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1. 发明申请

WO2006086111A3 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN LEUKEMIA SIGNALING PATHWAYS 审中-公开
标题翻译：用于检测白血病信号途径中蛋白质磷酸化的试剂
公开(公告)号：WO2006086111A3
公开(公告)日：2009-04-16
申请号：PCT/US2006000979
申请日：2006-01-12
申请人： CELL SIGNALING TECHNOLOGY INC , GOSS VALERIE , MORITZ ALBRECHT , GU TING-LEI , LEE KIMBERLY , POLAKIEWICZ ROBERTO
发明人： GOSS VALERIE , MORITZ ALBRECHT , GU TING-LEI , LEE KIMBERLY , POLAKIEWICZ ROBERTO
IPC分类号： G01N33/574
CPC分类号： G01N33/57426 , C07K14/47 , C07K16/18 , C07K16/40 , C07K16/44
摘要： The invention discloses 424 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor/Scaffold proteins, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.
摘要翻译：本发明公开了在信号转导蛋白中鉴定的424个新的磷酸化位点和人类白血病的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质作为使用试剂用于此目的的方法。所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。

2. 发明申请

WO2007027957A3 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN LEUKEMIA SIGNALING PATHWAYS 审中-公开
标题翻译：用于检测白血病信号途径中蛋白质磷酸化的试剂
公开(公告)号：WO2007027957A3
公开(公告)日：2009-01-29
申请号：PCT/US2006034126
申请日：2006-08-30
申请人： CELL SIGNALING TECHNOLOGY INC , POLAKIEWICZ ROBERTO , GOSS VALERIE , LEE KIMBERLY , GU TING-LEI , MORITZ ALBRECHT
发明人： POLAKIEWICZ ROBERTO , GOSS VALERIE , LEE KIMBERLY , GU TING-LEI , MORITZ ALBRECHT
IPC分类号： G01N33/53 , C07K16/00 , G01N33/573
CPC分类号： G01N33/57426 , C07B59/008 , C07K16/3061 , C07K16/44 , G01N33/6803 , G01N33/6842 , G01N2333/9121
摘要： The invention discloses nearly 480 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, acetyltransferases, actin binding proteins, adhesion proteins, apoptosis proteins, calcium-binding proteins, cell cycle regulation proteins, cell surface proteins, channel proteins, chaperone proteins, contractile proteins, cytokine proteins, cytoskeletal proteins, G protein regulators and GTPase activating proteins, guanine nucleotide exchange factors, helicase proteins, immunoglobulin superfamily proteins, inhibitor proteins, protein kinases, lipid kinases, ligases, lipid binding proteins, methytransferases, motor proteins, oxidoreductases, phosphotases, phosphodiesterases, phospholipases, proteases, receptor proteins, trascription factors, transferases, translation/transporter proteins, and ubiquitin conjugating system proteins.
摘要翻译：本发明公开了在信号转导蛋白中识别的近480个新的磷酸化位点和人类白血病的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，如以及使用试剂用于此目的的方法。鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：衔接子/支架蛋白，乙酰转移酶，肌动蛋白结合蛋白，粘附蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，细胞表面蛋白，通道蛋白，伴侣蛋白鸟嘌呤核苷酸交换因子，解旋酶蛋白，免疫球蛋白超家族蛋白，抑制蛋白，蛋白激酶，脂质激酶，连接酶，脂质结合蛋白，甲基转移酶，运动蛋白，肌动蛋白，氧化还原酶，磷酸二酯酶，磷脂酶，蛋白酶，受体蛋白，trascription因子，转移酶，翻译/转运蛋白和泛素缀合系统蛋白。

