PIK3C2A

Protein identityUniProt · HPA

UniProt accession

O00443

Gene

PIK3C2A

Ensembl

ENSG00000011405

Chromosome

11

Canonical length

1686 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Vesicles,Cytosol

OverviewNCBI Gene

The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1686 residues, UniProt reviewed canonical sequence.

>O00443|PIK3C2A
     1  MAQISSNSGF KECPSSHPEP TRAKDVDKEE ALQMEAEALA KLQKDRQVTD NQRGFELSSS
    61  TRKKAQVYNK QDYDLMVFPE SDSQKRALDI DVEKLTQAEL EKLLLDDSFE TKKTPVLPVT
   121  PILSPSFSAQ LYFRPTIQRG QWPPGLPGPS TYALPSIYPS TYSKQAAFQN GFNPRMPTFP
   181  STEPIYLSLP GQSPYFSYPL TPATPFHPQG SLPIYRPVVS TDMAKLFDKI ASTSEFLKNG
   241  KARTDLEITD SKVSNLQVSP KSEDISKFDW LDLDPLSKPK VDNVEVLDHE EEKNVSSLLA
   301  KDPWDAVLLE ERSTANCHLE RKVNGKSLSV ATVTRSQSLN IRTTQLAKAQ GHISQKDPNG
   361  TSSLPTGSSL LQEVEVQNEE MAAFCRSITK LKTKFPYTNH RTNPGYLLSP VTAQRNICGE
   421  NASVKVSIDI EGFQLPVTFT CDVSSTVEII IMQALCWVHD DLNQVDVGSY VLKVCGQEEV
   481  LQNNHCLGSH EHIQNCRKWD TEIRLQLLTF SAMCQNLART AEDDETPVDL NKHLYQIEKP
   541  CKEAMTRHPV EELLDSYHNQ VELALQIENQ HRAVDQVIKA VRKICSALDG VETLAITESV
   601  KKLKRAVNLP RSKTADVTSL FGGEDTSRSS TRGSLNPENP VQVSINQLTA AIYDLLRLHA
   661  NSGRSPTDCA QSSKSVKEAW TTTEQLQFTI FAAHGISSNW VSNYEKYYLI CSLSHNGKDL
   721  FKPIQSKKVG TYKNFFYLIK WDELIIFPIQ ISQLPLESVL HLTLFGILNQ SSGSSPDSNK
   781  QRKGPEALGK VSLPLFDFKR FLTCGTKLLY LWTSSHTNSV PGTVTKKGYV MERIVLQVDF
   841  PSPAFDIIYT TPQVDRSIIQ QHNLETLEND IKGKLLDILH KDSSLGLSKE DKAFLWEKRY
   901  YCFKHPNCLP KILASAPNWK WVNLAKTYSL LHQWPALYPL IALELLDSKF ADQEVRSLAV
   961  TWIEAISDDE LTDLLPQFVQ ALKYEIYLNS SLVQFLLSRA LGNIQIAHNL YWLLKDALHD
  1021  VQFSTRYEHV LGALLSVGGK RLREELLKQT KLVQLLGGVA EKVRQASGSA RQVVLQRSME
  1081  RVQSFFQKNK CRLPLKPSLV AKELNIKSCS FFSSNAVPLK VTMVNADPMG EEINVMFKVG
  1141  EDLRQDMLAL QMIKIMDKIW LKEGLDLRMV IFKCLSTGRD RGMVELVPAS DTLRKIQVEY
  1201  GVTGSFKDKP LAEWLRKYNP SEEEYEKASE NFIYSCAGCC VATYVLGICD RHNDNIMLRS
  1261  TGHMFHIDFG KFLGHAQMFG SFKRDRAPFV LTSDMAYVIN GGEKPTIRFQ LFVDLCCQAY
  1321  NLIRKQTNLF LNLLSLMIPS GLPELTSIQD LKYVRDALQP QTTDAEATIF FTRLIESSLG
  1381  SIATKFNFFI HNLAQLRFSG LPSNDEPILS FSPKTYSFRQ DGRIKEVSVF TYHKKYNPDK
  1441  HYIYVVRILR EGQIEPSFVF RTFDEFQELH NKLSIIFPLW KLPGFPNRMV LGRTHIKDVA
  1501  AKRKIELNSY LQSLMNASTD VAECDLVCTF FHPLLRDEKA EGIARSADAG SFSPTPGQIG
  1561  GAVKLSISYR NGTLFIMVMH IKDLVTEDGA DPNPYVKTYL LPDNHKTSKR KTKISRKTRN
  1621  PTFNEMLVYS GYSKETLRQR ELQLSVLSAE SLRENFFLGG VTLPLKDFNL SKETVKWYQL
  1681  TAATYL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PIK3C2A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PIK3C2A.

