diff --git a/pathways/WP241/WP241.gpml b/pathways/WP241/WP241.gpml index a74aa13152..b83d1c4ea5 100644 --- a/pathways/WP241/WP241.gpml +++ b/pathways/WP241/WP241.gpml @@ -1,5 +1,5 @@ - + This one-carbon metabolism pathway is centered around folate. Folate has two key carbon-carbon double bonds. Saturating one of them yields dihydrofolate (DHF) and adding an additional molecule of hydrogen across the second yields tetrahydrofolate (THF). Folates serve as donors of single carbons in any one of three oxidation states: 5-methyl-THF (CH3THF; reduced), 5,10 methylene-THF (CH2THF; intermediate) and 10-formyl-THF (CHOTHF; oxidized). The single carbon donor CH3THF is used to convert homocysteine into methionine which can then be used to methylate DNA, the donor CH2THF is used (along with a molecule of hydrogen at the site of one of the double bonds) to convert dUMP (deoxyuridylate) into dTMP (thymidylate) and the donor CHOTHF is used to set up ring closure reactions in de novo purine synthesis. CH3THF is the primary methyl-group donor for processes such as DNA methylation reactions. Purines are used both in RNA synthesis and in DNA synthesis and dTMP is synthesized srtictly for DNA synthesis, be it for DNA repair or DNA replication. The folate pathway is central to any study related to DNA methylation, dTMP synthesis or purine synthesis. @@ -8,7 +8,7 @@ Differential methylation (e.g. hypermethylation of tumor suppressors) as well as The pathway is also illustrative of the role of a number of B vitamins, including vitamin B12 (cobalamine) which is important for the sythesis of folate (vitamin B9) and of methionine. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP241 CPTAC Assay Portal] - + @@ -343,260 +343,265 @@ Proteins on this pathway have targeted assays available via the [https://assays. + + Wikidata: Q21123704 + + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - - + + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - - + + + - - + + - - + + - - + + - - + + - - - - + + + + - - + + - - + + - - + + - - - + + + - - + + - - + + - - + + - - + + @@ -604,70 +609,70 @@ Proteins on this pathway have targeted assays available via the [https://assays. - - + + - - - + + + - - + + - - + + - - + + - - - + + + - - + + - - + + - - + + @@ -675,134 +680,142 @@ Proteins on this pathway have targeted assays available via the [https://assays. - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - + + - - - + + + + + f38 + + + + + + - - + + @@ -815,22 +828,60 @@ Proteins on this pathway have targeted assays available via the [https://assays. - - - - - - - - - + + + + + + + + + + + 22634633 + PubMed + Glutaredoxin serves as a reductant for methionine sulfoxide reductases with or without resolving cysteine. + Acta Biochim Biophys Sin (Shanghai) + 2012 + Kim HY + + + 10762064 + PubMed + S-Adenosylmethionine. + Int J Biochem Cell Biol + 2000 + Lu SC + + + 13271447 + PubMed + Glutathione-homocystine transhydrogenase. + J Biol Chem + 1955 + RACKER E + folate mediated one-carbon metabolic pathway PW:0000189 Pathway Ontology + + 12466265 + PubMed + Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. + J Biol Chem + 2003 + Waditee R + Tanaka Y + Aoki K + Hibino T + Jikuya H + Takano J + Takabe T + 17389618 PubMed @@ -844,33 +895,6 @@ Proteins on this pathway have targeted assays available via the [https://assays. Giovannucci EL Hunter DJ - - 13271447 - PubMed - Glutathione-homocystine transhydrogenase. - J Biol Chem - 1955 - RACKER E - - - 22634633 - PubMed - Glutaredoxin serves as a reductant for methionine sulfoxide reductases with or without resolving cysteine. - Acta Biochim Biophys Sin (Shanghai) - 2012 - Kim HY - - - 8019414 - PubMed - The primary structure and properties of thioltransferase (glutaredoxin) from human red blood cells. - Protein Sci - 1994 - Papov VV - Gravina SA - Mieyal JJ - Biemann K - 8752328 PubMed @@ -891,19 +915,17 @@ Proteins on this pathway have targeted assays available via the [https://assays. Ludwig ML Matthews RG - - 12466265 + + 8019414 PubMed - Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. - J Biol Chem - 2003 - Waditee R - Tanaka Y - Aoki K - Hibino T - Jikuya H - Takano J - Takabe T + The primary structure and properties of thioltransferase (glutaredoxin) from human red blood cells. + Protein Sci + 1994 + Papov VV + Gravina SA + Mieyal JJ + Biemann K + diff --git a/pathways/WP4806/WP4806.gpml b/pathways/WP4806/WP4806.gpml index 02c9e4f11c..7330805475 100644 --- a/pathways/WP4806/WP4806.gpml +++ b/pathways/WP4806/WP4806.gpml @@ -1,1820 +1,1821 @@ - - - Tyrosine kinase inhibitors (TKIs) are drugs that inhibit the phosphorylation, and subsequent activation, of tyrosine kinases. TKIs are typically used as cancer therapeutics, but development of resistance to TKIs in cancers is common. This pathway describes several mechanisms of TKI resistance in the context of EGFR signaling. Epidermal Growth Factor Receptor, EGFR, is a transmembrane tyrosine kinase that binds to the EGF-family of ligands. It activates several downstream signaling cascades, including MAPK, and leads to DNA synthesis and cell proliferation. Mutations and over-expression in EGFR is implicated in many cancers. -The section of the pathway outlined in pink corresponds to mechanisms of TKI resistance. - - - - - - - - - - - - - - - - - - - - e70 - - - - - - - - - - - - - - - - - cc6 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - e90 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - b94 - - - - - parentid=P24385; parentsymbol=CCND1; site=EEVDLACtPtDVRDV; position=thr286; sitegrpid=447839; ptm=p; direction=d - - - - - parentid=P01106; parentsymbol=MYC; site=kkFELLPtPPLsPsR; position=thr58; sitegrpid=448496; ptm=p; direction=d - - - - - - - - - - - - - parentid=P40763; parentsymbol=STAT3; site=DPGsAAPyLKtKFIC; position=tyr705; sitegrpid=448192; ptm=p; direction=u - - - - - f79 - - - - - parentid=O43521; parentsymbol=BCL2L11; site=GPLAPPAsPGPFATR; position=ser69; sitegrpid=449330; ptm=p; direction=d - - - - - - - - - parentid=P21860; parentsymbol=ERBB2; site=CPAsEQGyEEMRAFQ; position=tyr1289; sitegrpid=449858; ptm=p; direction=u - - - - - T790M - d09 - - - - - T790M - d09 - - - - - T790M - d09 - - - - - - - - - a1c - - - - - a1c - - - - - f74 - - - - - parentid=P40763; parentsymbol=STAT3; site=DPGsAAPyLKtKFIC; position=tyr705; sitegrpid=448192; ptm=p; direction=u - - - - - parentid=P40763; parentsymbol=STAT3; site=NtIDLPMsPRTLDSL; position=ser727; sitegrpid=448191; ptm=p; direction=u - - - - - parentid=P40763; parentsymbol=STAT3; site=DPGsAAPyLKtKFIC; position=tyr705; sitegrpid=448192; ptm=p; direction=u - - - - - parentid=P31749; parentsymbol=AKT1; site=kDGAtMKtFCGtPEy; position=thr308; sitegrpid=447856; ptm=p; direction=u - - - - - parentid=P31749; parentsymbol=AKT1; site=RPHFPQFsysAsGtA; position=ser473; sitegrpid=447855; ptm=p; direction=u - - - - - parentid=P31751; parentsymbol=AKT2; site=sDGAtMKtFCGtPEy; position=thr309; sitegrpid=448537; ptm=p; direction=u - - - - - parentid=Q9Y243; parentsymbol=AKT3; site=tDAATMKtFCGtPEy; position=thr305; sitegrpid=448521; ptm=p; direction=u - - - - - parentid=P49841; parentsymbol=GSK3B; site=SGRPRttsFAEsCkP; position=ser9; sitegrpid=449111; ptm=p; direction=d - - - - - parentid=Q92934; parentsymbol=BAD; site=PFrGrsRsAPPNLWA; position=ser99; sitegrpid=47862; ptm=p; direction=d - - - - - parentid=Q13541; parentsymbol=EIF4EBP1; site=FLMECrNsPVtktPP; position=ser65; sitegrpid=447527; ptm=p; direction=d - - - - - parentid=Q13541; parentsymbol=EIF4EBP1; site=rNsPVtktPPRDLPt; position=thr70; sitegrpid=447528; ptm=p; direction=d - - - - - parentid=Q13541; parentsymbol=EIF4EBP1; site=PPGDysttPGGtLFs; position=thr37; sitegrpid=447497; ptm=p; direction=d - - - - - parentid=Q13541; parentsymbol=EIF4EBP1; site=GGtLFsttPGGtRII; position=thr46; sitegrpid=447496; ptm=p; direction=d - - - - - parentid=P42345; parentsymbol=MTOR; site=RkRHksDsIsLsFDE; position=ser2448; sitegrpid=447578; ptm=p; direction=u - - - - - parentid=O43524; parentsymbol=FOXO3; site=QsRPRsCtWPLQRPE; position=thr32; sitegrpid=448602; ptm=p; direction=d - - - - - parentid=O43524; parentsymbol=FOXO3; site=APRRRAVsMDNSNkY; position=ser253; sitegrpid=449108; ptm=p; direction=d - - - - - parentid=P23443; parentsymbol=RPS6KB1; site=NQVFLGFtyVAPsVL; position=thr412; sitegrpid=448607; ptm=p; direction=u - - - - - parentid=P23443; parentsymbol=RPS6KB1; site=TRQtPVDsPDDStLS; position=ser394; sitegrpid=448806; ptm=p; direction=u - - - - - parentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGTRSY; position=ser222; sitegrpid=448513; ptm=p; direction=u - - - - - parentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=u - - - - - parentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyR; position=tyr187; sitegrpid=447594; ptm=p; direction=u - - - - - parentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=u - - - - - G469A, V600E, V599E - d3d - - - - - parentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyR; position=tyr204; sitegrpid=447543; ptm=p; direction=u - - - - - parentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=u - - - - - - - - - d0c - - - - - parentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=u - - - - - parentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGTRSY; position=ser226; sitegrpid=448074; ptm=p; direction=u - - - - - parentid=P04049; parentsymbol=RAF1; site=IGDFGLAtVksRWsG; position=thr491; sitegrpid=447748; ptm=p; direction=u - - - - - parentid=P04049; parentsymbol=RAF1; site=RPRGQRDssyyWEIE; position=ser338; sitegrpid=447742; ptm=p; direction=u - - - - - parentid=P40763; parentsymbol=STAT3; site=DPGsAAPyLKtKFIC; position=tyr705; sitegrpid=448192; ptm=p; direction=u - - - - - parentid=P40763; parentsymbol=STAT3; site=NtIDLPMsPRTLDSL; position=ser727; sitegrpid=448191; ptm=p; direction=u - - - - - - - - - parentid=O00329; parentsymbol=PIK3CD; site=RRGsGELyEHEkDLV; position=tyr524; sitegrpid=454088; ptm=p; direction=u - - - - - parentid=O00329; parentsymbol=PIK3CD; site=NWLAHNVsKDNRQ__; position=ser1039; sitegrpid=466429; ptm=p; direction=u - - - - - parentid=P42338; parentsymbol=PIK3CB; site=TVRKDYRs_______; position=ser1070; sitegrpid=449881; ptm=p; direction=u - - - - - - - - - - - - - - - - - - - - - parentid=P27986; parentsymbol=PIK3R1; site=ENtEDQysLVEDDED; position=ser608; sitegrpid=448133; ptm=p; direction=u - - - - - parentid=P27986; parentsymbol=PIK3R1; site=kNEtEDQyALMEDED; position=tyr605; sitegrpid=451549; ptm=p; direction=u - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - c5e - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - cfa - - - - - - - b64 - - - - - - 25337673 - PubMed - AXL kinase as a novel target for cancer therapy. - Oncotarget - 2014 - Wu X - Liu X - Koul S - Lee CY - Zhang Z - Halmos B - - - 25984556 - PubMed - Insulin-like growth factor (IGF) signaling in tumorigenesis and the development of cancer drug resistance. - Genes Dis - 2015 - Denduluri SK - Idowu O - Wang Z - Liao Z - Yan Z - Mohammed MK - Ye J - Wei Q - Wang J - Zhao L - Luu HH - - - 24535670 - PubMed - Reduced NF1 expression confers resistance to EGFR inhibition in lung cancer. - Cancer Discov - 2014 - de Bruin EC - Cowell C - Warne PH - Jiang M - Saunders RE - Melnick MA - Gettinger S - Walther Z - Wurtz A - Heynen GJ - Heideman DA - Gómez-Román J - García-Castaño A - Gong Y - Ladanyi M - Varmus H - Bernards R - Smit EF - Politi K - Downward J - - - 11751408 - PubMed - Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells. - Cancer Res - 2001 - Conze D - Weiss L - Regen PS - Bhushan A - Weaver D - Johnson P - Rincón M - - - 19419954 - PubMed - Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion. - J Biol Chem - 2009 - Huang TH - Wu F - Loeb GB - Hsu R - Heidersbach A - Brincat A - Horiuchi D - Lebbink RJ - Mo YY - Goga A - McManus MT - - - - PubMed - - https://en.wikipedia.org/wiki/T790M - - - - 11397666 - PubMed - EGF mutant receptor vIII as a molecular target in cancer therapy. - Endocr Relat Cancer - 2001 - Kuan CT - Wikstrand CJ - Bigner DD - - - 25115383 - PubMed - FGFR1 activation is an escape mechanism in human lung cancer cells resistant to afatinib, a pan-EGFR family kinase inhibitor. - Oncotarget - 2014 - Azuma K - Kawahara A - Sonoda K - Nakashima K - Tashiro K - Watari K - Izumi H - Kage M - Kuwano M - Ono M - Hoshino T - - - altered growth factor signaling pathway - PW:0000298 - Pathway Ontology - - - 22773810 - PubMed - Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. - Proc Natl Acad Sci U S A - 2012 - Ohashi K - Sequist LV - Arcila ME - Moran T - Chmielecki J - Lin YL - Pan Y - Wang L - de Stanchina E - Shien K - Aoe K - Toyooka S - Kiura K - Fernandez-Cuesta L - Fidias P - Yang JC - Miller VA - Riely GJ - Kris MG - Engelman JA - Vnencak-Jones CL - Dias-Santagata D - Ladanyi M - Pao W - - - 22426421 - PubMed - A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. - Nat Med - 2012 - Ng KP - Hillmer AM - Chuah CT - Juan WC - Ko TK - Teo AS - Ariyaratne PN - Takahashi N - Sawada K - Fei Y - Soh S - Lee WH - Huang JW - Allen JC Jr - Woo XY - Nagarajan N - Kumar V - Thalamuthu A - Poh WT - Ang AL - Mya HT - How GF - Yang LY - Koh LP - Chowbay B - Chang CT - Nadarajan VS - Chng WJ - Than H - Lim LC - Goh YT - Zhang S - Poh D - Tan P - Seet JE - Ang MK - Chau NM - Ng QS - Tan DS - Soda M - Isobe K - Nöthen MM - Wong TY - Shahab A - Ruan X - Cacheux-Rataboul V - Sung WK - Tan EH - Yatabe Y - Mano H - Soo RA - Chin TM - Lim WT - Ruan Y - Ong ST - - - 17463250 - PubMed - MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. - Science - 2007 - Engelman JA - Zejnullahu K - Mitsudomi T - Song Y - Hyland C - Park JO - Lindeman N - Gale CM - Zhao X - Christensen J - Kosaka T - Holmes AJ - Rogers AM - Cappuzzo F - Mok T - Lee C - Johnson BE - Cantley LC - Jänne PA - - - altered tyrosine-specific protein kinase mediated signaling pathway - PW:0001537 - Pathway Ontology - - - tyrosine-specific protein kinase mediated signaling pathway - PW:0001195 - Pathway Ontology - - - 23533263 - PubMed - De-repression of PDGFRβ transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients. - Cancer Discov - 2013 - Akhavan D - Pourzia AL - Nourian AA - Williams KJ - Nathanson D - Babic I - Villa GR - Tanaka K - Nael A - Yang H - Dang J - Vinters HV - Yong WH - Flagg M - Tamanoi F - Sasayama T - James CD - Kornblum HI - Cloughesy TF - Cavenee WK - Bensinger SJ - Mischel PS - - - 23404247 - PubMed - KRAS gene amplification in colorectal cancer and impact on response to EGFR-targeted therapy. - Int J Cancer - 2013 - Valtorta E - Misale S - Sartore-Bianchi A - Nagtegaal ID - Paraf F - Lauricella C - Dimartino V - Hobor S - Jacobs B - Ercolani C - Lamba S - Scala E - Veronese S - Laurent-Puig P - Siena S - Tejpar S - Mottolese M - Punt CJ - Gambacorta M - Bardelli A - Di Nicolantonio F - - - - + + + Tyrosine kinase inhibitors (TKIs) are drugs that inhibit the phosphorylation, and subsequent activation, of tyrosine kinases. TKIs are typically used as cancer therapeutics, but development of resistance to TKIs in cancers is common. This pathway describes several mechanisms of TKI resistance in the context of EGFR signaling. Epidermal Growth Factor Receptor, EGFR, is a transmembrane tyrosine kinase that binds to the EGF-family of ligands. It activates several downstream signaling cascades, including MAPK, and leads to DNA synthesis and cell proliferation. Mutations and over-expression in EGFR is implicated in many cancers. +The section of the pathway outlined in pink corresponds to mechanisms of TKI resistance. +This pathway was based on [https://www.kegg.jp/kegg-bin/show_pathway?hsa01521 KEGG]. + + + + + + + + + + + + + + + + + + + + e70 + + + + + + + + + + + + + + + + + cc6 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + e90 + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + 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site=DPGsAAPyLKtKFIC; position=tyr705; sitegrpid=448192; ptm=p; direction=u + + + + + parentid=P40763; parentsymbol=STAT3; site=NtIDLPMsPRTLDSL; position=ser727; sitegrpid=448191; ptm=p; direction=u + + + + + parentid=P40763; parentsymbol=STAT3; site=DPGsAAPyLKtKFIC; position=tyr705; sitegrpid=448192; ptm=p; direction=u + + + + + parentid=P31749; parentsymbol=AKT1; site=kDGAtMKtFCGtPEy; position=thr308; sitegrpid=447856; ptm=p; direction=u + + + + + parentid=P31749; parentsymbol=AKT1; site=RPHFPQFsysAsGtA; position=ser473; sitegrpid=447855; ptm=p; direction=u + + + + + parentid=P31751; parentsymbol=AKT2; site=sDGAtMKtFCGtPEy; position=thr309; sitegrpid=448537; ptm=p; direction=u + + + + + parentid=Q9Y243; parentsymbol=AKT3; site=tDAATMKtFCGtPEy; position=thr305; sitegrpid=448521; ptm=p; direction=u + + + + + parentid=P49841; parentsymbol=GSK3B; site=SGRPRttsFAEsCkP; position=ser9; sitegrpid=449111; ptm=p; direction=d + + + + + parentid=Q92934; parentsymbol=BAD; site=PFrGrsRsAPPNLWA; 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parentid=P42338; parentsymbol=PIK3CB; site=TVRKDYRs_______; position=ser1070; sitegrpid=449881; ptm=p; direction=u + + + + + + + + + + + + + + + + + + + + + parentid=P27986; parentsymbol=PIK3R1; site=ENtEDQysLVEDDED; position=ser608; sitegrpid=448133; ptm=p; direction=u + + + + + parentid=P27986; parentsymbol=PIK3R1; site=kNEtEDQyALMEDED; position=tyr605; sitegrpid=451549; ptm=p; direction=u + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + c5e + + + + + + + + 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