关于FAT1、FAT2、FAT3和FAT4的比较整合组学。

Comparative integromics on FAT1, FAT2, FAT3 and FAT4.

作者信息

Katoh Yuriko, Katoh Masaru

机构信息

M&M Medical BioInformatics, Hongo 113-0033, Japan.

出版信息

Int J Mol Med. 2006 Sep;18(3):523-8.

PMID:16865240

Abstract

WNT5A, WNT5B, WNT11, FZD3, FZD6, VANGL1, VANGL2, DVL1, DVL2, DVL3, PRICKLE1, PRICKLE2, ANKRD6, NKD1, NKD2, DAAM1, DAAM2, CELSR1, CELSR2, CELSR3, ROR1 and ROR2 are planar cell polarity (PCP) signaling molecules implicated in the regulation of cellular polarity, convergent extension, and invasion. FAT1, FAT2, FAT3 and FAT4 are Cadherin superfamily members homologous to Drosophila Fat, functioning as a positive regulator of PCP in the Drosophila wing. Complete coding sequence (CDS) for human FAT1 (NM_005245.3) and FAT2 (NM_001447.1) are available, while artificial CDS for human FAT3 (XM_926199 and XM_936538) and partial CDS for FAT4 (NM_024582.2). Here, complete CDS of human FAT3 and FAT4 were determined by using bioinformatics and human intelligence (Humint). FAT3 gene, consisting of 26 exons, encoded a 4557-aa protein with extracellular 33 Cadherin repeats, one Laminin G (LamG) domain and two EGF domains. FAT4 gene encoded a 4924-aa protein with extracellular 34 Cadherin repeats, two LamG domains and three EGF domains. Cytoplasmic VCSVxPxLP and SDYxS motifs were identified as novel motifs conserved among FAT1, FAT2 and FAT3 orthologs. Domain architecture comparison and phylogenetic analysis revealed that FAT1, FAT2 and FAR3 were divergent from FAT4. FAT1-MTNR1A locus at 4q35.2 and FAT3-MTNR1B locus at 11q14.3-q21 were paralogous regions within the human genome. FAT1 mRNA was expressed in embryonic stem (ES) cells, neural tissues, gastric cancer, pancreatic cancer, colorectal cancer, breast cancer, lung cancer and brain tumors. FAT2 mRNA was expressed in infant brain, cerebellum, gastric cancer, pancreatic cancer, ovarian cancer, esophageal cancer, skin squamous cell carcinoma, head and neck cancer. FAT3 mRNA was expressed in ES cells, primitive neuroectoderm, fetal brain, infant brain, adult neural tissues and prostate. FAT4 mRNA was expressed in fetal brain, infant brain, brain tumor and colorectal cancer. FAT family members were revealed to be targets of systems medicine in the fields of oncology and neurology.

摘要

WNT5A、WNT5B、WNT11、FZD3、FZD6、VANGL1、VANGL2、DVL1、DVL2、DVL3、PRICKLE1、PRICKLE2、ANKRD6、NKD1、NKD2、DAAM1、DAAM2、CELSR1、CELSR2、CELSR3、ROR1和ROR2是平面细胞极性（PCP）信号分子，参与细胞极性、汇聚延伸和侵袭的调节。FAT1、FAT2、FAT3和FAT4是与果蝇Fat同源的钙黏蛋白超家族成员，在果蝇翅膀中作为PCP的正调节因子发挥作用。人类FAT1（NM_005245.3）和FAT2（NM_001447.1）的完整编码序列（CDS）可用，而人类FAT3的人工CDS（XM_926199和XM_936538）以及FAT4的部分CDS（NM_024582.2）。在此，通过生物信息学和人工情报（Humint）确定了人类FAT3和FAT4的完整CDS。FAT3基因由26个外显子组成，编码一个4557个氨基酸的蛋白质，具有细胞外33个钙黏蛋白重复序列、一个层粘连蛋白G（LamG）结构域和两个表皮生长因子（EGF）结构域。FAT4基因编码一个4924个氨基酸的蛋白质，具有细胞外34个钙黏蛋白重复序列、两个LamG结构域和三个EGF结构域。细胞质VCSVxPxLP和SDYxS基序被鉴定为在FAT1、FAT2和FAT3直系同源物中保守的新基序。结构域架构比较和系统发育分析表明，FAT1、FAT2和FAR3与FAT4不同。位于4q35.2的FAT1-MTNR1A位点和位于11q14.3-q21的FAT3-MTNR1B位点是人类基因组中的旁系同源区域。FAT1 mRNA在胚胎干细胞、神经组织、胃癌、胰腺癌、结直肠癌、乳腺癌、肺癌和脑肿瘤中表达。FAT2 mRNA在婴儿脑、小脑、胃癌、胰腺癌、卵巢癌、食管癌、皮肤鳞状细胞癌、头颈癌中表达。FAT3 mRNA在胚胎干细胞、原始神经外胚层、胎儿脑、婴儿脑、成人神经组织和前列腺中表达。FAT4 mRNA在胎儿脑、婴儿脑、脑肿瘤和结直肠癌中表达。FAT家族成员被揭示为肿瘤学和神经学领域系统医学的靶点。