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Reviewed, UniProtKB/Swiss-Prot O00329 (PK3CD_HUMAN)

Last modified February 9, 2010. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform
      Short name=PtdIns-3-kinase subunit delta
      Short name=PI3-kinase subunit delta
      Short name=PI3K-delta
    EC=2.7.1.153
Alternative name(s):
    Phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta
      Short name=PtdIns-3-kinase subunit p110-delta
Gene names
Name: PIK3CD
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1044 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Catalytic activity

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

Pathway

Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.

Subunit structure

Heterodimer of a p110 (catalytic) and a p85 (regulatory) subunit. Interacts with ERAS By similarity.

Tissue specificity

Expressed predominantly in leukocytes.

Post-translational modification

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

Sequence similarities

Belongs to the PI3/PI4-kinase family.

Contains 1 PI3K/PI4K domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NCK1P163331EBI-718309,EBI-389883

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10441044Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform
PRO_0000088790

Regions

Domain774 – 1041268PI3K/PI4K

Amino acid modifications

Modified residue4841Phosphotyrosine
Modified residue5201Phosphoserine
Modified residue5241Phosphotyrosine Ref.8
Modified residue10391Phosphoserine; by autocatalysis Ref.7

Experimental info

Mutagenesis8941R → P: Abolishes lipid and protein kinase activities. Ref.7
Mutagenesis10391S → A: Abolishes autophosphorylation, no effect on lipid kinase activity. Ref.7
Mutagenesis10391S → D or E: Abolishes autophosphorylation, reduced lipid kinase activity. Ref.7
Sequence conflict2531S → N in AAC25677. Ref.3

Sequences

Sequence LengthMass (Da)Tools
O00329-1 [UniParc].

Last modified June 7, 2005. Version 2.
Checksum: A38B5D1A1081A3D0

FASTA1,044119,479
        10         20         30         40         50         60 
MPPGVDCPME FWTKEENQSV VVDFLLPTGV YLNFPVSRNA NLSTIKQLLW HRAQYEPLFH 

        70         80         90        100        110        120 
MLSGPEAYVF TCINQTAEQQ ELEDEQRRLC DVQPFLPVLR LVAREGDRVK KLINSQISLL 

       130        140        150        160        170        180 
IGKGLHEFDS LCDPEVNDFR AKMCQFCEEA AARRQQLGWE AWLQYSFPLQ LEPSAQTWGP 

       190        200        210        220        230        240 
GTLRLPNRAL LVNVKFEGSE ESFTFQVSTK DVPLALMACA LRKKATVFRQ PLVEQPEDYT 

       250        260        270        280        290        300 
LQVNGRHEYL YGSYPLCQFQ YICSCLHSGL TPHLTMVHSS SILAMRDEQS NPAPQVQKPR 

       310        320        330        340        350        360 
AKPPPIPAKK PSSVSLWSLE QPFRIELIQG SKVNADERMK LVVQAGLFHG NEMLCKTVSS 

       370        380        390        400        410        420 
SEVSVCSEPV WKQRLEFDIN ICDLPRMARL CFALYAVIEK AKKARSTKKK SKKADCPIAW 

       430        440        450        460        470        480 
ANLMLFDYKD QLKTGERCLY MWPSVPDEKG ELLNPTGTVR SNPNTDSAAA LLICLPEVAP 

       490        500        510        520        530        540 
HPVYYPALEK ILELGRHSEC VHVTEEEQLQ LREILERRGS GELYEHEKDL VWKLRHEVQE 

       550        560        570        580        590        600 
HFPEALARLL LVTKWNKHED VAQMLYLLCS WPELPVLSAL ELLDFSFPDC HVGSFAIKSL 

       610        620        630        640        650        660 
RKLTDDELFQ YLLQLVQVLK YESYLDCELT KFLLDRALAN RKIGHFLFWH LRSEMHVPSV 

       670        680        690        700        710        720 
ALRFGLILEA YCRGSTHHMK VLMKQGEALS KLKALNDFVK LSSQKTPKPQ TKELMHLCMR 

       730        740        750        760        770        780 
QEAYLEALSH LQSPLDPSTL LAEVCVEQCT FMDSKMKPLW IMYSNEEAGS GGSVGIIFKN 

