CN112585470A - 用于监测样品中激酶活性的方法 - Google Patents
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- CN112585470A CN112585470A CN201980054788.5A CN201980054788A CN112585470A CN 112585470 A CN112585470 A CN 112585470A CN 201980054788 A CN201980054788 A CN 201980054788A CN 112585470 A CN112585470 A CN 112585470A
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Abstract
本发明涉及监测样品中激酶活性或活化的方法,该方法包括以下步骤:a)提供包含激酶的样品,b)将样品与蛋白酶一起温育以将步骤a)中提供的激酶裂解为蛋白酶特异性蛋白水解肽,c)对样品应用磷酸肽富集,d)通过液相色谱‑质谱法分析步骤c)中获得的样品,以及e)检测步骤a)中提供的激酶的磷酸化,其中,仅在鉴定出与激酶活化区域相关的蛋白水解肽的情况下才执行步骤e)的检测。
Description
详细说明
本发明涉及用于监测样品中激酶活性的方法。
蛋白激酶在细胞通信中起着关键作用,已经将异常的激酶活性与范围从癌症到糖尿病或心血管疾病的多种疾病联系起来了。激酶是细胞通信的关键调节剂,其抑制剂在靶向治疗和精准医学中发挥着核心作用。因此,对全身性激酶动力学(global kinasedynamics)的研究对于理解细胞功能和推动合理的药物开发至关重要。这种明确的激酶相关性引发了许多评估蛋白激酶组活性状态的努力。然而,它们中的大多数存在实质性缺陷。
在最初始的应用中,激酶的活性是从鸟枪法(shotgun)蛋白质组学实验中获得的它们的丰度中提取的。为了解决大多数蛋白激酶的低丰度问题,已经使用了激酶特异性富集方案,主要由固定化的广谱特异性激酶抑制剂和/或ATP模拟物组成。这种方法提供了明显的激酶富集,但是以灵敏度为代价,需要大量的输入原料,从而使该方法局限于基于细胞系的模型系统。重要的是,激酶丰度的评估本身并不能反映激酶活性,到目前为止,激酶活性主要还是从磷酸化蛋白质组学数据中提取的。在这里,在磷酸化蛋白质组学数据集中过度呈现或呈现不足(over-or underrepresented)的序列基序的比对是与已知的激酶共有序列相关联。然而,由于大多数检测到的磷酸化位点(phosphosites)尚未在功能(functionality)方面加以表征,并且针对许多激酶的底物特异性是冗余的或根本未知的,所以对该方法的认知尚有较大差距。
鉴于上述情况,迫切需要直接监测激酶活性,该激酶活性到目前为止主要是从激酶蛋白表达水平或底物磷酸化数据中提取的。
本发明为此提供了一种用于监测样品中激酶活性或活化的方法,该方法包括以下步骤:
a)提供包含激酶的样品;
b)将样品与蛋白酶一起温育以将步骤a)中提供的激酶裂解为蛋白酶特异性蛋白水解肽;
c)对所述样品进行磷酸肽富集;
d)通过液相色谱-质谱法(LC-MS)分析步骤c)中获得的样品;以及
e)检测步骤a)中提供的激酶的磷酸化,
其中,仅在鉴定出与激酶的活化区域相关的蛋白水解肽的情况下才进行步骤e)的检测。
为了鉴定和检测与激酶活化区域相关的蛋白水解肽,本发明的方法包括以下步骤:
i)确定须监测的激酶;
ii)确定与所关注的激酶的活化区域相关的蛋白酶特异性蛋白水解肽;以及
iii)调整质谱仪的设置,以便在步骤e)中仅检测在步骤ii)中确定的蛋白酶特异性蛋白水解肽。值得注意的是,在本发明方法的温育步骤b)中,样品与一种蛋白酶的温育将产生与使用另一种蛋白酶的情况相比不同的、与所关注的激酶的活化区域相关的蛋白酶特异性蛋白水解肽。结果,步骤ii)中确定的蛋白酶特异性蛋白水解肽可以基于所使用的蛋白酶而变化。因此,蛋白酶的选择也将导致步骤iii)中质谱仪的不同设置,以便仅检测与激酶的活化区域相关的蛋白水解肽。换言之,质谱仪仅用于鉴定(选择性地选择)那些关注的蛋白水解肽,即与所关注的激酶的活化区域相关的蛋白水解肽。另外,应注意,所确定的蛋白酶特异性蛋白水解肽的数量可以不同。一方面,确定多种蛋白酶特异性蛋白水解肽,以便检测所关注的激酶的任何活性或活化作用。另一方面,确定蛋白酶特异性蛋白水解肽的高度选择性的子集(subset),以便仅检测所关注激酶的特定相关活性或活化作用,例如检测与某种疾病的信号通路相关的特定蛋白水解肽。还应注意,在步骤ii)中的蛋白酶特异性蛋白水解肽的确定可以得到用于调节质谱仪设置的参考列表。换言之,所关注的蛋白酶特异性蛋白水解肽的鉴定(选择性选择)是基于步骤ii)中产生的参考列表。还应注意的是,所关注的蛋白水解肽的确定是基于所关注的激酶(即须监测的激酶)与所述温育步骤中使用的蛋白酶结合来进行的。
已经发现,通过提供本发明的方法,现在可以实现磷酸化位点丰度与激酶活性之间的直接关联。激酶中的活化区域是位于催化环附近的柔性环,当被磷酸化时,其将大多数激酶激活。激酶中的活化区域也被认为是t环以及紧挨着活化环(activation loop)之后的区域,其被称为P+1环,包含一个侧翼为Asp-Phe-Gly(DFG)和(Ala)-Pro-Glu((A)PE)基序的保守区域。注意,所述术语激酶的“保守区域”、“保守结构域”或“活化区域”是激酶领域中公知的术语。例如,国家生物技术信息中心(NCBI)提供了多种工具(例如,经由保守结构域数据库)来鉴别和确定多种激酶的活化区域。基于此类数据库提供的信息,本发明人能够鉴定激酶中的456个活化区域。
通过提供本发明的方法,现在可以监测激酶中与活化区域相关的磷酸化,例如t环磷酸化,t环磷酸化是在许多这些激酶中启动活性的关键开关。值得注意的是,这些位点的功能可以基于它们高度的序列相似性而被直接转用于许多待研究(understudied)的激酶上。已经发现,由于其丰度低、不利于LC-MS的特性以及酪氨酸磷酸化的高发生率,与活化区域相关的磷酸化、特别是t-环磷酸化,则在现有技术的方法(例如鸟枪法蛋白质组分析)中众所周知呈现不足。
本发明的方法可以进一步包括以下步骤:
f)对步骤e)中检测到的磷酸化进行定量。
优选地,所述定量通过靶向质谱法诸如基于靶向MS1(前体离子扫描)、MS2(串联质谱或碎片离子扫描)或MSn(串联质谱)的定量来实现,其中对于MSn,n是大于2的整数。
在一个优选的实施方案中,与激酶的活化区域相关的蛋白水解肽包括与激酶的t环相关的蛋白水解肽。通过仅在鉴定出与激酶的t环相关的蛋白水解肽的情况下进行步骤e)的检测,无需在应用本发明的方法之前进一步再次处理样品就能够监测激酶活性或活化。如已经指出的,与活化区域相关的蛋白水解肽根据所使用的蛋白酶而变化。在本发明的一个实施方案中,蛋白酶可以选自胰蛋白酶、内切蛋白酶Glu-C、胰凝乳蛋白酶和内切蛋白酶Asp-N,从而分别产生胰蛋白酶特异性蛋白水解肽(例如胰蛋白酶肽)、Glu-C特异性蛋白水解肽、胰凝乳蛋白酶特异性蛋白水解肽(例如胰凝乳蛋白酶肽)和Asp-N特异性蛋白水解肽。但是,在进行本发明的方法时,也可以选择本领域技术人员已知的其他蛋白酶。
所述磷酸肽富集优选选自固定金属离子亲和色谱法(IMAC)诸如Fe(III)-IMAC、Ga(III)-IMAC、Ti(IV)-IMAC或Zr(IV)-IMAC,以及金属氧化物亲和色谱法(MOAC)诸如TiO2-MOAC或ZrO2-MOAC等。在最优选的实施方案中,t-环磷酸肽富集包括Fe(III)-IMAC。已发现,使用Fe(III)-IMAC将得到特别是对于t-环磷酸化具有高特异性的方法。
在另一个优选的实施方案中,液相色谱法可以包括反相色谱法,并且可以选自纳米液相色谱法、毛细管流动液相色谱法(capillary flow liquid chromatography)和毛细管微流动液相色谱法(capillary micro-flow liquid chromatography)。而质谱法则可以包括选自以下的质谱采集方法:选择性反应监测(SRM)、多反应监测(MRM)、平行反应监测(PRM)和高分辨率多反应监测(MRM-HR)。甚至更进一步地,质谱采集方法可以选自基于数据非依赖性采集的质谱(DIA或SWATHTM)和靶向肽定量(例如,QuanDirectTM)。注意,质谱采集方法的选择取决于可用的质谱仪。已经发现,为了执行本发明的方法,可以选择上述任何一种质谱采集方法,即靶向质谱方法。甚至进一步地,质谱法可以包括串联质谱法。优选地,质谱法包括使用四极杆质谱仪,例如三重四极杆质谱仪,或飞行时间质谱仪。而且,质谱法可以包括使用离子阱质谱仪,如轨道阱质谱仪,或线性离子阱质谱仪。已发现,通过在三重四极杆质谱仪上以SRM模式将nano-LC与MS/MS结合起来,监测系统内宽泛的t环磷酸化以指示激酶活性,可以提供一种高度特异性的方法。
基于本发明的方法,提供了对178种蛋白激酶的t环磷酸化的测定法,约占全球人类激酶组(kinome)的33%。该技术的优势在于灵敏度(t环磷酸肽富集和LC-MS)与通量的结合,所述灵敏度即使从有限的起始原料开始也能实现实质性的激酶组覆盖(kinomecoverage)。这样的高灵敏度覆盖可以通过使用具有高达96个样品的并行磷酸肽富集的(自动)平台而得以促进。在多种(原生的(primary)和来源于患者的)细胞类型中,共检测到58种激酶的74种t环磷酸化。靶向激酶包括多种临床相关激酶,其具有FDA批准的抑制剂诸如MET、ABL、SRC、BTK、JAK3和KIT(另请参见:图1A和图1B)。表1提供了在各种细胞系中检测到的t环磷酸化的完整概述。图6提供了胰蛋白酶肽的完整列表。
表1.在各种细胞系中检测到的t环磷酸化的列表。
通过应用其他的蛋白酶、样品分级分离或对诸如细胞核或细胞膜之类的特定细胞腔室进行富集,可以提供激酶组覆盖率(kinome coverage)的进一步提升。
实验
在没有任何形式的刺激的情况下,分析了三种不同细胞系即Jurkat、PC9和Hek的基线激酶组活性状态(baseline kinome activity state)。这导致检测到三个细胞系的52个t环磷酸化位点(图2A)。由于激酶t环序列的高度保守性,代表性的胰蛋白酶肽并不总是唯一的。这导致一定程度的不确定性,例如对于激酶家族成员Mark1、Mark2、Mark3和Mark4,或经常表现出冗余功能的极其相关的激酶,诸如酪氨酸激酶FYN、YES1和SRC。为了解决这种不确定性,遵循了蛋白质分类的原则,并且在整个研究过程中将这些实例称为激酶组(kinase group)。对于观察到的52个磷酸化位点,这得到48个激酶组。此外,尽管通过侧翼的DFG和(A)PE基序明确定义了t环,但磷酸化在各种不同的或甚至多个残基上仍可进行。尽管对于许多激酶而言,活化残基被清楚地确定下来,但是对于其他激酶,t环内的这些位点则是未知的。因此,对于未知情形,则考虑了多种可能性,其带来对各种磷酸化位点(phosphosite)异构体的SRM测定法的研发。
所检测的48个激酶组中的很大一部分代表了典型的管家(housekeeping)激酶,这些激酶对于在典型培养条件下的细胞生长至关重要,诸如CDK和MAPK,以及两个高丰度的激酶PDK1和GSK3。另外,检测到若干种参与抗凋亡过程的激酶如HIPK3处于活性状态下。与Hek细胞相比,Jurkat细胞和PC9细胞二者均显示出增强的Ca2+/DAG依赖性信号转导活性,同时检测到来自CaMK类和PKC家族的若干种激酶处于其活性状态。这些包括CaMK1D、PKCθ和激酶组PKCα/PKCβ/PKCγ。另一方面,仅仅在Jurkat细胞中检测到CaMKIV活性。
有趣的是,许多激酶显示出细胞系依赖性活性谱。已知其中一些以组织特异性方式表达,如酪氨酸激酶ZAP70仅在与免疫系统相关的某些细胞类型(包括T细胞)中表达。因此,仅在Jurkat细胞中检测到ZAP70的t环磷酸化。
其他酪氨酸激酶诸如FAK、MET和两个激酶组EPHA3/4/5和HCK/LYN在Jurkat细胞中未能检测到,但它们在PC9细胞中尤其显示出高活性。这表明PC9中的酪氨酸激酶活性升高,其可能是由于激活的EGFR信号转导所致。值得注意的是,这些激活性的磷酸化发生在t环序列中的酪氨酸残基上,其控制大量激酶的初级活化(primary activation)。尤其是,酪氨酸激酶和MAP激酶需要在其t环中的酪氨酸磷酸化以达到完全活化,而大多数其他激酶的初级活化位点则为苏氨酸残基。
除非预先进行了特定的磷酸化酪氨酸富集,否则酪氨酸磷酸化在磷酸化蛋白质组分析中自然是呈现不足的。已发现Fe(III)-IMAC磷酸肽富集与灵敏的SRM分析相结合,酪氨酸t环磷酸化达到了相当大的回收率。
就FAK和MET而言,获取t环内磷酸化位点的定位信息以用于PC9中的测量,。
在未经刺激的细胞中成功检测到若干t环磷酸化后,由于激酶组(kinome)中很大一部分以未活化(未磷酸化)状态存在,所以进一步将该方法进行了微调,以揭示来自稳态背景中的特定激酶在选定刺激下的活化。Jurkat细胞用TNFα处理8小时,导致细胞死亡增加。在TNFα刺激后,受体-相互作用蛋白丝氨酸-苏氨酸激酶(RIPK)被募集到TNF受体复合物并介导凋亡(图2B)。TNFα处理后,可重复地检测到丝氨酸S161处的RIPK1磷酸化,未处理的Jurkat细胞中则未检测到磷酸化(图2C)。
尽管RIPK1在细胞死亡中具有众所周知的作用,但发现通过本发明的方法可以利用MS从细胞裂解物中直接检测出RIPK1的t环磷酸化。因此,该RIPK1测定法提供了一种新型全面的示数来监控细胞死亡的复杂调控,同时也证明了我们技术无与伦比的灵敏度。
基于本发明的方法开发的测定法包括以各种位置异构体存在的总共51个肽序列。其中有41个以2种不同的亚型(isoform)存在,10个则以3种不同的亚型存在。尽管通常认为,大多数磷酸化位点定位异构体(phosphosites localization isomers)是无法在反相LC上通过色谱保留时间来区分的,但是使用本发明的方法对于51个序列中的47个序列的所有位置异构体均显示出了基线色谱分离。在图3A中示出了激酶DDR2的三个磷酸化位点的实例。另外两个肽序列显示出部分色谱分离,其通过使用磷酸化位点定位的特异性转换来实现复杂样品中的不同磷酸化位点定位的明确区分。一个实例是图3B所示JAK3的残基Y980和Y981的酪氨酸磷酸化。
通过对来自原始细胞(primary cell)的激酶组动力学(kinome dynamics)进行深入分析,探索了激酶活性谱分析方法的灵敏度。本发明的技术被用于研究血小板活化的机制。分析了由模拟凝血酶的六肽所激活的血小板,该六肽与蛋白酶激活受体1(PAR1)结合1分钟和5分钟,并将这些血小板的激酶活性谱与初始血小板进行比较。通过每次磷酸肽富集仅使用300μg蛋白质输入,就可以检测并量化25个激酶组中的31个t环磷酸化。活化血小板与初始血小板之间的比较定量分析显示,经PAR1活化后,激酶组活性(kinomeactivity)水平发生了急剧变化。
图4A分别针对1分钟和5分钟活化以火山图(volcano plots)描述了定量差异。血小板活化涉及各种细胞内信号转导事件,其中大多数会聚到图4B所示的共同路径中。这里值得注意的是在两种Tec家族的酪氨酸激酶Btk和Tec中的t环磷酸化检测,这两个家族都与血小板活化有关。特别地,Btk作为PLCγ2的主要活化剂的作用已得到充分认同,而Tec则(例如)在发生X连锁无丙种球蛋白血症(X-linked agammaglobulinemia)的情况下与Btk缺失或不正常时的较多补偿性的作用相联系。本文介绍的激酶活性谱证实了Btk和Tec在血小板活化中的这些重要作用。
有趣的是,发现两种Tec家族激酶的激酶活化程度和动力学互不相同。Btk活性在Par1激活1分钟后增高了几乎4倍,并在5分钟时保持增长,Tec则显示低得多的活化,并且在后来也未增加,从而证实了Btk的主导作用(图4C)。
下游,PAR1刺激后的一个中心收敛点是磷脂酶C(PLC)的活化,其导致细胞内Ca2+的增多,从而提高了钙/钙调蛋白依赖性激酶(CaMK)的活性。发现可以通过定量t环中两个相邻的磷酸化位点(T305和T306,图4D)来监测CaMK2的活化状态。两个磷酸化位点均在PAR1激活1分钟后显示出显著的峰值,在5分钟后显著下降,表明参与激酶活化的时间较短。有趣的是,两个磷酸化位点的具体的动力学略有不同。尽管T306磷酸化在1分钟后增高了10倍以上,并在5分钟后恢复到接近基线,但T305尖峰的强度要低得多,不过衰减较慢,表明这两个发生在CaMK2的t环中的磷酸化事件的动态调节。
PLC活性的另一个靶标是PKC,其继而激活p38。已经发现,现在可以定量PKC家族成员的若干种t-环磷酸化,该PKC家族成员包括PKCδ、PKCθ和PKCα、PKCβ及PKCγ的冗余t-环序列。有趣的是,它们均未显示任何显著差异,而其下游靶标p38A却发生了非常急剧的变化。P38A需要在T179和Y181处进行双重磷酸化以达到完全的激酶活性,这一状态在Par1激活1分钟后尤其明显,在5分钟后急剧下降(图4E)。平行地,在Y181处被单一磷酸化的p38A在1分钟后仍保持在基线水平,并且在5分钟后仅略有增高,这表明在p38A的快速双重磷酸化之后发生缓慢的、部分的去磷酸化,导致观察到5分钟后单一Y181磷酸化的上调,与之前的研究一致。将所观察到的PKC的t环磷酸化与p38的t环磷酸化相结合表明:PKC活性中的极快速升高的尖峰在不到1分钟的时间内就消失了,但其能够在下游进一步激活p38;或者与PKC活性水平相比,p38活化的峰信号(massif signal)得以放大。
增高细胞内Ca2+水平的另一个经过充分研究的效果是经由RAS向质膜的转运而将其活化,以及随后激活MAPK级联途径。MAPK级联途径在血小板中的作用尚未完全阐明,因为血小板是无核的细胞,没有生长、分化或增殖的可能,然而,它似乎是维持升高的细胞内Ca2+水平的相关因素。对于MAPK信号级联途径的具体成员来说,则显示出激酶活性的增高。在Par1活化1分钟后观察到RAF活性略有增高,导致Erk1和Erk2的强烈激活(图4F)。最后,观察到了在其他血小板活化途径中起作用的激酶的数个t-环磷酸化,例如Fyn、Lyn、Yes、MKK4、JNK2和FAK2,但是未观察到磷酸化的实质差异,表明存在基线活性(baseline activity)。
在对原始细胞中的激酶活化进行有效分析之后,探索了本发明的方法用于研究疾病中激酶的活性失衡的用处。激酶已成为主要的药物靶标类别,尤其是在癌症方面,已有25种靶向激酶的药物获批,并且许多候选药物正在临床评价中。但是,在通过合成致死筛选(synthetic lethality screen)来区分这些候选物时,通常会忽略一种激酶对激酶组(kinome)中其余部分的(长期)抑制作用。由于信号转导网络的适应性,这始终导致针对靶向激酶抑制的治疗抗性(treatment resistance)。
为了证明本发明方法的潜力,研究了在黑色素瘤中的获得性耐药性。大多数黑色素瘤是由导致BRAF的组成性活性(constitutive activity)的BRAFV600E突变驱动的。尽管取得了初步的成功,但使用BRAF抑制剂(BRAFi)治疗患者通常会导致迅速获得获得性耐药性。在这里,研究了由患者来源的异种移植物形成的未治疗的、对治疗敏感的和耐药肿瘤状态的、匹配的患者来源的黑色素瘤细胞系中的t环磷酸化(图5A),其中获得性耐药性是基于NRASQ61K突变。
通过对全部三种状态下的激酶组活性(kinome activity)的差异比较,检测并定量了39个磷酸化位点,从而呈现了36个激酶组的t环磷酸化(图5B-5D)。