3. 发明申请

WO2007027957A9 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN LEUKEMIA SIGNALING PATHWAYS 审中-公开
标题翻译：用于检测白血病信号通路中的蛋白质磷酸化的试剂
公开(公告)号：WO2007027957A9
公开(公告)日：2007-05-31
申请号：PCT/US2006034126
申请日：2006-08-30
申请人： CELL SIGNALING TECHNOLOGY INC , POLAKIEWICZ ROBERTO , GOSS VALERIE , LEE KIMBERLY , GU TING-LEI , MORITZ ALBRECHT
发明人： POLAKIEWICZ ROBERTO , GOSS VALERIE , LEE KIMBERLY , GU TING-LEI , MORITZ ALBRECHT
IPC分类号： G01N33/574
CPC分类号： G01N33/57426 , C07B59/008 , C07K16/3061 , C07K16/44 , G01N33/6803 , G01N33/6842 , G01N2333/9121
摘要： The invention discloses nearly 480 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor/scaffold proteins, acetyltransferases, actin binding proteins, adhesion proteins, apoptosis proteins, calcium-binding proteins, cell cycle regulation proteins, cell surface proteins, channel proteins, chaperone proteins, contractile proteins, cytokine proteins, cytoskeletal proteins, G protein regulators and GTPase activating proteins, guanine nucleotide exchange factors, helicase proteins, immunoglobulin superfamily proteins, inhibitor proteins, protein kinases, lipid kinases, ligases, lipid binding proteins, methytransferases, motor proteins, oxidoreductases, phosphotases, phosphodiesterases, phospholipases, proteases, receptor proteins, trascription factors, transferases, translation/transporter proteins, and ubiquitin conjugating system proteins.
摘要翻译：本发明公开了在人白血病的信号转导蛋白和通路中鉴定的近480个新的磷酸化位点，并提供用于选择性检测和定量这些磷酸化位点/蛋白的磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），如以及为此目的使用试剂的方法。在鉴定的磷酸化位点中，有以下蛋白质类型发生的位点：衔接子/支架蛋白质，乙酰转移酶，肌动蛋白结合蛋白，粘附蛋白，凋亡蛋白，钙结合蛋白，细胞周期调节蛋白，细胞表面蛋白，通道蛋白，伴侣蛋白，收缩蛋白，细胞因子蛋白，细胞骨架蛋白，G蛋白调节剂和GTP酶活化蛋白，鸟嘌呤核苷酸交换因子，解旋酶蛋白，免疫球蛋白超家族蛋白，抑制蛋白，蛋白激酶，脂质激酶，连接酶，脂质结合蛋白，甲基转移酶，氧化还原酶，磷酸酶，磷酸二酯酶，磷脂酶，蛋白酶，受体蛋白，转录因子，转移酶，翻译/转运蛋白和泛素缀合系统蛋白。

4. 发明申请

WO2007064743A8 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN LEUKEMIA SIGNALING PATHWAYS 审中-公开
标题翻译：用于检测白血病信号通道中蛋白质磷酸化的试剂
公开(公告)号：WO2007064743A8
公开(公告)日：2008-09-04
申请号：PCT/US2006045760
申请日：2006-11-29
申请人： CELL SIGNALING TECHNOLOGY INC , POLAKIEWICZ ROBERTO , LEE KIMBERLY , GU TING-LEI , GOSS VALERIE
发明人： POLAKIEWICZ ROBERTO , LEE KIMBERLY , GU TING-LEI , GOSS VALERIE
IPC分类号： C12N9/00
CPC分类号： G01N33/57426
摘要： La présente invention a trait à presque 123 nouveaux sites de phosphorylation identifiés dans des protéines de transduction de signal et de voies sous-jacentes de la leucémie humaine, et fournit des anticorps spécifiques de sites de phosphorylation et de peptides étiquetés d'isotopes lourds (peptides AQUA) pour la détection sélective et la quantification de ces sites/protéines phosphorylés, ainsi que des procédés d'utilisation des réactifs à cette fin. Parmi les sites de phosphorylation identifiés se trouvent des sites présents dans les types de protéines suivants: des protéines kinases, des protéines adaptatrices/squelettiques, la phosphatase/phospholipases, les protéines G/de protéines d'activation de la GTPase /des facteurs d'échange de nucléotides à guanine, des enzymes de métabolisme cellulaire, des protéines de liaison à l'ARN, des protéines de transcription, des protéines complexes d'initiation de traduction, des transférases, des protéines du système de conjugaison d'ubiquitine, des protéines vésiculaires, des protéines de liaison à l'actine, des protéines de l'apoptose, des protéines de chimiokine, des protéines matricielles extracellulaires de protéines enzymatiques, des hélicases, des hydrolases, des protéines de la superfamille d'immunoglobulines, des protéines inhibitrices, des isomérases, des ligases, des protéines de liaison aux lipides, des méthyltransférases, des protéines motrices, des protéines réceptrices, et des protéines chaperones.

