Hypocretin is an early member of the incretin gene family

Histamine-N-methyltransferase (HMT) inactivates the neurotransmitter histamine. Central histaminergic deficits may contribute to the cognitive impairment of neurodegenerative disorders including Alzheimer's disease (AD) and Down syndrome (DS). However, there is no evidence for histaminergic deficits in Pick's disease (PiD). HMT levels were measured in the frontal cortex and cerebellum of brains of patients with AD, DS, and PiD, and normal aged subjects using proteomics techniques. In frontal cortex, HMT was significantly decreased in DS, but significantly increased in PiD compared with controls. HMT levels were comparable in cerebellum of all groups. Elevated HMT in PiD could lead to increased histamine degradation that in turn would be in agreement with impaired cognitive functions of PiD. Decreased HMT in DS would be compatible with findings of decreased histamine synthesis, thus reflecting a compensation mechanism to antagonize reduced synthesis by decreased degradation.     

ERp29, an unusual redox-inactive member of the thioredoxin family

Oxidative folding in the endoplasmic reticulum is accomplished by a group of oxidoreductases where the protein disulfide isomerase (PDI) plays a key role. Structurally, redox-active PDI domains, like many other enzymes utilizing cysteine chemistry, adopt characteristic thioredoxin folds. However, this structural unit is not necessarily associated with the redox function and the current review focuses on the interesting example of a loss-of-function PDI-like protein from the endoplasmic reticulum, ERp29. ERp29 shares a common predecessor with PDI; however in the course of divergent evolution it has lost a hallmark active site motif of redox enzymes but retained the characteristic structural fold in one of its domains. Although the functional characterization of ERp29 is far from completion, all available data point to its important role in the early secretory pathway and allow tentative categorization as a secretion factor/escort protein of a broad profile.     

Cloning and characterization of TNKL, a member of tankyrase gene family

By serological screening of a breast tumor cDNA library we have identified a novel human gene, tnkl, encoding an ankyrin-related protein with a high degree of similarity to tankyrase, the poly(ADP-ribose)polymerase associated with human telomeres (Smith et al, Science 282: 1484). The tnkl gene maps to chromosome 10, while the tnks gene encoding tankyrase is located on chromosome 8. The predicted 1166-aa protein product of the tnkl gene is 78% identical to human tankyrase and 62% to a putative D. melanogaster protein. Since the proteins have essentially identical domain structures, the corresponding genes form a distinct gene family. The possible link between TNKL and cancer justifies its further functional analysis.     

Aiolos: an ungrateful member of the Ikaros family

Ikaros family members play an important role in hematopoietic development. Thompson et al. (2007) show that pre-BCR signaling induces Aiolos expression, which in turn suppresses the expression of the pre-BCR component lambda5 and eliminates the very structure that signaled its appearance.     

原生动物阴道毛滴虫的酵酶长寿保障基因LAG1同源基因克隆和序列分析

为了探讨寄生性原虫阴道毛滴虫细胞生长和衰老相关基因,作者从阴道毛滴虫的cDNA表达文库中分离出一具910碱基对的cDNA克隆,其编码框长834 bp,推测蛋白质序列有277个氨基酸.序列分析显示该克隆与酵酶长寿保障基因LAG1同源性最高,其氨基酸序列中含有LAG1及其同源基因保守的Lag1结构域和TLC结构域以及6个跨膜螺旋区和一个C-未端的内质网保留信号域.因此推测该克隆系酵酶LAG1的同源基因,该基因可能参与阴道毛滴虫的神经酰胺生物合成以及调解细胞的生命期或细胞衰老.该基因的基因组DNA与其cDNA序列一致,提示该基因序列中可能无内含子.     

scbA from Streptococcus crista CC5A: an atypical member of the lraI gene family.

A new member of the lraI family of putative adhesin genes was cloned, from Streptococcus crista CC5A, and sequenced. The gene, scbA appears to be part of an ABC transport operon and encodes a putative peptide of 34.7 kDa. The protein contains a signal sequence with residues 17 to 21 (L-A-A-C-S) matching the consensus sequence for the prolipoprotein cleavage site of signal peptidase II. ScbA is 57 to 93% identical, at the amino acid level, with the five previous sequenced members of the LraI family. Surprisingly, ScbA does not exhibit adhesion properties characteristic of the other LraI proteins. Strain CC5A bound poorly to saliva-coated hydroxyapatite and did not coaggregate with Actinomyces naeslundii PK606. An scbA insertion-duplication mutation that abolished expression (of ScbA was created. There was no difference in fibrin binding between this mutant and wild-type CC5A. Since it is possible that ScbA could play a role in corncob formation between S. crista and Fusobacterium nucleatum, this property was examined. The mutant strain retained the ability to form corncobs. On the basis of the lack of adhesin properties it appears that ScbA is an atypical member of the LraI family.     

