PK3CD_HUMAN
ID PK3CD_HUMAN Reviewed; 1044 AA.
AC O00329; A6NCG0; G1FFP1; O15445; Q5SR49;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform;
DE Short=PI3-kinase subunit delta;
DE Short=PI3K-delta;
DE Short=PI3Kdelta;
DE Short=PtdIns-3-kinase subunit delta;
DE EC=2.7.1.137 {ECO:0000269|PubMed:9235916};
DE EC=2.7.1.153 {ECO:0000269|PubMed:15135396};
DE AltName: Full=Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta;
DE Short=PtdIns-3-kinase subunit p110-delta;
DE Short=p110delta {ECO:0000303|PubMed:9235916};
GN Name=PIK3CD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9113989; DOI=10.1073/pnas.94.9.4330;
RA Vanhaesebroeck B.A.M., Welham M.J., Kotani K., Stein R., Warne P.H.,
RA Zvelebil M.J., Higashi K., Volinia S., Downward J., Waterfield M.D.;
RT "P110delta, a novel phosphoinositide 3-kinase in leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:4330-4335(1997).
RN [2]
RP SEQUENCE REVISION TO 675.
RA Vanhaesebroeck B.A.M.;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RX PubMed=9235916; DOI=10.1074/jbc.272.31.19236;
RA Chantry D., Vojtek A., Kashishian A., Holtzman D.A., Wood C., Gray P.W.,
RA Cooper J.A., Hoekstra M.F.;
RT "p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that
RT associates with p85 and is expressed predominantly in leukocytes.";
RL J. Biol. Chem. 272:19236-19241(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBUNIT, INTERACTION WITH
RP HRAS, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=22020336; DOI=10.1038/onc.2011.492;
RA Fransson S., Uv A., Eriksson H., Andersson M.K., Wettergren Y., Bergo M.,
RA Ejeskar K.;
RT "p37delta is a new isoform of PI3K p110delta that increases cell
RT proliferation and is overexpressed in tumors.";
RL Oncogene 31:3277-3286(2012).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jou S.-T., Chien Y.-H., Yang Y.-H., Shyur S.-D., Chou C.-C., Chiang B.-L.;
RT "Variations in the human phosphoinositide-3-kinase p110 gene in children
RT with primary B-cell immunodeficiency of unknown etiology.";
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15135396; DOI=10.1016/j.pep.2003.12.010;
RA Meier T.I., Cook J.A., Thomas J.E., Radding J.A., Horn C., Lingaraj T.,
RA Smith M.C.;
RT "Cloning, expression, purification, and characterization of the human Class
RT Ia phosphoinositide 3-kinase isoforms.";
RL Protein Expr. Purif. 35:218-224(2004).
RN [9]
RP PROTEIN SEQUENCE OF 1031-1040, PHOSPHORYLATION AT SER-1039, AND MUTAGENESIS
RP OF ARG-894 AND SER-1039.
RX PubMed=10064595; DOI=10.1093/emboj/18.5.1292;
RA Vanhaesebroeck B., Higashi K., Raven C., Welham M., Anderson S.,
RA Brennan P., Ward S.G., Waterfield M.D.;
RT "Autophosphorylation of p110 delta phosphoinositide 3-kinase: a new
RT paradigm for the regulation of lipid kinases in vitro and in vivo.";
RL EMBO J. 18:1292-1302(1999).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-524 AND SER-1039, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [11]
RP FUNCTION IN T-CELLS, AND ACTIVITY REGULATION.
RX PubMed=20081091; DOI=10.1182/blood-2009-07-232330;
RA Soond D.R., Bjorgo E., Moltu K., Dale V.Q., Patton D.T., Torgersen K.M.,
RA Galleway F., Twomey B., Clark J., Gaston J.S.H., Tasken K., Bunyard P.,
RA Okkenhaug K.;
RT "PI3K p110delta regulates T-cell cytokine production during primary and
RT secondary immune responses in mice and humans.";
RL Blood 115:2203-2213(2010).
RN [12]
RP REVIEW ON FUNCTION.