5. 发明申请

WO2007027906A2 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN LEUKEMIA SIGNALING PATHWAYS 审中-公开
标题翻译：用于检测白血病信号途径中蛋白质磷酸化的试剂
公开(公告)号：WO2007027906A2
公开(公告)日：2007-03-08
申请号：PCT/US2006034050
申请日：2006-08-31
申请人： CELL SIGNALING TECHNOLOGY INC , POLAKIEWICZ ROBERTO , GOSS VALERIE , LEE KIMBERLY , GU TING-LEI , MORITZ ALBRECHT
发明人： POLAKIEWICZ ROBERTO , GOSS VALERIE , LEE KIMBERLY , GU TING-LEI , MORITZ ALBRECHT
IPC分类号： G06F19/00
CPC分类号： G01N33/6842 , C07K16/3061 , C07K16/44 , C07K2317/34 , G01N33/57426 , G01N2458/15
摘要： The invention discloses nearly 288 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor/Scaffold proteins, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair/RNA Binding/Transcription proteins, Serine/Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation/Transporter proteins.
摘要翻译：本发明公开了在信号转导蛋白中鉴定的近288个新的磷酸化位点和人类白血病潜在的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，如以及使用试剂用于此目的的方法。所鉴定的磷酸化位点是以下蛋白质类型的位点：适配器/支架蛋白，细胞骨架蛋白，细胞代谢酶，G蛋白/ GTP酶激活/鸟嘌呤核苷酸交换因子蛋白，免疫球蛋白超家族蛋白，抑制蛋白，脂质激酶，核DNA 修复/ RNA结合/转录蛋白，丝氨酸/苏氨酸蛋白激酶，酪氨酸激酶，蛋白磷酸酶和翻译/转运蛋白。

6. 发明申请

WO2007084630A2 MUTANT JAK3 KINASE IN HUMAN LEUKEMIA 审中-公开
标题翻译： MUTANT JAK3激活人类LEUKEMIA
公开(公告)号：WO2007084630A2
公开(公告)日：2007-07-26
申请号：PCT/US2007001359
申请日：2007-01-19
申请人： CELL SIGNALING TECHNOLOGY INC , GOSS VALERIE , GU TING-LEI , POLAKIEWICZ ROBERTO , DRUKER BRIAN , WALTERS DENISE
发明人： GOSS VALERIE , GU TING-LEI , POLAKIEWICZ ROBERTO , DRUKER BRIAN , WALTERS DENISE
IPC分类号： C12N9/12
CPC分类号： C12N9/1205 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136
摘要： In accordance with the invention, a novel activating mutation (alanine 572 to valine) in JAK3 kinase has been discovered in human acute myelogenous leukemia (AML). The mutant JAK3 kinase was confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant JAK3 kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the mutant polypeptides. The disclosed identification of this new mutant protein and enables new methods for determining the presence of mutant JAK3 kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the mutant proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译：根据本发明，已经在人急性骨髓性白血病（AML）中发现JAK3激酶中的新的活化突变（丙氨酸572至缬氨酸）。证实突变体JAK3激酶能够驱动急性巨核细胞白血病（AML-M7）的增殖和存活。因此，本发明部分地提供分离的多核苷酸和编码所公开的突变体JAK3激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测突变多肽的试剂。所公开的这种新突变蛋白质的鉴定，并且使得能够确定生物样品中突变体JAK3激酶多肽的存在的新方法，用于筛选抑制突变蛋白质的化合物的方法，以及抑制以突变体为特征的癌症进展的方法多核苷酸或多肽，其也由本发明提供。

