Reviewed, UniProtKB/Swiss-Prot O00329 (PK3CD_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1044 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	phosphoinositide phosphorylation Inferred from electronic annotation. Source: InterPro phosphoinositide-mediated signaling Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	phosphoinositide 3-kinase complex Ref.1 Ref.3 Non-traceable author statement. Source: UniProtKB
Molecular function	1-phosphatidylinositol-3-kinase activity Ref.3 Non-traceable author statement. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol-4,5-bisphosphate 3-kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	1	EBI-718309,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1044	1044	Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform		PRO_0000088790
Regions
	Domain	774 – 1041	268	PI3K/PI4K
Amino acid modifications
	Modified residue	484	1	Phosphotyrosine
	Modified residue	520	1	Phosphoserine
	Modified residue	524	1	Phosphotyrosine Ref.8
	Modified residue	1039	1	Phosphoserine; by autocatalysis Ref.7
Experimental info
	Mutagenesis	894	1	R → P: Abolishes lipid and protein kinase activities. Ref.7
	Mutagenesis	1039	1	S → A: Abolishes autophosphorylation, no effect on lipid kinase activity. Ref.7
	Mutagenesis	1039	1	S → D or E: Abolishes autophosphorylation, reduced lipid kinase activity. Ref.7
	Sequence conflict	253	1	S → N in AAC25677. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O00329-1 [UniParc]. Last modified June 7, 2005. Version 2. Checksum: A38B5D1A1081A3D0	FASTA	1,044	119,479
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00298410.
RefSeq	NP_005017.3.
UniGene	Hs.518451
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	O00329. 7 interactions.
STRING	O00329.
PTM databases
PhosphoSite	O00329.
Proteomic databases
PRIDE	O00329.
Genome annotation databases
Ensembl	ENST00000377346; ENSP00000366563; ENSG00000171608; Homo sapiens. [Genome view]
GeneID	5293.
KEGG	hsa:5293.
UCSC	uc001aqb.2. human.
Organism-specific databases
CTD	5293.
GeneCards	GC01P009646.
H-InvDB	HIX0028728.
HGNC	HGNC:8977. PIK3CD.
HPA	CAB015420.
MIM	602839. gene.
PharmGKB	PA33310.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11835.
HOVERGEN	O00329.
OrthoDB	EOG9TTK4J.
PhylomeDB	O00329.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000171608-MONOMER.
BRENDA	2.7.1.137. 247. 2.7.1.153. 247.
Pathway_Interaction_DB	pi3kcipathway. Class I PI3K signaling events. trail_pathway. TRAIL signaling pathway.
Gene expression databases
ArrayExpress	O00329.
Bgee	O00329.
CleanEx	HS_PIK3CD.
Genevestigator	O00329.
GermOnline	ENSG00000171608. Homo sapiens.
Family and domain databases
InterPro	IPR016024. 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]
Gene3D	G3DSA:1.10.1070.11. PI3/4_kinase_cat. 1 hit. G3DSA:1.25.40.70. PI3Ka. 1 hit.
PANTHER	PTHR10048. PI_Kinase. 1 hit.
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. [Graphical view]
SMART	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]
PROSITE	PS00915. PI3_4_KINASE_1. 1 hit. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	20454.
SOURCE	Search...

Entry information

Entry name

PK3CD_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.