RX PubMed=17290298; DOI=10.1038/nri2036;
RA Rommel C., Camps M., Ji H.;
RT "PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid
RT arthritis and beyond?";
RL Nat. Rev. Immunol. 7:191-201(2007).
RN [13]
RP REVIEW ON FUNCTION.
RX PubMed=20940048; DOI=10.1016/j.cellsig.2010.10.002;
RA Fung-Leung W.-P.;
RT "Phosphoinositide 3-kinase delta (PI3Kdelta) in leukocyte signaling and
RT function.";
RL Cell. Signal. 23:603-608(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1039, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INVOLVEMENT IN IMD14A, VARIANT IMD14A LYS-1021, AND CHARACTERIZATION OF
RP VARIANT IMD14A LYS-1021.
RX PubMed=24136356; DOI=10.1126/science.1243292;
RA Angulo I., Vadas O., Garcon F., Banham-Hall E., Plagnol V., Leahy T.R.,
RA Baxendale H., Coulter T., Curtis J., Wu C., Blake-Palmer K., Perisic O.,
RA Smyth D., Maes M., Fiddler C., Juss J., Cilliers D., Markelj G.,
RA Chandra A., Farmer G., Kielkowska A., Clark J., Kracker S., Debre M.,
RA Picard C., Pellier I., Jabado N., Morris J.A., Barcenas-Morales G.,
RA Fischer A., Stephens L., Hawkins P., Barrett J.C., Abinun M.,
RA Clatworthy M., Durandy A., Doffinger R., Chilvers E.R., Cant A.J.,
RA Kumararatne D., Okkenhaug K., Williams R.L., Condliffe A., Nejentsev S.;
RT "Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory
RT infection and airway damage.";
RL Science 342:866-871(2013).
RN [16]
RP INVOLVEMENT IN ROCHIS, VARIANT ROCHIS 721-GLN--GLN-1044 DEL, AND
RP CHARACTERIZATION OF VARIANT ROCHIS 721-GLN--GLN-1044 DEL.
RX PubMed=29180244; DOI=10.1016/j.jaci.2017.10.033;
RA Sharfe N., Karanxha A., Dadi H., Merico D., Chitayat D., Herbrick J.A.,
RA Freeman S., Grinstein S., Roifman C.M.;
RT "Dual loss of p110delta PI3-kinase and SKAP (KNSTRN) expression leads to
RT combined immunodeficiency and multisystem syndromic features.";
RL J. Allergy Clin. Immunol. 142:618-629(2018).
RN [17]
RP INVOLVEMENT IN IMD14B.
RX PubMed=30040974; DOI=10.1016/j.jaci.2018.06.039;
RA Sogkas G., Fedchenko M., Dhingra A., Jablonka A., Schmidt R.E.,
RA Atschekzei F.;
RT "Primary immunodeficiency disorder caused by phosphoinositide 3-kinase
RT delta deficiency.";
RL J. Allergy Clin. Immunol. 142:1650-1653(2018).
RN [18]
RP INVOLVEMENT IN IMD14B.
RX PubMed=30336224; DOI=10.1016/j.jaci.2018.10.005;
RA Cohen S.B., Bainter W., Johnson J.L., Lin T.Y., Wong J.C.Y., Wallace J.G.,
RA Jones J., Qureshi S., Mir F., Qamar F., Cantley L.C., Geha R.S., Chou J.;
RT "Human primary immunodeficiency caused by expression of a kinase-dead
RT p110delta mutant.";
RL J. Allergy Clin. Immunol. 143:797-799(2019).
CC -!- FUNCTION: Phosphoinositide-3-kinase (PI3K) phosphorylates
CC phosphatidylinositol (PI) and its phosphorylated derivatives at
CC position 3 of the inositol ring to produce 3-phosphoinositides
CC (PubMed:9235916). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-
CC bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate
CC (PIP3) (PubMed:15135396). PIP3 plays a key role by recruiting PH
CC domain-containing proteins to the membrane, including AKT1 and PDPK1,
CC activating signaling cascades involved in cell growth, survival,
CC proliferation, motility and morphology. Mediates immune responses.
