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

Details

Name
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
Synonyms
  • 2.7.1.153
  • p110delta
  • Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta
  • PI3-kinase subunit delta
  • PtdIns-3-kinase subunit p110-delta
Gene Name
PIK3CD
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004726|Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
MPPGVDCPMEFWTKEENQSVVVDFLLPTGVYLNFPVSRNANLSTIKQLLWHRAQYEPLFH
MLSGPEAYVFTCINQTAEQQELEDEQRRLCDVQPFLPVLRLVAREGDRVKKLINSQISLL
IGKGLHEFDSLCDPEVNDFRAKMCQFCEEAAARRQQLGWEAWLQYSFPLQLEPSAQTWGP
GTLRLPNRALLVNVKFEGSEESFTFQVSTKDVPLALMACALRKKATVFRQPLVEQPEDYT
LQVNGRHEYLYGSYPLCQFQYICSCLHSGLTPHLTMVHSSSILAMRDEQSNPAPQVQKPR
AKPPPIPAKKPSSVSLWSLEQPFRIELIQGSKVNADERMKLVVQAGLFHGNEMLCKTVSS
SEVSVCSEPVWKQRLEFDINICDLPRMARLCFALYAVIEKAKKARSTKKKSKKADCPIAW
ANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPTGTVRSNPNTDSAAALLICLPEVAP
HPVYYPALEKILELGRHSECVHVTEEEQLQLREILERRGSGELYEHEKDLVWKLRHEVQE
HFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDFSFPDCHVGSFAIKSL
RKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLDRALANRKIGHFLFWHLRSEMHVPSV
ALRFGLILEAYCRGSTHHMKVLMKQGEALSKLKALNDFVKLSSQKTPKPQTKELMHLCMR
QEAYLEALSHLQSPLDPSTLLAEVCVEQCTFMDSKMKPLWIMYSNEEAGSGGSVGIIFKN
GDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLRSDTIANIQLN
KSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIM
IRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYC
ERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFN
EALRESWKTKVNWLAHNVSKDNRQ
Number of residues
1044
Molecular Weight
119478.065
Theoretical pI
7.18
GO Classification
Functions
1-phosphatidylinositol-3-kinase activity / 1-phosphatidylinositol-4-phosphate 3-kinase activity / ATP binding / phosphatidylinositol 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Processes
adaptive immune response / B cell activation / B cell chemotaxis / B cell homeostasis / B cell receptor signaling pathway / cytokine production / defense response to fungus / epidermal growth factor receptor signaling pathway / Fc-epsilon receptor signaling pathway / fibroblast growth factor receptor signaling pathway / inflammatory response / innate immune response / mast cell chemotaxis / mast cell degranulation / mast cell differentiation / natural killer cell activation / natural killer cell chemotaxis / natural killer cell differentiation / neurotrophin TRK receptor signaling pathway / neutrophil chemotaxis / neutrophil extravasation / phosphatidylinositol 3-kinase signaling / phosphatidylinositol biosynthetic process / phosphatidylinositol-3-phosphate biosynthetic process / phosphatidylinositol-mediated signaling / phospholipid metabolic process / positive regulation of cell migration / positive regulation of gene expression / protein phosphorylation / respiratory burst involved in defense response / signal transduction / small molecule metabolic process / T cell activation / T cell chemotaxis / T cell differentiation / T cell receptor signaling pathway
