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O00329

- PK3CD_HUMAN

UniProt

O00329 - PK3CD_HUMAN

Protein

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform

Gene

PIK3CD

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 2 (07 Jun 2005)
      Previous versions | rss
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    Functioni

    Phosphoinositide-3-kinase (PI3K) that phosphorylates PftdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). 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. Have 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. Have 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. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.2 Publications

    Catalytic activityi

    ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate.

    Enzyme regulationi

    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 µM. IC87114 blocks T-cell receptor signaling in naive and memory T-cells and reduces cytokine production by memory T-cells.1 Publication

    Pathwayi

    GO - Molecular functioni

    1. 1-phosphatidylinositol-3-kinase activity Source: UniProtKB
    2. 1-phosphatidylinositol-4-phosphate 3-kinase activity Source: RefGenome
    3. ATP binding Source: UniProtKB-KW
    4. phosphatidylinositol 3-kinase activity Source: UniProtKB
    5. phosphatidylinositol-4,5-bisphosphate 3-kinase activity Source: RefGenome
    6. protein binding Source: IntAct

    GO - Biological processi

    1. adaptive immune response Source: UniProtKB
    2. B cell activation Source: UniProtKB
    3. B cell chemotaxis Source: UniProtKB
    4. B cell homeostasis Source: Ensembl
    5. B cell receptor signaling pathway Source: UniProtKB
    6. cytokine production Source: UniProtKB
    7. epidermal growth factor receptor signaling pathway Source: Reactome
    8. Fc-epsilon receptor signaling pathway Source: Reactome
    9. fibroblast growth factor receptor signaling pathway Source: Reactome
    10. inflammatory response Source: UniProtKB
    11. innate immune response Source: UniProtKB
    12. mast cell chemotaxis Source: UniProtKB
    13. mast cell degranulation Source: UniProtKB
    14. mast cell differentiation Source: UniProtKB
    15. natural killer cell activation Source: UniProtKB
    16. natural killer cell chemotaxis Source: UniProtKB
    17. natural killer cell differentiation Source: UniProtKB
    18. neurotrophin TRK receptor signaling pathway Source: Reactome
    19. neutrophil chemotaxis Source: UniProtKB
    20. neutrophil extravasation Source: UniProtKB
    21. phosphatidylinositol 3-kinase signaling Source: UniProtKB
    22. phosphatidylinositol-3-phosphate biosynthetic process Source: GOC
    23. phosphatidylinositol biosynthetic process Source: Reactome
    24. phosphatidylinositol-mediated signaling Source: Reactome
    25. phospholipid metabolic process Source: Reactome
    26. protein phosphorylation Source: UniProtKB
    27. respiratory burst involved in defense response Source: UniProtKB
    28. signal transduction Source: UniProtKB
    29. small molecule metabolic process Source: Reactome
    30. T cell activation Source: UniProtKB
    31. T cell chemotaxis Source: UniProtKB
    32. T cell differentiation Source: UniProtKB
    33. T cell receptor signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Adaptive immunity, Chemotaxis, Differentiation, Immunity, Inflammatory response, Innate immunity

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000171608-MONOMER.
    BRENDAi2.7.1.137. 2681.
    ReactomeiREACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_23787. Regulation of signaling by CBL.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinkiO00329.
    UniPathwayiUPA00220.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (EC:2.7.1.153)
    Short name:
    PI3-kinase subunit delta
    Short name:
    PI3K-delta
    Short name:
    PI3Kdelta
    Short name:
    PtdIns-3-kinase subunit delta
    Alternative name(s):
    Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta
    Short name:
    PtdIns-3-kinase subunit p110-delta
    Short name:
    p110delta
    Gene namesi
    Name:PIK3CD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:8977. PIK3CD.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. mast cell granule Source: GOC
    3. phosphatidylinositol 3-kinase complex Source: UniProtKB
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Activated PI3K-delta syndrome (APDS) [MIM:615513]: A disorder characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, reduced immunoglobulin G2 levels in serum, and impaired vaccine responses.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1021 – 10211E → K in APDS; results in gain of function causing enhanced membrane association and kinase activity. 1 Publication
    VAR_070918