CC Plays a role in B-cell development, proliferation, migration, and
CC function. Required for B-cell receptor (BCR) signaling. Mediates B-cell
CC proliferation response to anti-IgM, anti-CD40 and IL4 stimulation.
CC Promotes cytokine production in response to TLR4 and TLR9. Required for
CC antibody class switch mediated by TLR9. Involved in the antigen
CC presentation function of B-cells. Involved in B-cell chemotaxis in
CC response to CXCL13 and sphingosine 1-phosphate (S1P). Required for
CC proliferation, signaling and cytokine production of naive, effector and
CC memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates
CC TCR signaling events at the immune synapse. Activation by TCR leads to
CC antigen-dependent memory T-cell migration and retention to antigenic
CC tissues. Together with PIK3CG participates in T-cell development.
CC Contributes to T-helper cell expansion and differentiation. Required
CC for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and
CC S1PR1 and antigen dependent recruitment of T-cells. Together with
CC PIK3CG is involved in natural killer (NK) cell development and
CC migration towards the sites of inflammation. Participates in NK cell
CC receptor activation. Plays a role in NK cell maturation and cytokine
CC production. Together with PIK3CG is involved in neutrophil chemotaxis
CC and extravasation. Together with PIK3CG participates in neutrophil
CC respiratory burst. Plays important roles in mast-cell development and
CC mast cell mediated allergic response. Involved in stem cell factor
CC (SCF)-mediated proliferation, adhesion and migration. Required for
CC allergen-IgE-induced degranulation and cytokine release. The lipid
CC kinase activity is required for its biological function. Isoform 2 may
CC be involved in stabilizing total RAS levels, resulting in increased ERK
CC phosphorylation and increased PI3K activity.
CC {ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:20081091,
CC ECO:0000269|PubMed:22020336, ECO:0000269|PubMed:9235916}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-
CC bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
CC inositol-3,4,5-trisphosphate) + ADP + H(+); Xref=Rhea:RHEA:21292,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57836,
CC ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.153;
CC Evidence={ECO:0000269|PubMed:15135396};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21293;
CC Evidence={ECO:0000305|PubMed:15135396};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP +
CC H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC EC=2.7.1.137; Evidence={ECO:0000269|PubMed:9235916};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000305|PubMed:9235916};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-
CC 3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol 3,4,5-triphosphate) + ADP + H(+); Xref=Rhea:RHEA:43396,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77137,
CC ChEBI:CHEBI:83243, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000305|PubMed:15135396};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43397;
CC Evidence={ECO:0000305|PubMed:15135396};
CC -!- ACTIVITY REGULATION: Activated by growth factors and cytokine receptors
CC through a tyrosine-kinase-dependent mechanism. Activated by RAS.
CC IC87114 inhibits lipid kinase activity and is selective in cells at
CC doses up to 5-10 uM. IC87114 blocks T-cell receptor signaling in naive
CC and memory T-cells and reduces cytokine production by memory T-cells.
CC {ECO:0000269|PubMed:20081091}.
CC -!- PATHWAY: Phospholipid metabolism; phosphatidylinositol phosphate
CC biosynthesis. {ECO:0000305|PubMed:15135396,
CC ECO:0000305|PubMed:9113989}.
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory
CC subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS (By
CC similarity). Interacts with HRAS. {ECO:0000250,
CC ECO:0000269|PubMed:22020336}.
CC -!- INTERACTION:
CC O00329; P01112: HRAS; NbExp=2; IntAct=EBI-718309, EBI-350145;
CC O00329; P27986: PIK3R1; NbExp=8; IntAct=EBI-718309, EBI-79464;
CC O00329; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-718309, EBI-9090282;
CC O00329; Q92569: PIK3R3; NbExp=4; IntAct=EBI-718309, EBI-79893;
CC O00329-2; P01112: HRAS; NbExp=2; IntAct=EBI-6470902, EBI-350145;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22020336}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=p110-delta;
CC IsoId=O00329-1; Sequence=Displayed;
CC Name=2; Synonyms=p37-delta;
CC IsoId=O00329-2; Sequence=VSP_044409, VSP_044410;
CC -!- TISSUE SPECIFICITY: In humans, the highest levels of expression are
CC seen in peripheral blood mononuclear cells, spleen, and thymus, and low
CC levels of expression in testes, uterus, colon, and small intestine but
CC not in other tissues examined including prostate, heart, brain, and
CC liver (PubMed:9235916). Isoform 2 is expressed in normal thymus, lung
CC and spleen tissues, and is detected at low levels in normal lysates
CC from colon and ovarian biopsies, at elevated levels in lysates from
CC colorectal tumors and is abundantly expressed in some ovarian tumors
CC (at protein level). Both isoform 1 and isoform 2 are widely expressed.