7. 发明申请

WO2007075933A2 TRANSLOCATION AND MUTANT CSF1R KINASE IN HUMAN LEUKEMIA 审中-公开
标题翻译：人淋巴细胞转移和突变CSF1R激酶
公开(公告)号：WO2007075933A2
公开(公告)日：2007-07-05
申请号：PCT/US2006048867
申请日：2006-12-21
申请人： CELL SIGNALING TECHNOLOGY INC , GU TING-LEI , GOSS VALERIE , POLAKIEWICZ ROBERTO , DRUKER BRIAN , WALTERS DENISE
发明人： GU TING-LEI , GOSS VALERIE , POLAKIEWICZ ROBERTO , DRUKER BRIAN , WALTERS DENISE
IPC分类号： C07K14/705
CPC分类号： C12N9/12 , C07K2319/85
摘要： In accordance with the invention, a novel gene translocation, (3p21 , 5q33), in human myelogenous leukemia (AML) that results in a fusion protein combining part of RNA Binding Protein-6 (RBM6) with Macrophage Colony Stimulating Factor-1 Receptor (CSF1 R) kinase has now been identified. The RBM6-CSF1 R fusion protein and truncated CSF1R kinase itself, which both retain CSF1 R tyrosine kinase activity, were confirmed to drive the proliferation and survival of acute megakaryoblastic leukemia (AML-M7). The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant CSF1R kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein and truncated kinase enables new methods for determining the presence of these mutant CSF 1 R kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.
摘要翻译：根据本发明，在人骨髓性白血病（AML）中的新型基因易位（3p21,5q33），其导致将部分RNA结合蛋白-6（RBM6）与巨噬细胞集落刺激因子-1受体（RBF6）结合的融合蛋白 CSF1R）激酶已被鉴定。证实了RBM6-CSF1R融合蛋白和截短的CSF1R激酶本身都保留CSF1R酪氨酸激酶活性，以驱动急性巨核细胞白血病（AML-M7）的增殖和存活。因此，本发明部分地提供分离的多核苷酸和编码所公开的突变型CSF1R激酶多肽的载体，用于检测其的探针，分离的突变多肽，重组多肽和用于检测融合和截短的多肽的试剂。所公开的这种新的融合蛋白和截短的激酶的鉴定使得能够确定生物样品中这些突变型CSF1R激酶多肽的存在的新方法，用于筛选抑制蛋白质的化合物的方法，以及抑制癌症进展的方法其特征在于突变体多核苷酸或多肽，其也由本发明提供。

8. 发明申请

WO2007015886A8 PHOSPHORYLATED PROTEIN MARKERS OF GLEEVEC-RESISTANT CHRONIC MYELOGENOUS LEUKEMIA 审中-公开
标题翻译：耐药性慢性髓性白血病的磷酸化蛋白标记
公开(公告)号：WO2007015886A8
公开(公告)日：2008-10-30
申请号：PCT/US2006027936
申请日：2006-07-19
申请人： CELL SIGNALING TECHNOLOGY INC , GOSS VALERIE , LEE KIMBERLY , POLAKIEWICZ ROBERTO , DRUKER BRIAN , DENINGER MICHAEL , GRISWOLD IAN
发明人： GOSS VALERIE , LEE KIMBERLY , POLAKIEWICZ ROBERTO , DRUKER BRIAN , DENINGER MICHAEL , GRISWOLD IAN
IPC分类号： G01N33/53 , C07K14/00 , C07K16/00
CPC分类号： G01N33/57426 , C12Q1/485 , G01N2500/04 , G01N2800/52

