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UniProtKB - O35904 (PK3CD_MOUSE)

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Protein

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

Gene

Pik3cd

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.7 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. Among other effects, IC87114 reduces allergic responses, prevents the recruitment of antigen-specific T cells into target tissue, and affects natural killer cell chemotaxis.3 Publications

Pathwayi: phosphatidylinositol phosphate biosynthesis

This protein is involved in the pathway phosphatidylinositol phosphate biosynthesis, which is part of Phospholipid metabolism.
View all proteins of this organism that are known to be involved in the pathway phosphatidylinositol phosphate biosynthesis and in Phospholipid metabolism.

GO - Molecular functioni

Complete GO annotation...

GO - Biological processi

  • adaptive immune response Source: GO_Central
  • B cell activation Source: MGI
  • B cell homeostasis Source: MGI
  • cell chemotaxis Source: GO_Central
  • cell differentiation Source: UniProtKB-KW
  • cell surface receptor signaling pathway Source: MGI
  • defense response to fungus Source: MGI
  • homeostasis of number of cells Source: MGI
  • inflammatory response Source: GO_Central
  • innate immune response Source: GO_Central
  • phosphatidylinositol 3-kinase signaling Source: MGI
  • phosphorylation Source: MGI
  • platelet activation Source: GO_Central
  • positive regulation of cell migration Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of neutrophil apoptotic process Source: MGI
  • protein phosphorylation Source: GO_Central
Complete GO annotation...

Keywordsi

Molecular functionKinase, Transferase
Biological processAdaptive immunity, Chemotaxis, Differentiation, Immunity, Inflammatory response, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.153. 3474.
ReactomeiR-MMU-114604. GPVI-mediated activation cascade.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-1660499. Synthesis of PIPs at the plasma membrane.
R-MMU-392451. G beta:gamma signalling through PI3Kgamma.
R-MMU-512988. Interleukin-3, 5 and GM-CSF signaling.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-8853659. RET signaling.
R-MMU-912526. Interleukin receptor SHC signaling.
R-MMU-912631. Regulation of signaling by CBL.
R-MMU-983695. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1098211. Pik3cd.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

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.5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi910D → A: Inhibits lipid kinase activity. Mice are viable and fertile but display defective adaptive and innate immune responses Signaling defects in B-cells, T-cells, mast cells and natural killer cells. Reduced B and T-cell receptor signaling. Affects development and differentiation of B -ells. Reduced memory T-cell number. Affects B- and T-cell proliferation. Attenuates immune responses in vivo. Induces inflammatory bowel disease development. Lost TCR-induced migration and localization to antigenic tissue. Affects natural killer cell maturation and cytokine production. 4 Publications1

Chemistry databases

ChEMBLiCHEMBL2216745.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000887911 – 1043Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoformAdd BLAST1043

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei315PhosphoserineBy similarity1
Modified residuei523PhosphotyrosineBy similarity1
Modified residuei1038Phosphoserine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylation on Ser-1038 results in the almost complete inactivation of the lipid kinase activity.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO35904.
MaxQBiO35904.
PaxDbiO35904.
PRIDEiO35904.

PTM databases

iPTMnetiO35904.
PhosphoSitePlusiO35904.

Expressioni

Tissue specificityi

Isoform 1 is expressed in spleen and lung (at protein level). Isoform 1 is expressed predominantly in leukocytes.1 Publication

Gene expression databases

BgeeiENSMUSG00000039936.
ExpressionAtlasiO35904. baseline and differential.
GenevisibleiO35904. MM.

Interactioni

Subunit structurei

Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS and HRAS.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Pik3r1P264502EBI-6470774,EBI-641764

Protein-protein interaction databases

BioGridi202161. 2 interactors.
DIPiDIP-39841N.
IntActiO35904. 7 interactors.
STRINGi10090.ENSMUSP00000101315.

Chemistry databases

BindingDBiO35904.