CC Isoform 1 is expressed predominantly in leukocytes.
CC {ECO:0000269|PubMed:22020336, ECO:0000269|PubMed:9235916}.
CC -!- PTM: Autophosphorylation on Ser-1039 results in the almost complete
CC inactivation of the lipid kinase activity.
CC {ECO:0000269|PubMed:10064595}.
CC -!- DISEASE: Immunodeficiency 14A, autosomal dominant (IMD14A)
CC [MIM:615513]: A disorder characterized by recurrent respiratory
CC infections, progressive airway damage, lymphopenia, increased
CC circulating transitional B cells, increased immunoglobulin M, reduced
CC immunoglobulin G2 levels in serum, and impaired vaccine responses.
CC {ECO:0000269|PubMed:24136356}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Immunodeficiency 14B, autosomal recessive (IMD14B)
CC [MIM:619281]: An autosomal recessive, primary immunodeficiency
CC characterized by recurrent sinopulmonary infections apparent in early
CC childhood. Some patients may develop inflammatory bowel disease or
CC osteomyelitis. Immunological features include hypogammaglobulinemia,
CC decreased levels of B cells, and evidence of impaired immune-mediated
CC cytotoxicity and defective T-cell function.
CC {ECO:0000269|PubMed:30040974, ECO:0000269|PubMed:30336224}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Roifman-Chitayat syndrome (ROCHIS) [MIM:613328]: An autosomal
CC recessive digenic disorder characterized by global developmental delay,
CC variable neurologic features such as seizures and ataxia, optic
CC atrophy, dysmorphic facial features, distal skeletal anomalies, and
CC recurrent invasive infections due to combined immunodeficiency.
CC {ECO:0000269|PubMed:29180244}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry. Caused by the simultaneous occurrence of homozygous mutations in
CC PIK3CD and KNSTRN. {ECO:0000269|PubMed:29180244}.
CC -!- MISCELLANEOUS: IC87114 inhibitor reduces passive cutaneous anaphylaxis,
CC attenuates allergic airway inflammation and hyperresponsiveness and
CC allergen induced rhinitis response. Inhibitors may have therapeutic
CC potential for the treatment of immune system-mediated diseases such as
CC auto-immune diseases, inflammation and allergy (PubMed:20940048;
CC PubMed:17290298).
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00877, ECO:0000255|PROSITE-ProRule:PRU00879,
CC ECO:0000255|PROSITE-ProRule:PRU00880}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PIK3CDID46261ch1p36.html";
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DR EMBL; Y10055; CAA71149.2; -; mRNA.
DR EMBL; U86453; AAC25677.1; -; mRNA.
DR EMBL; JN190435; AEK81610.1; -; mRNA.
DR EMBL; DQ263594; ABB83814.1; -; mRNA.
DR EMBL; AL691449; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132919; AAI32920.1; -; mRNA.
DR EMBL; BC132921; AAI32922.1; -; mRNA.
DR CCDS; CCDS104.1; -. [O00329-1]
DR RefSeq; NP_005017.3; NM_005026.3. [O00329-1]
DR RefSeq; XP_006710750.1; XM_006710687.2. [O00329-1]
DR RefSeq; XP_006710752.1; XM_006710689.2. [O00329-1]
DR PDB; 5DXU; X-ray; 2.64 A; A=2-1044.
DR PDB; 5M6U; X-ray; 2.85 A; A=17-1027.
DR PDB; 5T8F; X-ray; 2.91 A; A=17-1031.
DR PDB; 5UBT; X-ray; 2.83 A; A=17-1029.