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi894 – 8941R → P: Abolishes lipid and protein kinase activities. 1 Publication
    Mutagenesisi1039 – 10391S → A: Abolishes autophosphorylation, no effect on lipid kinase activity. 1 Publication
    Mutagenesisi1039 – 10391S → D or E: Abolishes autophosphorylation, reduced lipid kinase activity. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi615513. phenotype.
    PharmGKBiPA33310.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10441044Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoformPRO_0000088790Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei524 – 5241Phosphotyrosine1 Publication
    Modified residuei1039 – 10391Phosphoserine; by autocatalysis2 Publications

    Post-translational modificationi

    Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity.2 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO00329.
    PaxDbiO00329.
    PRIDEiO00329.

    PTM databases

    PhosphoSiteiO00329.

    Expressioni

    Tissue specificityi

    Isoform 2 is expressed in normal thymus, lung and spleen tissues, and is detected at low levels in normal lysates from colon and ovarian biopsies, at elevated levels in lysates from colorectal tumors and is abundantly expressed in some ovarian tumors (at protein level). Both isoform 1 and isoform 2 are widely expressed. Isoform 1 is expressed predominantly in leukocytes.1 Publication

    Gene expression databases

    ArrayExpressiO00329.
    BgeeiO00329.
    CleanExiHS_PIK3CD.
    GenevestigatoriO00329.

    Organism-specific databases

    HPAiCAB015420.

    Interactioni

    Subunit structurei

    Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS By similarity. Interacts with HRAS.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HRASP011122EBI-6470902,EBI-350145

    Protein-protein interaction databases

    BioGridi111311. 9 interactions.
    IntActiO00329. 8 interactions.
    STRINGi9606.ENSP00000366563.

    Structurei

    3D structure databases

    ProteinModelPortaliO00329.
    SMRiO00329. Positions 20-102, 109-1027.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 10590PI3K-ABDPROSITE-ProRule annotationAdd
    BLAST
    Domaini187 – 27892PI3K-RBDPROSITE-ProRule annotationAdd
    BLAST
    Domaini319 – 476158C2 PI3K-typePROSITE-ProRule annotationAdd
    BLAST
    Domaini497 – 674178PIK helicalPROSITE-ProRule annotationAdd
    BLAST
    Domaini774 – 1041268PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation
    Contains 1 C2 PI3K-type domain.PROSITE-ProRule annotation
    Contains 1 PI3K-ABD 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

    Phylogenomic databases

    eggNOGiCOG5032.
    HOGENOMiHOG000252911.
    HOVERGENiHBG052721.
    KOiK00922.
    OrthoDBiEOG70CR65.
    PhylomeDBiO00329.
    TreeFamiTF102031.

    Family and domain databases

    Gene3Di1.10.1070.11. 1 hit.
    1.25.40.70. 1 hit.
    2.60.40.150. 1 hit.
    InterProiIPR016024. ARM-type_fold.
    IPR000008. C2_dom.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR003113. PI3K_adapt-bd_dom.
    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.
    PfamiPF00454. PI3_PI4_kinase. 1 hit.
    PF00792. PI3K_C2. 1 hit.
    PF02192. PI3K_p85B. 1 hit.
    PF00794. PI3K_rbd. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view]
    SMARTiSM00142. PI3K_C2. 1 hit.
    SM00143. PI3K_p85B. 1 hit.
    SM00144. PI3K_rbd. 1 hit.
    SM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view]
    SUPFAMiSSF48371. SSF48371. 1 hit.
    SSF49562. SSF49562. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    PS51544. PI3K_ABD. 1 hit.
    PS51547. PI3K_C2. 1 hit.
    PS51546. PI3K_RBD. 1 hit.
    PS51545. PIK_HELICAL. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O00329-1) [UniParc]FASTAAdd to Basket

