX-ray2.30A/B1561-1686[»]
ProteinModelPortaliQ61194.
SMRiQ61194.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202158. 4 interactors.
IntActiQ61194. 1 interactor.
STRINGi10090.ENSMUSP00000126092.

PTM databases

iPTMnetiQ61194.
PhosphoSitePlusiQ61194.

Proteomic databases

EPDiQ61194.
PaxDbiQ61194.
PeptideAtlasiQ61194.
PRIDEiQ61194.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi18704.
KEGGimmu:18704.

Organism-specific databases

CTDi5286.
MGIiMGI:1203729. Pik3c2a.

Phylogenomic databases

eggNOGiKOG0905. Eukaryota.
COG5032. LUCA.
HOGENOMiHOG000006920.
HOVERGENiHBG082099.
InParanoidiQ61194.
KOiK00923.
PhylomeDBiQ61194.

Enzyme and pathway databases

BRENDAi2.7.1.154. 3474.

Miscellaneous databases

ChiTaRSiPik3c2a. mouse.
EvolutionaryTraceiQ61194.
PROiQ61194.
SOURCEiSearch...

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. 2 hits.
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. 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]
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]
ProtoNetiSearch...

Entry informationi

Entry nameiP3C2A_MOUSE
AccessioniPrimary (citable) accession number: Q61194
Secondary accession number(s): Q61182
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: August 30, 2005
Last modified: November 2, 2016
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.