DR PDB; 5VLR; X-ray; 2.80 A; A=17-1029.
DR PDB; 6G6W; X-ray; 2.72 A; A=1-1044.
DR PDB; 6OCO; X-ray; 2.58 A; A=17-1031.
DR PDB; 6OCU; X-ray; 2.77 A; A=1-1044.
DR PDB; 6PYR; X-ray; 2.21 A; A=17-1034.
DR PDB; 6PYU; X-ray; 2.54 A; A=17-1034.
DR PDB; 7JIS; X-ray; 2.42 A; A=17-1034.
DR PDB; 7LM2; X-ray; 2.79 A; A=12-1031.
DR PDB; 7LQ1; X-ray; 2.96 A; A=1-1044.
DR PDBsum; 5DXU; -.
DR PDBsum; 5M6U; -.
DR PDBsum; 5T8F; -.
DR PDBsum; 5UBT; -.
DR PDBsum; 5VLR; -.
DR PDBsum; 6G6W; -.
DR PDBsum; 6OCO; -.
DR PDBsum; 6OCU; -.
DR PDBsum; 6PYR; -.
DR PDBsum; 6PYU; -.
DR PDBsum; 7JIS; -.
DR PDBsum; 7LM2; -.
DR PDBsum; 7LQ1; -.
DR AlphaFoldDB; O00329; -.
DR SMR; O00329; -.
DR BioGRID; 111311; 20.
DR ComplexPortal; CPX-5978; Phosphatidylinositol 3-kinase complex class IA, p110delta/p55gamma.
DR ComplexPortal; CPX-5980; Phosphatidylinositol 3-kinase complex class IA, p110delta/p85beta.
DR ComplexPortal; CPX-5983; Phosphatidylinositol 3-kinase complex class IA, p110delta/p85alpha.
DR ComplexPortal; CPX-5984; Phosphatidylinositol 3-kinase complex class IA, p110delta/p55alpha.
DR ComplexPortal; CPX-5985; Phosphatidylinositol 3-kinase complex class IA, p110delta/p50alpha.
DR IntAct; O00329; 12.
DR MINT; O00329; -.
DR STRING; 9606.ENSP00000366563; -.
DR BindingDB; O00329; -.
DR ChEMBL; CHEMBL3130; -.
DR DrugBank; DB06831; 2-((9H-PURIN-6-YLTHIO)METHYL)-5-CHLORO-3-(2-METHOXYPHENYL)QUINAZOLIN-4(3H)-ONE.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB12483; Copanlisib.
DR DrugBank; DB11952; Duvelisib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB09054; Idelalisib.
DR DrugBank; DB05552; TG100-115.
DR DrugBank; DB14989; Umbralisib.
DR DrugBank; DB05241; XL765.
DR DrugCentral; O00329; -.
DR GuidetoPHARMACOLOGY; 2155; -.
DR SwissLipids; SLP:000000908; -.
DR GlyGen; O00329; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00329; -.
DR PhosphoSitePlus; O00329; -.
DR BioMuta; PIK3CD; -.
DR CPTAC; CPTAC-1213; -.
DR EPD; O00329; -.
DR jPOST; O00329; -.
DR MassIVE; O00329; -.
DR MaxQB; O00329; -.
DR PaxDb; O00329; -.
DR PeptideAtlas; O00329; -.
DR PRIDE; O00329; -.
DR ProteomicsDB; 47850; -. [O00329-1]
DR Antibodypedia; 4215; 585 antibodies from 38 providers.
DR DNASU; 5293; -.
DR Ensembl; ENST00000377346.9; ENSP00000366563.4; ENSG00000171608.17. [O00329-1]
DR GeneID; 5293; -.
DR KEGG; hsa:5293; -.
DR MANE-Select; ENST00000377346.9; ENSP00000366563.4; NM_005026.5; NP_005017.3.
DR UCSC; uc001aqb.5; human. [O00329-1]
DR CTD; 5293; -.
DR DisGeNET; 5293; -.
DR GeneCards; PIK3CD; -.
DR HGNC; HGNC:8977; PIK3CD.
DR HPA; ENSG00000171608; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; PIK3CD; -.