与未治疗的和治疗敏感的细胞相比,若干种已定量的激酶在抗性细胞系中显示出增高的活性。这些激酶包括CaMKIV,PKC激酶家族的数个成员诸如PKCδ、PKCμ/ν,与MAPK级联反应相关的数个成员诸如p38A、Erk2、Erk4和MKK4,以及MAPK效应激酶NLK和与细胞周期相关的激酶CDK2/3和Chk2。令人惊讶地,在药物抗性细胞系中被特异性地活化的若干种激酶主要与肿瘤抑制活性有关,诸如Chk2、p38A和Erk4。
对于激酶Erk4则观察到最强的活化,由于其在活化环中缺乏酪氨酸结构域,所以它和同样观察到这一现象的Erk3一起都属于非典型的MAPK家族。到目前为止,MK5是Erk3和Erk4的唯一已知底物。MK5主要被认为具有肿瘤抑制功能,如激活p53和FOXO3。但是,最近的研究也显示出Erk3/Erk4/MK5组的致癌潜力,例如通过抑制JNK活性且支持血管生成。另外,MK5的mRNA表达增高与肿瘤转移发展的几率增高有关。
有趣的是,ERK3/ERK4表达的动力学与BRAFV600E和致癌RAS这二者的表达增高有关,其分别导致Erk3和Erk4的表达增高。数据显示,对BRAFV600E的抑制与Erk3的t环磷酸化降低同时发生,这伴随MK5的降低(图5E)。Erk3的水平在获得性耐药性后得以恢复,并且引人注目的是,致癌RAS大大提升了Erk4 t环的磷酸化,与初始细胞和敏感细胞相比提升了20倍以上。整体地,这会导致相比于未经治疗的细胞,在耐药细胞中的MK5激酶活性更高。结果表明ERK3/ERK4/MK5系统可能在黑色素瘤中的NRAS驱动的BRAFi耐药性(BRAFiresistance)方面有令人感兴趣的作用,并突出了本发明的方法在检测经靶向肿瘤疗法所改变的激酶组活性(kinome activity)的潜力。
序列表
<110> 乌得勒支大学控股有限责任公司
<120> 监测样品中激酶活性的方法
<130> 77770PC9
<150> EP18179104.7
<151> 2018-06-21
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Asn Thr Phe Val Gly Thr Pro Phe Trp Met Ala Pro Glu Val Ile Lys
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Asp Ile Tyr Glu Thr Asp Tyr Tyr Arg
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Asp Ile Tyr Glu Thr Asp Tyr Tyr Arg
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Asp Ile Tyr Glu Thr Asp Tyr Tyr Arg
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Leu Ile Glu Asp Asn Glu Tyr Thr Ala Arg
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Trp Thr Ala Pro Glu Ala Ala Leu Tyr Gly Arg
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Val Ile Glu Asp Asn Glu Tyr Thr Ala Arg
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Pro Pro Tyr Thr Asp Tyr Val Ser Thr Arg
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Pro Pro Tyr Thr Asp Tyr Val Ser Thr Arg
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Glu Tyr Gly Ser Pro Leu Lys
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<210> 18
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<223> PKAα (T198), PKAβ (T198), PKAγ (T198)
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<221> 残基的翻译后修饰
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Thr Trp Thr Leu Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Ile Ile
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Leu Ser Lys
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<211> 19
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<223> PKAα (T202), PKAβ (T202), PKAγ (T202)
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<221> 残基的翻译后修饰
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Thr Trp Thr Leu Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Ile Ile
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Leu Ser Lys
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<211> 7
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Gly Glu Glu Val Tyr Val Lys
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<210> 21
<211> 6
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<223> VGFR2 (Y1059), VGFR3 (Y1068)
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<221> 残基的翻译后修饰
<222> 4
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<400> 21
Asp Pro Asp Tyr Val Arg
1 5
<210> 22
<211> 22
<212> PRT
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<223> MEK1 (S218), MEK2 (S222)
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<221> 残基的翻译后修饰
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<221> 残基的翻译后修饰
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<223> 磷酸化
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<221> 残基的翻译后修饰
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Leu Cys Asp Phe Gly Val Ser Gly Gln Leu Ile Asp Ser Met Ala Asn
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Ser Phe Val Gly Thr Arg
20
<210> 23
<211> 14
<212> PRT
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<223> Abl (T392), Abl2/Arg (T438)
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<221> 残基的翻译后修饰
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Leu Met Thr Gly Asp Thr Tyr Thr Ala His Ala Gly Ala Lys
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<210> 24
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<223> Abl (T392), Abl2/Arg (T438)
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<221> 残基的翻译后修饰
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<223> 磷酸化
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Leu Met Thr Gly Asp Thr Tyr Thr Ala His Ala Gly Ala Lys
1 5 10
<210> 25
<211> 14
<212> PRT
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<220>
<223> Abl (Y393), Abl2/Arg (Y439)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 25
Leu Met Thr Gly Asp Thr Tyr Thr Ala His Ala Gly Ala Lys
1 5 10
<210> 26
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Abl (Y393), Abl2/Arg (Y439)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 26
Leu Met Thr Gly Asp Thr Tyr Thr Ala His Ala Gly Ala Lys
1 5 10
<210> 27
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Abl (T394), Abl2/Arg (T440)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 27
Leu Met Thr Gly Asp Thr Tyr Thr Ala His Ala Gly Ala Lys
1 5 10
<210> 28
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Abl (T394), Abl2/Arg (T440)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 28
Leu Met Thr Gly Asp Thr Tyr Thr Ala His Ala Gly Ala Lys
1 5 10
<210> 29
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GSK3A (Y279), GSK3B (Y216)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 29
Gly Glu Pro Asn Val Ser Tyr Ile Cys Ser Arg
1 5 10
<210> 30
<211> 22
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RSK1/p90RSK (T573), RSK2 (T577)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 30
Ala Glu Asn Gly Leu Leu Met Thr Pro Cys Tyr Thr Ala Asn Phe Val
1 5 10 15
Ala Pro Glu Val Leu Lys
20
<210> 31
<211> 22
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RSK1/p90RSK (T573), RSK2 (T577)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 31
Ala Glu Asn Gly Leu Leu Met Thr Pro Cys Tyr Thr Ala Asn Phe Val
1 5 10 15
Ala Pro Glu Val Leu Lys
20
<210> 32
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK1 (T183), JNK3 (T221)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 32
Thr Ala Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 33
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK1 (T183/Y185), JNK3 (T221/Y223)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 33
Thr Ala Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 34
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK1 (T183/Y185), JNK3 (T221/Y223)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 34
Thr Ala Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 35
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK1 (T183), JNK3 (T221)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 35
Thr Ala Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 36
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK1 (Y185), JNK3 (Y223)
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 36
Thr Ala Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 37
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK1 (Y185), JNK3 (Y223)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 37
Thr Ala Gly Thr Ser Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 38
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> EphA3 (Y779), EphA4 (Y779), EphA5 (Y833)
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 38
Val Leu Glu Asp Asp Pro Glu Ala Ala Tyr Thr Thr Arg
1 5 10
<210> 39
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> M3K10 (S262), M3K9 (S308)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 39
Met Ser Ala Ala Gly Thr Tyr Ala Trp Met Ala Pro Glu Val Ile Arg
1 5 10 15
<210> 40
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> M3K10 (T266), M3K9 (T312)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 40
Met Ser Ala Ala Gly Thr Tyr Ala Trp Met Ala Pro Glu Val Ile Arg
1 5 10 15
<210> 41
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK2 (T160), CDK3 (T160)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 41
Thr Tyr Thr His Glu Val Val Thr Leu Trp Tyr Arg
1 5 10
<210> 42
<211> 17
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PAK1 (T427), PAK2 (T406), PAK3 (T440)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 42
Ser Thr Met Val Gly Thr Pro Tyr Trp Met Ala Pro Glu Val Val Thr
1 5 10 15
Arg
<210> 43
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC2A (T305), KCC2B (T306), KCC2D (T306)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 43
