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Details on Person UniProt:O35904 Pik3cd

Class:IdReferenceGeneProduct:97549
_chainChangeLogchain:1-1043 added on Sat February 7 2015
_displayNameUniProt:O35904 Pik3cd
_timestamp2023-11-03 16:25:08
chainchain:1-1043
checksumAD8DE07D8F847795
commentFUNCTION Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:9235916). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function.CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+)CATALYTIC ACTIVITY 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol 3,4,5-triphosphate) + ADP + H(+)ACTIVITY REGULATION Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. Among other effects, IC87114 reduces allergic responses, prevents the recruitment of antigen-specific T cells into target tissue, and affects natural killer cell chemotaxis.PATHWAY Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.SUBUNIT Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS and HRAS.INTERACTION Abundantly expressed in adult mouse spleen as well as in testis (PubMed:9235916). Isoform 1 is expressed in spleen and lung (at protein level). Isoform 1 is expressed predominantly in leukocytes.PTM Autophosphorylation on Ser-1038 results in the almost complete inactivation of the lipid kinase activity.DISRUPTION PHENOTYPE Null mutants are viable and fertile but display defective adaptive and innate immune responses due to signaling defects in multiple cell types including B-, T- and mast and natural killer cells.SIMILARITY Belongs to the PI3/PI4-kinase family.
descriptionrecommendedName: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform shortName: PI3-kinase subunit delta shortName: PI3K-delta shortName: PI3Kdelta shortName: PtdIns-3-kinase subunit delta ecNumber evidence="2"2.7.1.137 ecNumber evidence="2"2.7.1.153 alternativeName: Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta shortName: PtdIns-3-kinase subunit p110-delta shortName: p110delta
geneNamePik3cd
identifierO35904
isSequenceChangedFALSE
keyword3D-structure
Adaptive immunity
Alternative splicing
ATP-binding
Chemotaxis
Cytoplasm
Differentiation
Immunity
Inflammatory response
Innate immunity
Kinase
Lipid metabolism
Nucleotide-binding
Phosphoprotein
Reference proteome
Transferase
modified[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
[InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12
[InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39
[InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18
[InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35
[InstanceEdit:423310] Kanapin, AA
[InstanceEdit:435478] Kanapin, AA
[InstanceEdit:435871] Kanapin, AA
[InstanceEdit:447347] Kanapin, AA
[InstanceEdit:525883] Kanapin, AA
[InstanceEdit:613449] Kanapin, AA
[InstanceEdit:797602] Kanapin, AA
[InstanceEdit:937368] Yung, CK
[InstanceEdit:1042053] Yung, CK
[InstanceEdit:1220657] Yung, CK
[InstanceEdit:1300696] Yung, CK
[InstanceEdit:1301627] Yung, CK
[InstanceEdit:1551960] Weiser, JD
[InstanceEdit:1995863] Weiser, JD
[InstanceEdit:2132304] Weiser, JD
[InstanceEdit:2265580] Weiser, JD
[InstanceEdit:2587579] Weiser, JD
[InstanceEdit:5263031] Weiser, JD
[InstanceEdit:5433710] Weiser, JD
[InstanceEdit:5618415] Weiser, JD
[InstanceEdit:5634237] Weiser, JD
[InstanceEdit:5673015] Weiser, JD
[InstanceEdit:9037114] Weiser, JD
[InstanceEdit:9627708] Weiser, JD
[InstanceEdit:9637257] Weiser, JD
[InstanceEdit:9657908] Weiser, JD
[InstanceEdit:9676415] Weiser, JD
[InstanceEdit:9688885] Weiser, JD
[InstanceEdit:9715482] Weiser, JD
[InstanceEdit:9730071] Weiser, JD
[InstanceEdit:9767224] Weiser, Joel
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
namePik3cd
referenceDatabase[ReferenceDatabase:2] UniProt
secondaryIdentifierPK3CD_MOUSE
Q8CJ28
sequenceLength1043
species[Species:48892] Mus musculus
(isoformParent)[ReferenceIsoform:8965295] UniProt:O35904-1 Pik3cd [Mus musculus]
[ReferenceIsoform:8965296] UniProt:O35904-2 Pik3cd [Mus musculus]
(referenceEntity)[EntityWithAccessionedSequence:9027215] Pik3cd [cytosol] [Mus musculus]
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