DR MIM; 602839; gene.
DR MIM; 613328; phenotype.
DR MIM; 615513; phenotype.
DR MIM; 619281; phenotype.
DR neXtProt; NX_O00329; -.
DR OpenTargets; ENSG00000171608; -.
DR Orphanet; 397596; Activated PI3K-delta syndrome.
DR Orphanet; 221139; Combined immunodeficiency with faciooculoskeletal anomalies.
DR PharmGKB; PA33310; -.
DR VEuPathDB; HostDB:ENSG00000171608; -.
DR eggNOG; KOG0904; Eukaryota.
DR GeneTree; ENSGT00940000159079; -.
DR InParanoid; O00329; -.
DR OMA; ICDMERN; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; O00329; -.
DR TreeFam; TF102031; -.
DR BioCyc; MetaCyc:ENSG00000171608-MON; -.
DR BRENDA; 2.7.1.137; 2681.
DR BRENDA; 2.7.1.153; 2681.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; O00329; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-8853659; RET signaling.
DR Reactome; R-HSA-9027276; Erythropoietin activates Phosphoinositide-3-kinase (PI3K).
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR Reactome; R-HSA-912631; Regulation of signaling by CBL.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; O00329; -.
DR SIGNOR; O00329; -.
DR UniPathway; UPA00220; -.
DR BioGRID-ORCS; 5293; 23 hits in 1079 CRISPR screens.
DR ChiTaRS; PIK3CD; human.
DR GeneWiki; P110%CE%B4; -.
DR GenomeRNAi; 5293; -.
DR Pharos; O00329; Tclin.
DR PRO; PR:O00329; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O00329; protein.
DR Bgee; ENSG00000171608; Expressed in granulocyte and 181 other tissues.
DR ExpressionAtlas; O00329; baseline and differential.
DR Genevisible; O00329; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005942; C:phosphatidylinositol 3-kinase complex; IBA:GO_Central.
DR GO; GO:0005943; C:phosphatidylinositol 3-kinase complex, class IA; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IBA:GO_Central.
DR GO; GO:0035005; F:1-phosphatidylinositol-4-phosphate 3-kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0035004; F:phosphatidylinositol 3-kinase activity; TAS:UniProtKB.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0052812; F:phosphatidylinositol-3,4-bisphosphate 5-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046934; F:phosphatidylinositol-4,5-bisphosphate 3-kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0002250; P:adaptive immune response; TAS:UniProtKB.
DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB.
DR GO; GO:0035754; P:B cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; IC:ComplexPortal.
DR GO; GO:0050853; P:B cell receptor signaling pathway; TAS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IC:ComplexPortal.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB.
DR GO; GO:0002551; P:mast cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; TAS:UniProtKB.
DR GO; GO:0060374; P:mast cell differentiation; TAS:UniProtKB.
DR GO; GO:0030101; P:natural killer cell activation; TAS:UniProtKB.
DR GO; GO:0035747; P:natural killer cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0001779; P:natural killer cell differentiation; TAS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; TAS:UniProtKB.
DR GO; GO:0072672; P:neutrophil extravasation; TAS:UniProtKB.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:CAFA.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IDA:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:CACAO.
DR GO; GO:0038089; P:positive regulation of cell migration by vascular endothelial growth factor signaling pathway; IGI:BHF-UCL.
DR GO; GO:0001819; P:positive regulation of cytokine production; TAS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IGI:BHF-UCL.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IGI:BHF-UCL.
DR GO; GO:1905278; P:positive regulation of epithelial tube formation; IGI:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:CACAO.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; IMP:CAFA.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
DR GO; GO:0002679; P:respiratory burst involved in defense response; TAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR GO; GO:0042110; P:T cell activation; TAS:UniProtKB.
DR GO; GO:0010818; P:T cell chemotaxis; TAS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; TAS:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; TAS:UniProtKB.
DR CDD; cd05174; PI3Kc_IA_delta; 1.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR002420; PI3K-type_C2_dom.
DR InterPro; IPR003113; PI3K_ABD.
DR InterPro; IPR001263; PI3K_accessory_dom.