Clinical and molecular spectrum of Wiedemann-Steiner syndrome,an emerging member of the chromatinopathy family

Wiedemann-Steiner syndrome (OMIM #605130) is a rare congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature; consistent facial features, including long eyelashes, thick or arched eyebrows with a lateral flare, wide nasal bridge, and downslanting and vertically narrow palpebral fissures; mild to moderate intellectual disability; behavioral difficulties; and hypertrichosis on the back. It is caused by heterozygous pathogenic variants in KMT2A. This gene has an established role in histone methylation, which explains the overlap of Wiedemann-Steiner syndrome with other chromatinopathies, a heterogeneous group of syndromic conditions that share a common trigger: The disruption of one of the genes involved in chromatin modification, leading to dysfunction of the epigenetic machinery.     

CLDN23 gene,frequently down-regulated in intestinal-type gastric cancer,is a novel member of CLAUDIN gene family

Microarray analyses combined with laser-capture microdissection have been applied for risk assessments of gastric cancer as well as for identification of novel genes associated with gastric cancer. EST AA393089 derived from an unknown gene has been reported to be frequently down-regulated in intestinal-type gastric cancer. Here, we identified and characterized the gene corresponding to EST AA393089 by using bioinformatics. EST AA393089 overlapped with BC016047 cDNA, and BC016047 overlapped with EST BM821052. Because the mRNA determined by assembling BM821052 and BC016047 was derived from a novel Claudin (CLDN) family gene, the gene corresponding to EST AA393089 was designated CLDN23. Human CLDN23 mRNA was expressed in germinal center B cells, placenta, stomach as well as in colon tumor. Mouse AK009330 and AK037108 cDNAs were derived from mouse Cldn23 gene. Human CLDN23 (292 aa) and mouse Cldn23 (296 aa) were four-transmembrane proteins, showing 79.5% total-amino-acid identity. WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C, was conserved among four-transmembrane proteins of CLDN family. CLDN23 gene, linked to MFHAS1 and PPP1R3B genes, was mapped to human chromosome 8p23.1. CLDN21, CLDN22, and CLDN24 genes were also identified in this study. CLDN21 and CLDN22 genes were located within human genomic contig NT_022792.13. CLDN24 gene on human chromosome 11q23 was located within human genomic contig NT_033899.3. Among 23 CLDN family genes within the human genome, CLDN1 and CLDN16 genes were clustered on human chromosome 3q28, CLDN3 and CLDN4 on 7q11, CLDN6 and CLDN9 on 16p13.3, CLDN8 and CLDN17 on 21q22.11, CLDN21 and CLDN22 on 4q35.1. This is the first report on comprehensive characterization of CLDN23 gene, a candidate tumor suppressor gene implicated in intestinal-type gastric cancer.     

Identification of a novel human DDX40 gene, a new member of the DEAH-box protein family

 The DExH/D-box superfamily of RNA helicases seems to play key roles during RNA metabolism, such as pre-mRNA splicing, ribosome biogenesis, and others. We have cloned a new gene of the DEAH-box protein subgroup, designated DDX40 (DEAD/H-box polypeptide 40 gene). DDX40 contains 3656 nucleotides and codes for a putative 779-amino-acid protein. Sequence analysis of the cDNA product revealed that it contained a DEAH (Asp-Glu-Ala-His) sequence motif and other conserved motifs. The DDX40 protein shared 53% and 43% amino acid identity with human DDX8 and yeast Drh1, respectively, in the conserved region. Northern blot analysis showed that DDX40 was expressed ubiquitously in the eight tissues examined, implying a general physiological function of the protein. We speculate that, like other members of the DExH/D-box superfamily, DDX40 may play roles in pre-mRNA splicing, ribosome biogenesis and other RNA processing functions. Received: August 7, 2002 / Accepted: September 12, 2002     

Identification of a novel human DDX40gene,a new member of the DEAH-box protein family

The DExH/D-box superfamily of RNA helicases seems to play key roles during RNA metabolism, such as pre-mRNA splicing, ribosome biogenesis, and others. We have cloned a new gene of the DEAH-box protein subgroup, designated DDX40 (DEAD/H-box polypeptide 40 gene). DDX40 contains 3656 nucleotides and codes for a putative 779-amino-acid protein. Sequence analysis of the cDNA product revealed that it contained a DEAH (Asp-Glu-Ala-His) sequence motif and other conserved motifs. The DDX40 protein shared 53% and 43% amino acid identity with human DDX8 and yeast Drh1, respectively, in the conserved region. Northern blot analysis showed that DDX40 was expressed ubiquitously in the eight tissues examined, implying a general physiological function of the protein. We speculate that, like other members of the DExH/D-box superfamily, DDX40 may play roles in pre-mRNA splicing, ribosome biogenesis and other RNA processing functions.     

