LYN

LYN
????????? ?????
PDB	?????? ?????????????: PDBe RCSB
????? ????????? PDB
	1W1F , 1WA7 , 3A4O
?????????????
??????? ????	LYN , LYN proto-oncogene, Src family tyrosine kinase, JTK8, p53Lyn, p56Lyn
????????? ??????	OMIM: 165120 MGI: 96892 HomoloGene: 55649 GeneCards: LYN
?????? ?? (???)
????????	???????? ? (???)
?????	3,813,122 bp
?????????? ??
?????? ??????	? transmembrane transporter binding ; ? SH3 domain binding ; ? GO:0032403 protein-containing complex binding ; ? kinase activity ; ? gamma-tubulin binding ; ? signaling receptor binding ; ? ATP binding ; ? protein kinase activity ; ? non-membrane spanning protein tyrosine kinase activity ; ? enzyme binding ; ? transferase activity ; ? platelet-derived growth factor receptor binding ; ? integrin binding ; ? GO:0001948? GO:0016582 ????? ???????? ; ? glycosphingolipid binding ; ? protein tyrosine kinase activity ; ? nucleotide binding ; ? phosphoprotein binding ; ? ubiquitin protein ligase binding ; ? ephrin receptor binding ; ? phosphorylation-dependent protein binding ;
??????? ?????	? ????????? ; ? ??????? ; ? membrane ; ? extrinsic component of cytoplasmic side of plasma membrane ; ? mitochondrial intermembrane space ; ? perinuclear region of cytoplasm ; ? ???? ????? ; ? mitochondrial membranes ; ? ????? ??? ; ? extracellular exosome ; ? ?????? ???? ; ? ????? ????? ; ? GO:0097483? GO:0097481 postsynaptic density ; ? mast cell granule ; ? integrin alpha2-beta1 complex ; ? mitochondrial crista ; ? intracellular membrane-bounded organelle ; ? glutamatergic synapse ; ? postsynaptic specialization, intracellular component ;
?????? ?????	? regulation of protein phosphorylation ; ? cellular response to extracellular stimulus ; ? cellular response to retinoic acid ; ? positive regulation of B cell receptor signaling pathway ; ? tolerance induction to self antigen ; ? regulation of mast cell activation ; ? regulation of cell adhesion mediated by integrin ; ? cellular response to heat ; ? response to amino acid ; ? ????????? ; ? adaptive immune response ; ? regulation of erythrocyte differentiation ; ? cellular response to DNA damage stimulus ; ? positive regulation of Fc receptor mediated stimulatory signaling pathway ; ? platelet activation ; ? Fc-epsilon receptor signaling pathway ; ? protein phosphorylation ; ? regulation of B cell apoptotic process ; ? positive regulation of dendritic cell apoptotic process ; ? positive regulation of glial cell proliferation ; ? response to carbohydrate ; ? regulation of platelet aggregation ; ? negative regulation of cell population proliferation ; ? B cell receptor signaling pathway ; ? negative regulation of myeloid leukocyte differentiation ; ? dendritic cell differentiation ; ? Fc receptor mediated inhibitory signaling pathway ; ? Fc-gamma receptor signaling pathway involved in phagocytosis ; ? transmembrane receptor protein tyrosine kinase signaling pathway ; ? regulation of B cell receptor signaling pathway ; ? stimulatory C-type lectin receptor signaling pathway ; ? response to sterol depletion ; ? positive regulation of stress-activated protein kinase signaling cascade ; ? GO:0032657 regulation of cytokine production ; ? response to insulin ; ? positive regulation of mast cell proliferation ; ? ?? ????? ; ? regulation of ERK1 and ERK2 cascade ; ? positive regulation of peptidyl-tyrosine phosphorylation ; ? erythrocyte differentiation ; ? protein autophosphorylation ; ? oligodendrocyte development ; ? regulation of mast cell degranulation ; ? positive regulation of phosphorylation ; ? GO:0022415 viral process ; ? response to toxic substance ; ? GO:0033128 negative regulation of protein phosphorylation ; ? Fc receptor mediated stimulatory signaling pathway ; ? growth hormone receptor signaling pathway via JAK-STAT ; ? ???????? ; ? immune system process ; ? regulation of release of sequestered calcium ion into cytosol ; ? positive regulation of tyrosine phosphorylation of STAT protein ; ? B cell homeostasis ; ? immune response-regulating cell surface receptor signaling pathway ; ? response to axon injury ; ? negative regulation of mast cell proliferation ; ? regulation of inflammatory response ; ? peptidyl-tyrosine autophosphorylation ; ? response to hormone ; ? regulation of monocyte chemotaxis ; ? leukocyte migration ; ? lipopolysaccharide-mediated signaling pathway ; ? histamine secretion by mast cell ; ? GO:0007243 intracellular signal transduction ; ? GO:1904578 response to organic cyclic compound ; ? negative regulation of intracellular signal transduction ; ? positive regulation of cell migration ; ? ephrin receptor signaling pathway ; ? negative regulation of toll-like receptor 2 signaling pathway ; ? T cell costimulation ; ? response to peptide hormone ; ? platelet degranulation ; ? ?????? ??? ; ? positive regulation of phosphatidylinositol 3-kinase activity ; ? positive regulation of oligodendrocyte progenitor proliferation ; ? negative regulation of immune response ; ? positive regulation of cell population proliferation ; ? positive regulation of neuron projection development ; ? negative regulation of ERK1 and ERK2 cascade ; ? peptidyl-tyrosine phosphorylation ; ? negative regulation of B cell proliferation ; ? negative regulation of toll-like receptor 4 signaling pathway ; ? GO:0072468 ???????? ???? ; ? ?????? ????? ???? ; ? neuron projection development ; ? central nervous system development ; ? inflammatory response ; ? positive regulation of protein phosphorylation ; ? positive regulation of phosphatidylinositol 3-kinase signaling ; ? ??????? ?????? ; ? positive regulation of Ras protein signal transduction ; ? positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process ;
	?????: ????? / ????????
?????????????
	4067
	17096
	ENSG00000254087
	ENSMUSG00000042228
	P07948
	P25911
	NM_002350? XM_011517529 NM_001111097? NM_002350? XM_011517529
	NM_010747? XM_030253285? XM_036163782 NM_001111096? NM_010747? XM_030253285? XM_036163782
	NP_002341? XP_011515831? XP_016868904? XP_016868905 NP_001104567? NP_002341? XP_011515831? XP_016868904? XP_016868905
	NP_034877? XP_030109145? XP_036019675 NP_001104566? NP_034877? XP_030109145? XP_036019675
	?????????
??????/?????? ?????	??????/?????? ???