Gly Ala Ile Leu Thr Thr Met Leu Ala Thr Arg
1 5 10
<210> 44
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC2A (T305/T306), KCC2B (T306/T307), KCC2D (T306/T307)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 44
Gly Ala Ile Leu Thr Thr Met Leu Ala Thr Arg
1 5 10
<210> 45
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC2A (T305/T306), KCC2B (T306/T307), KCC2D (T306/T307)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 45
Gly Ala Ile Leu Thr Thr Met Leu Ala Thr Arg
1 5 10
<210> 46
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC2A (T305), KCC2B (T306), KCC2D (T306)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 46
Gly Ala Ile Leu Thr Thr Met Leu Ala Thr Arg
1 5 10
<210> 47
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC2A (T306), KCC2B (T307), KCC2D T307)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 47
Gly Ala Ile Leu Thr Thr Met Leu Ala Thr Arg
1 5 10
<210> 48
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC2A (T306), KCC2B (T307), KCC2D T307)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 48
Gly Ala Ile Leu Thr Thr Met Leu Ala Thr Arg
1 5 10
<210> 49
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TrkB (Y702), TrkC (Y705)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 49
Asp Val Tyr Ser Thr Asp Tyr Tyr Arg
1 5
<210> 50
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TrkB (Y706), TrkC (Y709)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 50
Asp Val Tyr Ser Thr Asp Tyr Tyr Arg
1 5
<210> 51
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TrkB (Y707), TrkC (Y710)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 51
Asp Val Tyr Ser Thr Asp Tyr Tyr Arg
1 5
<210> 52
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> TTN (Y8490), [TBRG1 (Y234)]
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 52
Tyr Thr Cys Gln Ile Lys
1 5
<210> 53
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DMPK (S216), MRCKA (S222), MRCKB (S221)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 53
Leu Ala Asp Phe Gly Ser Cys Leu Lys
1 5
<210> 54
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PDK1 (S241), PDK2 (S241)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 54
Ala Asn Ser Phe Val Gly Thr Ala Gln Tyr Val Ser Pro Glu Leu Leu
1 5 10 15
Thr Glu Lys
<210> 55
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MARK1 (T215), MARK2 (T208), MARK3 (T211), MARK4 (T214)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 55
Leu Asp Thr Phe Cys Gly Ser Pro Pro Tyr Ala Ala Pro Glu Leu Phe
1 5 10 15
Gln Gly Lys
<210> 56
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MARK1 (T215/S219), MARK2 (T208/S212), MARK3 (T211/S215), MARK4
(T214/S218)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 56
Leu Asp Thr Phe Cys Gly Ser Pro Pro Tyr Ala Ala Pro Glu Leu Phe
1 5 10 15
Gln Gly Lys
<210> 57
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MARK1 (S219), MARK2 (S212), MARK3 (S215), MARK4 (S218)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 57
Leu Asp Thr Phe Cys Gly Ser Pro Pro Tyr Ala Ala Pro Glu Leu Phe
1 5 10 15
Gln Gly Lys
<210> 58
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JAK3 (Y980), PKR2 (Y113), PKR1 (Y122)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 58
Asp Tyr Tyr Val Val Arg
1 5
<210> 59
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JAK3 (Y980/Y981), PKR2 (Y113/Y114), PKR1 (Y122/Y123)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 59
Asp Tyr Tyr Val Val Arg
1 5
<210> 60
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JAK3 (Y981), PKR2 (Y114), PKR1 (Y123)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 60
Asp Tyr Tyr Val Val Arg
1 5
<210> 61
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DYRK2 (Y382), DYRK4 (Y264)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 61
Val Tyr Thr Tyr Ile Gln Ser Arg
1 5
<210> 62
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DYRK2 (T381/Y382), DYRK4 (T263/Y264)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 62
Val Tyr Thr Tyr Ile Gln Ser Arg
1 5
<210> 63
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DYRK2 (Y382), DYRK4 (Y264)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 63
Val Tyr Thr Tyr Ile Gln Ser Arg
1 5
<210> 64
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PAK6 (S560), PAK7 (S602)
<400> 64
Ser Leu Val Gly Thr Pro Tyr Trp Met Ala Pro Glu Val Ile Ser Arg
1 5 10 15
<210> 65
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PAK6 (S560), PAK7 (S602)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 65
Ser Leu Val Gly Thr Pro Tyr Trp Met Ala Pro Glu Val Ile Ser Arg
1 5 10 15
<210> 66
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Dyr1A (S310), Dyr1B (S262)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 66
Ile Val Asp Phe Gly Ser Ser Cys Gln Leu Gly Gln Arg
1 5 10
<210> 67
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Dyr1A (Y319/Y321), Dyr1B (Y271/Y273)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 67
Ile Tyr Gln Tyr Ile Gln Ser Arg
1 5
<210> 68
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Dyr1A (Y321), Dyr1B Y273)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 68
Ile Tyr Gln Tyr Ile Gln Ser Arg
1 5
<210> 69
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK9 (S175)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 69
Ala Phe Ser Leu Ala Lys
1 5
<210> 70
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ZAP70 (Y492)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 70
Ala Leu Gly Ala Asp Asp Ser Tyr Tyr Thr Ala Arg
1 5 10
<210> 71
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> AAK1 (Y234)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 71
Ala Pro Glu Met Val Asn Leu Tyr Ser Gly Lys
1 5 10
<210> 72
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> AAK1 (Y234/S235)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 72
Ala Pro Glu Met Val Asn Leu Tyr Ser Gly Lys
1 5 10
<210> 73
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> AAK1 (Y234/S235)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 73
Ala Pro Glu Met Val Asn Leu Tyr Ser Gly Lys
1 5 10
<210> 74
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> AAK1 (Y234)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 74
Ala Pro Glu Met Val Asn Leu Tyr Ser Gly Lys
1 5 10
<210> 75
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> AAK1 (S235)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 75
Ala Pro Glu Met Val Asn Leu Tyr Ser Gly Lys
1 5 10
<210> 76
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> AAK1 (S235)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 76
Ala Pro Glu Met Val Asn Leu Tyr Ser Gly Lys
1 5 10
<210> 77
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MNK2 (S74)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 77
Ala Thr Asp Ser Phe Ser Gly Arg
1 5
<210> 78
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TYK2 (1054)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 78
Ala Val Pro Glu Gly His Glu Tyr Tyr Arg
1 5 10
<210> 79
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK11B (Y594)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 79
Ala Tyr Thr Pro Val Val Val Thr Leu Trp Tyr Arg
1 5 10
<210> 80
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK11B (Y594/T595)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 80
Ala Tyr Thr Pro Val Val Val Thr Leu Trp Tyr Arg
1 5 10
<210> 81
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK11B (T595)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 81
Ala Tyr Thr Pro Val Val Val Thr Leu Trp Tyr Arg
1 5 10
<210> 82
<211> 17
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MSK1 (S212)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 82
Ala Tyr Ser Phe Cys Gly Thr Ile Glu Tyr Met Ala Pro Asp Ile Val
1 5 10 15
Arg
<210> 83
<211> 17
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MSK1 (S212)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 83
Ala Tyr Ser Phe Cys Gly Thr Ile Glu Tyr Met Ala Pro Asp Ile Val
1 5 10 15
Arg
<210> 84
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGR (412)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 84
Asp Asp Glu Tyr Asn Pro Cys Gln Gly Ser Lys
1 5 10
<210> 85
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> SRMS (Y849)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 85
Asp Asp Ile Tyr Ser Pro Ser Ser Ser Ser Lys
1 5 10
<210> 86
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PGFRA (Y849)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 86
