P110α

PIK3CA
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	2ENQ, 2RD0, 3HHM, 3HIZ, 3ZIM, 4JPS, 4L1B, 4L23, 4L2Y, 4OVU, 4OVV, 4TUU, 4TV3, 4WAF, 4YKN, 5DXH, 5DXT, 5FI4, 4ZOP
معین‌کننده‌ها
نام‌های دیگر	PIK3CA, CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, p110-alpha, PI3K-alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, CLAPO, CCM4
شناسه‌های بیرونی	OMIM: 171834 MGI: 1206581 HomoloGene: 21249 GeneCards: PIK3CA
عدد EC	2.7.11.1
موقعیت ژن (موش)
کروموزوم	کروموزوم ۳ (موش)
پایان	32,522,635 bp
الگوی گسترش RNA
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• transferase activity; • nucleotide binding; • protein kinase activator activity; • 1-phosphatidylinositol-4-phosphate 3-kinase activity; • protein serine/threonine kinase activity; • GO:0001948، GO:0016582 پیوند پروتئینی; • insulin receptor substrate binding; • ATP binding; • 1-phosphatidylinositol-3-kinase activity; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity; • kinase activity; • phosphatidylinositol 3-kinase activity; • phosphatidylinositol-3,4-bisphosphate 5-kinase activity;
ترکیبات سلولی	• phosphatidylinositol 3-kinase complex; • سیتوزول; • phosphatidylinositol 3-kinase complex, class IA; • پوسته یاخته; • پای‌لایه; • سیتوپلاسم; • membrane;
فرایند زیستی	• GO:1904089 negative regulation of neuron apoptotic process; • cardiac muscle contraction; • epidermal growth factor receptor signaling pathway; • protein kinase B signaling; • Fc-gamma receptor signaling pathway involved in phagocytosis; • regulation of multicellular organism growth; • T cell costimulation; • hypomethylation of CpG island; • positive regulation of peptidyl-serine phosphorylation; • platelet activation; • Fc-epsilon receptor signaling pathway; • phosphatidylinositol phosphate biosynthetic process; • vascular endothelial growth factor receptor signaling pathway; • vasculature development; • رگ‌زایی; • insulin receptor signaling pathway via phosphatidylinositol 3-kinase; • glucose metabolic process; • بیگانه‌خواری; • energy homeostasis; • negative regulation of fibroblast apoptotic process; • ساماندهی بیان ژن; • liver development; • adipose tissue development; • regulation of cellular respiration; • T cell receptor signaling pathway; • activation of protein kinase activity; • regulation of genetic imprinting; • negative regulation of anoikis; • cellular response to glucose stimulus; • endothelial cell migration; • phosphatidylinositol-mediated signaling; • leukocyte migration; • ERBB2 signaling pathway; • phosphatidylinositol-3-phosphate biosynthetic process; • هدایت آسه; • negative regulation of macroautophagy; • فسفرگیری; • positive regulation of TOR signaling; • anoikis; • adaptive immune response; • protein phosphorylation; • inflammatory response; • دستگاه ایمنی ذاتی; • cell chemotaxis; • G protein-coupled receptor signaling pathway; • positive regulation of protein kinase B signaling; • phosphatidylinositol 3-kinase signaling; • cytokine-mediated signaling pathway; • کوچ یاخته; • positive regulation of phosphatidylinositol 3-kinase signaling; • phosphatidylinositol biosynthetic process; • regulation of protein phosphorylation;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	5290
	18706
	ENSG00000121879
	ENSMUSG00000027665
	P42336
	P42337
	XM_006713658 NM_006218، XM_006713658
	XR_004941295 NM_008839، XR_004941295
	XP_006713721، XP_011511196 NP_006209، XP_006713721، XP_011511196
	NP_032865
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

فسفاتیدیل‌اینوزیتول-۴و۵-بیس‌فسفات ۳-کیناز، زیرواحد کاتالیزی آلفا (انگلیسی: phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) که با نام‌های اختصاری «p110α» و «PIK3CA» هم شناخته می‌شود، یک زیرواحد پروتئین است که در انسان توسط ژن «PIK3CA» کُدگذاری می‌شود.^[۴]