DR InterPro; IPR042236; PI3K_accessory_sf.
DR InterPro; IPR000341; PI3K_Ras-bd_dom.
DR InterPro; IPR037703; PI3Kdelta_dom.
DR InterPro; IPR015433; PI_Kinase.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10048; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF02192; PI3K_p85B; 1.
DR Pfam; PF00794; PI3K_rbd; 1.
DR Pfam; PF00613; PI3Ka; 1.
DR SMART; SM00142; PI3K_C2; 1.
DR SMART; SM00143; PI3K_p85B; 1.
DR SMART; SM00144; PI3K_rbd; 1.
DR SMART; SM00145; PI3Ka; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51547; C2_PI3K; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR PROSITE; PS51544; PI3K_ABD; 1.
DR PROSITE; PS51546; PI3K_RBD; 1.
DR PROSITE; PS51545; PIK_HELICAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding;
KW Chemotaxis; Cytoplasm; Differentiation; Direct protein sequencing;
KW Disease variant; Immunity; Inflammatory response; Innate immunity; Kinase;
KW Lipid metabolism; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transferase.
FT CHAIN 1..1044
FT /note="Phosphatidylinositol 4,5-bisphosphate 3-kinase
FT catalytic subunit delta isoform"
FT /id="PRO_0000088790"
FT DOMAIN 16..105
FT /note="PI3K-ABD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00877"
FT DOMAIN 187..278
FT /note="PI3K-RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00879"
FT DOMAIN 319..476
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 497..674
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 745..1027
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 287..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 751..757
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 890..898
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 909..935
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 524
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 1039
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10064595,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 201..300
FT /note="ESFTFQVSTKDVPLALMACALRKKATVFRQPLVEQPEDYTLQVNGRHEYLYG
FT SYPLCQFQYICSCLHSGLTPHLTMVHSSSILAMRDEQSNPAPQVQKPR -> VSPCVAC
FT GIQAALSMGSTSSVKLLSHPQAPLPQWHQMVFARCLCMCGAQLNVPPGELHLPGVHQGR
FT AAGADGLCPAEEGHSVPAAAGGAAGRLHAAGERQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:22020336"
FT /id="VSP_044409"
FT VAR_SEQ 302..1044
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:22020336"
FT /id="VSP_044410"
FT VARIANT 721..1044
FT /note="Missing (in ROCHIS; no protein can be detected by
FT Western blot in patient cells)"
FT /evidence="ECO:0000269|PubMed:29180244"
FT /id="VAR_085590"
FT VARIANT 1021
FT /note="E -> K (in IMD14A; results in gain of function
FT causing enhanced membrane association and kinase activity;
FT dbSNP:rs397518423)"
FT /evidence="ECO:0000269|PubMed:24136356"
FT /id="VAR_070918"
FT MUTAGEN 894
FT /note="R->P: Abolishes lipid and protein kinase
FT activities."
FT /evidence="ECO:0000269|PubMed:10064595"
FT MUTAGEN 1039
FT /note="S->A: Abolishes autophosphorylation, no effect on
FT lipid kinase activity."