Asp Ile Met His Asp Ser Asn Tyr Val Ser Lys
1 5 10
<210> 87
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PGFRA (Y849)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 87
Asp Ile Met His Asp Ser Asn Tyr Val Ser Lys
1 5 10
<210> 88
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR1 (Y653)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 88
Asp Ile His His Ile Asp Tyr Tyr Lys
1 5
<210> 89
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR1 (Y654)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 89
Asp Ile His His Ile Asp Tyr Tyr Lys
1 5
<210> 90
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CSF1R (Y809)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 90
Asp Ile Met Asn Asp Ser Asn Tyr Ile Val Lys
1 5 10
<210> 91
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CSF1R (Y809)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 91
Asp Ile Met Asn Asp Ser Asn Tyr Ile Val Lys
1 5 10
<210> 92
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FLT3 (Y842)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 92
Asp Ile Met Ser Asp Ser Asn Tyr Val Val Arg
1 5 10
<210> 93
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FLT3 (Y842)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 93
Asp Ile Met Ser Asp Ser Asn Tyr Val Val Arg
1 5 10
<210> 94
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR2 (Y656)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 94
Asp Ile Asn Asn Ile Asp Tyr Tyr Lys
1 5
<210> 95
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR2 (Y656/Y657)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 95
Asp Ile Asn Asn Ile Asp Tyr Tyr Lys
1 5
<210> 96
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR2 (Y657)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 96
Asp Ile Asn Asn Ile Asp Tyr Tyr Lys
1 5
<210> 97
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TrkA (Y676)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 97
Asp Ile Tyr Ser Thr Asp Tyr Tyr Arg
1 5
<210> 98
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TrkA (Y680)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 98
Asp Ile Tyr Ser Thr Asp Tyr Tyr Arg
1 5
<210> 99
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TrkA (Y681)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 99
Asp Ile Tyr Ser Thr Asp Tyr Tyr Arg
1 5
<210> 100
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PDGFRβ (Y857)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 100
Asp Ser Asn Tyr Ile Ser Lys
1 5
<210> 101
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR3 (Y647)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 101
Asp Val His Asn Leu Asp Tyr Tyr Lys
1 5
<210> 102
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR3 (Y647/Y648)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 102
Asp Val His Asn Leu Asp Tyr Tyr Lys
1 5
<210> 103
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RET (Y900)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 103
Asp Val Tyr Glu Glu Asp Ser Tyr Val Lys
1 5 10
<210> 104
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RET (Y900/Y905)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 104
Asp Val Tyr Glu Glu Asp Ser Tyr Val Lys
1 5 10
<210> 105
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RET (Y905)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 105
Asp Val Tyr Glu Glu Asp Ser Tyr Val Lys
1 5 10
<210> 106
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRR (Y1145)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 106
Asp Val Tyr Glu Thr Asp Tyr Tyr Arg
1 5
<210> 107
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRR (Y1145/Y1146)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 107
Asp Val Tyr Glu Thr Asp Tyr Tyr Arg
1 5
<210> 108
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRR (Y1146)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 108
Asp Val Tyr Glu Thr Asp Tyr Tyr Arg
1 5
<210> 109
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PTK6 (Y342)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 109
Glu Asp Val Tyr Leu Ser His Asp His Asn Ile Pro Tyr Lys
1 5 10
<210> 110
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PTK6 (Y342/Y351)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 110
Glu Asp Val Tyr Leu Ser His Asp His Asn Ile Pro Tyr Lys
1 5 10
<210> 111
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PTK6 (Y351)
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 111
Glu Asp Val Tyr Leu Ser His Asp His Asn Ile Pro Tyr Lys
1 5 10
<210> 112
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FES (Y713)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 112
Glu Glu Ala Asp Gly Val Tyr Ala Ala Ser Gly Gly Leu Arg
1 5 10
<210> 113
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ROR1 (Y645)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 113
Glu Ile Tyr Ser Ala Asp Tyr Tyr Arg
1 5
<210> 114
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KPCD (S503)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 114
Glu Asn Ile Phe Gly Glu Ser Arg
1 5
<210> 115
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TESK1 (S220)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 115
Glu Pro Leu Ala Val Val Gly Ser Pro Tyr Trp Met Ala Pro Glu Val
1 5 10 15
Leu Arg
<210> 116
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TESK1 (S220)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 12
<223> 磷酸化
<400> 116
Glu Pro Leu Ala Val Val Gly Ser Pro Tyr Trp Met Ala Pro Glu Val
1 5 10 15
Leu Arg
<210> 117
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ROR2 (Y646)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 117
Glu Val Tyr Ala Ala Asp Tyr Tyr Lys
1 5
<210> 118
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK11A (Y582)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 118
Ala Tyr Thr Pro Val Val Val Thr Gln Trp Tyr Arg
1 5 10
<210> 119
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK11A (Y582/T583)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 119
Ala Tyr Thr Pro Val Val Val Thr Gln Trp Tyr Arg
1 5 10
<210> 120
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MET (Y1234)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 120
Glu Tyr Tyr Ser Val His Asn Lys
1 5
<210> 121
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MET (Y1234/Y1235)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 121
Glu Tyr Tyr Ser Val His Asn Lys
1 5
<210> 122
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MET (Y1235)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 122
Glu Tyr Tyr Ser Val His Asn Lys
1 5
<210> 123
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RON (Y1238)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 123
Glu Tyr Tyr Ser Val Gln Gln His Arg
1 5
<210> 124
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RON (Y1238/Y1239)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 124
Glu Tyr Tyr Ser Val Gln Gln His Arg
1 5
<210> 125
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RON (Y1239)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 125
Glu Tyr Tyr Ser Val Gln Gln His Arg
1 5
<210> 126
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JAK1 (Y1034)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 126
Glu Tyr Tyr Thr Val Lys
1 5
<210> 127
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JAK1 (Y1035)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 127
Glu Tyr Tyr Thr Val Lys
1 5
<210> 128
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JAK1 (Y1034/Y1035)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 128
Glu Tyr Tyr Thr Val Lys
1 5
<210> 129
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JAK1 (Y1035)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 129
Glu Tyr Tyr Thr Val Lys
1 5
<210> 130
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRAK4 (T345)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 130
Phe Ala Gln Thr Val Met Thr Ser Arg
1 5
<210> 131
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRAK4 (T345)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 131
Phe Ala Gln Thr Val Met Thr Ser Arg
1 5
<210> 132
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRAK4 (S346)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 132
Phe Ala Gln Thr Val Met Thr Ser Arg
1 5
<210> 133
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRAK4 (S346)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 133
Phe Ala Gln Thr Val Met Thr Ser Arg
1 5
<210> 134