این پروتئین از آدنوزین تری‌فسفات برای فسفریله کردن فسفاتیدیل‌اینوزیتول، فسفاتیدیل‌اینوزیتول ۴-فسفات و فسفاتیدیل‌اینوزیتول (۴٬۵) بیس‌فسفات استفاده می‌کند.^[۵] از سال ۱۹۹۵ فرضیه‌ای دربارۀ شرکت این پروتئین در سرطان‌زایی مطرح بود^[۶] و کمی بعد مشخص شد که این مولکول نوعی آنکوژن است که در سرطان دهان رحم نقش دارد.^[۷]

با توجه به ارتباط بین p110α و سرطان،^[۸] این پروتئین ممکن است یک هدف دارویی مناسب باشد. شرکت‌های داروسازی در حال طراحی و شناسایی مهارکننده‌های خاص این پروتئین هستند.^[۹]^[۱۰] جهش در ژن «PIK3CA» موجب بروز سندرم کلیپل–ترنونه و ناهنجاری‌های وریدی می‌شود.^[۱۱]^[۱۲] وجود جهش در این ژن همچنین ممکن است دلیلی بر اثربخشی احتمالی آسپرین‌درمانی در سرطان روده بزرگ باشد.^[۱۳]^[۱۴]

تمامی فسفواینوزیتید ۳-کینازها توسط داروهای ورتمانین و ال‌وای۲۹۴۰۰۲ مهار می‌شوند، اما ورتمانین کارایی بهتری نسبت به ال‌وای۲۹۴۰۰۲ در موقعیت‌های مهم جهش نشان می‌دهد.^[۱۵]^[۱۶]

جستارهای وابسته

منابع

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000027665 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Hiles ID, Otsu M, Volinia S, Fry MJ, Gout I, Dhand R, Panayotou G, Ruiz-Larrea F, Thompson A, Totty NF (August 1992). "Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit". Cell. 70 (3): 419–29. doi:10.1016/0092-8674(92)90166-A. PMID 1322797.
↑ "Entrez Gene: PIK3CA".
↑ Samuels Y, Waldman T (2010-01-01). "Oncogenic mutations of PIK3CA in human cancers". In Rommel C, Vanhaesebroeck B, Vogt PK (eds.). Phosphoinositide 3-kinase in Health and Disease. Current Topics in Microbiology and Immunology. Vol. 347. Springer Berlin Heidelberg. pp. 21–41. doi:10.1007/82_2010_68. ISBN 9783642148156. PMC 3164550. PMID 20535651.
↑ Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY (May 2000). "PIK3CA as an oncogene in cervical cancer". Oncogene. 19 (23): 2739–44. doi:10.1038/sj.onc.1203597. PMID 10851074.
↑ Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (April 2004). "High frequency of mutations of the PIK3CA gene in human cancers". Science. 304 (5670): 554. doi:10.1126/science.1096502. PMID 15016963. S2CID 10147415.
↑ Stein RC (September 2001). "Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment". Endocrine-Related Cancer. Bioscientifica. 8 (3): 237–48. doi:10.1677/erc.0.0080237. PMID 11566615. S2CID 568427.
↑ Marone R, Cmiljanovic V, Giese B, Wymann MP (January 2008). "Targeting phosphoinositide 3-kinase: moving towards therapy". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1784 (1): 159–85. doi:10.1016/j.bbapap.2007.10.003. PMID 17997386.
↑ Limaye N, Kangas J, Mendola A, Godfraind C, Schlögel MJ, Helaers R, Eklund L, Boon LM, Vikkula M (December 2015). "Somatic Activating PIK3CA Mutations Cause Venous Malformation". American Journal of Human Genetics. 97 (6): 914–21. doi:10.1016/j.ajhg.2015.11.011. PMC 4678782. PMID 26637981.
↑ Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL, Guevara CJ, Alomari AI, Greene AK, Fishman SJ, Kozakewich HP, Maclellan RA, Mulliken JB, Rahbar R, Spencer SA, Trenor CC, Upton J, Zurakowski D, Perkins JA, Kirsh A, Bennett JT, Dobyns WB, Kurek KC, Warman ML, McCarroll SA, Murillo R (April 2015). "Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA". The Journal of Pediatrics. 166 (4): 1048–54.e1–5. doi:10.1016/j.jpeds.2014.12.069. PMC 4498659. PMID 25681199.
↑ Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S (October 2012). "Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival". The New England Journal of Medicine. 367 (17): 1596–606. doi:10.1056/nejmoa1207756. PMC 3532946. PMID 23094721.
↑ Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, Davidson B, Kerr DJ, Tomlinson IP, Midgley R (December 2013). "Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer". Journal of Clinical Oncology. 31 (34): 4297–305. doi:10.1200/jco.2013.50.0322. PMID 24062397.^{^{[پیوند مرده]}}
↑ Thirumal Kumar D, George Priya Doss C (September 2016). "Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a comparative computational approach". Journal of Biomolecular Structure & Dynamics. 35 (12): 2745–2757. doi:10.1080/07391102.2016.1231082. PMID 27581627.
↑ Kumar DT, Doss CG (2016-01-01). "Investigating the Inhibitory Effect of Wortmannin in the Hotspot Mutation at Codon 1047 of PIK3CA Kinase Domain: A Molecular Docking and Molecular Dynamics Approach". Advances in Protein Chemistry and Structural Biology. 102: 267–97. doi:10.1016/bs.apcsb.2015.09.008. PMID 26827608.