???????-??????? ????? Lyn ( ??????? : Tyrosine-protein kinase Lyn ) ?? ??????? ??? ?? ?? ????? ???? ?? ≪ LYN ≫ ???????? ??????. ^[?]

???????? Lyn ?? ??????? ????? ? ?? ????? ???????? ???????? Src ??? ?? ????? ?? ????????? ???????? ^[?] ???? ????? ^[?] ??? ? ???? ???? ^[?] ???? ??????.

??? ??????? ????? ???????????? ?? ????? ???? ???????? ???????? ???? ???? ? ??????? ???????? ???? ?? ?? ???? ??? ?? ??? ??????? ? ????????? ???????????? ????? ???????. ^[?]

???????? Lyn ?????? ??? ?? ??????????????? ??????? ??? ???? ????? ? ???? ?????? ????? ?????? ?? ??????? ?? ?????????????? ????? ???. ^[?]

???????? [ ?????? ]

???????? Lyn ?? ?????????? ??? ????? ???????-??????? ????:

????? [ ?????? ]

↑ ^??? ^??? ^??? GRCm38: Ensembl release 89: ENSMUSG00000042228 - 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 .
↑ Yamanashi Y, Fukushige S, Semba K, Sukegawa J, Miyajima N, Matsubara K, Yamamoto T, Toyoshima K (Jan 1987). "The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck" . Molecular and Cellular Biology . 7 (1): 237?43. doi : 10.1128/MCB.7.1.237 . PMC 365062 . PMID 3561390 .
↑ Yamanashi Y, Mori S, Yoshida M, Kishimoto T, Inoue K, Yamamoto T, Toyoshima K (Sep 1989). "Selective expression of a protein-tyrosine kinase, p56lyn, in hematopoietic cells and association with production of human T-cell lymphotropic virus type I" . Proceedings of the National Academy of Sciences of the United States of America . 86 (17): 6538?42. doi : 10.1073/pnas.86.17.6538 . PMC 297879 . PMID 2505253 .
↑ Umemori H, Wanaka A, Kato H, Takeuchi M, Tohyama M, Yamamoto T (Dec 1992). "Specific expressions of Fyn and Lyn, lymphocyte antigen receptor-associated tyrosine kinases, in the central nervous system". Brain Research. Molecular Brain Research . 16 (3?4): 303?10. doi : 10.1016/0169-328X(92)90239-8 . PMID 1337939 .
↑ Yamada E, Pessin JE, Kurland IJ, Schwartz GJ, Bastie CC (Feb 2010). "Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine phosphorylation of LKB1" . Cell Metabolism . 11 (2): 113?124. doi : 10.1016/j.cmet.2009.12.010 . PMC 2830006 . PMID 20142099 .
↑ Gringeri E, Carraro A, Tibaldi E, D'Amico FE, Mancon M, Toninello A, Pagano MA, Vio C, Cillo U, Brunati AM (December 2009). "Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration" (PDF) . The Biochemical Journal . 425 (2): 401?12. doi : 10.1042/BJ20090902 . PMID 19832701 . Archived from the original (PDF) on 24 July 2018 . Retrieved 29 August 2019 . ≪???? ????? ???≫ (PDF) . ??????????? ?? ???? ?? ?? ????? ???? . ?????????? ?? ?? ??? ???? .
↑ Gavali, Shubhangi; Gupta, Manoj Kumar; Daswani, Bhavna; Wani, Mohan R.; Sirdeshmukh, Ravi; Khatkhatay, M. Ikram (March 2019). "LYN, a key mediator in estrogen-dependent suppression of osteoclast differentiation, survival, and function". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1865 (3): 547?557. doi : 10.1016/j.bbadis.2018.12.016 . PMID 30579930 .