Components
cytosol / mast cell granule / phosphatidylinositol 3-kinase complex / plasma membrane
General Function
Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0019281|Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD)
ATGCCCCCTGGGGTGGACTGCCCCATGGAATTCTGGACCAAGGAGGAGAATCAGAGCGTT
GTGGTTGACTTCCTGCTGCCCACAGGGGTCTACCTGAACTTCCCTGTGTCCCGCAATGCC
AACCTCAGCACCATCAAGCAGCTGCTGTGGCACCGCGCCCAGTATGAGCCGCTCTTCCAC
ATGCTCAGTGGCCCCGAGGCCTATGTGTTCACCTGCATCAACCAGACAGCGGAGCAGCAA
GAGCTGGAGGACGAGCAACGGCGTCTGTGTGACGTGCAGCCCTTCCTGCCCGTCCTGCGC
CTGGTGGCCCGTGAGGGCGACCGCGTGAAGAAGCTCATCAACTCACAGATCAGCCTCCTC
ATCGGCAAAGGCCTCCACGAGTTTGACTCCTTGTGCGACCCAGAAGTGAACGACTTTCGC
GCCAAGATGTGCCAATTCTGCGAGGAGGCGGCCGCCCGCCGGCAGCAGCTGGGCTGGGAG
GCCTGGCTGCAGTACAGTTTCCCCCTGCAGCTGGAGCCCTCGGCTCAAACCTGGGGGCCT
GGTACCCTGCGGCTCCCGAACCGGGCCCTTCTGGTCAACGTTAAGTTTGAGGGCAGCGAG
GAGAGCTTCACCTTCCAGGTGTCCACCAAGGACGTGCCGCTGGCGCTGATGGCCTGTGCC
CTGCGGAAGAAGGCCACAGTGTTCCGGCAGCCGCTGGTGGAGCAGCCGGAAGACTACACG
CTGCAGGTGAACGGCAGGCATGAGTACCTGTATGGCAGCTACCCGCTCTGCCAGTTCCAG
TACATCTGCAGCTGCCTGCACAGTGGGTTGACCCCTCACCTGACCATGGTCCATTCCTCC
TCCATCCTCGCCATGCGGGATGAGCAGAGCAACCCTGCCCCCCAGGTCCAGAAACCGCGT
GCCAAACCACCTCCCATTCCTGCGAAGAAGCCTTCCTCTGTGTCCCTGTGGTCCCTGGAG
CAGCCGTTCCGCATCGAGCTCATCCAGGGCAGCAAAGTGAACGCCGACGAGCGGATGAAG
CTGGTGGTGCAGGCCGGGCTTTTCCACGGCAACGAGATGCTGTGCAAGACGGTGTCCAGC
TCGGAGGTGAGCGTGTGCTCGGAGCCCGTGTGGAAGCAGCGGCTGGAGTTCGACATCAAC
ATCTGCGACCTGCCCCGCATGGCCCGTCTCTGCTTTGCGCTGTACGCCGTGATCGAGAAA
GCCAAGAAGGCTCGCTCCACCAAGAAGAAGTCCAAGAAGGCGGACTGCCCCATTGCCTGG
GCCAACCTCATGCTGTTTGACTACAAGGACCAGCTTAAGACCGGGGAACGCTGCCTCTAC
ATGTGGCCCTCCGTCCCAGATGAGAAGGGCGAGCTGCTGAACCCCACGGGCACTGTGCGC
AGTAACCCCAACACGGATAGCGCCGCTGCCCTGCTCATCTGCCTGCCCGAGGTGGCCCCG
CACCCCGTGTACTACCCCGCCCTGGAGAAGATCTTGGAGCTGGGGCGACACAGCGAGTGT
GTGCATGTCACCGAGGAGGAGCAGCTGCAGCTGCGGGAAATCCTGGAGCGGCGGGGGTCT
GGGGAGCTGTATGAGCACGAGAAGGACCTGGTGTGGAAGCTGCGGCATGAAGTCCAGGAG
CACTTCCCGGAGGCGCTAGCCCGGCTGCTGCTGGTCACCAAGTGGAACAAGCATGAGGAT
GTGGCCCAGATGCTCTACCTGCTGTGCTCCTGGCCGGAGCTGCCCGTCCTGAGCGCCCTG
GAGCTGCTAGACTTCAGCTTCCCCGATTGCCACGTAGGCTCCTTCGCCATCAAGTCGCTG
CGGAAACTGACGGACGATGAGCTGTTCCAGTACCTGCTGCAGCTGGTGCAGGTGCTCAAG
TACGAGTCCTACCTGGACTGCGAGCTGACCAAATTCCTGCTGGACCGGGCCCTGGCCAAC
CGCAAGATCGGCCACTTCCTTTTCTGGCACCTCCGCTCCGAGATGCACGTGCCGTCGGTG
GCCCTGCGCTTCGGCCTCATCCTGGAGGCCTACTGCAGGGGCAGCACCCACCACATGAAG
GTGCTGATGAAGCAGGGGGAAGCACTGAGCAAACTGAAGGCCCTGAATGACTTCGTCAAG
CTGAGCTCTCAGAAGACCCCCAAGCCCCAGACCAAGGAGCTGATGCACTTGTGCATGCGG
CAGGAGGCCTACCTAGAGGCCCTCTCCCACCTGCAGTCCCCACTCGACCCCAGCACCCTG
CTGGCTGAAGTCTGCGTGGAGCAGTGCACCTTCATGGACTCCAAGATGAAGCCCCTGTGG
ATCATGTACAGCAACGAGGAGGCAGGCAGCGGCGGCAGCGTGGGCATCATCTTTAAGAAC
GGGGATGACCTCCGGCAGGACATGCTGACCCTGCAGATGATCCAGCTCATGGACGTCCTG
TGGAAGCAGGAGGGGCTGGACCTGAGGATGACCCCCTATGGCTGCCTCCCCACCGGGGAC
CGCACAGGCCTCATTGAGGTGGTACTCCGTTCAGACACCATCGCCAACATCCAACTCAAC
AAGAGCAACATGGCAGCCACAGCCGCCTTCAACAAGGATGCCCTGCTCAACTGGCTGAAG