Cloning and identification of the human LPAAT-zeta gene,a novel member of the lysophosphatidic acid acyltransferase family

Lysophosphatidic acid (LPA) is a naturally occurring component of phospholipid and plays a critical role in the regulation of many physiological and pathophysiological processes including cell growth, survival, and pro-angiogenesis. LPA is converted to phosphatidic acid by the action of lysophosphatidic acid acyltransferase (LPAAT). Five members of the LPAAT gene family have been detected in humans to date. Here, we report the identification of a novel LPAAT member, which is designated as LPAAT-. LPAAT- was predicted to encode a protein consisting of 456 amino acid residues with a signal peptide sequence and the acyltransferase domain. Northern blot analysis showed that LPAAT- was ubiquitously expressed in all 16 human tissues examined, with levels in the skeletal muscle, heart, and testis being relatively high and in the lung being relatively low. The human LPAAT- gene consisted of 13 exons and is positioned at chromosome 8p11.21.Electronic database information: the accession number for the data in this article is as follows: AF406612     

Genome-wide identification of the Penicillium digitatum bZIP gene family and the roles of one key member,PdatfA

Penicillium digitatum is the most common cause of postharvest decay in citrus fruits around the world. Previous studies revealed that the bZIP gene family plays crucial roles in development, stress adaptation, and pathogenicity in fungi. However, little is known about the bZIP genes in P. digitatum. In this study, we systematically identified the bZIP family in 23 Penicillium species and analyzed their evolutionary relationships. We found that gene loss and gene duplication shaped the evolution of the Penicillium bZIP family. P. digitatum experienced 3 bZIP gene loss events, but with no gene duplication. We subsequently characterized the biological functions of one important member, PdatfA in P. digitatum by constructing the deletion mutant. Results showed that ΔPdatfA exhibited a moderate growth defect, reduced pigmentation, and slightly increased resistance to fungicides iprodione and fludioxonil. However, ΔPdatfA displayed similar rot symptoms to that of the wild-type. The ΔPdatfA mycelia were not affected in response to oxidative stress while its conidia showed enhanced resistance due to the upregulation of catalases. Our results provide new insights into the evolution and functions of the bZIP gene family in Penicillium.     

Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1

We report the isolation and cloning of the Wrch-1 (Wnt-1 responsive Cdc42 homolog) cDNA. Wrch-1 is a novel gene whose mRNA level increases in response to Wnt-1 signaling in Wnt-1 transformed cells, Wnt-1 transgene induced mouse mammary tumors, and Wnt-1 retrovirus infected cells. Wrch-1 encodes a homolog of the Rho family of GTPases. It shares 57% amino acid sequence identity with Cdc42, but possesses a unique N-terminal domain that contains several putative PXXP SH3-binding motifs. Like Cdc42, Wrch-1 can activate PAK-1 and JNK-1, and induce filopodium formation and stress fiber dissolution. Active Wrch-1 stimulates quiescent cells to reenter the cell cycle. Moreover, overexpression of Wrch-1 phenocopies Wnt-1 in morphological transformation of mouse mammary epithelial cells. Taken together, Wrch-1 could mediate the effects of Wnt-1 signaling in the regulation of cell morphology, cytoskeletal organization, and cell proliferation.     

A cold-sensitive mRNA splicing mutant is a member of the RNA helicase gene family

We have isolated a cold-sensitive mutant of Saccharomyces cerevisiae in which the first step of mRNA splicing is inhibited. The growth and splicing defects are recessive and cosegregate, thus defining a single essential gene (PRP28). The wild-type PRP28 gene was cloned, and sequence analysis reveals extensive homology to a family of proteins that are thought to function as ATP-dependent RNA helicases. The cold sensitivity is caused by a glycine-to-glutamic acid change in a conserved sequence motif. Interestingly, double mutants containing conditional alleles of PRP28 and PRP24, which encodes a U6 snRNA-binding protein, are inviable. In addition, a suppressor of prp28-1 is a mutant allele of PRP8, which encodes a U5 protein, thus linking PRP28 with U5. These data are consistent with a scenario in which PRP28 acts to unwind the U4/U6 base-pairing interaction in the U4/U6/U5 snRNP, facilitating the first covalent step of splicing.