برای مطالعهٔ بیشتر

Foster FM, Traer CJ, Abraham SM, Fry MJ (August 2003). "The phosphoinositide (PI) 3-kinase family". Journal of Cell Science. 116 (Pt 15): 3037–40. doi:10.1242/jcs.00609. PMID 12829733.
Li VS, Wong CW, Chan TL, Chan AS, Zhao W, Chu KM, So S, Chen X, Yuen ST, Leung SY (March 2005). "Mutations of PIK3CA in gastric adenocarcinoma". BMC Cancer. 5: 29. doi:10.1186/1471-2407-5-29. PMC 1079799. PMID 15784156.
Huang CH, Mandelker D, Schmidt-Kittler O, Samuels Y, Velculescu VE, Kinzler KW, Vogelstein B, Gabelli SB, Amzel LM (December 2007). "The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations". Science. 318 (5857): 1744–8. Bibcode:2007Sci...318.1744H. doi:10.1126/science.1150799. PMID 18079394. S2CID 83474940.
Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, Pugh M, Jones L, Russell R, Sammut SJ, Tsui DW, Liu B, Dawson SJ, Abraham J, Northen H, Peden JF, Mukherjee A, Turashvili G, Green AR, McKinney S, Oloumi A, Shah S, Rosenfeld N, Murphy L, Bentley DR, Ellis IO, Purushotham A, Pinder SE, Børresen-Dale AL, Earl HM, Pharoah PD, Ross MT, Aparicio S, Caldas C (May 2016). "The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes". Nature Communications. 7: 11479. Bibcode:2016NatCo...711479P. doi:10.1038/ncomms11479. PMC 4866047. PMID 27161491.

این یک مقالهٔ خرد زیست‌شناسی مولکولی است. می‌توانید با گسترش آن به ویکی‌پدیا کمک کنید.

[refGRCm38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000027665 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1322797-4] Hiles ID, Otsu M, Volinia S, Fry MJ, Gout I, Dhand R, Panayotou G, Ruiz-Larrea F, Thompson A, Totty NF (August 1992). "Phosphatidylinositol 3-kinase: structure and expression of the 110 kd catalytic subunit". Cell. 70 (3): 419–29. doi:10.1016/0092-8674(92)90166-A. PMID 1322797.

[entrez-5] "Entrez Gene: PIK3CA".