TCCAAGAACCCGGGGGAGGCCCTGGATCGAGCCATTGAGGAGTTCACCCTCTCCTGTGCT
GGCTATTGTGTGGCCACATATGTGCTGGGCATTGGCGATCGGCACAGCGACAACATCATG
ATCCGAGAGAGTGGGCAGCTGTTCCACATTGATTTTGGCCACTTTCTGGGGAATTTCAAG
ACCAAGTTTGGAATCAACCGCGAGCGTGTCCCATTCATCCTCACCTACGACTTTGTCCAT
GTGATTCAGCAGGGGAAGACTAATAATAGTGAGAAATTTGAACGGTTCCGGGGCTACTGT
GAAAGGGCCTACACCATCCTGCGGCGCCACGGGCTTCTCTTCCTCCACCTCTTTGCCCTG
ATGCGGGCGGCAGGCCTGCCTGAGCTCAGCTGCTCCAAAGACATCCAGTATCTCAAGGAC
TCCCTGGCACTGGGGAAAACAGAGGAGGAGGCACTGAAGCACTTCCGAGTGAAGTTTAAC
GAAGCCCTCCGTGAGAGCTGGAAAACCAAAGTGAACTGGCTGGCCCACAACGTGTCCAAA
GACAACAGGCAGTAG
Chromosome Location
1
Locus
1p36.2
External Identifiers
ResourceLink
UniProtKB IDO00329
UniProtKB Entry NamePK3CD_HUMAN
GenBank Gene IDY10055
GenAtlas IDPIK3CD
HGNC IDHGNC:8977
General References
  1. Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD: P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4330-5. [Article]
  2. Chantry D, Vojtek A, Kashishian A, Holtzman DA, Wood C, Gray PW, Cooper JA, Hoekstra MF: p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J Biol Chem. 1997 Aug 1;272(31):19236-41. [Article]
  3. Fransson S, Uv A, Eriksson H, Andersson MK, Wettergren Y, Bergo M, Ejeskar K: p37delta is a new isoform of PI3K p110delta that increases cell proliferation and is overexpressed in tumors. Oncogene. 2012 Jul 5;31(27):3277-86. doi: 10.1038/onc.2011.492. Epub 2011 Oct 24. [Article]
  4. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Vanhaesebroeck B, Higashi K, Raven C, Welham M, Anderson S, Brennan P, Ward SG, Waterfield MD: Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo. EMBO J. 1999 Mar 1;18(5):1292-302. [Article]
  7. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  8. Soond DR, Bjorgo E, Moltu K, Dale VQ, Patton DT, Torgersen KM, Galleway F, Twomey B, Clark J, Gaston JS, Tasken K, Bunyard P, Okkenhaug K: PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans. Blood. 2010 Mar 18;115(11):2203-13. doi: 10.1182/blood-2009-07-232330. Epub 2010 Jan 15. [Article]
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  11. Angulo I, Vadas O, Garcon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debre M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S: Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science. 2013 Nov 15;342(6160):866-71. doi: 10.1126/science.1243292. Epub 2013 Oct 17. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05241XL765investigationalunknownDetails
DB068312-((9H-PURIN-6-YLTHIO)METHYL)-5-CHLORO-3-(2-METHOXYPHENYL)QUINAZOLIN-4(3H)-ONEexperimentalunknownDetails
DB00201CaffeineapprovedunknowninhibitorDetails
DB09054IdelalisibapprovedyesinhibitorDetails
DB12483Copanlisibapproved, investigationalyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB05552TG100-115investigationalyesinhibitorDetails
DB11952Duvelisibapproved, investigationalyesinhibitorDetails
DB14989Umbralisibapproved, investigationalyesinhibitorDetails