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK6 (T202)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 134
Phe Phe Ser Ser Glu Thr Thr Ala Ala His Ser Leu Val Gly Thr Pro
1 5 10 15
Tyr Tyr Met Ser Pro Glu Arg
20
<210> 135
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK6 (T202)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 19
<223> 磷酸化
<400> 135
Phe Phe Ser Ser Glu Thr Thr Ala Ala His Ser Leu Val Gly Thr Pro
1 5 10 15
Tyr Tyr Met Ser Pro Glu Arg
20
<210> 136
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK6 (S206)
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 136
Phe Phe Ser Ser Glu Thr Thr Ala Ala His Ser Leu Val Gly Thr Pro
1 5 10 15
Tyr Tyr Met Ser Pro Glu Arg
20
<210> 137
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK6 (S206)
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 19
<223> 磷酸化
<400> 137
Phe Phe Ser Ser Glu Thr Thr Ala Ala His Ser Leu Val Gly Thr Pro
1 5 10 15
Tyr Tyr Met Ser Pro Glu Arg
20
<210> 138
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ITK (Y512)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 138
Phe Val Leu Asp Asp Gln Tyr Thr Ser Ser Thr Gly Thr Lys
1 5 10
<210> 139
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IKKE (S172)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 139
Phe Val Ser Val Tyr Gly Thr Glu Glu Tyr Leu His Pro Asp Met Tyr
1 5 10 15
Glu Arg
<210> 140
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IKKE (S172)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 15
<223> 磷酸化
<400> 140
Phe Val Ser Val Tyr Gly Thr Glu Glu Tyr Leu His Pro Asp Met Tyr
1 5 10 15
Glu Arg
<210> 141
<211> 22
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC1D (T180)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 141
Gly Asp Val Met Ser Thr Ala Cys Gly Thr Pro Gly Tyr Val Ala Pro
1 5 10 15
Glu Val Leu Ala Gln Lys
20
<210> 142
<211> 22
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KCC1D (T180)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 142
Gly Asp Val Met Ser Thr Ala Cys Gly Thr Pro Gly Tyr Val Ala Pro
1 5 10 15
Glu Val Leu Ala Gln Lys
20
<210> 143
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK06 (S189)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 143
Gly His Leu Ser Glu Gly Leu Val Thr Lys
1 5 10
<210> 144
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> M3K7 (S192)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 144
Gly Ser Ala Ala Trp Met Ala Pro Glu Val Phe Glu Gly Ser Asn Tyr
1 5 10 15
Ser Glu Lys
<210> 145
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TIE2 (Y992)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 145
Gly Gln Glu Val Tyr Val Lys
1 5
<210> 146
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> M3K7 (S192)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 146
Gly Ser Ala Ala Trp Met Ala Pro Glu Val Phe Glu Gly Ser Asn Tyr
1 5 10 15
Ser Glu Lys
<210> 147
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RK (S21)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 147
Gly Ser Phe Asp Gly Ser Ser Ser Gln Pro Ser Arg
1 5 10
<210> 148
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ULK3 (S176)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 12
<223> 磷酸化
<400> 148
Gly Ser Pro Leu Tyr Met Ala Pro Glu Met Val Cys Gln Arg
1 5 10
<210> 149
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ULK3 (S176)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 12
<223> 磷酸化
<400> 149
Gly Ser Pro Leu Tyr Met Ala Pro Glu Met Val Cys Gln Arg
1 5 10
<210> 150
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> M3K8 (T290)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 150
Gly Thr Glu Ile Tyr Met Ser Pro Glu Val Ile Leu Cys Arg
1 5 10
<210> 151
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> M3K8 (T290)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 151
Gly Thr Glu Ile Tyr Met Ser Pro Glu Val Ile Leu Cys Arg
1 5 10
<210> 152
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> IRAK1 (T387)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 152
Gly Thr Leu Ala Tyr Leu Pro Glu Glu Tyr Ile Lys
1 5 10
<210> 153
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR4 (Y642)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 153
Gly Val His His Ile Asp Tyr Tyr Lys
1 5
<210> 154
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR4 (Y642/Y643)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 154
Gly Val His His Ile Asp Tyr Tyr Lys
1 5
<210> 155
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FGFR4 (Y643)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 155
Gly Val His His Ile Asp Tyr Tyr Lys
1 5
<210> 156
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK04 (S186)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 156
Gly Tyr Leu Ser Glu Gly Leu Val Thr Lys
1 5 10
<210> 157
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38δ (T180)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 157
His Ala Asp Ala Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 158
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38δ (T180/Y182)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 158
His Ala Asp Ala Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 159
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38δ (T180/Y182)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 159
His Ala Asp Ala Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 160
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38δ (T180)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 160
His Ala Asp Ala Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 161
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38δ (Y182)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 161
His Ala Asp Ala Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 162
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38δ (Y182)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 162
His Ala Asp Ala Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 163
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NLK (T298)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 163
His Met Thr Gln Glu Val Val Thr Gln Tyr Tyr Arg
1 5 10
<210> 164
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NLK (T298)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 164
His Met Thr Gln Glu Val Val Thr Gln Tyr Tyr Arg
1 5 10
<210> 165
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK14 (T180)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 165
His Thr Asp Asp Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 166
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK14 (T180/Y182)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 166
His Thr Asp Asp Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 167
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK14 (T180/Y182)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 167
His Thr Asp Asp Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 168
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK14 (T180)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 168
His Thr Asp Asp Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 169
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK14 (Y182)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 169
His Thr Asp Asp Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 170
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MK14 (Y182)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 170
His Thr Asp Asp Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 171
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RIPK1 (S161)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 171
Ile Ala Asp Leu Gly Leu Ala Ser Phe Lys
1 5 10
<210> 172
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ERK1 (T198)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 172
Ile Ala Asp Pro Glu His Asp His Thr Gly Phe Leu Thr Glu Tyr Val
1 5 10 15
Ala Thr Arg
<210> 173
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ERK1 (T202)
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 173
Ile Ala Asp Pro Glu His Asp His Thr Gly Phe Leu Thr Glu Tyr Val
1 5 10 15
Ala Thr Arg
<210> 174
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> ERK1 (Y204)
<220>
<221> 残基的翻译后修饰
<222> 15
<223> 磷酸化
<400> 174
Ile Ala Asp Pro Glu His Asp His Thr Gly Phe Leu Thr Glu Tyr Val
1 5 10 15
Ala Thr Arg
<210> 175
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MLTK (S155)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 175
Ile Cys Asp Phe Gly Ala Ser Arg