       790        800        810        820        830        840 
GDDLRQDMLT LQMIQLMDVL WKQEGLDLRM TPYGCLPTGD RTGLIEVVLR SDTIANIQLN 

       850        860        870        880        890        900 
KSNMAATAAF NKDALLNWLK SKNPGEALDR AIEEFTLSCA GYCVATYVLG IGDRHSDNIM 

       910        920        930        940        950        960 
IRESGQLFHI DFGHFLGNFK TKFGINRERV PFILTYDFVH VIQQGKTNNS EKFERFRGYC 

       970        980        990       1000       1010       1020 
ERAYTILRRH GLLFLHLFAL MRAAGLPELS CSKDIQYLKD SLALGKTEEE ALKHFRVKFN 

      1030       1040 
EALRESWKTK VNWLAHNVSK DNRQ 

« Hide

References

« Hide 'large scale' references
[1]"P110delta, a novel phosphoinositide 3-kinase in leukocytes."
Vanhaesebroeck B.A.M., Welham M.J., Kotani K., Stein R., Warne P.H., Zvelebil M.J., Higashi K., Volinia S., Downward J., Waterfield M.D.
Proc. Natl. Acad. Sci. U.S.A. 94:4330-4335(1997) [PubMed: 9113989] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 9235916] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"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].
[5]"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. expand/collapse author list , 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: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"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: 10064595] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1031-1040, PHOSPHORYLATION AT SER-1039, MUTAGENESIS OF ARG-894 AND SER-1039.
[8]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-524, MASS SPECTROMETRY.
[9]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-484; SER-520; TYR-524 AND SER-1039, MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y10055 mRNA. Translation: CAA71149.2.
U86453 mRNA. Translation: AAC25677.1.
DQ263594 mRNA. Translation: ABB83814.1.
AL691449 Genomic DNA. Translation: CAI15703.1.
BC132919 mRNA. Translation: AAI32920.1.
BC132921 mRNA. Translation: AAI32922.1.
IPIIPI00298410.
RefSeqNP_005017.3.
UniGeneHs.518451

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

IntActO00329. 7 interactions.
STRINGO00329.

PTM databases

PhosphoSiteO00329.

Proteomic databases

PRIDEO00329.

Genome annotation databases

EnsemblENST00000377346; ENSP00000366563; ENSG00000171608; Homo sapiens. [Genome view]
GeneID5293.
KEGGhsa:5293.
UCSCuc001aqb.2. human.

Organism-specific databases

CTD5293.
GeneCardsGC01P009646.
H-InvDBHIX0028728.
HGNCHGNC:8977. PIK3CD.
HPACAB015420.
MIM602839. gene.
PharmGKBPA33310.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG11835.
HOVERGENO00329.
OrthoDBEOG9TTK4J.
PhylomeDBO00329.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000171608-MONOMER.
BRENDA2.7.1.137. 247.
2.7.1.153. 247.
Pathway_Interaction_DBpi3kcipathway. Class I PI3K signaling events.
trail_pathway. TRAIL signaling pathway.

Gene expression databases

ArrayExpressO00329.
BgeeO00329.
CleanExHS_PIK3CD.
GenevestigatorO00329.
GermOnlineENSG00000171608. Homo sapiens.

Family and domain databases

InterProIPR016024. ARM-type_fold.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat.
IPR018936. PI3/4_kinase_CS.
IPR002420. PI3K_C2.
IPR003113. PI3K_p85_bd.
IPR000341. PI3K_ras_bd.
IPR015433. PI_Kinase.
IPR001263. PInositide-3_kin_accessory_dom.
[Graphical view]
Gene3DG3DSA:1.10.1070.11. PI3/4_kinase_cat. 1 hit.
G3DSA:1.25.40.70. PI3Ka. 1 hit.
PANTHERPTHR10048. PI_Kinase. 1 hit.
PfamPF00454. 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]
SMARTSM00142. PI3K_C2. 1 hit.
SM00143. PI3K_p85B. 1 hit.
SM00144. PI3K_rbd. 1 hit.
SM00145. PI3Ka. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
PROSITEPS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio20454.
SOURCESearch...

Entry information

Entry namePK3CD_HUMAN
AccessionPrimary (citable) accession number: O00329
Secondary accession number(s): A6NCG0, O15445, Q5SR49
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 7, 2005
Last modified: February 9, 2010
This is version 92 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents