Characterization of Human Homeodomain-interacting Protein Kinase 4 (HIPK4) as a Unique Member of the HIPK Family.
Characterization of Human Homeodomain-interacting Protein Kinase 4 (HIPK4) as a Unique Member of the HIPK Family.
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发表时间：
2010
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通讯作者：
Qin He;Jingxue Shi;Hong Sun;J. An;Ying Huang;M. Sheikh
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作者：
Qin He;Jingxue Shi;Hong Sun;J. An;Ying Huang;M. Sheikh
同源结构域相互作用蛋白激酶（包括 HIPK1、HIPK2 和 HIPK3）是丝氨酸/苏氨酸激酶，形成高度保守的激酶家族。 HIPK 参与多种细胞功能，包括调节细胞死亡、存活、增殖和分化。在此，我们报告了人类 HIPK4 的特征，该人类 HIPK4 是我们在努力解开与细胞死亡和存活相关的新标记物期间通过蛋白质组筛选鉴定的。人HIPK4蛋白由616个残基组成，预计分子量为69.425 kDa，并且在其N末端具有丝氨酸/苏氨酸蛋白激酶催化结构域。在体外激酶测定中，HIPK4表现出激酶活性，其催化结构域中保守的赖氨酸40或天冬氨酸136残基的突变使其激酶功能失活。人类 HIPK4 具有多个假定的丝氨酸/苏氨酸和酪氨酸特异性磷酸化位点，还包含四个高概率的苏酰化位点，这些发现表明其功能受到翻译后修饰的调节。 HIPK4 在数据库中如此命名是因为其与 HIPK1、2 和 3 的序列同源性主要集中在其催化结构域内。然而，HIPK4 的尺寸比已知的 HIPK 小，并且具有其他独特的特征，表明它是 HIPK 家族的独特成员。需要对 HIPK4 进行进一步的功能表征，这对于确定它是否执行不同的功能或与其他 HIPK 共享重叠的功能很有价值。
Homeodomain-interacting protein kinases including HIPK1, HIPK2 and HIPK3 are serine/threonine kinases that form a family of highly conserved kinases. HIPKs are involved in diverse cellular functions including regulation cell death, survival, proliferation and differentiation. Here we report the characterization of a human HIPK4 that we identified in a proteomic screen during our efforts to unravel novel markers linked to cell death and survival. Human HIPK4 protein is composed of 616 residues with predicted molecular mass of 69.425 kDa and harbors a serine/threonine protein kinase catalytic domain at its N-terminal end. In the in vitro kinase assay, HIPK4 exhibits kinase activity and mutation of the conserved lysine 40 or aspartic acid 136 residue in its catalytic domain inactivates its kinase function. Human HIPK4 harbors multiple putative serine/threonine- and tyrosine-specific phsophorylation sites and also contains four high probability sumoylation sites, findings that suggest its function to be modulated by post-translational modifications. HIPK4 has been so named in the database because of its sequence homology to HIPK1, 2 and 3 predominantly within its catalytic domain. However, HIPK4 is smaller in size than the known HIPKs and has additional distinct features suggesting it to be a unique member of the HIPK family. Further functional characterization of HIPK4 is needed and will prove valuable to ascertain whether it performs distinct functions or share overlapping functions with other HIPKs.