    Also known as: p110-delta

    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

    MPPGVDCPME FWTKEENQSV VVDFLLPTGV YLNFPVSRNA NLSTIKQLLW     50
    HRAQYEPLFH MLSGPEAYVF TCINQTAEQQ ELEDEQRRLC DVQPFLPVLR 100
    LVAREGDRVK KLINSQISLL IGKGLHEFDS LCDPEVNDFR AKMCQFCEEA 150
    AARRQQLGWE AWLQYSFPLQ LEPSAQTWGP GTLRLPNRAL LVNVKFEGSE 200
    ESFTFQVSTK DVPLALMACA LRKKATVFRQ PLVEQPEDYT LQVNGRHEYL 250
    YGSYPLCQFQ YICSCLHSGL TPHLTMVHSS SILAMRDEQS NPAPQVQKPR 300
    AKPPPIPAKK PSSVSLWSLE QPFRIELIQG SKVNADERMK LVVQAGLFHG 350
    NEMLCKTVSS SEVSVCSEPV WKQRLEFDIN ICDLPRMARL CFALYAVIEK 400
    AKKARSTKKK SKKADCPIAW ANLMLFDYKD QLKTGERCLY MWPSVPDEKG 450
    ELLNPTGTVR SNPNTDSAAA LLICLPEVAP HPVYYPALEK ILELGRHSEC 500
    VHVTEEEQLQ LREILERRGS GELYEHEKDL VWKLRHEVQE HFPEALARLL 550
    LVTKWNKHED VAQMLYLLCS WPELPVLSAL ELLDFSFPDC HVGSFAIKSL 600
    RKLTDDELFQ YLLQLVQVLK YESYLDCELT KFLLDRALAN RKIGHFLFWH 650
    LRSEMHVPSV ALRFGLILEA YCRGSTHHMK VLMKQGEALS KLKALNDFVK 700
    LSSQKTPKPQ TKELMHLCMR QEAYLEALSH LQSPLDPSTL LAEVCVEQCT 750
    FMDSKMKPLW IMYSNEEAGS GGSVGIIFKN GDDLRQDMLT LQMIQLMDVL 800
    WKQEGLDLRM TPYGCLPTGD RTGLIEVVLR SDTIANIQLN KSNMAATAAF 850
    NKDALLNWLK SKNPGEALDR AIEEFTLSCA GYCVATYVLG IGDRHSDNIM 900
    IRESGQLFHI DFGHFLGNFK TKFGINRERV PFILTYDFVH VIQQGKTNNS 950
    EKFERFRGYC ERAYTILRRH GLLFLHLFAL MRAAGLPELS CSKDIQYLKD 1000
    SLALGKTEEE ALKHFRVKFN EALRESWKTK VNWLAHNVSK DNRQ 1044
    Length:1,044
    Mass (Da):119,479
    Last modified:June 7, 2005 - v2
    Checksum:iA38B5D1A1081A3D0
    GO
    Isoform 2 (identifier: O00329-2) [UniParc]FASTAAdd to Basket

    Also known as: p37-delta

    The sequence of this isoform differs from the canonical sequence as follows:
         201-300: ESFTFQVSTK...NPAPQVQKPR → VSPCVACGIQ...GRLHAAGERQ
         302-1044: Missing.

    Show »
    Length:301
    Mass (Da):33,107
    Checksum:i18DF7554E3D50988
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti253 – 2531S → N in AAC25677. (PubMed:9235916)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1021 – 10211E → K in APDS; results in gain of function causing enhanced membrane association and kinase activity. 1 Publication
    VAR_070918

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei201 – 300100ESFTF…VQKPR → VSPCVACGIQAALSMGSTSS VKLLSHPQAPLPQWHQMVFA RCLCMCGAQLNVPPGELHLP GVHQGRAAGADGLCPAEEGH SVPAAAGGAAGRLHAAGERQ in isoform 2. 1 PublicationVSP_044409Add
    BLAST
    Alternative sequencei302 – 1044743Missing in isoform 2. 1 PublicationVSP_044410Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y10055 mRNA. Translation: CAA71149.2.
    U86453 mRNA. Translation: AAC25677.1.
    JN190435 mRNA. Translation: AEK81610.1.
    DQ263594 mRNA. Translation: ABB83814.1.
    AL691449 Genomic DNA. Translation: CAI15703.1.
    BC132919 mRNA. Translation: AAI32920.1.
    BC132921 mRNA. Translation: AAI32922.1.
    CCDSiCCDS104.1. [O00329-1]
    RefSeqiNP_005017.3. NM_005026.3. [O00329-1]
    XP_006710749.1. XM_006710686.1. [O00329-1]
    XP_006710750.1. XM_006710687.1. [O00329-1]
    XP_006710751.1. XM_006710688.1. [O00329-1]
    XP_006710752.1. XM_006710689.1. [O00329-1]
    UniGeneiHs.518451.