Disease | AllUniProt

Conditions PIK3C2A is implicated in, by any mechanism.

• Oculoskeletodental syndrome (OCSKD) MIM:618440

Disease | GeneticClinVar

30 pathogenic / likely-pathogenic of 616 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Oculocerebrodental syndrome
• Short stature
• Fetal anomalies with a likely genetic cause

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.36

gnomAD pLI

0.01

gnomAD missense Z

1.3

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell migration
• clathrin coat assembly
• endocytosis
• epidermal growth factor receptor signaling pathway
• exocytosis
• insulin receptor signaling pathway
• membrane organization
• phosphatidylinositol 3-kinase/protein kinase B signal transduction
• phosphatidylinositol biosynthetic process
• phosphatidylinositol-3-phosphate biosynthetic process
• phosphatidylinositol-mediated signaling
• platelet-derived growth factor receptor signaling pathway
• positive regulation of autophagy
• positive regulation of cell migration involved in sprouting angiogenesis
• vascular associated smooth muscle contraction

Molecular functions

• 1-phosphatidylinositol-3-kinase activity
• 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity
• 1-phosphatidylinositol-4-phosphate 3-kinase activity
• ATP binding
• clathrin binding
• phosphatidylinositol binding

Cellular components

• clathrin-coated vesicle
• cytoplasm
• cytosol
• extracellular exosome
• membrane
• nucleoplasm
• plasma membrane
• trans-Golgi network
• vesicle

Protein domainsUniProt · Pfam · InterPro

• C2 domain
• Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain
• Phosphatidylinositol 3-/4-kinase, catalytic domain
• Phosphoinositide 3-kinase, accessory (PIK) domain
• Phox homology
• C2 phosphatidylinositol 3-kinase-type domain
• Protein kinase-like domain superfamily
• Phosphatidylinositol 3-/4-kinase
• Armadillo-type fold
• Phosphatidylinositol 3-/4-kinase, conserved site
• Ubiquitin-like domain superfamily
• C2 domain superfamily
• PX domain superfamily
• Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily
• Phosphoinositide 3-kinase, accessory (PIK) domain superfamily
• C2 domain
• Phosphatidylinositol 3- and 4-kinase
• Phosphoinositide 3-kinase family, accessory domain (PIK domain)
• PX domain
• Phosphoinositide 3-kinase C2
• PI3-kinase family, ras-binding domain
• Phosphatidylinositol 3-kinase C2-alpha, catalytic domain
• Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha, PX domain

KeywordsUniProt

• Acetylation
• ATP-binding
• Cataract
• Cell membrane
• Cytoplasm
• Cytoplasmic vesicle
• Dwarfism
• Endocytosis
• Exocytosis
• Golgi apparatus
• Kinase
• Lipid metabolism
• Membrane
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Transferase

InteractionsUniProt · HPA

Protein binding partners of PIK3C2A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CLTA
• CLTB
• STAMBP
• YWHAB
• YWHAE
• YWHAG
• YWHAZ