9. 发明申请

WO2006113050A4 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN CARCINOMA SIGNALING PATHWAYS 审中-公开
标题翻译：检测CARCINOMA信号途径中蛋白质磷酸化的试剂
公开(公告)号：WO2006113050A4
公开(公告)日：2009-03-26
申请号：PCT/US2006010868
申请日：2006-03-24
申请人： CELL SIGNALING TECHNOLOGY INC , GUO AILAN , RIKOVA KLARISA , MORITZ ALBRECHT , LI YU , FARNSWORTH CHARLES , LEE KIMBERLY , POLAKIEWICZ ROBERTO
发明人： GUO AILAN , RIKOVA KLARISA , MORITZ ALBRECHT , LI YU , FARNSWORTH CHARLES , LEE KIMBERLY , POLAKIEWICZ ROBERTO
IPC分类号： G01N33/53 , C07K16/00
CPC分类号： G01N33/57496 , C07K14/4748 , C07K16/44
摘要： The invention discloses (214) novel phosphorylation sites identified in signal transduction proteins and pathways underlying human carcinoma, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor/Scaffold proteins, Cytoskeleton proteins, GTP Signaling proteins, Kinases, Metabolism proteins, Phosphatases/Phospho- diesterases/ Proteases, Receptor proteins, RNA Processing proteins, Transcription proteins, Translation proteins, Transporter proteins, and Ubitquitin proteins, as well as other protein types.
摘要翻译：本发明公开了（214）信号转导蛋白中鉴定的新型磷酸化位点和人癌基因的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及为此目的使用试剂的方法。鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：适配器/支架蛋白，细胞骨架蛋白，GTP信号蛋白，激酶，代谢蛋白，磷酸酶/磷酸二酯酶/蛋白酶，受体蛋白，RNA加工蛋白，转录蛋白，翻译蛋白质，转运蛋白和Ubitquitin蛋白质，以及其他蛋白质类型。

10. 发明申请

WO2006113050A3 REAGENTS FOR THE DETECTION OF PROTEIN PHOSPHORYLATION IN CARCINOMA SIGNALING PATHWAYS 审中-公开
标题翻译：检测CARCINOMA信号途径中蛋白质磷酸化的试剂
公开(公告)号：WO2006113050A3
公开(公告)日：2008-12-24
申请号：PCT/US2006010868
申请日：2006-03-24
申请人： CELL SIGNALING TECHNOLOGY INC , GUO AILAN , RIKOVA KLARISA , MORITZ ALBRECHT , LI YU , FARNSWORTH CHARLES , LEE KIMBERLY , POLAKIEWICZ ROBERTO
发明人： GUO AILAN , RIKOVA KLARISA , MORITZ ALBRECHT , LI YU , FARNSWORTH CHARLES , LEE KIMBERLY , POLAKIEWICZ ROBERTO
IPC分类号： G01N33/53 , C07K16/00
CPC分类号： G01N33/57496 , C07K14/4748 , C07K16/44
摘要： The invention discloses (214) novel phosphorylation sites identified in signal transduction proteins and pathways underlying human carcinoma, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor/Scaffold proteins, Cytoskeleton proteins, GTP Signaling proteins, Kinases, Metabolism proteins, Phosphatases/Phospho- diesterases/ Proteases, Receptor proteins, RNA Processing proteins, Transcription proteins, Translation proteins, Transporter proteins, and Ubitquitin proteins, as well as other protein types.
摘要翻译：本发明公开了（214）信号转导蛋白中鉴定的新型磷酸化位点和人癌基因的途径，并提供磷酸化位点特异性抗体和重同位素标记肽（AQUA肽），用于选择性检测和定量这些磷酸化位点/蛋白质，以及为此目的使用试剂的方法。鉴定的磷酸化位点是发生在以下蛋白质类型中的位点：适配器/支架蛋白，细胞骨架蛋白，GTP信号蛋白，激酶，代谢蛋白，磷酸酶/磷酸二酯酶/蛋白酶，受体蛋白，RNA加工蛋白，转录蛋白，翻译蛋白质，转运蛋白和Ubitquitin蛋白质，以及其他蛋白质类型。

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