1 5
<210> 176
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MAPK5 (T182)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 176
Ile Asp Gln Gly Asp Leu Met Thr Pro Gln Phe Thr Pro Tyr Tyr Val
1 5 10 15
Ala Pro Gln Val Leu Glu Ala Gln Arg
20 25
<210> 177
<211> 25
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MAPK5 (T182)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 177
Ile Asp Gln Gly Asp Leu Met Thr Pro Gln Phe Thr Pro Tyr Tyr Val
1 5 10 15
Ala Pro Gln Val Leu Glu Ala Gln Arg
20 25
<210> 178
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> BLK (Y389)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 178
Ile Ile Asp Ser Glu Tyr Thr Ala Gln Glu Gly Ala Lys
1 5 10
<210> 179
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> UFO (Y703)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 179
Ile Tyr Asn Gly Asp Tyr Tyr Arg
1 5
<210> 180
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MERTK (Y749) TYRO3 (Y681)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 180
Ile Tyr Ser Gly Asp Tyr Tyr Arg
1 5
<210> 181
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MERTK (Y753) TYRO3 (Y685)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 181
Ile Tyr Ser Gly Asp Tyr Tyr Arg
1 5
<210> 182
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MERTK (Y754) TYRO3 (Y686)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 182
Ile Tyr Ser Gly Asp Tyr Tyr Arg
1 5
<210> 183
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TESK2 (S219)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 183
Leu Ala Val Val Gly Ser Pro Phe Trp Met Ala Pro Glu Val Leu Arg
1 5 10 15
<210> 184
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> TESK2 (S219)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 184
Leu Ala Val Val Gly Ser Pro Phe Trp Met Ala Pro Glu Val Leu Arg
1 5 10 15
<210> 185
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MKK4 (S2570
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 185
Leu Cys Asp Phe Gly Ile Ser Gly Gln Leu Val Asp Ser Ile Ala Lys
1 5 10 15
<210> 186
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MRCKG (S216)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 186
Leu Ala Asp Phe Gly Ser Cys Leu Arg
1 5
<210> 187
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MARK1 (T208)
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 187
Ile Ala Asp Phe Gly Phe Ser Asn Glu Phe Thr Val Gly Asn Lys
1 5 10 15
<210> 188
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Dyrk3 (Y369)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 188
Leu Tyr Thr Tyr Ile Gln Ser Arg
1 5
<210> 189
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> RIPK2 (S176)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 189
Met Met Ser Leu Ser Gln Ser Arg
1 5
<210> 190
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> RIPK2 (S176)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 190
Met Met Ser Leu Ser Gln Ser Arg
1 5
<210> 191
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> M3KL4 (S303)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 191
Met Ser Thr Ala Gly Thr Tyr Ala Trp Met Ala Pro Glu Val Ile Lys
1 5 10 15
<210> 192
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> M3KL4 (S303)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 192
Met Ser Thr Ala Gly Thr Tyr Ala Trp Met Ala Pro Glu Val Ile Lys
1 5 10 15
<210> 193
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KIT (S821)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 193
Asn Asp Ser Asn Tyr Val Val Lys
1 5
<210> 194
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KIT (S821/Y823)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 194
Asn Asp Ser Asn Tyr Val Val Lys
1 5
<210> 195
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> KIT (Y823)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 195
Asn Asp Ser Asn Tyr Val Val Lys
1 5
<210> 196
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MUSK (Y755)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 196
Asn Ile Tyr Ser Ala Asp Tyr Tyr Lys
1 5
<210> 197
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DDR1 (Y792)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 197
Asn Leu Tyr Ala Gly Asp Tyr Tyr Arg
1 5
<210> 198
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DDR1 (Y796)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 198
Asn Leu Tyr Ala Gly Asp Tyr Tyr Arg
1 5
<210> 199
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DDR1 (Y797)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 199
Asn Leu Tyr Ala Gly Asp Tyr Tyr Arg
1 5
<210> 200
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DDR2 (Y736)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 200
Asn Leu Tyr Ser Gly Asp Tyr Tyr Arg
1 5
<210> 201
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DDR2 (Y740)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 201
Asn Leu Tyr Ser Gly Asp Tyr Tyr Arg
1 5
<210> 202
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> DDR2 (Y741)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 202
Asn Leu Tyr Ser Gly Asp Tyr Tyr Arg
1 5
<210> 203
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> BMPR2 (T379)
<220>
<221> 残基的翻译后修饰
<222> 14
<223> 磷酸化
<400> 203
Pro Gly Glu Glu Asp Asn Ala Ala Ile Ser Glu Val Gly Thr Ile Arg
1 5 10 15
<210> 204
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38B (T180)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 204
Gln Ala Asp Glu Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 205
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38B (T180/Y182)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 205
Gln Ala Asp Glu Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 206
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38B (T180/Y182)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 206
Gln Ala Asp Glu Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 207
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38B (T180)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 207
Gln Ala Asp Glu Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 208
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38B (Y182)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 208
Gln Ala Asp Glu Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 209
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38B (Y182)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 209
Gln Ala Asp Glu Glu Met Thr Gly Tyr Val Ala Thr Arg
1 5 10
<210> 210
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38G (T183)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 210
Gln Ala Asp Ser Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 211
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38G (T183/Y185)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 211
Gln Ala Asp Ser Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 212
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38G (T183/Y185)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 212
Gln Ala Asp Ser Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 213
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38G (T183)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 213
Gln Ala Asp Ser Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 214
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38G (Y185)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 214
Gln Ala Asp Ser Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 215
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> P38G (Y185)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 215
Gln Ala Asp Ser Glu Met Thr Gly Tyr Val Val Thr Arg
1 5 10
<210> 216
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MPSK1 (T185)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 216
Gln Ala Leu Thr Leu Gln Asp Trp Ala Ala Gln Arg
1 5 10
<210> 217
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MPSK1 (S197)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 217
Cys Thr Ile Ser Tyr Arg
1 5
<210> 218
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MPSK1 (S197/Y198)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 218
Cys Thr Ile Ser Tyr Arg
1 5
<210> 219
<211> 6
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MPSK1 (Y198)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 219
Cys Thr Ile Ser Tyr Arg
1 5
<210> 220
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Fer (Y714)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 220