Structurei

Secondary structure

11043
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi110 – 121Combined sources12
Helixi126 – 130Combined sources5
Helixi134 – 154Combined sources21
Helixi159 – 166Combined sources8
Turni173 – 175Combined sources3
Beta strandi189 – 198Combined sources10
Beta strandi202 – 208Combined sources7
Helixi213 – 227Combined sources15
Helixi236 – 238Combined sources3
Beta strandi239 – 243Combined sources5
Beta strandi252 – 254Combined sources3
Helixi256 – 258Combined sources3
Helixi260 – 268Combined sources9
Beta strandi273 – 278Combined sources6
Helixi279 – 288Combined sources10
Helixi316 – 318Combined sources3
Beta strandi321 – 331Combined sources11
Beta strandi340 – 349Combined sources10
Beta strandi352 – 355Combined sources4
Beta strandi363 – 365Combined sources3
Beta strandi370 – 380Combined sources11
Helixi381 – 383Combined sources3
Beta strandi389 – 397Combined sources9
Beta strandi416 – 426Combined sources11
Beta strandi430 – 432Combined sources3
Beta strandi435 – 440Combined sources6
Beta strandi455 – 457Combined sources3
Turni465 – 467Combined sources3
Beta strandi470 – 475Combined sources6
Beta strandi478 – 481Combined sources4
Helixi488 – 493Combined sources6
Helixi511 – 514Combined sources4
Helixi524 – 532Combined sources9
Helixi534 – 540Combined sources7
Helixi542 – 544Combined sources3
Helixi545 – 549Combined sources5
Beta strandi554 – 556Combined sources3
Helixi557 – 568Combined sources12
Helixi575 – 581Combined sources7
Helixi589 – 599Combined sources11
Helixi604 – 617Combined sources14
Helixi618 – 620Combined sources3
Beta strandi622 – 625Combined sources4
Helixi627 – 638Combined sources12
Helixi640 – 651Combined sources12
Turni652 – 655Combined sources4
Helixi657 – 673Combined sources17
Helixi675 – 701Combined sources27
Turni702 – 704Combined sources3
Helixi707 – 718Combined sources12
Helixi721 – 727Combined sources7
Beta strandi728 – 732Combined sources5
Beta strandi735 – 740Combined sources6
Helixi745 – 747Combined sources3
Beta strandi753 – 755Combined sources3
Beta strandi758 – 763Combined sources6
Turni765 – 767Combined sources3
Helixi768 – 771Combined sources4
Beta strandi773 – 781Combined sources9
Helixi784 – 802Combined sources19
Beta strandi814 – 818Combined sources5
Beta strandi821 – 825Combined sources5
Beta strandi828 – 832Combined sources5
Helixi833 – 837Combined sources5
Beta strandi841 – 843Combined sources3
Helixi850 – 852Combined sources3
Helixi853 – 861Combined sources9
Turni863 – 865Combined sources3
Helixi866 – 888Combined sources23
Beta strandi897 – 901Combined sources5
Beta strandi906 – 908Combined sources3
Helixi935 – 941Combined sources7
Turni942 – 944Combined sources3
Helixi949 – 968Combined sources20
Helixi970 – 980Combined sources11
Helixi981 – 983Combined sources3
Beta strandi988 – 990Combined sources3
Helixi991 – 1001Combined sources11
Turni1002 – 1004Combined sources3
Helixi1007 – 1024Combined sources18
Helixi1026 – 1030Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WXFX-ray1.90A106-1043[»]
2WXGX-ray2.00A106-1043[»]
2WXHX-ray1.90A106-1043[»]
2WXIX-ray2.80A106-1043[»]
2WXJX-ray2.60A106-1043[»]
2WXKX-ray2.90A106-1043[»]
2WXLX-ray1.99A106-1043[»]
2WXMX-ray2.80A106-1043[»]
2WXNX-ray2.60A106-1043[»]
2WXOX-ray2.49A106-1043[»]
2WXPX-ray2.30A106-1043[»]
2WXQX-ray2.70A106-1043[»]
2WXRX-ray2.50A106-1043[»]
2X38X-ray2.20A106-1043[»]
4AJWX-ray2.80A/B110-1043[»]
4V0IX-ray2.54A/B106-1043[»]
4XE0X-ray2.43A106-1043[»]
5AE8X-ray2.42A106-1043[»]
5AE9X-ray2.44A106-1043[»]
5I4UX-ray2.37A106-1043[»]
5I6UX-ray2.84A106-1043[»]
5IS5X-ray2.85A1-1043[»]
5L72X-ray3.06A106-1043[»]
5T27X-ray2.60A106-1043[»]
5T28X-ray2.80A106-507[»]
A509-1043[»]
5T2BX-ray2.30A106-1043[»]
5T2DX-ray2.90A106-1043[»]
5T2GX-ray2.55A106-1043[»]
5T2IX-ray2.30A106-1043[»]
5T2LX-ray2.55A106-1043[»]
5T2MX-ray2.80A106-1043[»]
5T7FX-ray2.60A/B106-1043[»]
5T8IX-ray2.60A106-1043[»]
ProteinModelPortaliO35904.
SMRiO35904.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO35904.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 105PI3K-ABDPROSITE-ProRule annotationAdd BLAST90
Domaini187 – 278PI3K-RBDPROSITE-ProRule annotationAdd BLAST92
Domaini319 – 476C2 PI3K-typePROSITE-ProRule annotationAdd BLAST158
Domaini496 – 673PIK helicalPROSITE-ProRule annotationAdd BLAST178
Domaini775 – 1028PI3K/PI4KPROSITE-ProRule annotationAdd BLAST254

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0904. Eukaryota.
COG5032. LUCA.
GeneTreeiENSGT00760000119110.
HOGENOMiHOG000252911.
HOVERGENiHBG052721.
InParanoidiO35904.
KOiK00922.