    Genome annotation databases

    EnsembliENST00000377346; ENSP00000366563; ENSG00000171608. [O00329-1]
    GeneIDi5293.
    KEGGihsa:5293.
    UCSCiuc001aqb.4. human. [O00329-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y10055 mRNA. Translation: CAA71149.2 .
    U86453 mRNA. Translation: AAC25677.1 .
    JN190435 mRNA. Translation: AEK81610.1 .
    DQ263594 mRNA. Translation: ABB83814.1 .
    AL691449 Genomic DNA. Translation: CAI15703.1 .
    BC132919 mRNA. Translation: AAI32920.1 .
    BC132921 mRNA. Translation: AAI32922.1 .
    CCDSi CCDS104.1. [O00329-1 ]
    RefSeqi NP_005017.3. NM_005026.3. [O00329-1 ]
    XP_006710749.1. XM_006710686.1. [O00329-1 ]
    XP_006710750.1. XM_006710687.1. [O00329-1 ]
    XP_006710751.1. XM_006710688.1. [O00329-1 ]
    XP_006710752.1. XM_006710689.1. [O00329-1 ]
    UniGenei Hs.518451.

    3D structure databases

    ProteinModelPortali O00329.
    SMRi O00329. Positions 20-102, 109-1027.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111311. 9 interactions.
    IntActi O00329. 8 interactions.
    STRINGi 9606.ENSP00000366563.

    Chemistry

    BindingDBi O00329.
    ChEMBLi CHEMBL2111432.
    GuidetoPHARMACOLOGYi 2155.

    PTM databases

    PhosphoSitei O00329.

    Proteomic databases

    MaxQBi O00329.
    PaxDbi O00329.
    PRIDEi O00329.

    Protocols and materials databases

    DNASUi 5293.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000377346 ; ENSP00000366563 ; ENSG00000171608 . [O00329-1 ]
    GeneIDi 5293.
    KEGGi hsa:5293.
    UCSCi uc001aqb.4. human. [O00329-1 ]

    Organism-specific databases

    CTDi 5293.
    GeneCardsi GC01P009711.
    HGNCi HGNC:8977. PIK3CD.
    HPAi CAB015420.
    MIMi 602839. gene.
    615513. phenotype.
    neXtProti NX_O00329.
    PharmGKBi PA33310.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5032.
    HOGENOMi HOG000252911.
    HOVERGENi HBG052721.
    KOi K00922.
    OrthoDBi EOG70CR65.
    PhylomeDBi O00329.
    TreeFami TF102031.

    Enzyme and pathway databases

    UniPathwayi UPA00220 .
    BioCyci MetaCyc:ENSG00000171608-MONOMER.
    BRENDAi 2.7.1.137. 2681.
    Reactomei REACT_118700. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
    REACT_121025. Synthesis of PIPs at the plasma membrane.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_23787. Regulation of signaling by CBL.
    REACT_23837. Interleukin-3, 5 and GM-CSF signaling.
    REACT_23891. Interleukin receptor SHC signaling.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinki O00329.

    Miscellaneous databases

    ChiTaRSi PIK3CD. human.
    GeneWikii P110%CE%B4.
    GenomeRNAii 5293.
    NextBioi 20454.
    PROi O00329.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O00329.
    Bgeei O00329.
    CleanExi HS_PIK3CD.
    Genevestigatori O00329.