Gln Glu Asp Gly Gly Val Tyr Ser Ser Ser Gly Leu Lys
1 5 10
<210> 221
<211> 8
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CaMKIIβ (T287)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 221
Gln Glu Thr Val Glu Cys Leu Lys
1 5
<210> 222
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK12 (S1053)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 222
Gln Ser Gly Val Val Val Glu Glu Pro Pro Pro Ser Lys
1 5 10
<210> 223
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK12 (S1083)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 223
Asn Ser Ser Pro Ala Pro Pro Gln Pro Ala Pro Gly Lys
1 5 10
<210> 224
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PAK4 (S475)
<400> 224
Ser Leu Val Gly Thr Pro Tyr Trp Met Ala Pro Glu Leu Ile Ser Arg
1 5 10 15
<210> 225
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PAK4 (S475)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 225
Ser Leu Val Gly Thr Pro Tyr Trp Met Ala Pro Glu Leu Ile Ser Arg
1 5 10 15
<210> 226
<211> 26
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GCN2 (T899)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 226
Ser Asp Pro Ser Gly His Leu Thr Gly Met Val Gly Thr Ala Leu Tyr
1 5 10 15
Val Ser Pro Glu Val Gln Gly Ser Thr Lys
20 25
<210> 227
<211> 26
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GCN2 (T899)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 227
Ser Asp Pro Ser Gly His Leu Thr Gly Met Val Gly Thr Ala Leu Tyr
1 5 10 15
Val Ser Pro Glu Val Gln Gly Ser Thr Lys
20 25
<210> 228
<211> 26
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GCN2 (T904)
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 228
Ser Asp Pro Ser Gly His Leu Thr Gly Met Val Gly Thr Ala Leu Tyr
1 5 10 15
Val Ser Pro Glu Val Gln Gly Ser Thr Lys
20 25
<210> 229
<211> 26
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GCN2 (T904)
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 229
Ser Asp Pro Ser Gly His Leu Thr Gly Met Val Gly Thr Ala Leu Tyr
1 5 10 15
Val Ser Pro Glu Val Gln Gly Ser Thr Lys
20 25
<210> 230
<211> 22
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Her4 (Y1056)
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 230
Ser Glu Ile Gly His Ser Pro Pro Pro Ala Tyr Thr Pro Met Ser Gly
1 5 10 15
Asn Gln Phe Val Tyr Arg
20
<210> 231
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK7 (S164)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 231
Ser Phe Gly Ser Pro Asn Arg
1 5
<210> 232
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK7 (T170)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 232
Ala Tyr Thr His Gln Val Val Thr Arg
1 5
<210> 233
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MASTL (S293)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 233
Cys Leu Thr Ser Asn Leu Leu Gln Ser Arg
1 5 10
<210> 234
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MASTL (S552)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 234
Asp Tyr Leu Ser Ser Ser Phe Leu Cys Ser Asp Asp Asp Arg
1 5 10
<210> 235
<211> 14
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MASTL (S552/S556)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 235
Asp Tyr Leu Ser Ser Ser Phe Leu Cys Ser Asp Asp Asp Arg
1 5 10
<210> 236
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MASTL (S631)
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 236
Gly Val Glu Asn Pro Ala Val Gln Glu Ser Asn Gln Lys
1 5 10
<210> 237
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MASTL (S657)
<400> 237
Ser Phe Asn Ser His Ile Asn Ala Ser Asn Asn Ser Glu Pro Ser Arg
1 5 10 15
<210> 238
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MASTL (S657/S668)
<220>
<221> 残基的翻译后修饰
<222> 12
<223> 磷酸化
<400> 238
Ser Phe Asn Ser His Ile Asn Ala Ser Asn Asn Ser Glu Pro Ser Arg
1 5 10 15
<210> 239
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MASTL (S668)
<220>
<221> 残基的翻译后修饰
<222> 12
<223> 磷酸化
<400> 239
Ser Phe Asn Ser His Ile Asn Ala Ser Asn Asn Ser Glu Pro Ser Arg
1 5 10 15
<210> 240
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MASTL (T741)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 240
Ile Leu Gly Thr Pro Asp Tyr Leu Ala Pro Glu Leu Leu Leu Gly Arg
1 5 10 15
<210> 241
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> SIK (T182)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 241
Ser Gly Glu Pro Leu Ser Thr Trp Cys Gly Ser Pro Pro Tyr Ala Ala
1 5 10 15
Pro Glu Val Phe Glu Gly Lys
20
<210> 242
<211> 21
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PRKD2 (S710)
<400> 242
Ser Val Val Gly Thr Pro Ala Tyr Leu Ala Pro Glu Val Leu Leu Asn
1 5 10 15
Gln Gly Tyr Asn Arg
20
<210> 243
<211> 21
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PRKD2 (Y717)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 243
Ser Val Val Gly Thr Pro Ala Tyr Leu Ala Pro Glu Val Leu Leu Asn
1 5 10 15
Gln Gly Tyr Asn Arg
20
<210> 244
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PLK2 (T239)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 244
Thr Ile Cys Gly Thr Pro Asn Tyr Leu Ser Pro Glu Val Leu Asn Lys
1 5 10 15
<210> 245
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Chk2/Rad53 (S379)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 245
Ile Leu Gly Glu Thr Ser Leu Met Arg
1 5
<210> 246
<211> 9
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Chk2/Rad53 (S379)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 246
Ile Leu Gly Glu Thr Ser Leu Met Arg
1 5
<210> 247
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> CaMK4 (T200)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 247
Thr Val Cys Gly Thr Pro Gly Tyr Cys Ala Pro Glu Ile Leu Arg
1 5 10 15
<210> 248
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MEK5 (T315)
<400> 248
Thr Tyr Val Gly Thr Asn Ala Tyr Met Ala Pro Glu Arg
1 5 10
<210> 249
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MEK5 (T315)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 249
Thr Tyr Val Gly Thr Asn Ala Tyr Met Ala Pro Glu Arg
1 5 10
<210> 250
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK2 (T183)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 250
Thr Ala Cys Thr Asn Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 251
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK2 (T183/Y185)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 251
Thr Ala Cys Thr Asn Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 252
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK2 (T183/Y185)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 252
Thr Ala Cys Thr Asn Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 253
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK2 (Y185)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 253
Thr Ala Cys Thr Asn Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 254
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> JNK2 (Y185)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 254
Thr Ala Cys Thr Asn Phe Met Met Thr Pro Tyr Val Val Thr Arg
1 5 10 15
<210> 255
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK2 (T170)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 255
Ile Leu Asn His Asp Thr Ser Phe Ala Lys
1 5 10
<210> 256
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK2 (T170/S171)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 256
Ile Leu Asn His Asp Thr Ser Phe Ala Lys
1 5 10
<210> 257
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK2 (S171)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 257
Ile Leu Asn His Asp Thr Ser Phe Ala Lys
1 5 10
<210> 258
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> NEK2 (T175)
<400> 258
Thr Phe Val Gly Thr Pro Tyr Tyr Met Ser Pro Glu Gln Met Asn Arg
1 5 10 15
<210> 259
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> NEK2 (T179)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 259
Thr Phe Val Gly Thr Pro Tyr Tyr Met Ser Pro Glu Gln Met Asn Arg
1 5 10 15
<210> 260
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PLK1 (T210)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 260
Thr Leu Cys Gly Thr Pro Asn Tyr Ile Ala Pro Glu Val Leu Ser Lys
1 5 10 15
<210> 261
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> PLK1 (T210/T214)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 261
Thr Leu Cys Gly Thr Pro Asn Tyr Ile Ala Pro Glu Val Leu Ser Lys
1 5 10 15
<210> 262
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PLK1 (T214)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 262
Thr Leu Cys Gly Thr Pro Asn Tyr Ile Ala Pro Glu Val Leu Ser Lys