Family and domain databases

Gene3Di1.10.1070.11. 1 hit.
2.60.40.150. 1 hit.
InterProiView protein in InterPro
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.
PANTHERiPTHR10048. PTHR10048. 1 hit.
PfamiView protein in Pfam
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.
SMARTiView protein in SMART
SM00142. PI3K_C2. 1 hit.
SM00143. PI3K_p85B. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
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.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35904-1) [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

        10         20         30         40         50
MPPGVDCPME FWTKEESQSV VVDFLLPTGV YLNFPVSRNA NLSTIKQVLW 
        60         70         80         90        100
HRAQYEPLFH MLSDPEAYVF TCVNQTAEQQ ELEDEQRRLC DIQPFLPVLR 
       110        120        130        140        150
LVAREGDRVK KLINSQISLL IGKGLHEFDS LRDPEVNDFR TKMRQFCEEA 
       160        170        180        190        200
AAHRQQLGWV EWLQYSFPLQ LEPSARGWRA GLLRVSNRAL LVNVKFEGSE 
       210        220        230        240        250
ESFTFQVSTK DMPLALMACA LRKKATVFRQ PLVEQPEEYA LQVNGRHEYL 
       260        270        280        290        300
YGNYPLCHFQ YICSCLHSGL TPHLTMVHSS SILAMRDEQS NPAPQVQKPR 
       310        320        330        340        350
AKPPPIPAKK PSSVSLWSLE QPFSIELIEG RKVNADERMK LVVQAGLFHG 
       360        370        380        390        400
NEMLCKTVSS SEVNVCSEPV WKQRLEFDIS VCDLPRMARL CFALYAVVEK 
       410        420        430        440        450
AKKARSTKKK SKKADCPIAW ANLMLFDYKD QLKTGERCLY MWPSVPDEKG 
       460        470        480        490        500
ELLNPAGTVR GNPNTESAAA LVIYLPEVAP HPVYFPALEK ILELGRHGER 
       510        520        530        540        550
GRITEEELQL REILERRGSG ELYEHEKDLV WKMRHEVQEH FPEALARLLL 
       560        570        580        590        600
VTKWNKHEDV AQMLYLLCSW PELPVLSALE LLDFSFPDCY VGSFAIKSLR 
       610        620        630        640        650
KLTDDELFQY LLQLVQVLKY ESYLDCELTK FLLGRALANR KIGHFLFWHL 
       660        670        680        690        700
RSEMHVPSVA LRFGLIMEAY CRGSTHHMKV LMKQGEALSK LKALNDFVKV 
       710        720        730        740        750
SSQKTTKPQT KEMMHMCMRQ ETYMEALSHL QSPLDPSTLL EEVCVEQCTF 
       760        770        780        790        800
MDSKMKPLWI MYSSEEAGSA GNVGIIFKNG DDLRQDMLTL QMIQLMDVLW 
       810        820        830        840        850
KQEGLDLRMT PYGCLPTGDR TGLIEVVLHS DTIANIQLNK SNMAATAAFN 
       860        870        880        890        900
KDALLNWLKS KNPGEALDRA IEEFTLSCAG YCVATYVLGI GDRHSDNIMI 
       910        920        930        940        950
RESGQLFHID FGHFLGNFKT KFGINRERVP FILTYDFVHV IQQGKTNNSE 
       960        970        980        990       1000
KFERFRGYCE RAYTILRRHG LLFLHLFALM RAAGLPELSC SKDIQYLKDS 
      1010       1020       1030       1040 
LALGKTEEEA LKHFRVKFNE ALRESWKTKV NWLAHNVSKD NRQ
Length:1,043
Mass (Da):119,712
Last modified:July 27, 2011 - v2
Checksum:iAD8DE07D8F847795
GO
Isoform 2 (identifier: O35904-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     201-212: ESFTFQVSTKDM → VSPSPIPSPSSI
     213-1043: Missing.

Note: No experimental confirmation available.
Show »
Length:212
Mass (Da):24,355
Checksum:iF61391FD8427F323
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti122G → A in AAC25676 (PubMed:9235916).Curated1
Sequence conflicti584F → S in AAC25676 (PubMed:9235916).Curated1
Sequence conflicti651R → H in AAC25676 (PubMed:9235916).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044411201 – 212ESFTF…STKDM → VSPSPIPSPSSI in isoform 2. CuratedAdd BLAST12
Alternative sequenceiVSP_044412213 – 1043Missing in isoform 2. CuratedAdd BLAST831

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U86587 mRNA. Translation: AAC25676.1.
AF532989 Genomic DNA. Translation: AAN05615.1.
AL607078 Genomic DNA. Translation: CAM23914.1.
CU207384 Genomic DNA. Translation: CAQ51667.1.
CH466594 Genomic DNA. Translation: EDL14872.1.
CCDSiCCDS51380.1. [O35904-1]
PIRiT43502.
RefSeqiNP_001157524.1. NM_001164052.1. [O35904-1]
XP_006538715.1. XM_006538652.3. [O35904-1]
UniGeneiMm.229108.

Genome annotation databases

EnsembliENSMUST00000105689; ENSMUSP00000101314; ENSMUSG00000039936. [O35904-1]
GeneIDi18707.
KEGGimmu:18707.
UCSCiuc008vwq.1. mouse. [O35904-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiPK3CD_MOUSE
AccessioniPrimary (citable) accession number: O35904
Secondary accession number(s): Q8CJ28
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: July 5, 2017
This is version 152 of the entry and version 2 of the sequence. See 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families