↑ Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (Apr 2002). "Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling". The Journal of Biological Chemistry . 277 (16): 13732?8. doi : 10.1074/jbc.M200277200 . PMID 11825908 .
↑ Linnekin D, DeBerry CS, Mou S (Oct 1997). "Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells". The Journal of Biological Chemistry . 272 (43): 27450?5. doi : 10.1074/jbc.272.43.27450 . PMID 9341198 .
↑ Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF (Jun 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". The Journal of Biological Chemistry . 275 (23): 17420?7. doi : 10.1074/jbc.M001892200 . PMID 10748054 .
↑ Greer SF, Justement LB (May 1999). "CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1". Journal of Immunology . 162 (9): 5278?86. PMID 10228003 .
↑ Brown VK, Ogle EW, Burkhardt AL, Rowley RB, Bolen JB, Justement LB (Jun 1994). "Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45". The Journal of Biological Chemistry . 269 (25): 17238?44. PMID 7516335 .

?????????????? ?????????. ≪ LYN ≫. ?? ????????? ?????????? ??????? ? ??????????? ?? ?? ??? ????.

???? ??????? ????? [ ?????? ]

Jouvin MH, Numerof RP, Kinet JP (Feb 1995). "Signal transduction through the conserved motifs of the high affinity IgE receptor Fc epsilon RI". Seminars in Immunology . 7 (1): 29?35. doi : 10.1016/1044-5323(95)90005-5 . PMID 7612892 .
Hibbs ML, Dunn AR (Mar 1997). "Lyn, a src-like tyrosine kinase" . The International Journal of Biochemistry & Cell Biology . 29 (3): 397?400. doi : 10.1016/S1357-2725(96)00104-5 . PMID 9202419 .
Blasioli, J.; Goodnow, C. C. (2002). Lyn/CD22/SHP-1 and Their Importance in Autoimmunity . Current Directions in Autoimmunity . Vol. 5. pp. 151?60. doi : 10.1159/000060551 . ISBN 978-3-8055-7308-5 . PMID 11826756 .
Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (Apr 2003). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". Journal of Biosciences . 28 (3): 323?35. doi : 10.1007/BF02970151 . PMID 12734410 .
Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M (Apr 2004). "HIV/SIV escape from immune surveillance: focus on Nef". Current HIV Research . 2 (2): 141?51. doi : 10.2174/1570162043484924 . PMID 15078178 .
Joseph AM, Kumar M, Mitra D (Jan 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research . 3 (1): 87?94. doi : 10.2174/1570162052773013 . PMID 15638726 .
Stove V, Verhasselt B (Jan 2006). "Modelling thymic HIV-1 Nef effects". Current HIV Research . 4 (1): 57?64. doi : 10.2174/157016206775197583 . PMID 16454711 .

??? ?? ?????? ??? ?????????? ??????? ???. ????????? ?? ????? ?? ?? ????????? ??? ????.

[refGRCm38Ensembl-1] ??? ^??? ^??? GRCm38: Ensembl release 89: ENSMUSG00000042228 - 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 .

[pmid3561390-4] Yamanashi Y, Fukushige S, Semba K, Sukegawa J, Miyajima N, Matsubara K, Yamamoto T, Toyoshima K (Jan 1987). "The yes-related cellular gene lyn encodes a possible tyrosine kinase similar to p56lck" . Molecular and Cellular Biology . 7 (1): 237?43. doi : 10.1128/MCB.7.1.237 . PMC 365062 . PMID 3561390 .