[6] Samuels Y, Waldman T (2010-01-01). "Oncogenic mutations of PIK3CA in human cancers". In Rommel C, Vanhaesebroeck B, Vogt PK (eds.). Phosphoinositide 3-kinase in Health and Disease. Current Topics in Microbiology and Immunology. Vol. 347. Springer Berlin Heidelberg. pp. 21–41. doi:10.1007/82_2010_68. ISBN 9783642148156. PMC 3164550. PMID 20535651.

[pmid10851074-7] Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, Liu JM, Yang DM, Yang WK, Shen CY (May 2000). "PIK3CA as an oncogene in cervical cancer". Oncogene. 19 (23): 2739–44. doi:10.1038/sj.onc.1203597. PMID 10851074.

[pmid15016963-8] Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE (April 2004). "High frequency of mutations of the PIK3CA gene in human cancers". Science. 304 (5670): 554. doi:10.1126/science.1096502. PMID 15016963. S2CID 10147415.

[pmid11566615-9] Stein RC (September 2001). "Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment". Endocrine-Related Cancer. Bioscientifica. 8 (3): 237–48. doi:10.1677/erc.0.0080237. PMID 11566615. S2CID 568427.

[pmid17997386-10] Marone R, Cmiljanovic V, Giese B, Wymann MP (January 2008). "Targeting phosphoinositide 3-kinase: moving towards therapy". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1784 (1): 159–85. doi:10.1016/j.bbapap.2007.10.003. PMID 17997386.

[11] Limaye N, Kangas J, Mendola A, Godfraind C, Schlögel MJ, Helaers R, Eklund L, Boon LM, Vikkula M (December 2015). "Somatic Activating PIK3CA Mutations Cause Venous Malformation". American Journal of Human Genetics. 97 (6): 914–21. doi:10.1016/j.ajhg.2015.11.011. PMC 4678782. PMID 26637981.

[12] Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL, Guevara CJ, Alomari AI, Greene AK, Fishman SJ, Kozakewich HP, Maclellan RA, Mulliken JB, Rahbar R, Spencer SA, Trenor CC, Upton J, Zurakowski D, Perkins JA, Kirsh A, Bennett JT, Dobyns WB, Kurek KC, Warman ML, McCarroll SA, Murillo R (April 2015). "Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA". The Journal of Pediatrics. 166 (4): 1048–54.e1–5. doi:10.1016/j.jpeds.2014.12.069. PMC 4498659. PMID 25681199.

[13] Liao X, Lochhead P, Nishihara R, Morikawa T, Kuchiba A, Yamauchi M, Imamura Y, Qian ZR, Baba Y, Shima K, Sun R, Nosho K, Meyerhardt JA, Giovannucci E, Fuchs CS, Chan AT, Ogino S (October 2012). "Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival". The New England Journal of Medicine. 367 (17): 1596–606. doi:10.1056/nejmoa1207756. PMC 3532946. PMID 23094721.

[14] Domingo E, Church DN, Sieber O, Ramamoorthy R, Yanagisawa Y, Johnstone E, Davidson B, Kerr DJ, Tomlinson IP, Midgley R (December 2013). "Evaluation of PIK3CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer". Journal of Clinical Oncology. 31 (34): 4297–305. doi:10.1200/jco.2013.50.0322. PMID 24062397.^{^{[پیوند مرده]}}

[15] Thirumal Kumar D, George Priya Doss C (September 2016). "Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a comparative computational approach". Journal of Biomolecular Structure & Dynamics. 35 (12): 2745–2757. doi:10.1080/07391102.2016.1231082. PMID 27581627.

[16] Kumar DT, Doss CG (2016-01-01). "Investigating the Inhibitory Effect of Wortmannin in the Hotspot Mutation at Codon 1047 of PIK3CA Kinase Domain: A Molecular Docking and Molecular Dynamics Approach". Advances in Protein Chemistry and Structural Biology. 102: 267–97. doi:10.1016/bs.apcsb.2015.09.008. PMID 26827608.

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