1 5 10 15
<210> 263
<211> 20
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PKCθ (T538)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 263
Thr Asn Thr Phe Cys Gly Thr Pro Asp Tyr Ile Ala Pro Glu Ile Leu
1 5 10 15
Leu Gly Gln Lys
20
<210> 264
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MLKL (S358)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<400> 264
Thr Gln Thr Ser Met Ser Leu Gly Thr Thr Arg
1 5 10
<210> 265
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MLKL (S358)
<220>
<221> 残基的翻译后修饰
<222> 4
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 265
Thr Gln Thr Ser Met Ser Leu Gly Thr Thr Arg
1 5 10
<210> 266
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MLKL (S360)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 266
Thr Gln Thr Ser Met Ser Leu Gly Thr Thr Arg
1 5 10
<210> 267
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> MLKL (S360)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 267
Thr Gln Thr Ser Met Ser Leu Gly Thr Thr Arg
1 5 10
<210> 268
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PKN2 (T816)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 268
Thr Ser Thr Phe Cys Gly Thr Pro Glu Phe Leu Ala Pro Glu Val Leu
1 5 10 15
Thr Glu Thr Ser Tyr Thr Arg
20
<210> 269
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PKN2 (T820)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 269
Thr Ser Thr Phe Cys Gly Thr Pro Glu Phe Leu Ala Pro Glu Val Leu
1 5 10 15
Thr Glu Thr Ser Tyr Thr Arg
20
<210> 270
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PKN3 (T718)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 270
Thr Ser Thr Phe Cys Gly Thr Pro Glu Phe Leu Ala Pro Glu Val Leu
1 5 10 15
Thr Gln Glu Ala Tyr Thr Arg
20
<210> 271
<211> 23
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> PKN3 (T722)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 271
Thr Ser Thr Phe Cys Gly Thr Pro Glu Phe Leu Ala Pro Glu Val Leu
1 5 10 15
Thr Gln Glu Ala Tyr Thr Arg
20
<210> 272
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<221> 残基的翻译后修饰
<222> 1
<223> 磷酸化
<220>
<223> MLK3 (T277)
<400> 272
Thr Thr Gln Met Ser Ala Ala Gly Thr Tyr Ala Trp Met Ala Pro Glu
1 5 10 15
Val Ile Lys
<210> 273
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> HIPK3 (Y359)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 273
Thr Val Cys Ser Thr Tyr Leu Gln Ser Arg
1 5 10
<210> 274
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Erk2 (T185)
<220>
<221> 残基的翻译后修饰
<222> 13
<223> 磷酸化
<400> 274
Val Ala Asp Pro Asp His Asp His Thr Gly Phe Leu Thr Glu Tyr Val
1 5 10 15
Ala Thr Arg
<210> 275
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Erk2 (Y187)
<220>
<221> 残基的翻译后修饰
<222> 15
<223> 磷酸化
<400> 275
Val Ala Asp Pro Asp His Asp His Thr Gly Phe Leu Thr Glu Tyr Val
1 5 10 15
Ala Thr Arg
<210> 276
<211> 19
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Erk2 (T190)
<220>
<221> 残基的翻译后修饰
<222> 18
<223> 磷酸化
<400> 276
Val Ala Asp Pro Asp His Asp His Thr Gly Phe Leu Thr Glu Tyr Val
1 5 10 15
Ala Thr Arg
<210> 277
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> FRK (Y387)
<220>
<221> 残基的翻译后修饰
<222> 7
<223> 磷酸化
<400> 277
Val Asp Asn Glu Asp Ile Tyr Glu Ser Arg
1 5 10
<210> 278
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> EphA7 (Y791)
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 278
Val Ile Glu Asp Asp Pro Glu Ala Val Tyr Thr Thr Thr Gly Gly Lys
1 5 10 15
<210> 279
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> EphA6 (Y830)
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 279
Val Leu Glu Asp Asp Pro Glu Ala Ala Tyr Thr Thr Thr Gly Gly Lys
1 5 10 15
<210> 280
<211> 13
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GAK (S456)
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 280
His Pro Gly His Tyr Ala Val Tyr Asn Leu Ser Pro Arg
1 5 10
<210> 281
<211> 21
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GAK (S829)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 281
Asp Glu Ser Glu Val Ser Asp Glu Gly Gly Ser Pro Ile Ser Ser Glu
1 5 10 15
Gly Gln Glu Pro Arg
20
<210> 282
<211> 21
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GAK (S834)
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 282
Asp Glu Ser Glu Val Ser Asp Glu Gly Gly Ser Pro Ile Ser Ser Glu
1 5 10 15
Gly Gln Glu Pro Arg
20
<210> 283
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GAK (S1176)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<400> 283
Val Ser Glu Asn Asp Phe Glu Asp Leu Leu Ser Asn Gln Gly Phe Ser
1 5 10 15
Ser Arg
<210> 284
<211> 18
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> GAK (S1176&S1185)
<220>
<221> 残基的翻译后修饰
<222> 2
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 11
<223> 磷酸化
<400> 284
Val Ser Glu Asn Asp Phe Glu Asp Leu Leu Ser Asn Gln Gly Phe Ser
1 5 10 15
Ser Arg
<210> 285
<211> 21
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CLK2 (T344)
<220>
<221> 残基的翻译后修饰
<222> 20
<223> 磷酸化
<400> 285
Val Val Asp Phe Gly Ser Ala Thr Phe Asp His Glu His His Ser Thr
1 5 10 15
Ile Val Ser Thr Arg
20
<210> 286
<211> 12
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK1 (T161)
<220>
<221> 残基的翻译后修饰
<222> 3
<223> 磷酸化
<400> 286
Val Tyr Thr His Glu Val Val Thr Leu Trp Tyr Arg
1 5 10
<210> 287
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> CDK1 (S178)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 287
Ser Pro Glu Val Leu Leu Gly Ser Ala Arg
1 5 10
<210> 288
<211> 16
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> EphA2 (T771/Y772)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 10
<223> 磷酸化
<400> 288
Val Leu Glu Asp Asp Pro Glu Ala Thr Tyr Thr Thr Ser Gly Gly Lys
1 5 10 15
<210> 289
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> EphA2 (S790)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<400> 289
Trp Thr Ala Pro Glu Ala Ile Ser Tyr Arg
1 5 10
<210> 290
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> EphA2 (S790/Y791)
<220>
<221> 残基的翻译后修饰
<222> 8
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 290
Trp Thr Ala Pro Glu Ala Ile Ser Tyr Arg
1 5 10
<210> 291
<211> 10
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> EphA2 (Y791)
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 291
Trp Thr Ala Pro Glu Ala Ile Ser Tyr Arg
1 5 10
<210> 292
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Syk (Y525)
<220>
<221> 残基的翻译后修饰
<222> 5
<223> 磷酸化
<400> 292
Ala Asp Glu Asn Tyr Tyr Lys
1 5
<210> 293
<211> 7
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Syk (Y526)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<400> 293
Ala Asp Glu Asn Tyr Tyr Lys
1 5
<210> 294
<211> 11
<212> PRT
<213> 智人(Homo sapiens)
<220>
<223> Syk (Y546)
<220>
<221> 残基的翻译后修饰
<222> 6
<223> 磷酸化
<220>
<221> 残基的翻译后修饰
<222> 9
<223> 磷酸化
<400> 294
Trp Tyr Ala Pro Glu Cys Ile Asn Tyr Tyr Lys
1 5 10
<210> 295
<211> 13
<212> PRT
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Claims (17)
1.用于监测样品中激酶活性或活化的方法,该方法包括以下步骤:
a)提供包含激酶的样品;
b)将所述样品与蛋白酶一起温育以将步骤a)中提供的所述激酶裂解为蛋白酶特异性蛋白水解肽;
c)对所述样品进行磷酸肽富集;
d)通过液相色谱-质谱法分析步骤c)中获得的所述样品;以及
e)检测步骤a)中提供的所述激酶的磷酸化,
其中,仅在鉴定出与所述激酶的活化区域相关的蛋白水解肽的情况下才执行步骤e)的所述检测。
2.根据权利要求1所述的方法,其中,所述方法进一步包括以下步骤:
i)确定所要监测的激酶;
ii)确定与所关注的激酶的活化区域相关的蛋白酶特异性蛋白水解肽;以及
iii)调整质谱仪的设置,以便在步骤e)中仅检测在步骤ii)中确定的蛋白酶特异性蛋白水解肽。
3.根据权利要求1或2所述的方法,其中,所述方法进一步包括以下步骤:
f)对步骤e)中检测到的所述磷酸化进行定量。
4.根据权利要求3的方法,其中,在步骤f)中,通过靶向质谱法来实现定量。
5.根据权利要求3或4所述的方法,其中,在步骤f)中,定量通过基于靶向MS1、MS2或MSn的定量来实现,其中,n是大于2的整数。
6.根据前述权利要求中任一项所述的方法,其中,与所述激酶的活化区域相关的蛋白水解肽包括与所述激酶的t环相关的蛋白水解肽。
7.根据前述权利要求中任一项所述的方法,其中,所述蛋白酶选自胰蛋白酶、内切蛋白酶Glu-C、胰凝乳蛋白酶和内切蛋白酶Asp-N。
8.根据前述权利要求中任一项所述的方法,其中,所述磷酸肽富集选自固定金属离子亲和色谱法(IMAC)诸如Fe(III)-IMAC、Ga(III)-IMAC、Ti(IV)-IMAC或Zr(IV)-IMAC,以及金属氧化物亲和色谱(MOAC)诸如TiO2-MOAC或ZrO2-MOAC。
9.根据前述权利要求中任一项所述的方法,其中,所述磷酸肽富集包括Fe(III)-IMAC。
10.根据前述权利要求中任一项所述的方法,其中,所述液相色谱法包括反相色谱法。
11.根据前述权利要求中任一项所述的方法,其中,所述液相色谱法选自纳米液相色谱法、毛细管流动液相色谱法和毛细管微流动液相色谱法。
12.根据前述权利要求中任一项所述的方法,其中,所述质谱法包括选自以下的质谱采集方法:选择性反应监测、多反应监测、平行反应监测和高分辨率的多反应监测。
13.根据前述权利要求中任一项所述的方法,其中,所述质谱法包括选自以下的质谱采集方法:基于数据非依赖性采集(DIA)的质谱法和靶向肽定量法。
14.根据前述权利要求中任一项所述的方法,其中,所述质谱法包括串联质谱法。
15.根据前述权利要求中任一项所述的方法,其中,所述质谱法包括使用四极杆质谱仪或飞行时间质谱仪。
16.根据前述权利要求中任一项所述的方法,其中,所述质谱法包括使用离子阱质谱仪,如轨道阱质谱仪或线性离子阱质谱仪。
17.根据前述权利要求中任一项所述的方法,其中,在步骤d)中,所述液相色谱-质谱法包括在三重四极杆质谱仪上以选择性反应监测模式将纳米液相色谱法与MS/MS结合起来使用。
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WO2019243590A1 (en) | 2019-12-26 |
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US20210262007A1 (en) | 2021-08-26 |
US11624082B2 (en) | 2023-04-11 |
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