[5] Yamanashi Y, Mori S, Yoshida M, Kishimoto T, Inoue K, Yamamoto T, Toyoshima K (Sep 1989). "Selective expression of a protein-tyrosine kinase, p56lyn, in hematopoietic cells and association with production of human T-cell lymphotropic virus type I" . Proceedings of the National Academy of Sciences of the United States of America . 86 (17): 6538?42. doi : 10.1073/pnas.86.17.6538 . PMC 297879 . PMID 2505253 .

[6] Umemori H, Wanaka A, Kato H, Takeuchi M, Tohyama M, Yamamoto T (Dec 1992). "Specific expressions of Fyn and Lyn, lymphocyte antigen receptor-associated tyrosine kinases, in the central nervous system". Brain Research. Molecular Brain Research . 16 (3?4): 303?10. doi : 10.1016/0169-328X(92)90239-8 . PMID 1337939 .

[7] Yamada E, Pessin JE, Kurland IJ, Schwartz GJ, Bastie CC (Feb 2010). "Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine phosphorylation of LKB1" . Cell Metabolism . 11 (2): 113?124. doi : 10.1016/j.cmet.2009.12.010 . PMC 2830006 . PMID 20142099 .

[8] Gringeri E, Carraro A, Tibaldi E, D'Amico FE, Mancon M, Toninello A, Pagano MA, Vio C, Cillo U, Brunati AM (December 2009). "Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration" (PDF) . The Biochemical Journal . 425 (2): 401?12. doi : 10.1042/BJ20090902 . PMID 19832701 . Archived from the original (PDF) on 24 July 2018 . Retrieved 29 August 2019 . ≪???? ????? ???≫ (PDF) . ??????????? ?? ???? ?? ?? ????? ???? . ?????????? ?? ?? ??? ???? .

[9] Gavali, Shubhangi; Gupta, Manoj Kumar; Daswani, Bhavna; Wani, Mohan R.; Sirdeshmukh, Ravi; Khatkhatay, M. Ikram (March 2019). "LYN, a key mediator in estrogen-dependent suppression of osteoclast differentiation, survival, and function". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1865 (3): 547?557. doi : 10.1016/j.bbadis.2018.12.016 . PMID 30579930 .

[pmid11825908-10] Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (Apr 2002). "Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling". The Journal of Biological Chemistry . 277 (16): 13732?8. doi : 10.1074/jbc.M200277200 . PMID 11825908 .

[pmid9341198-11] Linnekin D, DeBerry CS, Mou S (Oct 1997). "Lyn associates with the juxtamembrane region of c-Kit and is activated by stem cell factor in hematopoietic cell lines and normal progenitor cells". The Journal of Biological Chemistry . 272 (43): 27450?5. doi : 10.1074/jbc.272.43.27450 . PMID 9341198 .

[pmid10748054-12] Poe JC, Fujimoto M, Jansen PJ, Miller AS, Tedder TF (Jun 2000). "CD22 forms a quaternary complex with SHIP, Grb2, and Shc. A pathway for regulation of B lymphocyte antigen receptor-induced calcium flux". The Journal of Biological Chemistry . 275 (23): 17420?7. doi : 10.1074/jbc.M001892200 . PMID 10748054 .

[pmid10228003-13] Greer SF, Justement LB (May 1999). "CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1". Journal of Immunology . 162 (9): 5278?86. PMID 10228003 .

[pmid7516335-14] Brown VK, Ogle EW, Burkhardt AL, Rowley RB, Bolen JB, Justement LB (Jun 1994). "Multiple components of the B cell antigen receptor complex associate with the protein tyrosine phosphatase, CD45". The Journal of Biological Chemistry . 269 (25): 17238?44. PMID 7516335 .

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??????	?????? ???? ?????? ????? ??????? ????????? Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme ??????? ???????? ??????? ?????
?????	?????????? Cooperativity ????????? ????? ?????????? ?????
?????????	??? ???? ????? ?????????? ????? ??????? ????? ????? ????????
??????	?????? ????????????? ??? ??? ?????? ??? ???????? ??? ??? ???? ????
?????	?????? ??????????????? ( ????? ) ?????? ??????????? ( ????? ) ?????? ?????????? ( ????? ) ?????? ?????? ( ????? ) ?????? ?????????? ( ????? ) ?????? ??????? ( ????? ) ?????? ??????????? ( ????? )