    Family and domain databases

    Gene3Di 1.10.1070.11. 1 hit.
    1.25.40.70. 1 hit.
    2.60.40.150. 1 hit.
    InterProi IPR016024. ARM-type_fold.
    IPR000008. C2_dom.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR003113. PI3K_adapt-bd_dom.
    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 PF00454. PI3_PI4_kinase. 1 hit.
    PF00792. PI3K_C2. 1 hit.
    PF02192. PI3K_p85B. 1 hit.
    PF00794. PI3K_rbd. 1 hit.
    PF00613. PI3Ka. 1 hit.
    [Graphical view ]
    SMARTi SM00142. PI3K_C2. 1 hit.
    SM00143. PI3K_p85B. 1 hit.
    SM00144. PI3K_rbd. 1 hit.
    SM00145. PI3Ka. 1 hit.
    SM00146. PI3Kc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48371. SSF48371. 1 hit.
    SSF49562. SSF49562. 1 hit.
    SSF54236. SSF54236. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00915. PI3_4_KINASE_1. 1 hit.
    PS00916. PI3_4_KINASE_2. 1 hit.
    PS50290. PI3_4_KINASE_3. 1 hit.
    PS51544. PI3K_ABD. 1 hit.
    PS51547. PI3K_C2. 1 hit.
    PS51546. PI3K_RBD. 1 hit.
    PS51545. PIK_HELICAL. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. Vanhaesebroeck B.A.M.
      Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION TO 675.
    3. "p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes."
      Chantry D., Vojtek A., Kashishian A., Holtzman D.A., Wood C., Gray P.W., Cooper J.A., Hoekstra M.F.
      J. Biol. Chem. 272:19236-19241(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "p37delta is a new isoform of PI3K p110delta that increases cell proliferation and is overexpressed in tumors."
      Fransson S., Uv A., Eriksson H., Andersson M.K., Wettergren Y., Bergo M., Ejeskar K.
      Oncogene 31:3277-3286(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBUNIT, INTERACTION WITH HRAS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Tissue: Peripheral blood leukocyte.
    5. "Variations in the human phosphoinositide-3-kinase p110 gene in children with primary B-cell immunodeficiency of unknown etiology."
      Jou S.-T., Chien Y.-H., Yang Y.-H., Shyur S.-D., Chou C.-C., Chiang B.-L.
      Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    6. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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).
    8. "Autophosphorylation of p110 delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo."
      Vanhaesebroeck B., Higashi K., Raven C., Welham M., Anderson S., Brennan P., Ward S.G., Waterfield M.D.
      EMBO J. 18:1292-1302(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1031-1040, PHOSPHORYLATION AT SER-1039, MUTAGENESIS OF ARG-894 AND SER-1039.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-524 AND SER-1039, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans."
      Soond D.R., Bjorgo E., Moltu K., Dale V.Q., Patton D.T., Torgersen K.M., Galleway F., Twomey B., Clark J., Gaston J.S.H., Tasken K., Bunyard P., Okkenhaug K.
      Blood 115:2203-2213(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN T-CELLS, ENZYME REGULATION.
    11. "PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?"
      Rommel C., Camps M., Ji H.
      Nat. Rev. Immunol. 7:191-201(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    12. "Phosphoinositide 3-kinase delta (PI3Kdelta) in leukocyte signaling and function."
      Fung-Leung W.-P.
      Cell. Signal. 23:603-608(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    13. Cited for: VARIANT APDS LYS-1021, CHARACTERIZATION OF VARIANT APDS LYS-1021.

    Entry informationi

    Entry nameiPK3CD_HUMAN
    AccessioniPrimary (citable) accession number: O00329
    Secondary accession number(s): A6NCG0
    , G1FFP1, O15445, Q5SR49
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: June 7, 2005
    Last modified: October 1, 2014
    This is version 139 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

    Miscellaneous

    IC87114 inhibitor reduces passive cutaneous anaphylaxis, attenuates allergic airway inflammation and hyperresponsiveness and allergen induced rhinitis response. Inhibitors may have therapeutic potential for the treatment of immune system-mediated diseases such as auto-immune diseases, inflammation and allergy (PubMed:20940048; PubMed:17290298).

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3