FT /evidence="ECO:0000269|PubMed:10064595"
FT MUTAGEN 1039
FT /note="S->D,E: Abolishes autophosphorylation, reduced lipid
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:10064595"
FT CONFLICT 253
FT /note="S -> N (in Ref. 3; AAC25677)"
FT /evidence="ECO:0000305"
FT TURN 13..15
FT /evidence="ECO:0007829|PDB:7LM2"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 31..37
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 42..53
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 79..81
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:6OCO"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 94..103
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 108..120
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:6PYU"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 134..155
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 159..166
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 189..196
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 202..208
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 213..225
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:7JIS"
FT STRAND 239..243
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:6PYU"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 260..268
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:7JIS"
FT STRAND 321..332
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 339..349
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 370..380
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 389..397
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 416..426
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 435..440
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 455..457
FT /evidence="ECO:0007829|PDB:6OCU"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 470..475
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 479..481
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 488..495
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 505..515
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:5M6U"
FT HELIX 525..533
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 535..541
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 546..552
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 558..570
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 576..582
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 590..600
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 605..617
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 618..621
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 623..626
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 628..639
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 641..652
FT /evidence="ECO:0007829|PDB:6PYR"
FT TURN 653..656
FT /evidence="ECO:0007829|PDB:6PYR"
FT TURN 658..660
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 661..673
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 676..703
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 704..706
FT /evidence="ECO:0007829|PDB:5VLR"
FT HELIX 708..719
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 722..728
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 729..732
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 739..741
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 746..748
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 753..756
FT /evidence="ECO:0007829|PDB:6OCO"
FT STRAND 759..764
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 770..772
FT /evidence="ECO:0007829|PDB:6PYU"
FT STRAND 774..782
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 785..803
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 815..819
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 822..826
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 829..833
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 834..839
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 854..862
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 865..867
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 868..889
FT /evidence="ECO:0007829|PDB:6PYR"
FT TURN 896..898
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 899..902
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 907..909
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 936..942
FT /evidence="ECO:0007829|PDB:6PYR"
FT TURN 943..945
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 950..969
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 971..981
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 982..984
FT /evidence="ECO:0007829|PDB:6PYR"
FT STRAND 989..991
FT /evidence="ECO:0007829|PDB:5VLR"
FT HELIX 992..1001
FT /evidence="ECO:0007829|PDB:6PYR"
FT TURN 1002..1005
FT /evidence="ECO:0007829|PDB:6PYR"
FT HELIX 1008..1031
FT /evidence="ECO:0007829|PDB:6PYR"
SQ SEQUENCE 1044 AA; 119479 MW; A38B5D1A1081A3D0 CRC64;
MPPGVDCPME FWTKEENQSV VVDFLLPTGV YLNFPVSRNA NLSTIKQLLW HRAQYEPLFH
MLSGPEAYVF TCINQTAEQQ ELEDEQRRLC DVQPFLPVLR LVAREGDRVK KLINSQISLL
IGKGLHEFDS LCDPEVNDFR AKMCQFCEEA AARRQQLGWE AWLQYSFPLQ LEPSAQTWGP
GTLRLPNRAL LVNVKFEGSE ESFTFQVSTK DVPLALMACA LRKKATVFRQ PLVEQPEDYT
LQVNGRHEYL YGSYPLCQFQ YICSCLHSGL TPHLTMVHSS SILAMRDEQS NPAPQVQKPR
AKPPPIPAKK PSSVSLWSLE QPFRIELIQG SKVNADERMK LVVQAGLFHG NEMLCKTVSS
SEVSVCSEPV WKQRLEFDIN ICDLPRMARL CFALYAVIEK AKKARSTKKK SKKADCPIAW
ANLMLFDYKD QLKTGERCLY MWPSVPDEKG ELLNPTGTVR SNPNTDSAAA LLICLPEVAP
HPVYYPALEK ILELGRHSEC VHVTEEEQLQ LREILERRGS GELYEHEKDL VWKLRHEVQE
HFPEALARLL LVTKWNKHED VAQMLYLLCS WPELPVLSAL ELLDFSFPDC HVGSFAIKSL
RKLTDDELFQ YLLQLVQVLK YESYLDCELT KFLLDRALAN RKIGHFLFWH LRSEMHVPSV
ALRFGLILEA YCRGSTHHMK VLMKQGEALS KLKALNDFVK LSSQKTPKPQ TKELMHLCMR
QEAYLEALSH LQSPLDPSTL LAEVCVEQCT FMDSKMKPLW IMYSNEEAGS GGSVGIIFKN
GDDLRQDMLT LQMIQLMDVL WKQEGLDLRM TPYGCLPTGD RTGLIEVVLR SDTIANIQLN
KSNMAATAAF NKDALLNWLK SKNPGEALDR AIEEFTLSCA GYCVATYVLG IGDRHSDNIM
IRESGQLFHI DFGHFLGNFK TKFGINRERV PFILTYDFVH VIQQGKTNNS EKFERFRGYC
ERAYTILRRH GLLFLHLFAL MRAAGLPELS CSKDIQYLKD SLALGKTEEE ALKHFRVKFN
EALRESWKTK VNWLAHNVSK DNRQ
